WorldWideScience
 
 
1

Standard error of inverse prediction for dose-response relationship: approximate and exact statistical inference.  

UK PubMed Central (United Kingdom)

This paper develops a new metric, the standard error of inverse prediction (SEIP), for a dose-response relationship (calibration curve) when dose is estimated from response via inverse regression. SEIP can be viewed as a generalization of the coefficient of variation to regression problem when x is predicted using y-value. We employ nonstandard statistical methods to treat the inverse prediction, which has an infinite mean and variance due to the presence of a normally distributed variable in the denominator. We develop confidence intervals and hypothesis testing for SEIP on the basis of the normal approximation and using the exact statistical inference based on the noncentral t-distribution. We derive the power functions for both approaches and test them via statistical simulations. The theoretical SEIP, as the ratio of the regression standard error to the slope, is viewed as reciprocal of the signal-to-noise ratio, a popular measure of signal processing. The SEIP, as a figure of merit for inverse prediction, can be used for comparison of calibration curves with different dependent variables and slopes. We illustrate our theory with electron paramagnetic resonance tooth dosimetry for a rapid estimation of the radiation dose received in the event of nuclear terrorism.

Demidenko E; Williams BB; Flood AB; Swartz HM

2013-05-01

2

When is statistical significance not significant?  

Scientific Electronic Library Online (English)

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

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

2013-01-01

3

Statistical significance of combinatorial regulations.  

Science.gov (United States)

More than three transcription factors often work together to enable cells to respond to various signals. The detection of combinatorial regulation by multiple transcription factors, however, is not only computationally nontrivial but also extremely unlikely because of multiple testing correction. The exponential growth in the number of tests forces us to set a strict limit on the maximum arity. Here, we propose an efficient branch-and-bound algorithm called the "limitless arity multiple-testing procedure" (LAMP) to count the exact number of testable combinations and calibrate the Bonferroni factor to the smallest possible value. LAMP lists significant combinations without any limit, whereas the family-wise error rate is rigorously controlled under the threshold. In the human breast cancer transcriptome, LAMP discovered statistically significant combinations of as many as eight binding motifs. This method may contribute to uncover pathways regulated in a coordinated fashion and find hidden associations in heterogeneous data. PMID:23882073

Terada, Aika; Okada-Hatakeyama, Mariko; Tsuda, Koji; Sese, Jun

2013-07-23

4

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

UK PubMed Central (United Kingdom)

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

Parfett C; Williams A; Zheng JL; Zhou G

2013-10-01

5

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

Science.gov (United States)

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

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

2013-07-04

6

Dose-response relationship in skin sensitization.  

UK PubMed Central (United Kingdom)

The dose-response relationship (challenge phase) of the skin sensitization response was investigated in previously sensitized Hartley guinea pigs. Larger numbers of animals were used per group at the lower doses so that statistically significant observations could be made. Model compounds known to be skin sensitizers were used: a strong sensitizer, dinitrochlorobenzene (DNCB), and a weaker sensitizer, p-phenylenediamine (PPDA). A gradation in response to changing DNCB doses was easily observed by using either the open epicutaneous test (OET) or the Buehler occlusive patch test. The Buehler test was used to study the dose-response relationship of DNCB sensitization. The sensitivity of the OET and Buehler test was judged not adequate to measure the dose response for PPDA, because at high doses a high incidence of responders was not obtained. Therefore, the maximization test was used to evaluate PPDA. Similar, non-linear dose-response curves were obtained with each compound. The higher doses produced a somewhat linear relationship, but at lower doses the curves flattened out and more slowly approached a zero response. Thus, for potent sensitizers, concentrations found in exposure situations might be in the linear portion of the dose-response curve. For weak responders, use concentrations might be in the shallow portion of the curve, where reactions would be underestimated if a linear dose-response curve were assumed.

Bronaugh RL; Roberts CD; McCoy JL

1994-02-01

7

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

International Nuclear Information System (INIS)

[en] 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

1997-01-01

8

Statistical Significance of the Gallium Anomaly  

CERN Document Server

We calculate the statistical significance of the anomalous deficit of electron neutrinos measured in the radioactive source experiments of the GALLEX and SAGE solar neutrino detectors taking into account the uncertainty of the detection cross section. We found that the statistical significance of the anomaly is about 2.9 sigma. A fit of the data in terms of neutrino oscillations favors at about 3.5 sigma short-baseline electron neutrino disappearance with respect to the null hypothesis of no oscillations.

Giunti, Carlo

2010-01-01

9

THE STATISTICAL SIGNIFICANCE OF THE 'DARK FLOW'  

International Nuclear Information System (INIS)

We revisit recent claims of a significant detection of a bulk flow of distant galaxy clusters. We do not find a statistically significant detection of a bulk flow. Instead we find that cosmic microwave background correlations between the eight Wilkinson Microwave Anisotropy Probe channels used in this analysis decrease the inferred significance of the detection to 0.7?.

2009-12-10

10

Statistical significance of cis-regulatory modules  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. Results We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. Conclusion The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM) and MODSTORM software.

Schones Dustin E; Smith Andrew D; Zhang Michael Q

2007-01-01

11

Finding statistically significant communities in networks  

CERN Multimedia

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, ...

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

2010-01-01

12

Assessment of statistical significance and clinical relevance  

DEFF Research Database (Denmark)

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

Kieser, M.; Friede, T.

2013-01-01

13

Statistical significance of close pairs of QSOs  

Energy Technology Data Exchange (ETDEWEB)

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

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

1985-10-03

14

The Significant Digit Law in Statistical Physics  

CERN Document Server

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

Shao, Lijing; 10.1016/j.physa.2010.04.021

2010-01-01

15

Statistical significance tests for autoradiographic data  

International Nuclear Information System (INIS)

The purpose of this paper is to develop statistical methods that take radiation spread into account in analyzing data from different autoradiographic experiments. The method uses the probability circle analysis of Salpeter and McHenry to obtain the probable source of each radioactive emission and the circle and point counting method of Williams to estimate the relative area occupied by each cellular site. Two levels of analysis are presented. The first level of analysis is concerned with estimating relative activities and standard errors for cellular items that are larger than the probability circle. The second level of analysis involves estimating relative activities and standard errors for cellular sites that are smaller than the probability circle and are therefore observed in circles containing another item such as cytoplasmic matrix. Two different tests of hypotheses are discussed. The first null hypothesis is that the radioactivity is randomly distributed among the cellular sites. The second null hypothesis is that there is no difference between two different treatments in the relative activities for a given site.

1985-01-01

16

Significance analysis and statistical mechanics: an application to clustering.  

UK PubMed Central (United Kingdom)

This Letter addresses the statistical significance of structures in random data: given a set of vectors and a measure of mutual similarity, how likely is it that a subset of these vectors forms a cluster with enhanced similarity among its elements? The computation of this cluster p value for randomly distributed vectors is mapped onto a well-defined problem of statistical mechanics. We solve this problem analytically, establishing a connection between the physics of quenched disorder and multiple-testing statistics in clustering and related problems. In an application to gene expression data, we find a remarkable link between the statistical significance of a cluster and the functional relationships between its genes.

?uksza M; Lässig M; Berg J

2010-11-01

17

Clinical trials in wound care. II: Achieving statistical significance.  

Science.gov (United States)

Clinical trials must be well designed in order to produce statistically and clinically significant results. This article describes the randomisation techniques that can prevent bias, the importance of sample size and the concept of power analysis. PMID:11998597

Venkatraman, P; Anand, S; Dean, C; Nettleton, R

2002-04-01

18

Clinical trials in wound care. II: Achieving statistical significance.  

UK PubMed Central (United Kingdom)

Clinical trials must be well designed in order to produce statistically and clinically significant results. This article describes the randomisation techniques that can prevent bias, the importance of sample size and the concept of power analysis.

Venkatraman P; Anand S; Dean C; Nettleton R

2002-04-01

19

Caveats for using statistical significance tests in research assessments  

DEFF Research Database (Denmark)

This article raises concerns about the advantages of using statistical significance tests in research assessments as has recently been suggested in the debate about proper normalization procedures for citation indicators by Opthof and Leydesdorff (2010). Statistical significance tests are highly controversial and numerous criticisms have been leveled against their use. Based on examples from articles by proponents of the use statistical significance tests in research assessments, we address some of the numerous problems with such tests. The issues specifically discussed are the ritual practice of such tests, their dichotomous application in decision making, the difference between statistical and substantive significance, the implausibility of most null hypotheses, the crucial assumption of randomness, as well as the utility of standard errors and confidence intervals for inferential purposes. We argue that applying statistical significance tests and mechanically adhering to their results are highly problematic and detrimental to critical thinking. We claim that the use of such tests do not provide any advantages in relation to deciding whether differences between citation indicators are important or not. On the contrary their use may be harmful. Like many other critics, we generally believe that statistical significance tests are over- and misused in the empirical sciences including scientometrics and we encourage a reform on these matters.

Schneider, Jesper Wiborg

2013-01-01

20

Significance analysis and statistical mechanics: an application to clustering.  

Science.gov (United States)

This Letter addresses the statistical significance of structures in random data: given a set of vectors and a measure of mutual similarity, how likely is it that a subset of these vectors forms a cluster with enhanced similarity among its elements? The computation of this cluster p value for randomly distributed vectors is mapped onto a well-defined problem of statistical mechanics. We solve this problem analytically, establishing a connection between the physics of quenched disorder and multiple-testing statistics in clustering and related problems. In an application to gene expression data, we find a remarkable link between the statistical significance of a cluster and the functional relationships between its genes. PMID:21231375

?uksza, Marta; Lässig, Michael; Berg, Johannes

2010-11-23

 
 
 
 
21

Cancer dose-response extrapolations  

Energy Technology Data Exchange (ETDEWEB)

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

Sielken, R.L. Jr.

1987-11-01

22

Dose response relationship and Alara  

International Nuclear Information System (INIS)

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

1986-01-01

23

Sequence-specific sequence comparison using pairwise statistical significance.  

UK PubMed Central (United Kingdom)

There has been a deluge of biological sequence data in the public domain, which makes sequence comparison one of the most fundamental computational problems in bioinformatics. The biologists routinely use pairwise alignment programs to identify similar, or more specifically, related sequences (having common ancestor). It is a well-known fact that almost everything in bioinformatics depends on the inter-relationship between sequence, structure, and function (all encapsulated in the term relatedness), which is far from being well understood. The potential relatedness of two sequences is better judged by statistical significance of the alignment score rather than by the alignment score alone. This chapter presents a summary of recent advances in accurately estimating statistical significance of pairwise local alignment for the purpose of identifying related sequences, by making the sequence comparison process more sequence specific. Comparison of using pairwise statistical significance to rank database sequences, with well-known database search programs like BLAST, PSI-BLAST, and SSEARCH, is also presented. As expected, the sequence-comparison performance (evaluated in terms of retrieval accuracy) improves significantly as the sequence comparison process is made more and more sequence specific. Shortcomings of currently used approaches and some potentially useful directions for future work are also presented.

Agrawal A; Choudhary A; Huang X

2011-01-01

24

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

Science.gov (United States)

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

Little, M P; Muirhead, C R

1997-01-01

25

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

International Nuclear Information System (INIS)

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

1993-01-01

26

Mahalanobis distance and variable selection to optimize dose response  

International Nuclear Information System (INIS)

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

1979-01-01

27

Increasing the statistical significance of entanglement detection in experiments  

International Nuclear Information System (INIS)

[en] Entanglement is often verified by a violation of an inequality like a Bell inequality or an entanglement witness. Considerable effort has been devoted to the optimization of such inequalities in order to obtain a high violation. We demonstrate theoretically and experimentally that such an optimization does not necessarily lead to a better entanglement test, if the statistical error is taken into account. Theoretically, we show for different error models that reducing the violation of an inequality can improve the significance. We show this to be the case for an error model in which the variance of an observable is interpreted as its error and for the standard error model in photonic experiments. Specifically, we demonstrate that the Mermin inequality yields a Bell test which is statistically more significant than the Ardehali inequality in the case of a photonic four-qubit state that is close to a GHZ state. Experimentally, we observe this phenomenon in a four-photon experiment, testing the above inequalities for different levels of noise.

2010-01-01

28

Why selective publication of statistically significant results can be effective.  

Science.gov (United States)

Concerns exist within the medical and psychological sciences that many published research findings are not replicable. Guidelines accordingly recommend that the file drawer effect should be eliminated and that statistical significance should not be a criterion in the decision to submit and publish scientific results. By means of a simulation study, we show that selectively publishing effects that differ significantly from the cumulative meta-analytic effect evokes the Proteus phenomenon of poorly replicable and alternating findings. However, the simulation also shows that the selective publication approach yields a scientific record that is content rich as compared to publishing everything, in the sense that fewer publications are needed for obtaining an accurate meta-analytic estimation of the true effect. We conclude that, under the assumption of self-correcting science, the file drawer effect can be beneficial for the scientific collective. PMID:23840479

de Winter, Joost; Happee, Riender

2013-06-20

29

Statistical versus quantitative significance in the socioeconomic evaluation of medicines.  

Science.gov (United States)

This article examines the twin concepts of the statistical significance and quantitative importance of observed differences in studies comparing medicines in terms of economic parameters such as cost-effectiveness and measures of health-related quality of life (HRQOL). Central to the design and interpretation of any comparative study, such as a randomised controlled trial, is some prior judgement about the order of magnitude of a difference that would make one switch from one therapy to another. Starting with current definitions of clinically important differences we argue by analogy that the importance of differences in HRQOL require a shift of focus from the physician to the patient for preferences and judgements concerning what is important to them. Whether an intervention offers sufficient value for money (cost effectiveness or cost utility) to warrant resources being reallocated to it is a collective decision requiring the input of public preferences about the relative importance of alternative therapies and health benefits. Ultimately, the importance of the health benefits offered by a new drug is revealed by societal willingness-to-pay. This may be stated implicitly through committees using cost-effectiveness 'league tables' for decision making, or explicitly by consumer surveys of willingness-to-pay in the context of cost-benefit analysis and stemming from the theoretical foundation of welfare economics. PMID:10147230

O'Brien, B J; Drummond, M F

1994-05-01

30

Statistical versus quantitative significance in the socioeconomic evaluation of medicines.  

UK PubMed Central (United Kingdom)

This article examines the twin concepts of the statistical significance and quantitative importance of observed differences in studies comparing medicines in terms of economic parameters such as cost-effectiveness and measures of health-related quality of life (HRQOL). Central to the design and interpretation of any comparative study, such as a randomised controlled trial, is some prior judgement about the order of magnitude of a difference that would make one switch from one therapy to another. Starting with current definitions of clinically important differences we argue by analogy that the importance of differences in HRQOL require a shift of focus from the physician to the patient for preferences and judgements concerning what is important to them. Whether an intervention offers sufficient value for money (cost effectiveness or cost utility) to warrant resources being reallocated to it is a collective decision requiring the input of public preferences about the relative importance of alternative therapies and health benefits. Ultimately, the importance of the health benefits offered by a new drug is revealed by societal willingness-to-pay. This may be stated implicitly through committees using cost-effectiveness 'league tables' for decision making, or explicitly by consumer surveys of willingness-to-pay in the context of cost-benefit analysis and stemming from the theoretical foundation of welfare economics.

O'Brien BJ; Drummond MF

1994-05-01

31

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

International Nuclear Information System (INIS)

Cytogenetic data, derived from cultured lymphocytes of atomic bomb survivors and controls in the ABCC-RERF Adult Health Study cohort, have been analyzed to determine differences in the dose-response relationships for chromosome aberrations between the T65D and DS86 dose estimates and to assess differences between Hiroshima and Nagasaki. For a linear dose-response model, the average percentage of cells with at least one chromosome aberration increases less rapidly with dose in Nagasaki than in Hiroshima. The magnitude of the intercity difference in the percentage of cells with aberrations per gray is less for DS86 than for T65D, though the difference is statistically significant for both kerma and bone marrow dose with either dosimetry. The percentage of cells with aberrations per gray for DS86 kerma estimates is about 60 % greater than the corresponding T65D slope. Analyses to test nonlinearity in the dose-response function indicate significant departures (p

1989-01-01

32

In vitro human cytogenetic dose-response systems  

International Nuclear Information System (INIS)

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

1979-10-20

33

On the statistical significance of the conductance quantization  

CERN Multimedia

Recent experiments on atomic-scale metallic contacts have shown that the quantization of the conductance appears clearly only after the average of the experimental results. Motivated by these results we have analyzed a simplified model system in which a narrow neck is randomly coupled to wide ideal leads, both in absence and presence of time reversal invariance. Based on Random Matrix Theory we study analytically the probability distribution for the conductance of such system. As the width of the leads increases the distribution for the conductance becomes sharply peaked close to an integer multiple of the quantum of conductance. Our results suggest a possible statistical origin of conductance quantization in atomic-scale metallic contacts.

Bascones, E; Sáenz, J J

1997-01-01

34

Exploring the dose response of radiochromic dosimeters  

International Nuclear Information System (INIS)

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

2013-06-26

35

Animal and human dose-response models for Brucella species.  

Science.gov (United States)

Human Brucellosis is one of the most common zoonotic diseases worldwide. Disease transmission often occurs through the handling of domestic livestock, as well as ingestion of unpasteurized milk and cheese, but can have enhanced infectivity if aerosolized. Because there is no human vaccine available, rising concerns about the threat of Brucellosis to human health and its inclusion in the Center for Disease Control's Category B Bioterrorism/Select Agent List make a better understanding of the dose-response relationship of this microbe necessary. Through an extensive peer-reviewed literature search, candidate dose-response data were appraised so as to surpass certain standards for quality. The statistical programming language, "R," was used to compute the maximum likelihood estimation to fit two models, the exponential and the approximate beta-Poisson (widely used for quantitative risk assessment) to dose-response data. Dose-response models were generated for prevalent species of Brucella: Br. suis, Br. melitensis, and Br. abortus. Dose-response models were created for aerosolized Br. suis exposure to guinea pigs from pooled studies. A parallel model for guinea pigs inoculated through both aerosol and subcutaneous routes with Br. melitensis showed that the median infectious dose corresponded to a 30 colony-forming units (CFU) dose of Br. suis, much less than the N(50) dose of about 94 CFU for Br. melitensis organisms. When Br. melitensis was tested subcutaneously on mice, the N(50) dose was higher, 1,840 CFU. A dose-response model was constructed from pooled data for mice, rhesus macaques, and humans inoculated through three routes (subcutaneously/aerosol/intradermally) with Br. melitensis. PMID:21449960

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

2011-03-30

36

Animal and human dose-response models for Brucella species.  

UK PubMed Central (United Kingdom)

Human Brucellosis is one of the most common zoonotic diseases worldwide. Disease transmission often occurs through the handling of domestic livestock, as well as ingestion of unpasteurized milk and cheese, but can have enhanced infectivity if aerosolized. Because there is no human vaccine available, rising concerns about the threat of Brucellosis to human health and its inclusion in the Center for Disease Control's Category B Bioterrorism/Select Agent List make a better understanding of the dose-response relationship of this microbe necessary. Through an extensive peer-reviewed literature search, candidate dose-response data were appraised so as to surpass certain standards for quality. The statistical programming language, "R," was used to compute the maximum likelihood estimation to fit two models, the exponential and the approximate beta-Poisson (widely used for quantitative risk assessment) to dose-response data. Dose-response models were generated for prevalent species of Brucella: Br. suis, Br. melitensis, and Br. abortus. Dose-response models were created for aerosolized Br. suis exposure to guinea pigs from pooled studies. A parallel model for guinea pigs inoculated through both aerosol and subcutaneous routes with Br. melitensis showed that the median infectious dose corresponded to a 30 colony-forming units (CFU) dose of Br. suis, much less than the N(50) dose of about 94 CFU for Br. melitensis organisms. When Br. melitensis was tested subcutaneously on mice, the N(50) dose was higher, 1,840 CFU. A dose-response model was constructed from pooled data for mice, rhesus macaques, and humans inoculated through three routes (subcutaneously/aerosol/intradermally) with Br. melitensis.

Teske SS; Huang Y; Tamrakar SB; Bartrand TA; Weir MH; Haas CN

2011-10-01

37

A reanalysis of curvature in the dose response for cancer and modifications by age at exposure following radiation therapy for benign disease.  

UK PubMed Central (United Kingdom)

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(-1) of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. CONCLUSIONS: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

Little MP; Stovall M; Smith SA; Kleinerman RA

2013-02-01

38

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

UK PubMed Central (United Kingdom)

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

Pedersen E; Waye KP

2004-12-01

39

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

Science.gov (United States)

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

Pedersen, Eja; Persson Waye, Kerstin

2004-12-01

40

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

Science.gov (United States)

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

Pedersen, Eja; Waye, Kerstin Persson

2004-12-01

 
 
 
 
41

Dose-response relationship in local radiotherapy for hepatocellular carcinoma  

International Nuclear Information System (INIS)

Purpose: Dose escalation using three-dimensional conformal radiotherapy (3D-CRT) is based on the hypothesis that increasing the dose can enhance tumor control. This study aimed to determine whether a dose-response relationship exists in local radiotherapy for primary hepatocellular carcinoma (HCC). Methods and Materials: One hundred fifty-eight patients were enrolled in the present study between January 1992 and March 2000. The exclusion criteria included the presence of an extrahepatic metastasis, liver cirrhosis of Child class C, tumors occupying more than two-thirds of the entire liver, and a performance status on the Eastern Cooperative Oncology Group scale of more than 3. Radiotherapy was given to the field, including the tumor, with generous margin using 6- or 10-MV X-rays. The mean radiation dose was 48.2 ± 7.9 Gy in daily 1.8-Gy fractions. The tumor response was assessed based on diagnostic radiologic examinations, including a computed tomography scan, magnetic resonance imaging, and hepatic artery angiography 4-8 weeks after the completion of treatment. Liver toxicity and gastrointestinal complications were evaluated. Results: An objective response was observed in 106 of 158 (67.1%) patients. Statistical analysis revealed that the total dose was the most significant factor associated with the tumor response. The response rates in patients treated with doses 50 Gy were 29.2%, 68.6%, and 77.1%, respectively. Survivals at 1 and 2 years after radiotherapy were 41.8% and 19.9%, respectively, with a median survival time of 10 months. The rate of liver toxicity according to the doses 50 Gy was 4.2%, 5.9%, and 8.4%, respectively, and the rate of gastrointestinal complications was 4.2%, 9.9%, and 13.2%, respectively. Conclusions: The present study showed the existence of a dose-response relationship in local radiotherapy for primary HCC. Only the radiation dose was a significant factor for predicting an objective response. The results of this study showed that 3D-CRT can theoretically be used for treating primary HCC.

2002-09-01

42

Nonparametric analysis of dose-response relationships.  

UK PubMed Central (United Kingdom)

A nonparametric method, isotonic regression, is proposed for analyzing a dose-response relationship and for assessing a threshold value. There are several advantages of this method compared to parametric models. No specific form of the relationship (type of model and use of the covariates) is required. The only assumption is monotonicity. Rejection of specific hypothesis can be based on the result of a permutation test. Several applications (para-aramid, crystalline silica, and PNOC) are presented. In these examples the dose-response relationships are analyzed. Where a relationship is present the existence of a threshold is investigated.

Ulm K

1999-01-01

43

Early radiation dose-response in lung: an ultrastructural study  

International Nuclear Information System (INIS)

A systematic fine-structural study of dog lungs was undertaken to ascertain the radiation dose response in the lungs of large animals. The capillary endothelium appeared to be the initial site of the post-irradiation pulmonary damage. This subpheural response included diffuse septal thickening, fibrosis, edema, and reduced alveolar lumina. The deep parenchymal response involved perivascular fibrosis, which was associated with perivascular hyperplasia of Type II pneumocytes, increased number and sizes of lamellar bodies, increased production and release of lamellar surfactant. No changes of alveolar luminar size were noted. The most significant changes were observed in those dose zones exposed to greater than 2400 rad, suggesting the possibility of an identifiable dose-response relationship. Early detection of radiation pneumonitis by electron microscopy is demonstrated, and qualitative and quantitative correlation of injury with both postirradiation time and dose is presented.

1977-01-01

44

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

Energy Technology Data Exchange (ETDEWEB)

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 be elevated at the end of follow-up. These data are consistent with the tumorigenic effects of radiation lasting at least 40 yr.

Schneider, A.B.; Gierlowski, T.C. (Univ. of Illinois, Chicago, IL (United States)); Ron, E.; Lubin, J. (National Cancer Institute, Bethesda, MD (United States)); Stovall, M. (Univ. of Texas, Houston, TX (United States))

1993-08-01

45

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 be elevated at the end of follow-up. These data are consistent with the tumorigenic effects of radiation lasting at least 40 yr.

1993-01-01

46

An efficient method for statistical significance calculation of transcription factor binding sites  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Various statistical models have been developed to describe the DNA binding preference of transcription factors, by which putative transcription factor binding sites (TFBS) can be identified according to scores assigned. Statistical significance of these scores, usually known as the p-value, play ...

Qian, Ziliang; Lu, Lingyi; Qi, Liu; Li, Yixue

47

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 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.

2010-07-15

48

Analytical modelling of regional radiotherapy dose response of lung  

International Nuclear Information System (INIS)

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

2012-06-07

49

Limits to chemical hormesis as a dose-response model in health risk assessment.  

UK PubMed Central (United Kingdom)

This review presents and discusses the extent to which chemical hormesis meets five important requirements for performance of any dose-response model in the toxicological and regulatory sciences. These include (1) the requirement that there be a documented and accepted mechanistic basis for the dose-response model's plausible role and use in health risk assessment; (2) the requirement that any newly proposed dose-response methodology can be compared with current models as to reliability and scientific validity; (3) the requirement that the underlying reliability and stability of the model be established as to its temporal aspects, that is, minimal temporal lag between stressor contact and biological or toxicological response and temporal stability expressed throughout the prevailing relationship; (4) the requirement that the dose-response model be as broadly applicable as other dose-response methodologies being applied in human health risk assessment; and, (5) the requirement that any dose-response model proposed as default methodology can be characterized as to variability and uncertainty and will have a minimal likelihood of harm to the health of impacted populations. This review includes a brief treatment of definitions of hormesis and its place in nonmonotonic dose-response relationships. Overall, critical evaluation of chemical hormesis as a dose-response model in risk assessment shows it to have significant limits within the five requirements. These limits will impede any acceptance of chemical hormesis as a default approach in health risk assessment.

Mushak P

2013-01-01

50

A Probabilistic Model of Local Sequence Alignment That Simplifies Statistical Significance Estimation  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Sequence database searches require accurate estimation of the statistical significance of scores. Optimal local sequence alignment scores follow Gumbel distributions, but determining an important parameter of the distribution (?) requires time-consuming computational simulation. Moreover, optimal al...

Eddy, Sean R.

51

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

DEFF Research Database (Denmark)

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

Engsted, Tom

2009-01-01

52

Clinical versus statistical significance as they relate to the efficacy of periodontal therapy.  

UK PubMed Central (United Kingdom)

BACKGROUND: The author discusses the shortcomings of using statistical significance testing as a method to infer that results of periodontal clinical trials are clinically meaningful. To compensate for these deficiencies, he also identifies criteria and periodontal parameters that can be used to reflect clinically significant outcomes. TYPES OF STUDIES REVIEWED: The author searched the medical and dental literature to identify commentaries that addressed the problems associated with interpreting statistical significance testing, or hypothesis testing, and defining clinical significance. RESULTS: The limitations of statistical significance testing related to identifying clinically significant changes include failure to indicate if the detected differences between variables in test and control groups are large or important. After reviewing various definitions of the term "clinical significance," the author reviews and proposes a comprehensive working definition of it. Regarding the efficacy of periodontal therapy, he delineates the advantages and limitations of specific criteria (such as absolute values, cut points) that can be used to define clinical significance. CLINICAL IMPLICATIONS: The author suggests that clinically significant results should be defined before initiating a study and statistical significance testing should be used to validate that findings did not occur by chance. This would help place the importance of clinical data into perspective, and it would enhance clinicians' ability to select the most appropriate therapies for particular sites in periodontal patients.

Greenstein G

2003-05-01

53

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

Energy Technology Data Exchange (ETDEWEB)

We examined how to select the method of statistical significance test as to the evaluation obtained by diagnostic imaging. We used 6-10 pairs of small data, and classified the distribution style using skewness and kurtosis. In statistical significance test, we used the paired t-test as a parametric test, and the Wilcoxon test as a non-parametric test. We tried to select the method of the statistical significance test in consideration of the power of test in each distribution style. The result of the X{sup 2} test, which is a test of normalization, there was no significance. In the case the paired t-test may be adecuate, considering the power of test, we should use the Wilcoxon test, in case that the both bottoms spread or the right bottom spreads. (author)

Tabata, Youji [Nara Hospital (Japan)

2000-02-01

54

Method for assessing the statistical significance of mass spectral similarities using basic local alignment search tool statistics.  

UK PubMed Central (United Kingdom)

A novel method for assessing the statistical significance of mass spectral similarities was developed using modified basic local alignment search tool (BLAST; Karlin-Altschul) statistics. In gas chromatography/mass spectrometry-based metabolomics, many signals in raw metabolome data are identified on the basis of unexpected similarities among mass spectra and the spectra of standards. Since there is inevitably noise in the observed spectra, a list of identified metabolites includes some false positives. In the developed method, electron ionization (EI) mass spectrometry-BLAST, a similarity score of two mass spectra is calculated using a general scoring scheme, from which the probability of obtaining the score by chance (P value) is calculated. For this purpose, a simple rule for converting a unit EI mass spectrum to a mass spectral sequence as well as a score matrix for aligned mass spectral sequences was developed. A Monte Carlo simulation using randomly generated mass spectral sequences demonstrated that the null distribution or the expected number of hits (E value) follows modified Karlin-Altschul statistics. A metabolite data set obtained from green tea extract was analyzed using the developed method. Among 171 metabolite signals in the metabolome data, 93 signals were identified on the basis of significant similarities (P < 0.015) with reference data. Since the expected number of false positives is 2.6, the false discovery rate was estimated to be 2.8%, indicating that the search threshold (P < 0.015) is reasonable for metabolite identification.

Matsuda F; Tsugawa H; Fukusaki E

2013-09-01

55

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

Directory of Open Access Journals (Sweden)

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

Lee-Ann C. Hayek; W. Ronald Heyer

2005-01-01

56

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

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Genetic mutation, selective pressure for translational efficiency and accuracy, level of gene expression, and protein function through natural selection are all believed to lead to codon usage bias (CUB). Therefore, informative measurement of CUB is of fundamental importance to making inferences regarding gene function and genome evolution. However, extant measures of CUB have not fully accounted for the quantitative effect of background nucleotide composition and have not statistically evaluated the significance of CUB in sequence analysis. Results Here we propose a novel measure--Codon Deviation Coefficient (CDC)--that provides an informative measurement of CUB and its statistical significance without requiring any prior knowledge. Unlike previous measures, CDC estimates CUB by accounting for background nucleotide compositions tailored to codon positions and adopts the bootstrapping to assess the statistical significance of CUB for any given sequence. We evaluate CDC by examining its effectiveness on simulated sequences and empirical data and show that CDC outperforms extant measures by achieving a more informative estimation of CUB and its statistical significance. Conclusions As validated by both simulated and empirical data, CDC provides a highly informative quantification of CUB and its statistical significance, useful for determining comparative magnitudes and patterns of biased codon usage for genes or genomes with diverse sequence compositions.

Zhang Zhang; Li Jun; Cui Peng; Ding Feng; Li Ang; Townsend Jeffrey P; Yu Jun

2012-01-01

57

Modeling dose response using generalized linear models  

Energy Technology Data Exchange (ETDEWEB)

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

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

1996-03-01

58

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

UK PubMed Central (United Kingdom)

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

Clark DJ; Lipworth BJ

1997-01-01

59

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

Science.gov (United States)

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

Clark, D J; Lipworth, B J

1997-01-01

60

Citation bias favoring statistically significant studies was present in medical research.  

UK PubMed Central (United Kingdom)

OBJECTIVE: Statistically significant studies may be cited more than negative studies on the same topic. We aimed to assess here whether such citation bias is present across the medical literature. STUDY DESIGN AND SETTING: We conducted a cohort study of the association between statistical significance and citations. We selected all therapeutic intervention studies included in meta-analyses published between January and March 2010 in the Cochrane database, and retrieved citation counts of all individual studies using ISI Web of Knowledge. The association between the statistical significance of each study and the number of citations it received between 2008 and 2010 was assessed in mixed Poisson models. RESULTS: We identified 89 research questions addressed in 458 eligible articles. Significant studies were cited twice as often as nonsignificant studies (multiplicative effect of significance: 2.14, 95% confidence interval: 1.38-3.33). This association was partly because of the higher impact factor of journals where significant studies are published (adjusted multiplicative effect of significance: 1.14, 95% confidence interval: 0.87-1.51). CONCLUSION: A citation bias favoring significant results occurs in medical research. As a consequence, treatments may seem more effective to the readers of medical literature than they really are.

Jannot AS; Agoritsas T; Gayet-Ageron A; Perneger TV

2013-03-01

 
 
 
 
61

Dose-response effects of oral yohimbine in unrestrained primates.  

UK PubMed Central (United Kingdom)

Six unrestrained bonnet macaques were each observed after oral administration of four dosages of yohimbine hydrochloride (0.10, 0.25, 0.50, and 0.75 mg/kg) and a placebo. Yohimbine significantly increased episodes of motoric activation and affective response interspersed with intervals of behavioral enervation. Yohimbine scores correlated closely with baseline levels; there was no dose-response relationship. Response to oral yohimbine differed in several ways from subcutaneous and intravenous sodium lactate infusions, including prominent enervative symptoms and the appearance of sexual arousal. In light of the appearance of cyclic enervative episodes, this study suggests limitations to primate models of panic disorder utilizing oral yohimbine.

Rosenblum LA; Coplan JD; Friedman S; Bassoff T

1991-04-01

62

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

Directory of Open Access Journals (Sweden)

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

Larsen Thomas; Krogh Anders

2003-01-01

63

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2010-11-01

64

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

International Nuclear Information System (INIS)

A data analysis, which incorporates time dependencies, is demonstrated for the dose response of leukemia mortality in the atomic bomb survivors. The time dependencies are initially left unspecified and the data are used to infer them. Two principal findings based on the T65 revised dose estimates are obtained. First, it is shown that the fits to the data of constant risk L-Q-L, L-L, and Q-L dose-response models are significantly improved (p

1983-01-01

65

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

CERN Multimedia

This book presents our case in defense of a constructivist epistemological framework and the use of compatible statistical theory and inference tools. The basic metaphor of decision theory is the maximization of a gambler's expected fortune, according to his own subjective utility, prior beliefs an learned experiences. This metaphor has proven to be very useful, leading the development of Bayesian statistics since its XX-th century revival, rooted on the work of de Finetti, Savage and others. The basic metaphor presented in this text, as a foundation for cognitive constructivism, is that of an eigen-solution, and the verification of its objective epistemic status. The FBST - Full Bayesian Significance Test - is the cornerstone of a set of statistical tolls conceived to assess the epistemic value of such eigen-solutions, according to their four essential attributes, namely, sharpness, stability, separability and composability. We believe that this alternative perspective, complementary to the one ofered by dec...

Stern, J M

2010-01-01

66

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

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Evidence-based medicine posits that health care research is founded upon clinically important differences in patient centered outcomes. Statistically significant differences between two treatments may not necessarily reflect a clinically important difference. We aimed to quantify the sample sizes and magnitude of treatment effects in a review of orthopaedic randomized trials with statistically significant findings. Methods We conducted a comprehensive search (PubMed, Cochrane) for all randomized controlled trials between 1/1/95 to 12/31/04. Eligible studies include those that focused upon orthopaedic trauma. Baseline characteristics and treatment effects were abstracted by two reviewers. Briefly, for continuous outcome measures (ie functional scores), we calculated effect sizes (mean difference/standard deviation). Dichotomous variables (ie infection, nonunion) were summarized as absolute risk differences and relative risk reductions (RRR). Effect sizes >0.80 and RRRs>50% were defined as large effects. Using regression analysis we examined the association between the total number of outcome events and treatment effect (dichotomous outcomes). Results Our search yielded 433 randomized controlled trials (RCTs), of which 76 RCTs with statistically significant findings on 184 outcomes (122 continuous/62 dichotomous outcomes) met study eligibility criteria. The mean effect size across studies with continuous outcome variables was 1.7 (95% confidence interval: 1.43–1.97). For dichotomous outcomes, the mean risk difference was 30% (95%confidence interval:24%–36%) and the mean relative risk reduction was 61% (95% confidence interval: 55%–66%; range: 0%–97%). Fewer numbers of total outcome events in studies was strongly correlated with increasing magnitude of the treatment effect (Pearson's R = -0.70, p Conclusion Our review suggests that statistically significant results in orthopaedic trials have the following implications-1) On average large risk reductions are reported 2) Large treatment effects (>50% relative risk reduction) are correlated with few number of total outcome events. Readers should interpret the results of such small trials with these issues in mind.

Sung Jinsil; Siegel Judith; Tornetta Paul; Bhandari Mohit

2008-01-01

67

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

International Nuclear Information System (INIS)

[en] 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

1994-01-01

68

Efficient statistical significance approximation for local similarity analysis of high-throughput time series data.  

UK PubMed Central (United Kingdom)

MOTIVATION: Local similarity analysis of biological time series data helps elucidate the varying dynamics of biological systems. However, its applications to large scale high-throughput data are limited by slow permutation procedures for statistical significance evaluation. RESULTS: We developed a theoretical approach to approximate the statistical significance of local similarity analysis based on the approximate tail distribution of the maximum partial sum of independent identically distributed (i.i.d.) random variables. Simulations show that the derived formula approximates the tail distribution reasonably well (starting at time points > 10 with no delay and > 20 with delay) and provides P-values comparable with those from permutations. The new approach enables efficient calculation of statistical significance for pairwise local similarity analysis, making possible all-to-all local association studies otherwise prohibitive. As a demonstration, local similarity analysis of human microbiome time series shows that core operational taxonomic units (OTUs) are highly synergetic and some of the associations are body-site specific across samples. AVAILABILITY: The new approach is implemented in our eLSA package, which now provides pipelines for faster local similarity analysis of time series data. The tool is freely available from eLSA's website: http://meta.usc.edu/softs/lsa. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online. CONTACT: fsun@usc.edu.

Xia LC; Ai D; Cram J; Fuhrman JA; Sun F

2013-01-01

69

On determining the statistical significance of discontinuities within ordered ecological data  

International Nuclear Information System (INIS)

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

1992-01-01

70

Publication bias in clinical trials due to statistical significance or direction of trial results.  

UK PubMed Central (United Kingdom)

BACKGROUND: The tendency for authors to submit, and of journals to accept, manuscripts for publication based on the direction or strength of the study findings has been termed publication bias. OBJECTIVES: To assess the extent to which publication of a cohort of clinical trials is influenced by the statistical significance, perceived importance, or direction of their results. SEARCH STRATEGY: We searched the Cochrane Methodology Register (The Cochrane Library [Online] Issue 2, 2007), MEDLINE (1950 to March Week 2 2007), EMBASE (1980 to Week 11 2007) and Ovid MEDLINE In-Process & Other Non-Indexed Citations (March 21 2007). We also searched the Science Citation Index (April 2007), checked reference lists of relevant articles and contacted researchers to identify additional studies. SELECTION CRITERIA: Studies containing analyses of the association between publication and the statistical significance or direction of the results (trial findings), for a cohort of registered clinical trials. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data. We classified findings as either positive (defined as results classified by the investigators as statistically significant (P < 0.05), or perceived as striking or important, or showing a positive direction of effect) or negative (findings that were not statistically significant (P >/= 0.05), or perceived as unimportant, or showing a negative or null direction in effect). We extracted information on other potential risk factors for failure to publish, when these data were available. MAIN RESULTS: Five studies were included. Trials with positive findings were more likely to be published than trials with negative or null findings (odds ratio 3.90; 95% confidence interval 2.68 to 5.68). This corresponds to a risk ratio of 1.78 (95% CI 1.58 to 1.95), assuming that 41% of negative trials are published (the median among the included studies, range = 11% to 85%). In absolute terms, this means that if 41% of negative trials are published, we would expect that 73% of positive trials would be published.Two studies assessed time to publication and showed that trials with positive findings tended to be published after four to five years compared to those with negative findings, which were published after six to eight years. Three studies found no statistically significant association between sample size and publication. One study found no significant association between either funding mechanism, investigator rank, or sex and publication. AUTHORS' CONCLUSIONS: Trials with positive findings are published more often, and more quickly, than trials with negative findings.

Hopewell S; Loudon K; Clarke MJ; Oxman AD; Dickersin K

2009-01-01

71

Convergent Island Statistics: a fast method for determining local alignment score significance.  

UK PubMed Central (United Kingdom)

MOTIVATION: Background distribution statistics for profile-based sequence alignment algorithms cannot be calculated analytically, and hence such algorithms must resort to measuring the significance of an alignment score by assessing its location among a distribution of background alignment scores. The Gumbel parameters that describe this background distribution are usually pre-computed for a limited number of scoring systems, gap schemes, and sequence lengths and compositions. The use of such look-ups is known to introduce errors, which compromise the significance assessment of a remote homology relationship. One solution is to estimate the background distribution for each pair of interest by generating a large number of sequence shuffles and use the distribution of their scores to approximate the parameters of the underlying extreme value distribution. This is computationally very expensive, as a large number of shuffles are needed to precisely estimate the score statistics. RESULTS: Convergent Island Statistics (CIS) is a computationally efficient solution to the problem of calculating the Gumbel distribution parameters for an arbitrary pair of sequences and an arbitrary set of gap and scoring schemes. The basic idea behind our method is to recognize the lack of similarity for any pair of sequences early in the shuffling process and thus save on the search time. The method is particularly useful in the context of profile-profile alignment algorithms where the normalization of alignment scores has traditionally been a challenging task. CONTACT: aleksandar@eidogen.com SUPPLEMENTARY INFORMATION: http://www.eidogen-sertanty.com/Documents/convergent_island_stats_sup.pdf.

Poleksic A; Danzer JF; Hambly K; Debe DA

2005-06-01

72

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

UK PubMed Central (United Kingdom)

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

Poleksic A

2009-01-01

73

Caffeine and sprinting performance: dose responses and efficacy.  

UK PubMed Central (United Kingdom)

The aims of this study were to evaluate the effects of caffeine supplementation on sprint cycling performance and to determine if there was a dose-response effect. Using a randomized, double-blind, placebo-controlled design, 17 well-trained men (age: 24 ± 6 years, height: 1.82 ± 0.06 m, and body mass(bm): 82.2 ± 6.9 kg) completed 7 maximal 10-second sprint trials on an electromagnetically braked cycle ergometer. Apart from trial 1 (familiarization), all the trials involved subjects ingesting a gelatine capsule containing either caffeine or placebo (maltodextrin) 1 hour before each sprint. To examine dose-response effects, caffeine doses of 2, 4, 6, 8, and 10 mg·kg bm(-1) were used. There were no significant (p ? 0.05) differences in baseline measures of plasma caffeine concentration before each trial (grand mean: 0.14 ± 0.28 ?g·ml(-1)). There was, however, a significant supplement × time interaction (p < 0.001), with larger caffeine doses producing higher postsupplementation plasma caffeine levels. In comparison with placebo, caffeine had no significant effect on peak power (p = 0.11), mean power (p = 0.55), or time to peak power (p = 0.17). There was also no significant effect of supplementation on pretrial blood lactate (p = 0.58), but there was a significant time effect (p = 0.001), with blood lactate reducing over the 50 minute postsupplementation rest period from 1.29 ± 0.36 to 1.06 ± 0.33 mmol·L(-1). The results of this study show that caffeine supplementation has no effect on short-duration sprint cycling performance, irrespective of the dosage used.

Glaister M; Patterson SD; Foley P; Pedlar CR; Pattison JR; McInnes G

2012-04-01

74

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.

2009-01-01

75

Cloud-based solution to identify statistically significant MS peaks differentiating sample categories.  

UK PubMed Central (United Kingdom)

BACKGROUND: Mass spectrometry (MS) has evolved to become the primary high throughput tool for proteomics based biomarker discovery. Until now, multiple challenges in protein MS data analysis remain: large-scale and complex data set management; MS peak identification, indexing; and high dimensional peak differential analysis with the concurrent statistical tests based false discovery rate (FDR). "Turnkey" solutions are needed for biomarker investigations to rapidly process MS data sets to identify statistically significant peaks for subsequent validation. FINDINGS: Here we present an efficient and effective solution, which provides experimental biologists easy access to "cloud" computing capabilities to analyze MS data. The web portal can be accessed at http://transmed.stanford.edu/ssa/. CONCLUSIONS: Presented web application supplies large scale MS data online uploading and analysis with a simple user interface. This bioinformatic tool will facilitate the discovery of the potential protein biomarkers using MS.

Ji J; Ling J; Jiang H; Wen Q; Whitin JC; Tian L; Cohen HJ; Ling XB

2013-01-01

76

Lack-of-fit tests for assessing mean structures for continuous dose-response data  

DEFF Research Database (Denmark)

We review a range of lack-of-fit tests suitable for assessing the appropriateness of the mean function in dose-response models. The review encompasses both well-known tests and new tests based on recent developments in statistics, which we have extended to the dose-response case. We argue that the classical methods are inadequate in certain situations, where the new tests may be applied. Power comparisons are carried out by means of extensive simulation studies, covering both designs with and without replicates at small and large sample sizes. Three datasets from dose-response applications illustrate differences and similarities between the tests. The results suggest that the new tests perform better and exhibit a wider applicability.

Ritz, Christian; Martinussen, Torben

2011-01-01

77

An adaptive two-stage dose-response design method for establishing proof of concept.  

UK PubMed Central (United Kingdom)

We propose an adaptive two-stage dose-response design where a prespecified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics. The stage-wise test results are then combined to establish "global" PoC using a conditional error function. Our simulation studies showed good and more robust power in our design method compared to conventional and fixed designs.

Franchetti Y; Anderson SJ; Sampson AR

2013-01-01

78

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

UK PubMed Central (United Kingdom)

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, D50,i, and the normalized dose-response gradient, ?50,i. RESULTS: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D50,TRG1=92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), ?50,TRG1=0.982 (CI 0.533-1.429), and for major response (TRG1-2) D50,TRG1&2=72.1 Gy (CI 65.3-94.0 Gy), ?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.

Appelt AL; Pløen J; Vogelius IR; Bentzen SM; Jakobsen A

2013-01-01

79

Statistical, practical, clinical, and personal significance: definitions and applications in speech-language pathology.  

UK PubMed Central (United Kingdom)

PURPOSE: To discuss constructs and methods related to assessing the magnitude and the meaning of clinical outcomes, with a focus on applications in speech-language pathology. METHOD: Professionals in medicine, allied health, psychology, education, and many other fields have long been concerned with issues referred to variously as practical significance, clinical significance, social validity, patient satisfaction, treatment effectiveness, or the meaningfulness or importance of beyond-clinic or real-world treatment outcomes. Existing literature addressing these issues from multiple disciplines was reviewed and synthesized. CONCLUSIONS: Practical significance, an adjunct to statistical significance, refers to the magnitude of a change or a difference between groups. The appropriate existing term for the interpretation of treatment outcomes, or the attribution of meaning or value to treatment outcomes, is clinical significance. To further distinguish between important constructs, the authors suggest incorporating as definitive the existing notion that clinical significance may refer to measures selected or interpreted by professionals or with respect to groups of clients. The term personal significance is introduced to refer to goals, variables, measures, and changes that are of demonstrated value to individual clients.

Bothe AK; Richardson JD

2011-08-01

80

Statistical significance of probabilistic sequence alignment and related local hidden Markov models.  

UK PubMed Central (United Kingdom)

The score statistics of probabilistic gapped local alignment of random sequences is investigated both analytically and numerically. The full probabilistic algorithm (e.g., the "local" version of maximum-likelihood or hidden Markov model method) is found to have anomalous statistics. A modified "semi-probabilistic" alignment consisting of a hybrid of Smith-Waterman and probabilistic alignment is then proposed and studied in detail. It is predicted that the score statistics of the hybrid algorithm is of the Gumbel universal form, with the key Gumbel parameter lambda taking on a fixed asymptotic value for a wide variety of scoring systems and parameters. A simple recipe for the computation of the "relative entropy," and from it the finite size correction to lambda, is also given. These predictions compare well with direct numerical simulations for sequences of lengths between 100 and 1,000 examined using various PAM substitution scores and affine gap functions. The sensitivity of the hybrid method in the detection of sequence homology is also studied using correlated sequences generated from toy mutation models. It is found to be comparable to that of the Smith-Waterman alignment and significantly better than the Viterbi version of the probabilistic alignment.

Yu YK; Hwa T

2001-01-01

 
 
 
 
81

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

UK PubMed Central (United Kingdom)

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

Renard D; Looby M; Kramer B; Lawrence D; Morris D; Stanski DR

2011-01-01

82

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

Science.gov (United States)

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

2011-01-01

83

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

Directory of Open Access Journals (Sweden)

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

Renard Didier; Looby Michael; Kramer Benjamin; Lawrence David; Morris David; Stanski Donald R

2011-01-01

84

Dose-response effects of oral yohimbine in unrestrained primates.  

Science.gov (United States)

Six unrestrained bonnet macaques were each observed after oral administration of four dosages of yohimbine hydrochloride (0.10, 0.25, 0.50, and 0.75 mg/kg) and a placebo. Yohimbine significantly increased episodes of motoric activation and affective response interspersed with intervals of behavioral enervation. Yohimbine scores correlated closely with baseline levels; there was no dose-response relationship. Response to oral yohimbine differed in several ways from subcutaneous and intravenous sodium lactate infusions, including prominent enervative symptoms and the appearance of sexual arousal. In light of the appearance of cyclic enervative episodes, this study suggests limitations to primate models of panic disorder utilizing oral yohimbine. PMID:1647226

Rosenblum, L A; Coplan, J D; Friedman, S; Bassoff, T

1991-04-01

85

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

Directory of Open Access Journals (Sweden)

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

Cezary Wata?a

2007-01-01

86

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

CERN Multimedia

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

Hu, R; Hu, Rui; Wang, Bin

2000-01-01

87

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1994-12-31

88

Statistical uncertainty in long-term distributions of significant wave height  

Energy Technology Data Exchange (ETDEWEB)

This work examines some aspects involved in the estimation of the parameters of the probability distribution of significant wave height, in particular the homogeneity of the data sets and the statistical methods of fitting a distribution to data. More homogeneous data sets are organized by collecting the data on a monthly basis and by separating the simple sea states from the combined ones. A three-parameter Weibull distribution is fitted to the data. The parameters of the fitted distribution are estimated by the methods of maximum likelihood, of regression, and of the moments. The uncertainty involved in estimating the probability distribution with the three methods is compared with the one that results from using more homogeneous data sets, and it is concluded that the uncertainty involved in the fitting procedure can be more significant unless the method of moments is not considered.

Guedes Soares, C.; Henriques, A.C. [Univ. Tecnica de Lisboa (Portugal). Inst. Superior Tecnica

1996-11-01

89

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

International Nuclear Information System (INIS)

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

1997-01-01

90

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

Directory of Open Access Journals (Sweden)

Full Text Available Rationale/statement of the problem : Intranasal oxytocin attenuates cortisol levels during social stress inductions. However, no research to date has documented the dose–response relationship between intranasal oxytocin administration and cortisol, and researchers examining intranasal oxytocin have not examined the cortisol response to physical stress. We, therefore, examined the effects of 24 and 48 IU of intranasal oxytocin on the cortisol response to vigorous exercise. Methods : Seventeen males participated in a randomized, placebo-controlled, double-blind, and within-subject experiment. Participants engaged in vigorous exercise for 60 minutes following the administration of placebo or intranasal oxytocin on three occasions. Saliva samples and mood ratings were collected at 8 intervals across each session. Results : Salivary cortisol concentrations changed over time, peaking after 60 minutes of exercise [Quadratic: F(1,16)?=?7.349, p=0.015, partial ?2=0.32]. The 24 IU dose of oxytocin attenuated cortisol levels relative to placebo [F(1,16)?=?4.496, p=0.05, partial ?2=0.22) and the 48 IU dose, although the latter fell just short of statistical significance [F(1,16)?=?3.054, p=0.10, partial ?2=0.16). There was no difference in the cortisol response to exercise in participants who were administered 48 IU of intranasal oxytocin relative to placebo. Intranasal oxytocin had no effect on mood. Conclusion : This is the first study to demonstrate that the effect of intranasal oxytocin on salivary cortisol is dose-dependent, and that intranasal oxytocin attenuates cortisol levels in response to physical stress. Future research using exogenous oxytocin will need to consider the possibility of dose–response relations.

Christopher Cardoso; Mark A. Ellenbogen; Mark Anthony Orlando; Simon L. Bacon; Ridha Joober

2012-01-01

91

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

UK PubMed Central (United Kingdom)

INTRODUCTION: Intranasal oxytocin attenuates cortisol levels during social stress inductions. However, no research to date has documented the dose-response relation between intranasal oxytocin administration and cortisol, and researchers examining intranasal oxytocin have not examined the cortisol response to physical stress. We therefore examined the effects of 24IU and 48IU of intranasal oxytocin on the cortisol response to vigorous exercise. METHOD: Seventeen males participated in a randomized, placebo-controlled, double-blind, and within-subject experiment. Participants engaged in vigorous exercise for 60min following the administration of placebo or intranasal oxytocin on three occasions. Saliva samples and mood ratings were collected at eight intervals across each session. RESULTS: Salivary cortisol concentrations changed over time, peaking after 60min of exercise (quadratic: F(1,16)=7.349, p=.015, partial ?(2)=.32). The 24IU dose of oxytocin attenuated cortisol levels relative to placebo (F(1,16)=4.496, p=.05, partial ?(2)=.22) and the 48IU dose, although the latter fell just short of statistical significance (F(1,16)=3.054, p=.10, partial ?(2)=.16). There was no difference in the cortisol response to exercise in participants who were administered 48IU of intranasal oxytocin relative to placebo. Intranasal oxytocin had no effect on mood. CONCLUSION: This is the first study to demonstrate that the effect of intranasal oxytocin on salivary cortisol is dose-dependent, and that intranasal oxytocin attenuates cortisol levels in response to physical stress. Future research using exogenous oxytocin will need to consider the possibility of dose-response relations.

Cardoso C; Ellenbogen MA; Orlando MA; Bacon SL; Joober R

2013-03-01

92

The dose-response relationship between in-ear occupational noise exposure and hearing loss.  

UK PubMed Central (United Kingdom)

OBJECTIVES: Current understanding of the dose-response relationship between occupational noise and hearing loss is based on cross-sectional studies prior to the widespread use of hearing protection, and with limited data regarding noise exposures below 85 dBA. We report on the hearing loss experience of a unique cohort of industrial workers, with daily monitoring of noise inside of hearing protection devices. METHODS: At an industrial facility, workers exhibiting accelerated hearing loss were enrolled in a mandatory programme to monitor daily noise exposures inside of hearing protection. We compared these noise measurements (as time-weighted LAVG) to interval rates of high-frequency hearing loss over a 6-year period using a mixed-effects model, adjusting for potential confounders. RESULTS: Workers' high-frequency hearing levels at study inception averaged more than 40 dB Hearing threshold level (HTL). Most noise exposures were less than 85 dBA (mean LAVG 76 dBA, IQR 74-80 dBA). We found no statistical relationship between LAvg and high-frequency hearing loss (p=0.53). Using a metric for monthly maximum noise exposure did not improve model fit. CONCLUSIONS: At-ear noise exposures below 85 dBA did not show an association with risk of high-frequency hearing loss among workers with substantial past noise exposure and hearing loss at baseline. Therefore, effective noise control to below 85 dBA may lead to significant reduction in occupational hearing loss risk in such individuals. Further research is needed on the dose-response relationship of noise and hearing loss in individuals with normal hearing and little prior noise exposure.

Rabinowitz PM; Galusha D; Dixon-Ernst C; Clougherty JE; Neitzel RL

2013-07-01

93

Significance of Z-value statistics of Smith-Waterman scores for protein alignments.  

UK PubMed Central (United Kingdom)

The Z-value is an attempt to estimate the statistical significance of a Smith-Waterman dynamic alignment score (SW-score) through the use of a Monte-Carlo process. It partly reduces the bias induced by the composition and length of the sequences. This paper is not a theoretical study on the distribution of SW-scores and Z-values. Rather, it presents a statistical analysis of Z-values on large datasets of protein sequences, leading to a law of probability that the experimental Z-values follow. First, we determine the relationships between the computed Z-value, an estimation of its variance and the number of randomizations in the Monte-Carlo process. Then, we illustrate that Z-values are less correlated to sequence lengths than SW-scores. Then we show that pairwise alignments, performed on 'quasi-real' sequences (i.e., randomly shuffled sequences of the same length and amino acid composition as the real ones) lead to Z-value distributions that statistically fit the extreme value distribution, more precisely the Gumbel distribution (global EVD, Extreme Value Distribution). However, for real protein sequences, we observe an over-representation of high Z-values. We determine first a cutoff value which separates these overestimated Z-values from those which follow the global EVD. We then show that the interesting part of the tail of distribution of Z-values can be approximated by another EVD (i.e., an EVD which differs from the global EVD) or by a Pareto law. This has been confirmed for all proteins analysed so far, whether extracted from individual genomes, or from the ensemble of five complete microbial genomes comprising altogether 16956 protein sequences.

Comet JP; Aude JC; Glémet E; Risler JL; Hénaut A; Slonimski PP; Codani JJ

1999-06-01

94

Dose-response effects of spectrum research cigarettes.  

UK PubMed Central (United Kingdom)

INTRODUCTION: Experimental cigarettes are needed to conduct studies examining the effects of varying doses of nicotine content on smoking behavior. The National Institute on Drug Abuse contracted with Research Triangle Institute to make such cigarettes available to researchers. The goal of this study was to determine whether cigarettes that vary in nicotine content produce an expected dose-response effect. METHOD: Two studies were conducted. The first study recruited subjects from 3 sites and consisted of a single, within-subject laboratory session. Subjects first smoked 4 puffs on their usual-brand cigarette and then in double-blind, random-order, smoked 4 puffs on each experimental cigarette that contained either low nicotine (LN, 0.4 mg/g), intermediate nicotine (IN, 5.7-5.8 mg/g), or high nicotine (HN, 11.4-12.8 mg/g). Each puffing bout was separated by a 30-min interval. Subjects completed questionnaires and were assessed for vital signs after each cigarette. The second study involved 1 site and used a between-subject design in which subjects were assigned to 1 of the 3 experimental cigarettes for 1 week. Subjective responses and biomarkers of exposure were assessed. RESULTS: In the first study, significant dose-response effects were observed, particularly between the LN and HN cigarettes. The second study showed decreases in cigarette smoking and exposure biomarkers predominantly in the LN group, with no changes in the HN cigarette group. CONCLUSIONS: These results are similar to those observed in prior literature, confirming that these experimental cigarettes can be used safely and with the expected pharmacological effects.

Hatsukami DK; Heishman SJ; Vogel RI; Denlinger RL; Roper-Batker AN; Mackowick KM; Jensen J; Murphy SE; Thomas BF; Donny E

2013-06-01

95

Mining Statistically Significant Substrings Based on the Chi-Square Measure  

CERN Multimedia

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

Bhattacharya, Sourav Dutta Arnab

2010-01-01

96

Discovery of a statistically significant and interpretable relationship between redox reactivity and lethality of drugs.  

Science.gov (United States)

A statistically significant and interpretable relationship between electrophilicity as a redox reactivity indicator and LD50 as a lethality indicator of drugs was discovered, and this relationship could be interpreted by the action of the cytochrome P450. The drugs chosen in this study were Topoisomerase II inhibitor anticancer drugs, and the electrophilicity of drugs was obtained by quantum chemical calculation. Since the P450 detoxification mechanism is the catalytic oxidation of drug molecules, it may infer that the drug molecules being easily oxidized (low electrophilicity) will be weak in lethality in general. In addition, this relationship revealed two structural scaffolds for the anthracycline-based topoisomerase II inhibitors, and their lethality mechanisms are not totally the same. Such relationship can assist in designing new drugs that candidates possessing low electrophilicity are recommended for lowering of lethality, and moieties providing a large inductive effect can reduce the electrophilicity of the anthracycline-based topoisomerase II inhibitors. PMID:23826857

Pang, Siu-Kwong

2013-09-01

97

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

UK PubMed Central (United Kingdom)

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

Horvát EÁ; Zhang JD; Uhlmann S; Sahin O; Zweig KA

2013-01-01

98

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

Directory of Open Access Journals (Sweden)

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

Agrawal Ankit; Huang Xiaoqiu

2009-01-01

99

Only first intravitreal bevacizumab injection achieves statistically significant visual improvement in naïve myopic choroidal neovascularization  

Directory of Open Access Journals (Sweden)

Full Text Available Paolo Milani, Amedeo Massacesi, Stefano Ciaccia, Marco Setaccioli, Stefania Moschini, Fulvio BergaminiDipartimento di Oculistica, Istituto Auxologico Italiano, Milano, ItalyBackground: The aim of this study was to evaluate the efficacy of intravitreal bevacizumab when administered on an as-needed basis for the treatment of myopic choroidal neovascularization (CNV), and to assess visual changes upon treatment.Methods: This study was designed as a retrospective, interventional case series, for which the inclusion criteria were pathologic myopia, and documentation of untreated active macular CNV on fluorescein angiography and optical coherence tomography. Monthly changes in best-corrected visual acuity (BCVA), visual gain after each treatment, and correlation with refraction, age, location, and dimension of CNV were considered. The data were analyzed using the one-tailed, paired Wilcoxon test.Results: Nineteen naive eyes were found suitable for the study. The mean number of treatments was 3.32 ± 2.36 (confidence interval 2.25–4.37) during a mean follow-up period of 18.95 ± 8.3 months. At baseline, mean BCVA was 0.58 ± 0.37 logarithm of the minimum angle of resolution (logMAR) units. At 12 months, mean BCVA was 0.39 ± 0.35 logMAR and at 24 months was 0.39 ± 0.40. Mean improvement in BCVA from baseline was +0.17 ± 0.25 logMAR (P < 0.05) at month 12, +0.14 ± 0.25 logMAR (P = 0.1) at month 18, and +0.09 ± 0.32 logMAR (P = 0.5) at month 24. Improvement on pretreatment BCVA was significant (+0.16 logMAR, P < 0.01) after the first injection, but not after the second (?0.01 logMAR, P = 0.5) or third (+0.02 logMAR, P = 0.5) injections. There was a statistically significant correlation between age and number of treatments, and between improvement in BCVA of foveal versus extrafoveal location of CNV.Conclusion: The use of intravitreal bevacizumab "as needed" is an effective treatment for myopic CNV, but visual gain is statistically significant only after the first injection and decreases in the second year.Keywords: choroidal neovascularization, macular degeneration, pathologic myopia, bevacizumab, optical coherence tomography

Milani P; Massacesi A; Ciaccia S; Setaccioli M; Moschini S; Bergamini F

2012-01-01

100

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

Directory of Open Access Journals (Sweden)

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

Érika Cristina Ferreira; Paula Fernanda Massini; Caroline Felicio Braga; Ricardo Nascimento Drozino; Neide Martins Moreira; Denise Lessa Aleixo; Ana Lúcia Falavigna Guilherme; Silvana Marques de Araujo

2011-01-01

 
 
 
 
101

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

International Nuclear Information System (INIS)

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

1998-03-01

102

Phase II dose-response study of abatacept in Japanese patients with active rheumatoid arthritis with an inadequate response to methotrexate.  

UK PubMed Central (United Kingdom)

OBJECTIVE: The objective of this study was to assess the response to abatacept at doses of 2 mg/kg and 10 mg/kg compared to placebo in patients with active rheumatoid arthritis (RA) with an inadequate clinical response to methotrexate (MTX). METHODS: In this multicenter, placebo-controlled, double-blind, parallel-group, dose-response study, 195 Japanese patients with active RA with an inadequate response to MTX were randomized 1:1:1 to receive 10 mg/kg or 2 mg/kg abatacept plus MTX, or placebo plus MTX, for 24 weeks. RESULTS: Abatacept demonstrated a dose-response relationship when given at 2 and 10 mg/kg. Based on the American College of Rheumatology criteria (20, 50, and 70 %), the responses to 10 mg/kg abatacept were significantly greater than those to placebo at week 24 (p < 0.001). Smaller yet statistically significant responses were also seen in the 2 mg/kg abatacept group. Overall rates of adverse events, serious adverse events, and treatment discontinuations because of adverse events were comparable in all three groups. CONCLUSIONS: Abatacept (2 mg/kg and 10 mg/kg) showed a dose-response relationship in Japanese patients with active RA with an inadequate clinical response to MTX. Administration of abatacept in combination with MTX for 24 weeks was well tolerated.

Takeuchi T; Matsubara T; Nitobe T; Suematsu E; Ohta S; Honjo S; Abe T; Yamamoto A; Miyasaka N

2013-03-01

103

A probabilistic model of local sequence alignment that simplifies statistical significance estimation.  

Science.gov (United States)

Sequence database searches require accurate estimation of the statistical significance of scores. Optimal local sequence alignment scores follow Gumbel distributions, but determining an important parameter of the distribution (lambda) requires time-consuming computational simulation. Moreover, optimal alignment scores are less powerful than probabilistic scores that integrate over alignment uncertainty ("Forward" scores), but the expected distribution of Forward scores remains unknown. Here, I conjecture that both expected score distributions have simple, predictable forms when full probabilistic modeling methods are used. For a probabilistic model of local sequence alignment, optimal alignment bit scores ("Viterbi" scores) are Gumbel-distributed with constant lambda = log 2, and the high scoring tail of Forward scores is exponential with the same constant lambda. Simulation studies support these conjectures over a wide range of profile/sequence comparisons, using 9,318 profile-hidden Markov models from the Pfam database. This enables efficient and accurate determination of expectation values (E-values) for both Viterbi and Forward scores for probabilistic local alignments. PMID:18516236

Eddy, Sean R

2008-05-30

104

A probabilistic model of local sequence alignment that simplifies statistical significance estimation.  

UK PubMed Central (United Kingdom)

Sequence database searches require accurate estimation of the statistical significance of scores. Optimal local sequence alignment scores follow Gumbel distributions, but determining an important parameter of the distribution (lambda) requires time-consuming computational simulation. Moreover, optimal alignment scores are less powerful than probabilistic scores that integrate over alignment uncertainty ("Forward" scores), but the expected distribution of Forward scores remains unknown. Here, I conjecture that both expected score distributions have simple, predictable forms when full probabilistic modeling methods are used. For a probabilistic model of local sequence alignment, optimal alignment bit scores ("Viterbi" scores) are Gumbel-distributed with constant lambda = log 2, and the high scoring tail of Forward scores is exponential with the same constant lambda. Simulation studies support these conjectures over a wide range of profile/sequence comparisons, using 9,318 profile-hidden Markov models from the Pfam database. This enables efficient and accurate determination of expectation values (E-values) for both Viterbi and Forward scores for probabilistic local alignments.

Eddy SR

2008-05-01

105

Statistical Significance of Small Scale Anisotropy in Arrival Directions of Ultra-High Energy Cosmic Rays  

CERN Multimedia

Recently, the High Resolution Fly's Eye (HiRes) experiment claims that there is no small scale anisotropy in the arrival distribution of ultra-high energy cosmic rays (UHECRs) above $E>10^{19}$ eV contrary to the Akeno Giant Air Shower Array (AGASA) observation. In this paper, we discuss the statistical significance of this discrepancy between the two experiments. We calculate arrival distribution of UHECRs above $10^{19}$ eV predicted by the source models constructed using the Optical Redshift Survey galaxy sample. We apply the new method developed by us for calculating arrival distribution in the presence of the galactic magnetic field. The great advantage of this method is that it enables us to calculate UHECR arrival distribution with lower energy ($\\sim 10^{19}$ eV) than previous studies within reasonable time by following only the trajectories of UHECRs actually reaching the earth. It has been realized that the small scale anisotropy observed by the AGASA can be explained with the source number density ...

Yoshiguchi, H; Sato, K; Yoshiguchi, Hiroyuki; Nagataki, Shigehiro; Sato, Katsuhiko

2004-01-01

106

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

Directory of Open Access Journals (Sweden)

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

Hulshizer Randall; Blalock Eric M

2007-01-01

107

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

Directory of Open Access Journals (Sweden)

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

Santosh H. Shinde; T. Mukherjee

2010-01-01

108

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

DEFF Research Database (Denmark)

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

Christensen, Hanne Risager; Larsen, C.N.

2006-01-01

109

Dose response for travoprost® in the glaucomatous beagle.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To evaluate the changes in intraocular pressure (IOP) and pupil size in 12 Beagles with inherited glaucoma after instillations of 0.033, 0.0033, 0.001, 0.00033, and 0.0001% travoprost (Travatan®-Alcon Laboratories, Inc., Ft Worth, TX, USA) in multiple single-dose studies. PROCEDURES: Intraocular pressure and pupil diameter (PD) measurements were obtained at 9 am, 12 pm, 3 pm, and 9 am the following day (24 h) in two groups of six glaucoma dogs. After 7 days, the vehicle or concentration was repeated in the contralateral eye of the same animals. RESULTS: Concentrations of 0.00033, 0.001, and 0.0033% travoprost significantly lowered IOP and PD, but the 0.0001% concentration provided limited IOP changes, although PD changes were still significant. This suggests travoprost is effective in the dog to lower IOP and reduce pupil size at concentrations starting between 0.0001 and 0.00033%. CONCLUSIONS: The dose response for travoprost in the glaucomatous Beagle indicates this model is highly sensitive to this group of drugs, even at concentrations as low as 0.00033% (1/12 the commercially available concentration).

Mackay EO; McLaughlin M; Plummer CE; Ben-Shlomo A; Gelatt KN

2012-03-01

110

Using the bootstrap to establish statistical significance for relative validity comparisons among patient-reported outcome measures.  

UK PubMed Central (United Kingdom)

BACKGROUND: Relative validity (RV), a ratio of ANOVA F-statistics, is often used to compare the validity of patient-reported outcome (PRO) measures. We used the bootstrap to establish the statistical significance of the RV and to identify key factors affecting its significance. METHODS: Based on responses from 453 chronic kidney disease (CKD) patients to 16 CKD-specific and generic PRO measures, RVs were computed to determine how well each measure discriminated across clinically-defined groups of patients compared to the most discriminating (reference) measure. Statistical significance of RV was quantified by the 95% bootstrap confidence interval. Simulations examined the effects of sample size, denominator F-statistic, correlation between comparator and reference measures, and number of bootstrap replicates. RESULTS: The statistical significance of the RV increased as the magnitude of denominator F-statistic increased or as the correlation between comparator and reference measures increased. A denominator F-statistic of 57 conveyed sufficient power (80%) to detect an RV of 0.6 for two measures correlated at r = 0.7. Larger denominator F-statistics or higher correlations provided greater power. Larger sample size with a fixed denominator F-statistic or more bootstrap replicates (beyond 500) had minimal impact. CONCLUSIONS: The bootstrap is valuable for establishing the statistical significance of RV estimates. A reasonably large denominator F-statistic (F > 57) is required for adequate power when using the RV to compare the validity of measures with small or moderate correlations (r < 0.7). Substantially greater power can be achieved when comparing measures of a very high correlation (r > 0.9).

Deng N; Allison JJ; Fang HJ; Ash AS; Ware JE Jr

2013-01-01

111

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

Directory of Open Access Journals (Sweden)

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

Helmut Kern; Stefan Loefler; Christian Hofer; Michael Vogelauer; Samantha Burggraf; Martina Grim-Stieger; Jan Cvecka; Dusan Hamar; Nejc Sarabon; Feliciano Protasi; Antonio Musarò; Marco Sandri; Katia Rossini; Ugo Carraro; Sandra Zampieri

2012-01-01

112

Dose-response relationships and threshold levels in skin and respiratory allergy.  

Science.gov (United States)

A literature study was performed to evaluate dose-response relationships and no-effect levels for sensitization and elicitation in skin- and respiratory allergy. With respect to the skin, dose-response relationships and no-effect levels were found for both intradermal and topical induction, as well as for intradermal and topical elicitation of allergenic responses in epidemiological, clinical, and animal studies. Skin damage or irritation may result in a significant reduction of the no-effect level for a specific compound. With respect to the respiratory tract, dose-response relationships and no-effect levels for induction were found in several human as well as animal studies. Although dose-response relationships for elicitation were found in some epidemiological studies, concentration-response relationships were present only in a limited number of animal studies. Reported results suggest that especially relatively high peak concentrations can induce sensitization, and that prevention of such concentrations will prevent workers from developing respiratory allergy. Moreover, induction of skin sensitization may result in subsequent heightened respiratory responsiveness following inhalation exposure. The threshold concentration for the elicitation of allergic airway reactions in sensitized subjects is generally lower than the threshold to induce sensitization. Therefore, it is important to consider the low threshold levels for elicitation for recommendation of health-based occupational exposure limits, and to avoid high peak concentrations. Notwithstanding the observation of dose-response relationships and no-effect levels, due to a number of uncertainties, no definite conclusions can be drawn about absolute threshold values for allergens with respect to sensitization of and elicitation reactions in the skin and respiratory tract. Most predictive tests are generally meant to detect the potential of a chemical to induce skin and/or respiratory allergy at relatively high doses. Consequently, these tests do not provide information of dose-response relationships at lower doses such as found in, for example, occupational situations. In addition, the observed dose-response relationships and threshold values have been obtained by a wide variety of test methods using different techniques, such as intradermal exposure versus topical or inhalation exposure at the workplace, or using different endpoints, which all appear important for the outcome of the test. Therefore, especially with regard to respiratory allergy, standardized and validated dose-response test methods are urgently required in order to be able to recommend safe exposure levels for allergens at the workplace. PMID:16686423

Arts, Josje H E; Mommers, Carolien; de Heer, Cees

2006-03-01

113

Dose-response relation between physical activity and sick leave  

Science.gov (United States)

Objective To investigate the dose–response relation between moderate and vigorous physical activity and sick leave in a working population. Methods Data were used from three large Dutch databases: two continuous, cross sectional surveys among a representative sample of the Dutch population and one prospective cohort study. A distinction was made between duration, frequency and intensity of physical activity. The outcome measure was the number of days of sick leave. Analyses of variance were used to compare sick leave (in days) for workers with different amounts of physical activity, in particular workers meeting the physical activity recommendations v those who did not. Linear and logistic regression analyses were used to obtain effect estimates in the prospective cohort study, with the generalised estimating equation (GEE) method. Results No relation was found between moderate physical activity and sick leave. In two databases, workers meeting the recommendation of vigorous physical activity (active at a vigorous level for at least three times a week) had significantly less sick leave: more than one day over two months and more than four days over a year. The duration of vigorous physical activity was not associated with sick leave. Conclusion Physical activity at a vigorous intensity level for at least three times a week, as in the CDC/ACSM recommendation, has a positive effect on sick leave.

Proper, K I; van den Heuvel, S G; De Vroome, E M; Hildebrandt, V H; Van der Beek, A J

2006-01-01

114

Dose response of ESR signals in tooth enamel  

International Nuclear Information System (INIS)

Radiation-induced growth in the g = 2.0018 signal in fossil tooth enamel can be used to determine the age of fossil teeth. Porat and Schwarcz (1994) [Integrative Paths to the Past: Palaeoanthropological Advances in Honor of F. C. Howell (eds Corrucini R. and Ciochon R.), pp. 521-530. Prentice-Hall, Englewood Cliffs] suggested that the radiation sensitivity of all tooth enamel is quite similar, and have constructed a Universal Growth Curve (UGC) to estimate equivalent dose (DE). To further test this concept, we use a saturating exponential of the form I = Imax (1 - exp[- D/DO] to fit normalized ESR intensity (I) data for teeth from various sites. We show that the ranges of fitting parameters Imax and DO overlap for modern and fossil enamels. This suggests that no significant diagenetic changes in the enamel have occurred to affect the ESR signal in most samples. Sensitivity, as measured by normalized intensity at D = 32 Gy, varies by 22% (n = 24); modern samples have the same mean sensitivity, but show less variation (8%). The normalized dose-response curve (natural intensity vs DE) is a good predictor of DE, although there are some outliers. Imax is strongly correlated with DO, suggesting a relationship between trap concentration and capture cross-section for migrating charges. (Author).

1994-01-01

115

Proton therapy radiation pneumonitis local dose-response in esophagus cancer patients.  

UK PubMed Central (United Kingdom)

PURPOSE: This study quantifies pulmonary radiation toxicity in patients who received proton therapy for esophagus cancer. MATERIALS/METHODS: We retrospectively studied 100 esophagus cancer patients treated with proton therapy. The linearity of the enhanced FDG uptake vs. proton dose was evaluated using the Akaike Information Criterion (AIC). Pneumonitis symptoms (RP) were assessed using the Common Toxicity Criteria for Adverse Events version 4.0 (CTCAEv4). The interaction of the imaging response with dosimetric parameters and symptoms was evaluated. RESULTS: The RP scores were: 0 grade 4/5, 7 grade 3, 20 grade 2, 37 grade 1, and 36 grade 0. Each dosimetric parameter was significantly higher for the symptomatic group. The AIC winning models were 30 linear, 52 linear quadratic, and 18 linear logarithmic. There was no significant difference in the linear coefficient between models. The slope of the FDG vs. proton dose response was 0.022 for the symptomatic and 0.012 for the asymptomatic (p=0.014). Combining dosimetric parameters with the slope did not improve the sensitivity or accuracy in identifying symptomatic cases. CONCLUSIONS: The proton radiation dose response on FDG PET/CT imaging exhibited a predominantly linear dose response on modeling. Symptomatic patients had a higher dose response slope.

Echeverria AE; McCurdy M; Castillo R; Bernard V; Ramos NV; Buckley W; Castillo E; Liu P; Martinez J; Guerrero T

2013-01-01

116

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

International Nuclear Information System (INIS)

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

2005-03-15

117

Statistics  

Science.gov (United States)

Statistics Search : Stay updated on the latest bladder health news! Share this site with a friend 1: ... 10: Continence Care Champions NAFC Home >> Newsroom >> Statistics Statistics Prevalence Comorbidities Associated with Urinary Incontinence Nursing Homes/ ...

118

LOGIT: a program for dose-response analysis.  

UK PubMed Central (United Kingdom)

We describe a FORTRAN computer program for fitting the logistic distribution function: (formula: see text) Where x represents dose or time, to dose-response data. The program determines both weighted least squares and maximum likelihood estimates for the parameters alpha and beta. It also calculates the standard errors of alpha and beta under both estimation methods, as well as the median lethal dose (LD50) and its standard error. Dose--response curves found by both fitting methods can be plotted as well as the 95% confidence bands for these lines.

Koshiver J; Moore D

1979-07-01

119

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

International Nuclear Information System (INIS)

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

1994-01-01

120

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

Science.gov (United States)

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

Seo, Junwon

2013-06-01

 
 
 
 
121

Biphasic Dose Response in Low Level Light Therapy – An Update  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has...

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

122

Alcohol and cirrhosis: dose--response or threshold effect?  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Udgivelsesdato: 2004-Jul , BACKGROUND/AIMS: General population studies have shown a strong association between alcohol intake and death from alcoholic cirrhosis, but whether this is a dose-response or a threshold effect remains unknown, and the relation among alcohol misusers has not been studied. METH...

Kamper-Jørgensen, Mads; Grønbaek, Morten; Tolstrup, Janne; Becker, Ulrik

123

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

2006-06-01

124

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

Directory of Open Access Journals (Sweden)

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

Huei-An Chu; Douglas J. Crawford-Brown

2006-01-01

125

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

Directory of Open Access Journals (Sweden)

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

K. Snekvik; R. Nakamura; N. Østgaard; S. Haaland; A. Retinò

2008-01-01

126

Method for expressing clinical and statistical significance of ocular and corneal wave front error aberrations.  

UK PubMed Central (United Kingdom)

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

Smolek MK

2012-03-01

127

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

DEFF Research Database (Denmark)

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

Pedersen, Mogens Theisen; Andersen, Lars Louis

2013-01-01

128

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

International Nuclear Information System (INIS)

[en] 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)

1983-01-01

129

Dose-response Relationship between Exercise and Respiratory Disease Mortality.  

UK PubMed Central (United Kingdom)

PURPOSE: To assess prospectively the dose-response relationship between respiratory disease (ICD10: J1-99), pneumonia (ICD10: J12.0-18.9), and asperation pneumonia mortality (ICD10: J69) vs. baseline walking and running energy expenditure (MET-hours/d, 1 MET = 3.5 ml O2/kg/min). METHODS: Cox proportional hazard analyses of 109,352 runners and 40,798 walkers adjusted for age, sex, smoking, diet, alcohol, and education. RESULTS: There were 236 deaths with respiratory disease listed as the underlying cause, and 833 deaths that were respiratory disease related (entity axis diagnosis). Included among these were 79 deaths with pneumonia listed as the underlying cause and 316 pneumonia-related deaths, and 77 deaths due to aspiration pneumonia. There was no significant difference in the effect of running compared to walking (per MET-hours/d) on mortality, thus runners and walkers were combined for analysis. Respiratory disease mortality decreased 7.9% per MET-hours/d as the underlying cause (95%CI: 1.6% to 14.0%, P=0.01) and 7.3% for all respiratory disease-related deaths (95%CI: 4.2% to 10.4%, P=10). Pneumonia mortality decreased 13.1% per MET-hours/d as the underlying cause (95%CI: 2.6% to 23.2%, P=0.01) and 10.5% per MET-hours/d for all pneumonia-related deaths (95%CI: 5.4% to 15.5%, P=0.0001). The risk for aspiration pneumonia mortality also did not differ between running and walking, and decreased 19.9% per MET-hours/d run or walked (95%CI: 8.9% to 30.2%, P=0.0004). These results remained significant when additionally adjusted for BMI. CONCLUSIONS: Higher doses of running and walking were associated with lower risk of respiratory disease, pneumonia, and aspiration pneumonia mortality in a dose-dependent manner, and the effects of running and walking appear equivalent. These effects appear to be independent of the effects of exercise on cardiovascular disease.

Williams PT

2013-08-01

130

Radiation dose response of strand breaks in SINPV-DNA  

International Nuclear Information System (INIS)

[en] The Spodoplera litura Nuclear Polyhedrosis Viruses (SINPV) is a kind of insectile virus with a simple structure, in which a double helix DNA is encapsulated in a protein coat and there is no function of enzymatic repair. The SINPV samples in dry powdered form held in sealed plastic tube were irradiated by 1-100 kGy gamma rays. The single strand breaks (SSB) and double strand breaks (DSB) induced in SINPV after irradiation were measured by neutral and alkaline agarose gel electrophoresis. A dose-response function combining the responses of one-hit and two-hit events was used to describe the SSB and DSB dose-response curves. It is shown that the SSB are one-hit events and the DSB are the combination of both one-hit, and two-hit events, and two-hit events are predominant in the DSB process

1995-01-01

131

Dose-response relationships for hand-transmitted vibration.  

Science.gov (United States)

Few dose-response relationships have been reported for signs and symptoms resulting from occupational exposure of the hand to vibration. For population groups whose members operate the same vibrating power tool or industrial process throughout the workday, a simple model may be constructed to provide functional dose-response relationships for the onset of episodes of finger blanching. In such groups, the latency interval for various population percentiles may be expressed in terms of a frequency-weighted, root-mean-square, component acceleration at a surface in contact with the hand. Of the two constitutive equations required by the model, one appears to be supported by epidemiologic data published since its derivation, but the second may require modification to be applicable to very short daily exposure durations. PMID:3775313

Brammer, A J

1986-08-01

132

Dose-response relationships for hand-transmitted vibration.  

UK PubMed Central (United Kingdom)

Few dose-response relationships have been reported for signs and symptoms resulting from occupational exposure of the hand to vibration. For population groups whose members operate the same vibrating power tool or industrial process throughout the workday, a simple model may be constructed to provide functional dose-response relationships for the onset of episodes of finger blanching. In such groups, the latency interval for various population percentiles may be expressed in terms of a frequency-weighted, root-mean-square, component acceleration at a surface in contact with the hand. Of the two constitutive equations required by the model, one appears to be supported by epidemiologic data published since its derivation, but the second may require modification to be applicable to very short daily exposure durations.

Brammer AJ

1986-08-01

133

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

Directory of Open Access Journals (Sweden)

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

La Piana GE; Corda L; Bertella E; Taranto Montemurro L; Pini L; Tantucci C

2011-01-01

134

Key statistics related to CO/sub 2/ emissions: Significant contributing countries  

Energy Technology Data Exchange (ETDEWEB)

This country selection task report describes and applies a methodology for identifying a set of countries responsible for significant present and anticipated future emissions of CO/sub 2/ and other radiatively important gases (RIGs). The identification of countries responsible for CO/sub 2/ and other RIGs emissions will help determine to what extent a select number of countries might be capable of influencing future emissions. Once identified, those countries could potentially exercise cooperative collective control of global emissions and thus mitigate the associated adverse affects of those emissions. The methodology developed consists of two approaches: the resource approach and the emissions approach. While conceptually very different, both approaches yield the same fundamental conclusion. The core of any international initiative to control global emissions must include three key countries: the US, USSR, and the People's Republic of China. It was also determined that broader control can be achieved through the inclusion of sixteen additional countries with significant contributions to worldwide emissions.

Kellogg, M.A.; Edmonds, J.A.; Scott, M.J.; Pomykala, J.S.

1987-07-01

135

Dose-response curves and their modification by specific mechanisms  

International Nuclear Information System (INIS)

[en] 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.)

1975-04-07

136

The dilemma of choosing the ideal permutation strategy while estimating statistical significance of genome-wide enrichment.  

UK PubMed Central (United Kingdom)

Integrative analyses of genomic, epigenomic and transcriptomic features for human and various model organisms have revealed that many such features are nonrandomly distributed in the genome. Significant enrichment (or depletion) of genomic features is anticipated to be biologically important. Detection of genomic regions having enrichment of certain features and estimation of corresponding statistical significance rely on the expected null distribution generated by a permutation model. We discuss different genome-wide permutation approaches, present examples where the permutation strategy affects the null model and show that the confidence in estimating statistical significance of genome-wide enrichment might depend on the choice of the permutation approach. In those cases, where biologically relevant constraints are unclear, it is preferable to examine whether key conclusions are consistent, irrespective of the choice of the randomization strategy.

De S; Pedersen BS; Kechris K

2013-08-01

137

Controlled Optimal Design Program for the Logit Dose Response Model  

Directory of Open Access Journals (Sweden)

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

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

2010-01-01

138

Biphasic Dose Response in Low Level Light Therapy - An Update  

Science.gov (United States)

Low-level laser (light) therapy (LLLT) has been known since 1967 but still remains controversial due to incomplete understanding of the basic mechanisms and the selection of inappropriate dosimetric parameters that led to negative studies. The biphasic dose-response or Arndt-Schulz curve in LLLT has been shown both in vitro studies and in animal experiments. This review will provide an update to our previous (Huang et al. 2009) coverage of this topic. In vitro mediators of LLLT such as adenosine triphosphate (ATP) and mitochondrial membrane potential show biphasic patterns, while others such as mitochondrial reactive oxygen species show a triphasic dose-response with two distinct peaks. The Janus nature of reactive oxygen species (ROS) that may act as a beneficial signaling molecule at low concentrations and a harmful cytotoxic agent at high concentrations, may partly explain the observed responses in vivo. Transcranial LLLT for traumatic brain injury (TBI) in mice shows a distinct biphasic pattern with peaks in beneficial neurological effects observed when the number of treatments is varied, and when the energy density of an individual treatment is varied. Further understanding of the extent to which biphasic dose responses apply in LLLT will be necessary to optimize clinical treatments.

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

2011-01-01

139

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

UK PubMed Central (United Kingdom)

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.

Bette Meek ME; Bolger M; Bus JS; Christopher J; Conolly RB; Lewis RJ; Paolini GM; Schoeny R; Haber LT; Rosenstein AB; Dourson ML

2013-07-01

140

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

Directory of Open Access Journals (Sweden)

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

Li Qingbo; Roxas Bryan AP

2009-01-01

 
 
 
 
141

Statistical protein quantification and significance analysis in label-free LC-MS experiments with complex designs  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Background Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is widely used for quantitative proteomic investigations. The typical output of such studies is a list of identified and quantified peptides. The biological and clinical interest is, however, usually focused on quantitative conclusions at the protein level. Furthermore, many investigations ask complex biological questions by studying multiple interrelated experimental conditions. Therefore, there is a need in the field for generic statistical models to quantify protein levels even in complex study designs. Results We propose a general statistical modeling approach for protein quantification in arbitrary complex experimental designs, such as time course studies, or those involving multiple experimental factors. The approach summarizes the quantitative experimental information from all the features and all the conditions that pertain to a protein. It enables both protein significance analysis between conditions, and protein quantification in individual samples or conditions. We implement the approach in an open-source R-based software package MSstats suitable for researchers with a limited statistics and programming background. Conclusions We demonstrate, using as examples two experimental investigations with complex designs, that a simultaneous statistical modeling of all the relevant features and conditions yields a higher sensitivity of protein significance analysis and a higher accuracy of protein quantification as compared to commonly employed alternatives. The software is available at http://www.stat.purdue.edu/~ovitek/Software.html.

Clough Timothy; Thaminy Safia; Ragg Susanne; Aebersold Ruedi; Vitek Olga

2012-01-01

142

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

Science.gov (United States)

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

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

2012-03-22

143

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

UK PubMed Central (United Kingdom)

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

Schöllnberger H; Kaiser JC; Jacob P; Walsh L

2012-05-01

144

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 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.

2010-01-01

145

Dose-response model of Rocky Mountain spotted fever (RMSF) for human.  

UK PubMed Central (United Kingdom)

Rickettsia rickettsii is the causative agent of Rocky Mountain spotted fever (RMSF) and is the prototype bacterium in the spotted fever group of rickettsiae, which is found in North, Central, and South America. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through tick bites; however, some cases of aerosol transmission also have been reported. The disease can be difficult to diagnose in the early stages, and without prompt and appropriate treatment, it can be fatal. This article develops dose-response models of different routes of exposure for RMSF in primates and humans. The beta-Poisson model provided the best fit to the dose-response data of aerosol-exposed rhesus monkeys, and intradermally inoculated humans (morbidity as end point of response). The average 50% infectious dose among (ID??) exposed human population, N??, is 23 organisms with 95% confidence limits of 1 to 89 organisms. Similarly, ID?? and ID?? are 2.2 and 5.0, respectively. Moreover, the data of aerosol-exposed rhesus monkeys and intradermally inoculated humans could be pooled. This indicates that the dose-response models fitted to different data sets are not significantly different and can be described by the same relationship.

Tamrakar SB; Haas CN

2011-10-01

146

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

Science.gov (United States)

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).

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

2009-05-01

147

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 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.

2005-01-01

148

Statistics  

International Nuclear Information System (INIS)

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

1999-01-01

149

Regression analysis of ESR/TL dose-response data  

International Nuclear Information System (INIS)

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

1992-01-01

150

Can hormesis be a default for dose-response?  

UK PubMed Central (United Kingdom)

Since the 1920s, interest in hormesis has peaked and ebbed. Hormesis had been a forgotten theory until recent investigation by Dr Ed Calabrese at the University of Massachusetts, along with others, resurrected it from obscurity. This renewed interest is demonstrated by recent articles in prestigious scientific journals such as Nature and Science as well as the popular press (Discovery, US News and World Report and newspapers such as the Boston Globe). Currently, a strong interest in this theory of dose-response (which predicts contrasting effects at low versus high doses) exists and is explored in this issue.

Callahan BG

2005-05-01

151

Can hormesis be a default for dose-response?  

Science.gov (United States)

Since the 1920s, interest in hormesis has peaked and ebbed. Hormesis had been a forgotten theory until recent investigation by Dr Ed Calabrese at the University of Massachusetts, along with others, resurrected it from obscurity. This renewed interest is demonstrated by recent articles in prestigious scientific journals such as Nature and Science as well as the popular press (Discovery, US News and World Report and newspapers such as the Boston Globe). Currently, a strong interest in this theory of dose-response (which predicts contrasting effects at low versus high doses) exists and is explored in this issue. PMID:16004192

Callahan, Barbara G

2005-05-01

152

Prediction of the mortality dose-response relationship in man  

International Nuclear Information System (INIS)

[en] 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

1987-05-11

153

Maximum likelihood estimation for cytogenetic dose-response curves  

International Nuclear Information System (INIS)

[en] 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

1983-01-01

154

Prenatal cocaine and neonatal outcome: evaluation of dose-response relationship.  

UK PubMed Central (United Kingdom)

OBJECTIVE: The aim of this study was to evaluate the hypothesis that prenatal cocaine exposure would negatively affect newborn behavior. METHODS: A prospective observational study of term infants recruited from the low-risk nursery used a structured, standardized interview to obtain maternal data. Cocaine exposure was determined by radioimmunoassay of the infant's meconium stool. An examiner blinded to the infant's cocaine status administered the Brazelton Neonatal Behavioral Assessment Scales. RESULTS: The sample was composed of 23 exposed and 29 nonexposed infants. On six of the seven Brazelton Neonatal Behavioral Assessment Scale clusters, cocaine-exposed infants performed less well than control infants, with significant differences observed for autonomic stability. In addition, a dose-response relationship was suggested. Significant negative, within-group relationships were evident in the exposed group, indicating poorer performance with increasing meconium cocaine concentration for orientation (r = -.40) and regulation of state (r = -.40). Regression model testing of the influence of meconium cocaine concentration on neurobehavioral outcomes, after controlling for significant confounders, identified a significant independent, negative effect of meconium cocaine concentration on two clusters-motor and regulation of state. CONCLUSION: In otherwise healthy full-term infants, prenatal cocaine exposure identified by quantitative analysis of cocaine concentration in meconium had a significant, independent negative association with motor and regulation of state that remained after controlling for other significant confounders. A dose-response relationship was evident.

Delaney-Black V; Covington C; Ostrea E Jr; Romero A; Baker D; Tagle MT; Nordstrom-Klee B; Silvestre MA; Angelilli ML; Hack C; Long J

1996-10-01

155

Dependence of nonlinearity of dose response on heating rate in TLD  

International Nuclear Information System (INIS)

[en] The kinetics model is used to study the effects of heating rate on nonlinearity of dose response in thermoluminescence. The expression of dose response to heating rate is deduced based on second order kinetics model. The derived heating rate dependent nonlinearity of dose response is shown to be in agreement with experimental results

1993-01-01

156

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

UK PubMed Central (United Kingdom)

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

Pedersen MT; Andersen LL; Jørgensen MB; Søgaard K; Sjøgaard G

2013-01-01

157

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

International Nuclear Information System (INIS)

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

2011-01-01

158

Dose-response characteristics of an amorphous silicon EPID.  

UK PubMed Central (United Kingdom)

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

Winkler P; Hefner A; Georg D

2005-10-01

159

Dose-response characteristics of an amorphous silicon EPID.  

Science.gov (United States)

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

Winkler, Peter; Hefner, Alfred; Georg, Dietmar

2005-10-01

160

Dose response curves for effects of low-level radiation  

International Nuclear Information System (INIS)

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

1980-01-01

 
 
 
 
161

Multifraction dose response of growing and resting phase hair follicles  

International Nuclear Information System (INIS)

It has been established in both the clinic and the laboratory that there is a differentiation response to changes in dose per fraction in early and late responding tissues. To study one possible biological reason for differences in early and late responses. The authors selected one kind of cellular entity, the hair follicle, in two different phases of mitotic activity. The follicles are usually in a resting phase (7-12 wks), but mitotic activity can be initiated by plucking the club hairs. This was done on one half of the thorax and then exposing mice to doses of radiation (cesium gamma-ray). Dose responses for epilation between growing (early) and resting (late) follicles were compared for the same mouse. The fractionated response was studied by reducing the dose down to 2.5 Gy/fx. As the literature suggests, the total dose tolerated by a resting (late) follicle increased more than that for a growing (early) follicle

1987-01-01

162

Prediction of the mortality dose-response relationship in man  

Energy Technology Data Exchange (ETDEWEB)

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 LD/sub 05/, LD/sub 10/, LD/sub 25/, LD/sub 50/, LD/sub 75/, LD/sub 90/, and LD/sub 95/, for dose rates ranging from 1 to 50 R/min. 6 refs., 5 tabs.

Morris, M.D.; Jones, T.D.

1987-01-01

163

Total dose response of transconductance in MOSFETs at low temperature  

Energy Technology Data Exchange (ETDEWEB)

N and p channel MOSFETs from four bulk CMOS technologies and two CMOS/SIMOX technologies were characterized for total dose response up to 1 Mrad (SiO[sub 2]) at temperatures from 10K to 120K. The peak transconductance in the linear region increased in n channel devices and decreased in p channel devices for devices with lightly doped drain (LDD) implants. These changes were much larger as the temperature was decreased and were as much as a factor of 50 in p MOSFETs at 10K. The one technology without LDD showed only a minor change in g[sub m] with dose even at 10K. The changes in transconductance are most likely a result of hole trapping in the spacer oxide affecting the series resistance.

Pease, R.L. (RLP Research, Inc., Albuquerque, NM (United States)); Clark, S.D.; Cole, P.L.; Krieg, J.F. (Naval Surface Warfare Center, Crane, IN (United States)); Pickel, J.C. (S-Cubed, Mission Viejo, CA (United States))

1994-06-01

164

Total dose response of transconductance in MOSFETs at low temperature  

International Nuclear Information System (INIS)

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

1994-01-01

165

D optimal designs for three Poisson dose-response models.  

UK PubMed Central (United Kingdom)

The objective of this paper was to find and investigate the performance of the D optimal designs for three Poisson dose-response models. Phase II dose ranging studies are pivotal in the drug development program, being used to select dose(s) for phase III. Count data is encountered in a number of clinical areas. The Poisson distribution provides an intuitive platform for modelling such data, especially when combined with random effects which allow subjects to differ in their response rates. This work investigated three Poisson dose-response models of increasing complexity. A simple E(max) model was used to describe the drug effect, and D optimal designs under a range of different parameter values (scenarios) were found. The relative performances between scenarios were assessed using: the precision of all parameters, the precision of the drug effect parameters, and the percent coefficient of variation (%CV) of the ED(50) parameter. The results showed that the D optimal designs were similar across models and scenarios, with the D optimal designs consisting of placebo, the maximum dose, and a dose just below the ED(50). However the relative performance of the optimal designs was very different. For example, with 1,000 subjects, the %CV of the ED(50) parameter ranged from 1.4 to 91 %. Performance typically improved with higher baseline counts, smaller random effects, and larger E(max). This work introduces a framework for determining and evaluating the performance of D optimal designs for phase II dose ranging studies with count data as the primary endpoint.

Maloney A; Simonsson US; Schaddelee M

2013-04-01

166

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2010-11-01

167

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

UK PubMed Central (United Kingdom)

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

Edwards DS; Milne LM; Morrow K; Sheridan P; Verlander NQ; Mulla R; Richardson JF; Pender A; Lilley M; Reacher M

2013-05-01

168

[The dose-response relationship of chrysotile asbestos exposure and lung cancer in cohort study].  

UK PubMed Central (United Kingdom)

OBJECTIVE: To clarify the dose-response relationship between asbestos dust exposure and lung cancer incidence in chrysotile asbestos miners by fixed cohort study and to investigate the incidence rates of lung cancer in exposure to different concentrations of asbestos dust. METHODS: A retrospective cohort study was conducted in 1932 asbestos miners who registered from January 1, 1981 to December 31, 1988, had worked for at least 1 year, and had no obvious cardiopulmonary diseases; the cohort study began in July 2009 and covered a time span of 29 years (1981 - 2009). The personal information, occupational history, disease history, and health data of these miners were recorded, and the monitoring data on dust concentrations in the mine over the years were collected. The dose-response relationship between asbestos dust concentration and lung cancer incidence was established by the method of life table; a regression equation was fitted to predict the excess incidence rates of lung cancer under the conditions of different working years and dust concentrations. RESULTS: A significant dose-response relationship was observed between cumulative exposure (Ce) and cumulative probability (Px) of lung cancer incidence, and the smokers hada higher Px than nonsmokers. When Ce was less than 2000 mg/m(3)·each year, Px reached 6.58/10000; when Ce was not less than 2000 mg/m(3)·and less than 3000 mg/m(3)·each year, Px reached 91.72/10000; when Ce was more than 5000 mg/m(3)·each year, Px was as high as 141.02/10000. The three models were fitted to obtain the optimal regression equation: Px = -0.0004Ce(2) + 0.0052Ce - 0.0011 (r(2) = 0.9387). In the workshop of asbestos mine in this study, the average dust concentration was 85 times higher than the limit in 2009, so the excess incidence rate of lung cancer was 112.598/10000 if the miners worked under this condition for 40 years, according to the equation. CONCLUSION: There is a significant dose-response relationship between cumulative asbestos exposure and lung cancer incidence in chrysotile asbestos miners. The risk for lung cancer rises as asbestos exposure increases.

Ren XH; Zhou DL; Du LL; Wang MZ; Lan YJ

2013-03-01

169

Linear dose response curves in fungi and tradescantia  

Energy Technology Data Exchange (ETDEWEB)

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

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

1999-07-15

170

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

Energy Technology Data Exchange (ETDEWEB)

This study assesses the sensitivity of the baboon model under anaesthesia to determine by single photon emission computed tomography (SPECT) and [sup 99]Tc[sup m]-hexamethylpropyleneamine oxime (HMPAO) dose responses from drugs (acetazolamide) with known regional cerebral blood flow (rCBF) effects on humans. Three dosages of acetazolamide were chosen: 250, 500 and 750 mg. The effects of these were studied by conventional SPECT 5 min after intravenous (i.v.) administration and compared to previous studies of rCBF with the baboons under anaesthesia only. An additional study concerned the effect of 500 mg acetazolamide at 15 min after administration. Haemodynamic parameters and blood gases were also monitored. No statistically significant regional effects were noted. The largest increase in CBF (39%) was observed from 500 mg acetazolamide after 5 min. This was statistically significantly different from control values only at a 10% level of confidence; then following a 27% increase above control values after 750 mg (5 min). At 15 min 500 mg yielded values lower by 10% than the high dose. No effects were observed from 250 mg acetazolamide; only pO[sub 2] showed changes which largely confirm the CBF findings. The model did not give significant results at a 5% level of confidence but large fluctuations were observed, also in the haemodynamic and blood gas values. At a 10% level a significant dose response was confirmed for acetazolamide. (author).

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

1993-07-01

171

Local antimicrobials in addition to scaling and root planing provide statistically significant but not clinically important benefit.  

Science.gov (United States)

Data sourcesThe databases Medline, Embase and the Cochrane Oral Health Group Trials Register were searched. Handsearching of the Journal of Periodontology, Journal of Clinical Periodontology and Journal of Periodontal Research was also carried out.Study selectionRandomised controlled trials published in English were included.Data extraction and synthesisRisk of bias and quality assessment were conducted following Cochrane recommendations with data being extracted independently in duplicate. Because of the nature of the available data, qualitative summary is presented with meta-analysis conducted where appropriate.ResultsThe overall effect of the subgingival application of antimicrobials was statistically significant (p = 0.000) for both changes in probing pocket depth (PPD) and clinical attachment level (CAL), with a weighted mean difference (WMD) of -0.407 and -0.310 mm respectively. No significant differences occurred for changes in bleeding on probing (BOP) and plaque index (PlI). Subgingival application of tetracycline fibres, sustained released doxycycline and minocycline demonstrated a significant benefit in PPD reduction (WMD between 0.5 and 0.7 mm). The rest of the tested outcomes demonstrated a high heterogeneity. The local application of chlorhexidine and metronidazole showed a minimal effect when compared with placebo (WMD between 0.1 and 0.4 mm).ConclusionsIn conclusion, the scientific evidence supports the adjunctive use of local antimicrobials to SRP in deep or recurrent periodontal sites, mostly when the vehicle has shown pharmacodynamic properties assuring the sustained release of the antimicrobial. This evidence must be interpreted with caution, as the reported data were highly heterogeneous and most of the selected studies were categorised with a high degree of bias. PMID:24071680

Matthews, Debora

2013-09-01

172

Local antimicrobials in addition to scaling and root planing provide statistically significant but not clinically important benefit.  

UK PubMed Central (United Kingdom)

Data sourcesThe databases Medline, Embase and the Cochrane Oral Health Group Trials Register were searched. Handsearching of the Journal of Periodontology, Journal of Clinical Periodontology and Journal of Periodontal Research was also carried out.Study selectionRandomised controlled trials published in English were included.Data extraction and synthesisRisk of bias and quality assessment were conducted following Cochrane recommendations with data being extracted independently in duplicate. Because of the nature of the available data, qualitative summary is presented with meta-analysis conducted where appropriate.ResultsThe overall effect of the subgingival application of antimicrobials was statistically significant (p = 0.000) for both changes in probing pocket depth (PPD) and clinical attachment level (CAL), with a weighted mean difference (WMD) of -0.407 and -0.310 mm respectively. No significant differences occurred for changes in bleeding on probing (BOP) and plaque index (PlI). Subgingival application of tetracycline fibres, sustained released doxycycline and minocycline demonstrated a significant benefit in PPD reduction (WMD between 0.5 and 0.7 mm). The rest of the tested outcomes demonstrated a high heterogeneity. The local application of chlorhexidine and metronidazole showed a minimal effect when compared with placebo (WMD between 0.1 and 0.4 mm).ConclusionsIn conclusion, the scientific evidence supports the adjunctive use of local antimicrobials to SRP in deep or recurrent periodontal sites, mostly when the vehicle has shown pharmacodynamic properties assuring the sustained release of the antimicrobial. This evidence must be interpreted with caution, as the reported data were highly heterogeneous and most of the selected studies were categorised with a high degree of bias.

Matthews D

2013-09-01

173

Mutans streptococci dose response to xylitol chewing gum.  

Science.gov (United States)

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

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

2006-02-01

174

Dose response of alanine detectors irradiated with carbon ion beams  

Energy Technology Data Exchange (ETDEWEB)

Purpose: The dose response of the alanine detector shows a dependence on particle energy and type when irradiated with ion beams. The purpose of this study is to investigate the response behavior of the alanine detector in clinical carbon ion beams and compare the results to model predictions. Methods: Alanine detectors have been irradiated with carbon ions with an energy range of 89-400 MeV/u. The relative effectiveness of alanine has been measured in this regime. Pristine and spread out Bragg peak depth-dose curves have been measured with alanine dosimeters. The track structure based alanine response model developed by Hansen and Olsen has been implemented in the Monte Carlo code FLUKA and calculations were compared to experimental results. Results: Calculations of the relative effectiveness deviate less than 5% from the measured values for monoenergetic beams. Measured depth-dose curves deviate from predictions in the peak region, most pronounced at the distal edge of the peak. Conclusions: The used model and its implementation show a good overall agreement for quasimonoenergetic measurements. Deviations in depth-dose measurements are mainly attributed to uncertainties of the detector geometry implemented in the Monte Carlo simulations.

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

2011-04-15

175

Dose-response patterns of Radix Glycyrrhizae in Shanghan Lun  

Directory of Open Access Journals (Sweden)

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

Xue YANG; Xiao-qiang YUE

2009-01-01

176

Aripiprazole: dose-response relationship in schizophrenia and schizoaffective disorder.  

Science.gov (United States)

Aripiprazole is an atypical antipsychotic that has been shown to be more effective than placebo and at least as effective as haloperidol and risperidone in the treatment of schizophrenia and schizoaffective disorder. Despite having a well defined licensed dose range, the optimum dose for aripiprazole is yet to be established. Aripiprazole exhibits high affinity for dopamine D(2) receptors, with near maximal receptor occupancy at a dose of 30 mg. Even doses as low as 2 mg, thought not to be clinically effective, have produced striatal D(2) receptor occupancies exceeding 70%, higher than the accepted threshold for antipsychotic effect. In this review we examined the efficacy data from short-term studies of aripiprazole in relapsed schizophrenia or schizoaffective disorder, in order to establish a dose-response relationship for aripiprazole. Results of five fixed-dose studies suggest that the threshold for clinical effect is between 5 and 10 mg/day. In addition, the highest response rate is seen at 10 mg/day. Doses above 20 mg/day do not appear to provide any additional benefit and may be associated with a smaller change in symptom scores. In summary, the data available so far indicate that the optimum dose for aripiprazole is 10 mg/day and that doses above 20 mg/day provide no additional benefit. PMID:19689167

Mace, Shubhra; Taylor, David

2009-09-01

177

Dose response characteristics in polymer gel for the composition ratio  

International Nuclear Information System (INIS)

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

2010-01-01

178

Dose-response plasma appearance of coffee chlorogenic and phenolic acids in adults.  

UK PubMed Central (United Kingdom)

SCOPE: Coffee contains phenolic compounds, mainly chlorogenic acids (CGAs). Even though coffee intake has been associated with some health benefits in epidemiological studies, the bioavailability of coffee phenolics is not fully understood. OBJECTIVE AND STUDY DESIGN: We performed a dose-response study measuring plasma bioavailability of phenolics after drinking three increasing, but still nutritionally relevant doses of instant pure soluble coffee. The study design was a one treatment (coffee) three-dose randomized cross-over design, with a washout period of 2 wks between visits. RESULTS: CGAs, phenolic acids, and late-appearing metabolites all increased with increasing ingested dose. Hence, the sum of area under the curve was significantly higher for the medium to low dose, and high to medium dose, by 2.23- and 2.38-fold, respectively. CGAs were not well absorbed in their intact form, regardless of the dose. CGA and phenolic acids appeared rapidly in plasma, indicating an early absorption in the gastrointestinal tract. Late-appearing metabolites were the most abundant, regardless of the dose. CONCLUSION: This study confirmed previous findings about coffee bioavailability but also showed that coffee phenolics appear in a positive dose-response manner in plasma when drank at nutritionally relevant doses.

Renouf M; Marmet C; Giuffrida F; Lepage M; Barron D; Beaumont M; Williamson G; Dionisi F

2013-09-01

179

Macro-indicators of citation impacts of six prolific countries: InCites data and the statistical significance of trends.  

UK PubMed Central (United Kingdom)

Using the InCites tool of Thomson Reuters, this study compares normalized citation impact values calculated for China, Japan, France, Germany, United States, and the UK throughout the time period from 1981 to 2010. InCites offers a unique opportunity to study the normalized citation impacts of countries using (i) a long publication window (1981 to 2010), (ii) a differentiation in (broad or more narrow) subject areas, and (iii) allowing for the use of statistical procedures in order to obtain an insightful investigation of national citation trends across the years. Using four broad categories, our results show significantly increasing trends in citation impact values for France, the UK, and especially Germany across the last thirty years in all areas. The citation impact of papers from China is still at a relatively low level (mostly below the world average), but the country follows an increasing trend line. The USA exhibits a stable pattern of high citation impact values across the years. With small impact differences between the publication years, the US trend is increasing in engineering and technology but decreasing in medical and health sciences as well as in agricultural sciences. Similar to the USA, Japan follows increasing as well as decreasing trends in different subject areas, but the variability across the years is small. In most of the years, papers from Japan perform below or approximately at the world average in each subject area.

Bornmann L; Leydesdorff L

2013-01-01

180

Macro-indicators of citation impacts of six prolific countries: InCites data and the statistical significance of trends.  

Science.gov (United States)

Using the InCites tool of Thomson Reuters, this study compares normalized citation impact values calculated for China, Japan, France, Germany, United States, and the UK throughout the time period from 1981 to 2010. InCites offers a unique opportunity to study the normalized citation impacts of countries using (i) a long publication window (1981 to 2010), (ii) a differentiation in (broad or more narrow) subject areas, and (iii) allowing for the use of statistical procedures in order to obtain an insightful investigation of national citation trends across the years. Using four broad categories, our results show significantly increasing trends in citation impact values for France, the UK, and especially Germany across the last thirty years in all areas. The citation impact of papers from China is still at a relatively low level (mostly below the world average), but the country follows an increasing trend line. The USA exhibits a stable pattern of high citation impact values across the years. With small impact differences between the publication years, the US trend is increasing in engineering and technology but decreasing in medical and health sciences as well as in agricultural sciences. Similar to the USA, Japan follows increasing as well as decreasing trends in different subject areas, but the variability across the years is small. In most of the years, papers from Japan perform below or approximately at the world average in each subject area. PMID:23418600

Bornmann, Lutz; Leydesdorff, Loet

2013-02-13

 
 
 
 
181

Analysis of thermal-dose response to heat  

International Nuclear Information System (INIS)

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

1987-01-01

182

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

Science.gov (United States)

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

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

2013-05-02

183

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

UK PubMed Central (United Kingdom)

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.

Wylie LJ; Kelly J; Bailey SJ; Blackwell JR; Skiba PF; Winyard PG; Jeukendrup AE; Vanhatalo A; Jones AM

2013-08-01

184

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

UK PubMed Central (United Kingdom)

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

Ried K; Frank OR; Stocks NP

2013-01-01

185

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

International Nuclear Information System (INIS)

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

1983-01-01

186

Coffee consumption and risk of colorectal cancer: a dose-response analysis of observational studies.  

UK PubMed Central (United Kingdom)

Coffee consumption has been linked to risk of colorectal cancer theoretically, but the findings were conflicting from observational studies. Results from the recent meta-analysis suggested a moderate favorable effect of coffee consumption on colorectal cancer risk, especially for colon cancer. However, the relationship, if exists, between coffee consumption and colorectal cancer risk is unclear. Thus, the dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. The results suggested that a significant association was found between coffee consumption and decreased risk of colorectal and colon cancer among subjects consuming ?4 cups of coffee per day. A potential nonlinear relationship should be assessed before assuming a linear relationship.

Tian C; Wang W; Hong Z; Zhang X

2013-06-01

187

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

DEFF Research Database (Denmark)

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

Appelt, Ane Lindegaard; Vogelius, Ivan R

2012-01-01

188

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

Background: Prenatal exposure to mercury has been associated with adverse childhood neurologic outcomes in epidemiologic studies. Dose–response information for this relationship is useful for estimating benefits of reduced mercury exposure. Objectives: We estimated a dose–response relationship betwe...

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

189

Dose-response study of spinal hyperbaric ropivacaine for cesarean section  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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% effect...

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

190

Parity and Risk of Colorectal Cancer: A Dose-Response Meta-Analysis of Prospective Studies  

Science.gov (United States)

Background Association between parity and colorectal cancer (CRC) risk has been investigated by several epidemiological studies but results are controversial, yet a comprehensive and quantitative assessment of this association has not been reported so far. Methods Relevant published studies of parity and CRC were identified using MEDLINE, EMBASE and Web of Science databases through end of April 2013. Two authors independently assessed eligibility and extracted data. Eleven prospective studies reported relative risk (RR) estimates and 95% confidence intervals (CIs) of CRC risk associated with parity. We pooled the RR from individual studies using fixed- or random-effects models and carried out heterogeneity and publication bias analyses. Results The summary RR for the ever parity vs. nulliparous was 0.95 (95% CI: 0.88–1.02), with no heterogeneity (Q?=?9.04, P?=?0.443, I2?=?0.5%). Likewise, no significant association was yielded for the highest vs. lowest parity number (RR?=?1.02, 95% CI: 0.89–1.17), with moderate heterogeneity (Q?=?17.48, P?=?0.094, I2?=?37.1%). Dose-response analysis still indicated no effect of parity on CRC risk and the summary RR of per one livebirth was 0.99 (95% CI: 0.96–1.02), with moderate of heterogeneity (Q?=?16.50, P<0.021, I2?=?57.6%). Similar results were observed among all the subgroup analyses. No evidence of publication bias and significant heterogeneity between subgroups were detected by meta-regression analyses. Conclusion Results of this dose-response meta-analysis of prospective studies found that there was little evidence of an association between parity and CRC risk.

Guan, Hong-Bo; Wu, Qi-Jun; Gong, Ting-Ting; Lin, Bei; Wang, Yong-Lai; Liu, Cai-Xia

2013-01-01

191

Dose response effect of methylphenidate on ventral tegmental area neurons and animal behavior.  

Science.gov (United States)

Methylphenidate (MPD) is the drug of choice prescribed to treat ADHD patients. More recently, MPD is also used as a cognitive enhancement and recreationally by young adults and its therapeutic effects are not fully understood. One of the neuroanatomical sites is reported to be the ventral tegmental area (VTA). The ventral tegmental area neuronal activity was recorded from freely behaving non-anesthetized rats implanted bilaterally with semi-permanent electrodes which were recorded from a wireless telemetric system. Thirty-three animals, divided randomly into four groups, were used: saline (n=10), 0.6 mg/kg (n=6), 2.5 mg/kg (n=7) and 10.0 mg/kg MPD (n=10). MPD caused an increase in locomotor activity with a dose response characteristic; 0.6 mg/kg MPD elicited some increase in locomotion, but not significantly, while 2.5 and 10.0 mg/kg MPD elicited significant increases in behavior of 191% and 870% respectively. A total of 209 ventral tegmental area units were recorded; 100% (36/36) units showed no response to saline; 89% (154/173) of the neurons responded to MPD, with the majority 66% (101/154) showing an increase in activity. In response to 0.6 mg/kg (n=52), the majority of units 54% (28/52) showed a decrease in activity. For both 2.5 (n=60) and 10.0 mg/kg (n=61), the majority of ventral tegmental area units responded with an increase in activity with 63% (38/60) and 70% (43/61) respectively. This study demonstrated that the majority of ventral tegmental area neurons respond to acute MPD in a dose response characteristic and are not related to the animal's locomotor activity. PMID:23651545

Jones, Zachary; Dafny, Nachum

2013-05-04

192

A dose-response study comparing suppression of plasma cortisol induced by fluticasone propionate from Diskhaler and budesonide from Turbuhaler.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To compare the systemic potency of inhaled fluticasone propionate delivered via Diskhaler (FP-DH), and inhaled budesonide delivered via Turbuhaler (BUD-TBH) over the clinically recommended dose range using plasma cortisol suppression as a marker for systemic activity. METHODS: The systemic potency was examined in a dose-response study in 81 healthy male volunteers. The study was of an open, randomized, parallel-group (four groups) design, where two treatments were given in crossover fashion within each group. FP-DH and BUD-TBH were given b.i.d. for 7 days (14 doses): 100 and 100 micrograms (group 1); 200 and 200 micrograms (group 2); 500 and 400 micrograms (group 3); 1000 and 800 micrograms (group 4). There was a washout period of 7 days within each treatment group. All doses were administered at 08:00 and 20:00 hours. Multiple plasma cortisol samples were taken every 2 h over 24-h periods prior to randomization (baseline) and during steady state (i.e., the last two dosing intervals). Cortisol suppression was determined by comparing average plasma concentrations of cortisol before and during treatment. Dose-response curves for cortisol suppression were analyzed using multivariate non-linear regression (Hill modeling). RESULTS: Multiple dosing for 7 days with FP-DH and BUD-TBH resulted in dose-dependent cortisol suppression by both drugs, most pronounced at the two highest dose levels. FP-DH-induced suppression was 41% at 500 micrograms and 86% at 1000 micrograms b.i.d., while that induced by BUD-TBH was 19% at 400 micrograms and 47% at 800 micrograms b.i.d. Statistically significant differences were found when comparing the two steroids at these two dose levels. Doses producing 50% of maximum suppression (ED50) were estimated at 833 micrograms b.i.d. for BUD-TBH and 479 micrograms b.i.d. for FP-DH. This gave an estimated relative cortisol suppression over the dose range of 1.74:1 (FP-DH:BUD-TBH). ED50 values, estimated from cortisol concentrations at 08:00 hours (12 h after the last dose), were 1212 micrograms b.i.d. for BUD-TBH and 527 micrograms b.i.d. for FP-DH giving a relative cortisol suppression of 2.30:1 (FP-DH:BUD-TBH). Fourteen subjects on the highest FP-DH dose and 3 at the next highest dose had morning plasma cortisol levels below the lower reference limit. No subject taking budesonide, however, had morning plasma cortisol levels below the reference limit. Analysis of the time for return to pretreatment baseline levels showed that cortisol suppression, 12-24 h after the last dose, was statistically significant compared with the baseline for the highest dose of FP-DH but not for any of the BUD-TBH doses. CONCLUSIONS: The results of the present study show that FP-DH suppresses plasma cortisol more than BUD-TBH on a equivalent basis with regard to both magnitude and duration.

Grahnén A; Jansson B; Brundin RM; Ling-Andersson A; Lönnebo A; Johansson M; Eckernäs SA

1997-01-01

193

Dose-response relationship of neutrons and ? rays to leukemia incidence among atomic bomb survivors in Hiroshima and Nagasaki by type of leukemia, 1950--1971  

International Nuclear Information System (INIS)

[en] The incidence of leukemia during 1950 to 1971 in a fixed mortality sample of atomic bomb survivors in Hiroshima and Nagasaki was analyzed as a function of neutron and ? kerma and marrow doses. Two dose-response models were tested for acute leukemia, chronic granulocytic leukemia, and all types of leukemia, respectively. Each model postulates that the leukemia incidence depends upon the sum of separate risks imposed by ? and neutron doses. In Model I the risk from both types of radiation is assumed to be directly proportional to the respective doses, while Model II assumes that whereas the risk from neutrons is directly proportional to the dose, the risk from ? rays is proportional to dose-squared. The analysis demonstrated that the dose-response of the two types of leukemia differed by type of radiation. The data suggested that the response of acute leukemia was best explained by Model II, while the response of chronic granulocytic leukemia depended almost linearly upon neutron dose alone, because the regression coefficients associated with ? radiation for both Models I and II were not significant. The relative biological effectiveness (RBE) of neutrons in relation to ? rays for incidence of acute leukemia was estimated to be approximately 30/(Dn)/sup 1/2/ [95% confidence limits; 17/(Dn)/sup 1/2/ approx. 54/(Dn)/sup 1/2/] for kerma and 32/(Dn)/sup 1/2/ [95% confidence limits; 18/(Dn)/sup 1/2/ approx. 58/(Dn)/sup 1/2/] for marrow dose (Dn = neutron dose). If acute and chronic granulocytic leukemias are considered together as all types of leukemia, Model II appears to fit the data slightly better than Model I, but neither model is statistically rejected by the data

1979-01-01

194

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

International Nuclear Information System (INIS)

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

1990-01-01

195

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1990-05-01

196

Biological dosimetry using the micronucleus assay for lymphocytes: interindividual differences in dose response.  

UK PubMed Central (United Kingdom)

The dose response of the number of micronuclei in cytokinesis-blocked lymphocytes after in-vitro irradiation of whole blood with x rays in the dose range 0-4 Gy was studied for a heterogeneous population of 10 donors. One thousand binucleated cells were systematically scored for micronuclei. A linear-quadratic dose dependency of the micronucleus yields was observed. The data were used to derive the accuracy of the dose assessment with the technique in case of a radiation accident. It was shown that for doses of 2 Gy and higher, the uncertainty of the dose was predominantly due to interindividual differences in the x-ray-induced micronucleus yields. At the 95% confidence level, doses lower than 0.3 Gy could not be unequivocally detected with the cytokinesis-blocked micronucleus assay due to the variability of the baseline micronucleus frequency within the donor population and the poor statistical accuracy when scoring 1,000 cells. The precision and sensitivity of the method in the low-dose range could be improved by the knowledge of individual pre-irradiation baseline values and an increase of the number of cells scored by automation of the technique.

Thierens H; Vral A; de Ridder L

1991-11-01

197

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

CERN Document Server

We use p-values to identify the threshold level at which a regression function takes off from its baseline value, a problem motivated by applications in toxicological and pharmacological dose-response studies and environmental statistics. We study the problem in two sampling settings: one where multiple responses can be obtained at a number of different covariate-levels and the other the standard regression setting involving limited number of response values at each covariate. Our procedure involves testing the hypothesis that the regression function is at its baseline at each covariate value and then computing the potentially approximate p-value of the test. An estimate of the threshold is obtained by fitting a piecewise constant function with a single jump discontinuity, otherwise known as a stump, to these observed p-values, as they behave in markedly different ways on the two sides of the threshold. The estimate is shown to be consistent and its finite sample properties are studied through simulations. Ou...

Mallik, Atul; Banerjee, Moulinath; Michailidis, George

2011-01-01

198

Procedures for determining the statistical significance of changes in variability simulated by an atmospheric general circulation model  

Energy Technology Data Exchange (ETDEWEB)

A statistical procedure is described for making inferences about differences in variability that would be appropriate when dealing with time series generated by an atmospheric general circulation model (GCM). The fundamental question of how to define climatic variability is first addressed. A definition of ''intrinsic'' climatic variability based on ''pre-whitening'' the data is advocated. A test for changes in variability that is not sensitive to departures from the assumption of a Gaussian distribution for the data is outlined. The use of this test is demonstrated by means of an application involving daily mean surface air temperature time series generated by the Oregon State University atmospheric GCM.

Katz, R.W.

1983-01-01

199

Non-linear dose-response relationships for later health effects: a sensitivity analysis  

International Nuclear Information System (INIS)

The use of non-linear dose-response relationships in predicting the incidence of late health effects following three hypothetical accidental releases of radioactive material has been investigated. Two forms of non-linear dose-response relationship were considered: 1) the linear-quadratic and 2) the pure quadratic relationships, both containing a dose-squared term. For the three release categories, a comparison was made of the ratios of the expectation value of the probability distribution of health effects evaluated using a non-linear dose-response relationship to that using a linear relationship. For larger releases the ratio varies with the health effect and the form of the non-linear relationship. For smaller releases, the ratio depends only on the non-linear dose-response relationship. (U.K.)

1983-01-01

200

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

UK PubMed Central (United Kingdom)

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.

Calabrese EJ

2013-08-01

 
 
 
 
201

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)

2008-01-01

202

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

Science.gov (United States)

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

Grieve, Andrew P; Krams, Michael

2005-01-01

203

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

Science.gov (United States)

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

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

2009-01-12

204

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

International Nuclear Information System (INIS)

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

2009-02-04

205

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

International Nuclear Information System (INIS)

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

2005-11-01

206

Excess body mass index and risk of liver cancer: a nonlinear dose-response meta-analysis of prospective studies.  

UK PubMed Central (United Kingdom)

BACKGROUND: Excess body weight measured as body mass index (BMI) has a positive association with risk of common cancers. However, previous meta-analyses related to BMI and liver cancer had inconsistent results. The purpose of the current study is to establish a nonlinear dose-response relationship between BMI and incidence risk of liver cancer. METHODS: A systematic literature search for relevant articles published from 1966 to November 2011 was conducted in PUBMED and EMBASE digital databases. Additional articles were manually searched by using the reference lists of identified papers. Restricted cubic splines and generalized least-squares regression methods were used to model a potential curvilinear relationship and to make a dose-response meta-analysis. Stratified analysis, sensitivity analysis and assessment of bias were performed in our meta-analysis. RESULTS: 8 articles including 1,779,471 cohort individuals were brought into meta-analysis. A non-linear dose-response association between BMI and risk of liver cancer was visually significant (P for nonlinearity<0.001), besides, the point value of BMI also enhanced the results quantitatively, where relative risks were 1.02 (95%CI?=?1.02-1.03), 1.35 (95%CI?=?1.24-1.47) and 2.22-fold (95%CI?=?1.74-2.83) when BMI was at the point of 25, 30 and 35 kg/m(2) compared with reference (the median value of the lowest category), respectively. The ethnicity of the population was found as the main source of heterogeneity. In subsequent stratified analysis, no evidence of heterogeneity was showed in Asian and White populations (P for heterogeneity>0.1), and all value of BMI still presented significantly increased risk of cancer. CONCLUSIONS: The findings from meta-analysis provided that excess BMI had significant increased association with risk of liver cancer, although the biological mechanisms underlying the obesity-cancer link still need to be clarified.

Rui R; Lou J; Zou L; Zhong R; Wang J; Xia D; Wang Q; Li H; Wu J; Lu X; Li C; Liu L; Xia J; Xu H

2012-01-01

207

Antihypertensive and biochemical dose-response study of tripamide.  

UK PubMed Central (United Kingdom)

Tripamide is an experimental sulfonamide-derived diuretic antihypertensive agent. Twenty-four hospitalized patients with essential hypertension received placebo followed by 10, 25, 50, or 100 mg of tripamide daily in a randomized, double-blind design. All doses of tripamide significantly lowered standing arterial pressure. Changes in blood pressure, heart rate, and weight were not dose related, but the decrease in mean arterial pressure was significantly related to both age (P less than 0.02) and pretreatment blood pressure (P less than 0.05). Serum potassium levels were lowered significantly by the 25 and 100 mg daily doses of tripamide, whereas all doses of tripamide significantly reduced serum chloride levels and produced an increase in serum uric acid levels. Disparate time courses of antihypertensive and diuretic effects and the lack of a relationship between the increase in urine volume and the change in blood pressure suggest an additional antihypertensive action of tripamide or a delayed physiologic adaptation to volume depletion. Equal antihypertensive effects over the range of 10 to 100 mg/day, but greater hypokalemia at higher doses, suggest that future studies should employ the lower doses of tripamide.

Fagan TC; Conrad KA; Lee S; Mar JH; Simons J

1986-09-01

208

The dose-response relationship between the patch test and ROAT and the potential use for regulatory purposes.  

UK PubMed Central (United Kingdom)

BACKGROUND: Allergic contact dermatitis is common and can be prevented. The relationship between thresholds for patch tests and the repeated open application test (ROAT) is unclear. It would be desirable if patch test and ROAT data from already sensitized individuals could be used in prevention. OBJECTIVES: The aim was to develop an equation that could predict the response to an allergen in a ROAT based on the dose-response curve derived by patch testing. MATERIALS/METHODS: Results from two human experimental elicitation studies with non-volatile allergens, nickel and the preservative methyldibromo glutaronitrile (MDBGN), were analysed by logistic dose-response statistics. The relation for volatile compounds was investigated using the results from experiments with the fragrance chemicals hydroxyisohexyl 3-cyclohexene carboxaldehyde and isoeugenol. RESULTS: For non-volatile compounds, the outcome of a ROAT can be estimated from the patch test by: ED(xx)(ROAT) = 0.0296 ED(xx)(patch test). For volatile compounds, the equation predicts that the response in the ROAT is more severe than the patch test response, but it overestimates the response. CONCLUSIONS: This equation may be used for non-volatile compounds other than nickel and MDBGN, after further validation. The relationship between the patch test and the ROAT can be used for prevention, to set safe levels of allergen exposure based on patch test data.

Fischer LA; Voelund A; Andersen KE; Menné T; Johansen JD

2009-10-01

209

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

UK PubMed Central (United Kingdom)

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

Gaonkar B; Davatzikos C

2013-09-01

210

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

Science.gov (United States)

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

Gaonkar, Bilwaj; Davatzikos, Christos

2013-04-10

211

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

Science.gov (United States)

The scaling of displacement as a function of length is important for a variety of applications which depend on the mechanical and hydraulic properties of faults and fractures. Recently it has been suggested that the power-law exponent ? which has been found to characterise this relationship may change significantly at a characteristic length for a variety of reasons, for example when cracks begin to interact, or when faults grow to a length comparable to a characteristic size in the brittle layer. Such a break of slope requires a second straight line, requiring two extra model parameters. Here we present a new method for analysing such data, which penalises the extra parameters using a modified form of Schwarz's Information Criterion, and a Bayesian approach which represents uncertainty in the unknown parameters. We apply the method to data from the Krafla fissure zone in the north of Iceland, and find a significant break of slope, from ? ? 3/2 to ? ? 2/3, at a characteristic length of 12m.

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

212

Gender difference in efficacy and dose response in Japanese patients with nocturia treated with four different doses of desmopressin orally disintegrating tablet in a randomized, placebo-controlled trial.  

UK PubMed Central (United Kingdom)

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Desmopressin orally disintegrating tablet (ODT) 60-240??g has proved an effective and well-tolerated antidiuretic treatment in male and female patients with nocturia. The main adverse event is hyponatraemia. Recent studies suggest that female patients are more sensitive to desmopressin ODT, achieving the same efficacy at lower doses than male patients. The study demonstrates the efficacy of desmopressin ODT in male and female Japanese patients with nocturia. It provides further evidence that the optimum desmopressin dose for the treatment of nocturia is lower in females than in males. Tailoring the dose according to gender provides an improved therapeutic window with the benefits of a decreased risk of hyponatraemia without compromising efficacy. OBJECTIVES: To establish the dose-response efficacy of desmopressin in a Japanese patient population for the treatment of nocturia. To explore gender differences in sensitivity to desmopressin in Japanese patients with nocturia. PATIENTS AND METHODS: A phase II multicentre, randomized, placebo-controlled, double-blind, parallel-group, comparative clinical trial was conducted. Subjects aged 55-75 years, with a mean of ?2 voids per night, were included and randomized to receive placebo or one of four doses of desmopressin orally disintegrating tablet (ODT): 10??g, 25??g, 50??g or 100??g. The dose-response relationship of pharmacodynamic variables measured after a single dose of desmopressin administered to water-loaded subjects (treatment period 1) was compared with the primary clinical endpoint of change from baseline in mean number of nocturnal voids, after 28 days of desmopressin treatment (treatment period 2). RESULTS: A total of 116 patients were treated in treatment period 1 of whom 113 qualified for treatment period 2, and 111 completed the study. In treatment period 1 a dose-response relationship was observed, both overall and in each gender group. Overall, the duration of antidiuretic action (DOA; time with urine osmolality >200?mOsm/kg) for the 25, 50 and 100??g doses was 2?h (P = 0.010), 3.45?h (P < 0.001) and 5.74?h (P < 0.001), respectively; all statistically significant compared with placebo. Female patients were found to be more sensitive to desmopressin; DOA in female patients was longer than in male patients after desmopressin 25 and 50??g. Extrapolation suggests that male patients require ?58??g to achieve similar DOA to females receiving 25??g. A dose-response relationship was also seen in treatment period 2 for the group overall with a greater reduction in mean number of nocturnal voids from baseline to day 28 at higher doses, and with significant reductions in the 25- (P = 0.015) 50- (P < 0.001) and 100-?g (P = 0.001) dose groups compared with placebo. Similar dose-response relationships were also seen when the data were analysed by gender. Desmopressin ODT was well tolerated with no serious or severe adverse events. CONCLUSIONS: A dose-response relationship for desmopressin ODT was shown in a population of Japanese patients with nocturia. The study suggests that the optimum desmopressin dose for the treatment of nocturia is lower in females than in males, indicating a gender-specific therapeutic window with a decreased risk of hyponatraemia without compromising efficacy on reduction of nocturnal voids. Further dose-finding studies are planned to confirm the recommended dose for the treatment of nocturia in a Japanese patient population.

Yamaguchi O; Nishizawa O; Juul KV; Nørgaard JP

2013-03-01

213

Habitual chocolate consumption may increase body weight in a dose-response manner.  

UK PubMed Central (United Kingdom)

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

Greenberg JA; Buijsse B

2013-01-01

214

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

Science.gov (United States)

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

Greenberg, James A.; Buijsse, Brian

2013-01-01

215

A dose-response study of dexmedetomidine administered as the primary sedative in infants following open heart surgery.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To evaluate the dose-response relationship of dexmedetomidine in infants with congenital heart disease postoperative from open heart surgery. DESIGN: Prospective open-label dose-escalation pharmacokinetic-pharmacodynamic study. SETTING: Tertiary pediatric cardiac ICU. PATIENTS: Thirty-six evaluable infants, 1-24 months old, postoperative from open heart surgery requiring mechanical ventilation. INTERVENTIONS: Cohorts of 12 infants were enrolled sequentially to one of the three IV loading doses of dexmedetomidine (0.35, 0.7, and 1 mcg/kg) over 10 minutes followed by respective continuous infusions (0.25, 0.5, and 0.75 mcg/kg/hr) for up to 24 hours. MEASUREMENTS AND MAIN RESULTS: Dexmedetomidine plasma concentrations were obtained at timed intervals during and following discontinuation of infusion. Pharmacodynamic variables evaluated included sedation scores, supplemental sedation and analgesia medication administration, time to tracheal extubation, respiratory function, and hemodynamic parameters. Infants achieved a deeper sedation measured by the University of Michigan Sedation Scale score (2.6 vs 1) despite requiring minimal supplemental sedation (0 unit doses/hr) and fewer analgesic medications (0.07 vs 0.15 unit doses/hr) while receiving dexmedetomidine compared with the 12-hour follow-up period. Thirty-one patients were successfully extubated while receiving the dexmedetomidine infusion. Only one patient remained intubated due to oversedation during the infusion. While receiving dexmedetomidine, there was a decrease in heart rate compared with baseline, 132 versus 161 bpm, but there was an increase in heart rate compared with postinfusion values, 132 versus 128 bpm. There was no statistically or clinically significant change in mean arterial blood pressure. CONCLUSIONS: Dexmedetomidine administration in infants following open heart surgery can provide improved sedation with reduction in supplemental medication requirements, leading to successful extubation while receiving a continuous infusion. The postoperative hemodynamic changes that occur in infants postoperative from open heart surgery are multifactorial. Although dexmedetomidine may play a role in decreasing heart rate immediately postoperative, the changes were not clinically significant and did not fall below postinfusion heart rates.

Su F; Nicolson SC; Zuppa AF

2013-06-01

216

Dose-response relationship between Selective Serotonin Reuptake Inhibitors and Injurious Falls: A study in Nursing Home Residents with Dementia.  

UK PubMed Central (United Kingdom)

Aim:? The contribution of selective serotonin reuptake inhibitors (SSRIs) to injurious fall risk in patients with dementia has not been quantified precisely until now. Our objective was to determine whether a dose-response relationship exists for the use of SSRIs and injurious falls in a population of nursing home residents with dementia. Methods:? Daily drug use and daily falls were recorded in 248 nursing home residents with dementia from 1 January 2006 until 1 January 2008. For each resident and for each day of the study period, data on drug use were abstracted from the prescription database, and information on falls and subsequent injuries was retrieved from a standardised incident report system, resulting in a dataset of 85,074 person-days. Results:? We found a significant dose-response relationship between injurious falls and the use of SSRIs. The risk of an injurious fall increased significantly with 31% at 0.25 of the Defined Daily Dose (DDD) of a SSRI, 73% at 0.50 DDD, and 198% at 1.00 DDD (Hazard Rate = 2.98; 95% confidence interval 1.94-4.57). The risk increased further in combination with a hypnotic or sedative. Conclusions:? Even at low doses, SSRIs are associated with increased risk of an injurious fall in nursing home residents with dementia. Higher doses increase the risk further with a threefold risk at 1.00 DDD. New treatment protocols might be needed that take into account the dose-response relationship between SSRIs and injurious falls. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

Sterke CS; Ziere G; van Beeck EF; Looman CW; van der Cammen TJ

2012-01-01

217

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

Science.gov (United States)

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

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

2013-04-28

218

Dose response, prevention, and treatment of a transplantable lymphoid tumor.  

UK PubMed Central (United Kingdom)

Transplantable lymphoid tumor (TLT) cells in doses ranging from 10(2.43) to 10(6.80) were transplanted into 3-week-old chicks. A total of 199 chicks in 31 dosage groups was included in this 2-year study. Overall mortality was nearly 100% and analysis of the results revealed no significant differences in mortality among the groups. A significant (P less than 0.001) linear relationship existed between log10 of the TLT cell dose and mean survival time. Serum obtained from chickens which survived TLT growth, regression, and challenge inoculation was administered to chicks 4, 7, or 11 days before TLT induction. Of the chickens in each of these 3 groups, 80 to 100% survived compared with 0 to 20% in those given control serum. In chicks with actively growing TLT that were treated with 2 injections of plasma from TLT-resistant chickens, mean survival time was lengthened and survival was increased by 36%. Lymphocytes from resistant chickens or plasma od and survival was increased by 36%. Lymphocytes from resistant chickens or plasma or lymphocytes from control chickens did not affect survival time or percentage of survival. In the present study, results demonstrated a similarity to the TLT model studied 30 years ago and established the usefulness of this model in the study of serum immunotherapy.

Walser MM; Fletcher OJ Jr; Brown J

1977-08-01

219

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

International Nuclear Information System (INIS)

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

2011-01-01

220

Dose-response effect of cocaine on newborn head circumference.  

UK PubMed Central (United Kingdom)

OBJECTIVE: To evaluate the relationship between head circumference, birth weight, and cocaine dose in healthy term and near-term newborns exposed to cocaine in utero. METHODS: We used radioimmune assay (RIAH) of cocaine metabolite in maternal hair to quantify third trimester cocaine exposure in 240 healthy newborn infants (gestational age: >36 weeks). Cocaine exposure was categorized into 3 levels: no exposure (n = 136), low cocaine exposure (n = 52; RIAH: 2-66 ng/10 mg hair), and high cocaine exposure (n = 52; RIAH: 81-4457 ng/10 mg hair). We collected information on maternal demographic characteristics, the pregnancy, and the use of substances through a structured interview and from the medical record. RESULTS: Means of birth weight, length, and head circumference of infants with high cocaine exposure differed significantly from those with low exposure and no exposure, but were similar between low exposure and no exposure. We used a multiple linear regression model to assess the association between newborn head circumference and cocaine level, adjusting for the effects of birth weight; gestational age; infant sex; and several maternal factors, including height, weight gain during pregnancy, syphilis during pregnancy, and the use of alcohol, cigarettes, marijuana, and opiates during pregnancy. Only birth weight, sex, and high cocaine exposure were significantly associated with newborn head circumference. The predicted head circumference deficit associated with high cocaine exposure (.44 cm) represents 34% of the unadjusted difference (1.28 cm) between mean head circumferences of infants in the high cocaine exposure and no exposure groups. CONCLUSION: Newborns exposed to a high level of cocaine in utero (RIAH: >81 ng/10 mg hair) exhibit asymmetric intrauterine growth retardation in which the head circumference is disproportionately smaller than would be predicted from the birth weight (head wasting). The deficit in head size associated with cocaine exposure may reflect the effects of a specific central nervous system insult that interferes with prenatal brain growth.

Bateman DA; Chiriboga CA

2000-09-01

 
 
 
 
221

A rat model for dose-response relationships of Salmonella Enteritidis infection.  

UK PubMed Central (United Kingdom)

AIMS: To develop an animal model to study dose-response relationships of enteropathogenic bacteria. METHODS AND RESULTS: Adult, male Wistar Unilever rats were exposed orally to different doses of Salmonella enterica serovar Enteritidis after overnight starvation and neutralization of gastric acid by sodium bicarbonate. The spleen was the most sensitive and reproducible organ for detection of dose-dependent systemic infection. Illness was only observed in animals exposed to doses of 10(8) cfu or more. At lower doses, histopathological changes in the gastro-intestinal tract were observed, but these were not accompanied by illness. Marked changes in numbers and types of white blood cells, as well as delayed-type hyperresponsiveness, indicated a strong, dose-dependent cellular immune response to Salm. Enteritidis. CONCLUSION: The rat model is a sensitive and reproducible tool for studying the effects of oral exposure to Salm. Enteritidis over a wide dose range. SIGNIFICANCE AND IMPACT OF THE STUDY: The rat model allows controlled quantification of different factors related to the host, pathogen and food matrix on initial stages of infection by food-borne bacterial pathogens.

Havelaar AH; Garssen J; Takumi K; Koedam MA; Dufrenne JB; van Leusden FM; de La Fonteyne L; Bousema JT; Vos JG

2001-09-01

222

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

Directory of Open Access Journals (Sweden)

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

S.B. Pajovi; G. Joksi; S. Peji; J. Kasapovi; G. Cuttone; L. Masotti

2001-01-01

223

Low-level microwave irradiation and central cholinergic activity: a dose-response study  

Energy Technology Data Exchange (ETDEWEB)

Rats were irradiated with circularly polarized, 2,450-MHz pulsed microwaves (2-microseconds pulses, 500 pulses per second (pps)) for 45 min in the cylindrical waveguide system of Guy et al. Immediately after exposure, sodium-dependent high-affinity choline uptake, an indicator of cholinergic activity in neural tissue, was measured in the striatum, frontal cortex, hippocampus, and hypothalamus. The power density was set to give average whole-body specific absorption rates (SAR) of 0.3, 0.45, 0.6, 0.75, 0.9, or 1.2 W/kg to study the dose-response relationship between the rate of microwave energy absorption and cholinergic activity in the different areas of the brain. Decrease in choline uptake was observed in the striatum at a SAR of 0.75 W/kg and above, whereas for the frontal cortex and hippocampus, decreases in choline uptake were observed at a SAR of 0.45 W/kg and above. No significant effect was observed in the hypothalamus at the irradiation power densities studied. The probit analysis was used to determine the SAR50 in each brain area, i.e., the SAR at which 50% of maximum response was elicited. SAR50 values for the striatum, frontal cortex, and hippocampus were 0.65, 0.38, and 0.44 W/kg, respectively.

Lai, H.; Carino, M.A.; Horita, A.; Guy, A.W.

1989-01-01

224

Meat, fish, and esophageal cancer risk: a systematic review and dose-response meta-analysis.  

UK PubMed Central (United Kingdom)

Risk factors for esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are well defined, while the role of diet in these conditions remains controversial. To help elucidate the role of particular dietary components, major bibliographic databases were searched for published studies (1990-2011) on associations between esophageal cancer risk (EC) and consumption of various types of meat and fish. Random-effects models and dose-response meta-analyses were used to pool study results. Subgroup analyses were conducted by histological subtype, study design, and nationality. Four cohorts and 31 case-control studies were identified. The overall pooled relative risk (RR) of EC and the confidence intervals (CIs) for the groups with the highest versus the lowest levels of intake were as follows: 0.99 (95% CI: 0.85-1.15) for total meat; 1.40 (95%CI: 1.09-1.81) for red meat; 1.41 (95%CI: 1.13-1.76) for processed meat; 0.87 (95%CI: 0.60-1.24) for poultry; and 0.80 (95%CI: 0.64-1.00) for fish. People with the highest levels of red meat intake had a significantly increased risk of ESCC. Processed meat intake was associated with increased risk of EAC. These results suggest that low levels of red and processed meat consumption and higher levels of fish intake might reduce EC risk.

Salehi M; Moradi-Lakeh M; Salehi MH; Nojomi M; Kolahdooz F

2013-05-01

225

Relative sensitivity to naloxone of multiple indices of opiate withdrawal: a quantitative dose-response analysis.  

UK PubMed Central (United Kingdom)

In addition to classic somatic signs of opiate withdrawal, a number of behavioral measures are known to be sensitive, reliable indices of naloxone-precipitated opiate withdrawal in rats. It has been suggested that some behavioral indices of withdrawal may be more sensitive to precipitation by naloxone than some somatic signs of withdrawal. The purpose of the present study was to permit a quantitative assessment of the relative sensitivity to naloxone of a variety of behavioral and somatic indices of opiate withdrawal. Male Wistar rats were implanted s.c. with either two morphine (each 75 mg of base) or two placebo pellets. No sooner than 3 days after implantation, naloxone dose-response functions were determined with several behavioral paradigms and ratings of a variety of somatic withdrawal signs. In dependent rats, very low (0.004 or 0.01 mg/kg) doses of naloxone produced the following behavioral effects: 1) a reduction in spontaneous locomotor activity, 2) a disruption of schedule-controlled (fixed ratio 15) operant responding for food, 3) an elevation in intracranial self-stimulation thresholds and 4) a conditioned place aversion. These same doses of naloxone produced no significant effects in nondependent (placebo pellet-implanted) rats. The ED50 values for naloxone precipitation of all behavioral signs of withdrawal were below 0.013 mg/kg; the ED50 values for naloxone precipitation of most somatic withdrawal signs were higher. The behavioral measures used in these studies therefore represent highly sensitive indices of opiate withdrawal.

Schulteis G; Markou A; Gold LH; Stinus L; Koob GF

1994-12-01

226

Dose-Response Relationship of Phototherapy for Hyperbilirubinemia  

DEFF Research Database (Denmark)

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

Vandborg, Pernille Kure; Hansen, Bo Moelholm

2012-01-01

227

Parameterizing dose-response models to estimate relative potency functions directly.  

UK PubMed Central (United Kingdom)

Many comparative analyses of toxicity assume that the potency of a test chemical relative to a reference chemical is constant, but employing such a restrictive assumption uncritically may generate misleading conclusions. Recent efforts to characterize non-constant relative potency rely on relative potency functions and estimate them secondarily after fitting dose-response models for the test and reference chemicals. We study an alternative approach of specifying a relative potency model a priori and estimating it directly using the dose-response data from both chemicals. We consider a power function in dose as a relative potency model and find that it keeps the two chemicals' dose-response functions within the same family of models for families typically used in toxicology. When differences in the response limits for the test and reference chemicals are attributable to the chemicals themselves, the older two-stage approach is the more convenient. When differences in response limits are attributable to other features of the experimental protocol or when response limits do not differ, the direct approach is straightforward to apply with nonlinear regression methods and simplifies calculation of simultaneous confidence bands. We illustrate the proposed approach using Hill models with dose-response data from U.S. National Toxicology Program bioassays. Though not universally applicable, this method of estimating relative potency functions directly can be profitably applied to a broad family of dose-response models commonly used in toxicology.

Dinse GE; Umbach DM

2012-10-01

228

Parameterizing dose-response models to estimate relative potency functions directly.  

Science.gov (United States)

Many comparative analyses of toxicity assume that the potency of a test chemical relative to a reference chemical is constant, but employing such a restrictive assumption uncritically may generate misleading conclusions. Recent efforts to characterize non-constant relative potency rely on relative potency functions and estimate them secondarily after fitting dose-response models for the test and reference chemicals. We study an alternative approach of specifying a relative potency model a priori and estimating it directly using the dose-response data from both chemicals. We consider a power function in dose as a relative potency model and find that it keeps the two chemicals' dose-response functions within the same family of models for families typically used in toxicology. When differences in the response limits for the test and reference chemicals are attributable to the chemicals themselves, the older two-stage approach is the more convenient. When differences in response limits are attributable to other features of the experimental protocol or when response limits do not differ, the direct approach is straightforward to apply with nonlinear regression methods and simplifies calculation of simultaneous confidence bands. We illustrate the proposed approach using Hill models with dose-response data from U.S. National Toxicology Program bioassays. Though not universally applicable, this method of estimating relative potency functions directly can be profitably applied to a broad family of dose-response models commonly used in toxicology. PMID:22700543

Dinse, Gregg E; Umbach, David M

2012-06-14

229

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

International Nuclear Information System (INIS)

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

1982-01-01

230

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

Science.gov (United States)

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

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

2013-05-28

231

The dose-response of time served in prison on mortality: New York State, 1989-2003.  

UK PubMed Central (United Kingdom)

OBJECTIVES: I investigated the differential impact of the dose-response of length of stay on postprison mortality among parolees. METHODS: Using 1989-2003 New York State parole administrative data from the Bureau of Justice Statistics on state correctional facilities, I employed multinomial logistic regression analyses and formal demographic techniques that used the life table of the populations to deduce changes in life expectancy. RESULTS: Each additional year in prison produced a 15.6% increase in the odds of death for parolees, which translated to a 2-year decline in life expectancy for each year served in prison. The risk was highest upon release from prison and declined over time. The time to recovery, or the lowest risk level, was approximately two thirds of the time served in prison. CONCLUSIONS: Incarceration reduces life span. Future research should investigate the pathways to this higher mortality and the possibilities of recovery.

Patterson EJ

2013-03-01

232

Dose Response Effects of 810 nm Laser Light on Mouse Primary Cortical Neurons  

Science.gov (United States)

Background and Objectives In the past four decades numerous studies have reported the efficacy of low level light (laser) therapy (LLLT) as a treatment for diverse diseases and injuries. Recent studies have shown that LLLT can biomodulate processes in the central nervous system and has been extensively studied as a stroke treatment. However there is still a lack of knowledge on the effects of LLLT at the cellular level in neurons. The present study aimed to study the effect of 810 nm laser on several cellular processes in primary cortical neurons cultured from embryonic mouse brains. Study Design/Materials and Methods Neurons were irradiated with fluences of 0.03, 0.3, 3, 10, or 30 J/cm2 of 810-nm laser delivered over varying times at 25 mW/cm2 and intracellular levels of reactive oxygen species (ROS), nitric oxide and calcium were measured using fluorescent probes within 5 minutes of the end of irradiation. The changes in mitochondrial function in response to light were studied in terms of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP). Results Light induced a significant increase in calcium, ATP and MMP at lower fluences and a decrease at higher fluences. ROS was significantly induced at low fluences, followed by a decrease and a second larger increase at 30 J/cm2. Nitric oxide levels showed a similar pattern of a double peak but values were less significant compared to ROS. Conclusions The results suggest that LLLT at lower fluences is capable of inducing mediators of cell signaling processes which in turn may be responsible for the beneficial stimulatory effects of the low level laser. At higher fluences beneficial mediators are reduced and high levels of Janus-type mediators such as ROS and NO (beneficial at low concentrations and harmful at high concentrations) may be responsible for the damaging effects of high-fluence light and the overall biphasic dose response.

Sharma, Sulbha K.; Kharkwal, Gitika B.; Sajo, Mari; Huang, Ying-Ying; De Taboada, Luis; McCarthy, Thomas; Hamblin, Michael R.

2011-01-01

233

Statistical significance of quantitative PCR  

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 experimen...

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

234

Dose-Response of Women's Health-Related Quality of Life (HRQoL) and Life Satisfaction to Physical Activity.  

UK PubMed Central (United Kingdom)

BACKGROUND: To examine the dose-response relationship between health related quality of life (HRQoL) and life satisfaction (outcomes) and duration of recreational physical activity (PA) (exposure). Further, to explore whether these relationships depend on type of PA. METHODS: 793 Australian rural-living women self-reported on: duration of recreational PA; HRQoL via SF-36 Mental Component Summary (MCS) and Physical Component Summary (PCS); and a life satisfaction scale. ANOVAs and ANCOVAs investigated differences in outcomes (MCS, PCS and life satisfaction) between tertiles of exposure to recreational PA, and types of PA (club sport, gymnasium, walking), with adjustment for potential confounders. RESULTS: A significant positive dose-response relationship was found between PCS and level of PA. Furthermore, this relationship depended on type of PA, with club-sport participants recording higher PCS than non-club-sport participants in all but the highest tertile of exposure. Life satisfaction and MCS were not significantly related to level of PA. CONCLUSION: Physical health was positively associated with level of recreational PA, with club sport participation contributing greater benefits at low to moderate exposures than participation in gymnasium or walking activities.

Eime R; Harvey J; Payne W

2013-01-01

235

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

UK PubMed Central (United Kingdom)

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

Szomolay B; Shahrezaei V

2012-01-01

236

Changes in post-traumatic symptom pattern during and after exposure to extreme war stress: an uncontrolled, preliminary study supporting the dose-response model.  

UK PubMed Central (United Kingdom)

INTRODUCTION: Exposure to prolonged war stress is understudied. While there is debate regarding the empirical data of the dose-response model for posttraumatic stress disorder (PTSD), little is known about how weekly changes in external stress influences the level of PTSD symptoms. The purpose of this study was to measure the relation between objective external stress and PTSD symptoms across time, and thus, gain a deeper understating of the dose-response model. HYPOTHESIS: The study hypothesis postulates that the more severe the external stressor, the more severe the exhibition of traumatic symptoms. METHODS: Thirteen special army administrative staff (SAAS) members from the Rambam Medical Center in Haifa attended seven intervention meetings during the war. These personnel answered a battery of questionnaires regarding demographics and PTSD symptoms during each session. A non-parametric test was used in order to measure the changes in PTSD symptoms between sessions. Pearson correlations were used in order to study the relationship between the magnitude of external stressors and the severity of PTSD symptoms. RESULTS: The results suggested that there was a significant relationship between the magnitude of external stressors and the severity of PTSD symptoms. These results are in line with the dose-response model. CONCLUSIONS: The results suggest that a pattern of decline in PTSD symptoms confirm the dose-response model for PTSD.

Ben-Ezra M; Palgi Y; Shrira A; Sternberg D; Essar N

2010-01-01

237

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

Directory of Open Access Journals (Sweden)

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

Szomolay Barbara; Shahrezaei Vahid

2012-01-01

238

Dose response effects of lithium chloride on conditioned place aversions and locomotor activity in rats.  

UK PubMed Central (United Kingdom)

The present study examined the multi-variable locomotor activity effects of lithium chloride (LiCl) treatment in male rats. Of interest was a determination of which variables might show a dose-response relationship in LiCl-induced conditioned place aversions. Automated open-fields were partitioned into two chambers distinct in tactile and visual cues. A control group [n=8] received saline (NaCl; 0.15 M) paired with both chambers while three LiCl groups (0.15 M; 32 mg/kg [n=7], 95 mg/kg [n=7], 127 mg/kg [n=7]) received LiCl paired with the normally preferred chamber and saline paired with the non-preferred chamber. During extinction trials, rats were allowed to choose between the two chambers to provide an index of conditioned place aversions. Locomotor activity and its distribution within the chambers were also assessed during both conditioning and extinction trials. Dose-dependent decreases occurred in all measures of locomotor activity following LiCl administration during conditioning. During extinction trials, place aversions developed in animals conditioned with LiCl. LiCl-treated rats spent significantly less time in the LiCl-paired chamber relative to controls but not in a dose-dependent manner. Animals that had been conditioned with 95 or 127 but not 32 mg/kg LiCl, displayed significantly more vertical activity in the LiCl-paired chamber than controls during extinction trials. These findings indicate that, in addition to producing dose-dependent unconditioned effects on locomotor activity, LiCl also produces dose-dependent conditioned effects on vertical activity. These conditioned rearing response effects provide a valid measure of the conditioned avoidance response that provides evidence for dose-dependent LiCl-induced conditioned place aversions.

Tenk CM; Kavaliers M; Ossenkopp KP

2005-05-01

239

Dose response effects of lithium chloride on conditioned place aversions and locomotor activity in rats.  

Science.gov (United States)

The present study examined the multi-variable locomotor activity effects of lithium chloride (LiCl) treatment in male rats. Of interest was a determination of which variables might show a dose-response relationship in LiCl-induced conditioned place aversions. Automated open-fields were partitioned into two chambers distinct in tactile and visual cues. A control group [n=8] received saline (NaCl; 0.15 M) paired with both chambers while three LiCl groups (0.15 M; 32 mg/kg [n=7], 95 mg/kg [n=7], 127 mg/kg [n=7]) received LiCl paired with the normally preferred chamber and saline paired with the non-preferred chamber. During extinction trials, rats were allowed to choose between the two chambers to provide an index of conditioned place aversions. Locomotor activity and its distribution within the chambers were also assessed during both conditioning and extinction trials. Dose-dependent decreases occurred in all measures of locomotor activity following LiCl administration during conditioning. During extinction trials, place aversions developed in animals conditioned with LiCl. LiCl-treated rats spent significantly less time in the LiCl-paired chamber relative to controls but not in a dose-dependent manner. Animals that had been conditioned with 95 or 127 but not 32 mg/kg LiCl, displayed significantly more vertical activity in the LiCl-paired chamber than controls during extinction trials. These findings indicate that, in addition to producing dose-dependent unconditioned effects on locomotor activity, LiCl also produces dose-dependent conditioned effects on vertical activity. These conditioned rearing response effects provide a valid measure of the conditioned avoidance response that provides evidence for dose-dependent LiCl-induced conditioned place aversions. PMID:15899481

Tenk, Christine M; Kavaliers, Martin; Ossenkopp, Klaus-Peter

2005-05-16

240

Anti-hypertensive dose-response effects of nicardipine in stable essential hypertension.  

Science.gov (United States)

The dose-response effects of oral nicardipine on the systemic blood pressure were examined in 54 patients with uncomplicated essential hypertension (DBP greater than or equal to 100 mm Hg). The study was designed in four sequential stages. A 2 week single-blind placebo run-in period was followed by dose titration with nicardipine at 2 week intervals. Patients achieving the target DBP less than or equal to 95 mm Hg were then crossed over to placebo for 2 weeks, following which the previous dose of nicardipine was readministered for 6 weeks. Forty-eight patients completed the dose-titration phase. The target DBP 95 mm Hg was achieved in 33; in eight after 10 mg three times daily, in 21 after 20 mg three times daily, in three after 30 mg three times daily and in one after 40 mg three times daily. In the 48 patients, systolic blood pressure was reduced from 188 +/- 25 to 158 +/- 21 mm Hg (P less than 0.001) and diastolic blood pressure from 111 +/- 9 to 93 +/- 13 mm Hg (P less than 0.001); heart rate increased from 81 +/- 7 to 87 +/- 13 beats min-1 (P less than 0.01). Thirty-one of the 33 patients completed the crossover to placebo, which was accompanied by a significant increase towards pretreatment blood pressure levels. Reinstitution of nicardipine at the previous dose resulted in a reduction of SBP and DBP to levels not significantly different from those at the end of the dose-titration stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3896280

Taylor, S H; Frais, M A; Lee, P; Verma, S P; Jackson, N; Silke, B

1985-01-01

 
 
 
 
241

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

Science.gov (United States)

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

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

2012-11-30

242

Modification by cis-diamminedichloroplatinum (II) of the radiation dose-response curve for intestinal crypt cells in mice  

Energy Technology Data Exchange (ETDEWEB)

The effect of cis-diamminedichloroplatinum (II) (c-DDP) on the shape of the radiation dose-response curve for mouse duodenal crypt cells was investigated. A priming X-ray dose was followed 18 h later by graded test doses (single doses or five equal fractions at 3-h intervals) with or without c-DDP. Curves were fitted by a linear quadratic (LQ) relationship. The drug modified the dose-response curve by enhancing both the alpha and the beta terms. Repair kinetics were analyzed in split-dose experiments. c-DDP caused a minor, nonsignificant decrease in the rate of repair after irradiation. The survival ratio after split-dose irradiation, when the same X-ray doses were given, was actually slightly increased by the drug. This paradoxical effect can be explained by the fact that c-DDP mainly increased the beta term in the LQ relationship. There was no significant increase in crypt cell survival when split-drug doses were given alone at increasing intervals, suggesting no cellular repair after c-DDP treatment. The data are discussed in the light of the recently proposed lethal and potentially lethal (LPL) unified repair model of Curtis.

Dewit, L.; Oussoren, Y.; Hart, G.

1987-09-01

243

Modification by cis-diamminedichloroplatinum (II) of the radiation dose-response curve for intestinal crypt cells in mice  

International Nuclear Information System (INIS)

The effect of cis-diamminedichloroplatinum (II) (c-DDP) on the shape of the radiation dose-response curve for mouse duodenal crypt cells was investigated. A priming X-ray dose was followed 18 h later by graded test doses (single doses or five equal fractions at 3-h intervals) with or without c-DDP. Curves were fitted by a linear quadratic (LQ) relationship. The drug modified the dose-response curve by enhancing both the alpha and the beta terms. Repair kinetics were analyzed in split-dose experiments. c-DDP caused a minor, nonsignificant decrease in the rate of repair after irradiation. The survival ratio after split-dose irradiation, when the same X-ray doses were given, was actually slightly increased by the drug. This paradoxical effect can be explained by the fact that c-DDP mainly increased the beta term in the LQ relationship. There was no significant increase in crypt cell survival when split-drug doses were given alone at increasing intervals, suggesting no cellular repair after c-DDP treatment. The data are discussed in the light of the recently proposed lethal and potentially lethal (LPL) unified repair model of Curtis

1987-01-01

244

Modification by cis-diamminedichloroplatinum (II) of the radiation dose-response curve for intestinal crypt cells in mice.  

UK PubMed Central (United Kingdom)

The effect of cis-diamminedichloroplatinum (II) (c-DDP) on the shape of the radiation dose-response curve for mouse duodenal crypt cells was investigated. A priming X-ray dose was followed 18 h later by graded test doses (single doses or five equal fractions at 3-h intervals) with or without c-DDP. Curves were fitted by a linear quadratic (LQ) relationship. The drug modified the dose-response curve by enhancing both the alpha and the beta terms. Repair kinetics were analyzed in split-dose experiments. c-DDP caused a minor, nonsignificant decrease in the rate of repair after irradiation. The survival ratio after split-dose irradiation, when the same X-ray doses were given, was actually slightly increased by the drug. This paradoxical effect can be explained by the fact that c-DDP mainly increased the beta term in the LQ relationship. There was no significant increase in crypt cell survival when split-drug doses were given alone at increasing intervals, suggesting no cellular repair after c-DDP treatment. The data are discussed in the light of the recently proposed "lethal and potentially lethal" (LPL) unified repair model of Curtis.

Dewit L; Oussoren Y; Hart G

1987-09-01

245

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

UK PubMed Central (United Kingdom)

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.

Azizoglu RO; Lyman R; Anderson KL

2013-02-01

246

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

Science.gov (United States)

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

El Naqa, I.; Suneja, G.; Lindsay, P. E.; Hope, A. J.; Alaly, J. R.; Vicic, M.; Bradley, J. D.; Apte, A.; Deasy, J. O.

2006-11-01

247

Use of the proportionality equations for analyses of dose-response curves.  

Science.gov (United States)

A proportionality-oriented theory was applied to analyze dose-response curves commonly generated in pharmacology. The principle of the proportionality theory is to express changes of two associated variables in reference to their asymptotes. Thus, a linear relationship between the two associated variables can be obtained if proper dimensions and scales are used. Based on this proportionality approach, we have developed equations which are used to analyze dose-response curves (1). generated by simulation data based on the Michaelis-Menten equation and the Hill equation and (2). obtained from the contractile effect of acetylcholine (ACh) in isolated guinea pig ileum and the contractile effect of neurokinin NK(1) agonists (NK(1)) in guinea pig trachea muscle strips. Graphic methods are provided for plotting the graphs and for simultaneous determination of asymptote, slope parameter, and position constant. The slope parameter and position constant relate the concentration of an agonist to its response. Apparent equilibrium dissociation constant (K(A)), which is the product of position constant and asymptote in this approach, can be determined directly from the analysis of agonist dose-response curves. It is demonstrated that the proportionality theory and equations are useful for analyzing dose-response curves and for interpreting drug-receptor interactions. PMID:12543065

Cheng, Hsien C; Lai, Ralph W

2003-02-01

248

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

Energy Technology Data Exchange (ETDEWEB)

The shape of the dose-response curve for cancer mortality in the A-bomb survivor data is analyzed in the context of linear-quadratic 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 curve with upward curvature, the emphasis here is not on estimating the best-fitting dose-response curve, but rather on assessing the maximum curvature under linear-quadratic models which is consistent with the data. The apparent shape of the dose-response curve is substantially affected by imprecision in the dose estimates, and methods are applied to correct for this. The extent of curvature can be expressed as the factor by which linear risk estimates from these data should be divided to arrive at appropriate estimates of risk at low doses. Influential committees have in the past recommended ranges of 1.5-4 and of 2-10 for such a factor. Results here suggest that values greater than about 2.0-2.5 are at least moderately inconsistent with these data, within the context of linear-quadratic models. It is emphasized, however, that there is little direct information in these data regarding risks following low doses; the inferences here depend strongly on the assumption of a linear-quadratic model.

Pierce, D.A.; Vaeth, M. (Oregon State Univ., Corvallis (USA))

1991-04-01

249

Dose-Response Relationship between Dietary Polyphenols from Acorns and Parotid Gland Hypertrophy in Pigs  

Digital Repository Infrastructure Vision for European Research (DRIVER)

Proline contents of parotid glands (PG) in pigs constantly increase after the inclusion of different amounts of ripe hulled acorns in the diet providing high polyphenols levels. The dose-response relationship was estimated on natural hydrolizable tannins (expressed as tannic acid equivalent TAE) amo...

Maria Grazia Cappai; Petra Wolf; Walter Pinna; Josef Kamphues

250

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

Digital Repository Infrastructure Vision for European Research (DRIVER)

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 ma...

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

251

In vitro fluoride dose-response study of sterilized enamel lesions.  

Science.gov (United States)

Currently our intra-oral model uses enamel specimens that have been disinfected by soaking in buffered formalin (pH 6.8). However, because of increasing emphasis on infection control, it is important to identify a way to sterilize these specimens. The aim of this study was to determine if autoclaved, or gas sterilized, lesioned enamel responds to fluoride (F) in the same way alcohol-disinfected enamel lesions do. Seventy-two formalin-disinfected, human enamel specimens (3 mm) were lesioned in demineralizing solution for 96 h and were then divided into three groups. One group was autoclaved; one group was gas sterilized (ethylene oxide), and the remaining 24 specimens were further disinfected in 70% ethanol for 10 min. Specimens in each group were then treated 4 times/day for 4 weeks with 0, 250 or 1,100 ppm F dentifrice slurries in an in vitro cycling, remin/demin model. Following treatment, fluoride uptake was analyzed by microdrill biopsy, and lesion depth and mineral content changes (DeltaM) were determined by transverse microradiography. Data were analyzed by one-way ANOVA analysis. In all three groups of specimens there were significant (p<0.05) differences in fluoride uptake in response to different fluoride treatments. Autoclaved lesions failed to provide dose- response data with regard to changes in lesion mineral content. Because formalin and 70% alcohol are only disinfectants, and autoclaving altered the responsiveness of enamel lesions, results from this study suggest that, of the methods tested, gas sterilization is the preferred method for sterilizing enamel specimens that will be used in intra-oral studies. PMID:10867424

Toro, M J; Lukantsova, L L; Williamson, M; Hinesley, R; Eckert, G J; Dunipace, A J

252

In vitro fluoride dose-response study of sterilized enamel lesions.  

UK PubMed Central (United Kingdom)

Currently our intra-oral model uses enamel specimens that have been disinfected by soaking in buffered formalin (pH 6.8). However, because of increasing emphasis on infection control, it is important to identify a way to sterilize these specimens. The aim of this study was to determine if autoclaved, or gas sterilized, lesioned enamel responds to fluoride (F) in the same way alcohol-disinfected enamel lesions do. Seventy-two formalin-disinfected, human enamel specimens (3 mm) were lesioned in demineralizing solution for 96 h and were then divided into three groups. One group was autoclaved; one group was gas sterilized (ethylene oxide), and the remaining 24 specimens were further disinfected in 70% ethanol for 10 min. Specimens in each group were then treated 4 times/day for 4 weeks with 0, 250 or 1,100 ppm F dentifrice slurries in an in vitro cycling, remin/demin model. Following treatment, fluoride uptake was analyzed by microdrill biopsy, and lesion depth and mineral content changes (DeltaM) were determined by transverse microradiography. Data were analyzed by one-way ANOVA analysis. In all three groups of specimens there were significant (p<0.05) differences in fluoride uptake in response to different fluoride treatments. Autoclaved lesions failed to provide dose- response data with regard to changes in lesion mineral content. Because formalin and 70% alcohol are only disinfectants, and autoclaving altered the responsiveness of enamel lesions, results from this study suggest that, of the methods tested, gas sterilization is the preferred method for sterilizing enamel specimens that will be used in intra-oral studies.

Toro MJ; Lukantsova LL; Williamson M; Hinesley R; Eckert GJ; Dunipace AJ

2000-05-01

253

Relative sensitivity to naloxone of multiple indices of opiate withdrawal: a quantitative dose-response analysis.  

Science.gov (United States)

In addition to classic somatic signs of opiate withdrawal, a number of behavioral measures are known to be sensitive, reliable indices of naloxone-precipitated opiate withdrawal in rats. It has been suggested that some behavioral indices of withdrawal may be more sensitive to precipitation by naloxone than some somatic signs of withdrawal. The purpose of the present study was to permit a quantitative assessment of the relative sensitivity to naloxone of a variety of behavioral and somatic indices of opiate withdrawal. Male Wistar rats were implanted s.c. with either two morphine (each 75 mg of base) or two placebo pellets. No sooner than 3 days after implantation, naloxone dose-response functions were determined with several behavioral paradigms and ratings of a variety of somatic withdrawal signs. In dependent rats, very low (0.004 or 0.01 mg/kg) doses of naloxone produced the following behavioral effects: 1) a reduction in spontaneous locomotor activity, 2) a disruption of schedule-controlled (fixed ratio 15) operant responding for food, 3) an elevation in intracranial self-stimulation thresholds and 4) a conditioned place aversion. These same doses of naloxone produced no significant effects in nondependent (placebo pellet-implanted) rats. The ED50 values for naloxone precipitation of all behavioral signs of withdrawal were below 0.013 mg/kg; the ED50 values for naloxone precipitation of most somatic withdrawal signs were higher. The behavioral measures used in these studies therefore represent highly sensitive indices of opiate withdrawal. PMID:7996451

Schulteis, G; Markou, A; Gold, L H; Stinus, L; Koob, G F

1994-12-01

254

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1995-12-31

255

Haemodynamic dose-response effects of intravenous indoramin in acute heart failure complicating myocardial infarction.  

Science.gov (United States)

The haemodynamic dose-response effects of intravenous indoramin were evaluated in 12 patients with acute heart failure (pulmonary artery occluded pressure of greater than 20 mm Hg) complicating a recent myocardial infarction. Following a 1-h control period with confirmed stable haemodynamics, the effects of three intravenous bolus doses of indoramin (0.125, 0.125, and 0.25 mg/kg at 15-min intervals) were determined in the 10- to 15-min period following each intravenous injection. Plasma drug concentrations rose with the administered dose and were in the previously established therapeutic range. Ten patients tolerated all three doses of the drug; two patients were withdrawn following the second dose owing to clinically evident hypotension (systolic blood pressure of less than 100 mm Hg). Indoramin resulted in progressive falls in systolic, diastolic, and mean systemic arterial pressures (p less than 0.01) without change in cardiac index. There was a dose-related reduction in the heart rate (0.5 mg/kg; -7 beats/min; p less than 0.01). The left ventricular filling pressure showed a significant and quadratic reduction over the dose range (0.5 mg/kg, -5 mm Hg; p less than 0.01). The systemic vascular resistance index was reduced (-333 dynes X s X cm-5 X m2; p less than 0.001) and the stroke volume index increased (+3 ml/m2; p less than 0.05) following the maximum cumulative dosage. These data established the therapeutic safety of indoramin (0.125-0.5 mg/kg) in acute heart failure following myocardial infarction. An improvement in cardiac performance in these patients was compatible with circulatory actions on both cardiac preload and afterload. PMID:2423781

Silke, B; Nelson, G I; Verma, S P; Frais, M A; Reynolds, G; Jackson, N; Taylor, S H

1986-01-01

256

A goodness-of-fit approach to inference procedures for the kappa statistic: confidence interval construction, significance-testing and sample size estimation.  

Science.gov (United States)

We propose a new procedure for constructing a confidence interval about the kappa statistic in the case of two raters and a dichotomous outcome. The procedure is based on a chi-square goodness-of-fit test as applied to a model frequently used for clustered binary data. The procedure provides coverage levels that are accurate in samples of smaller size than those required for other procedures. The procedure also has use for significance-testing and the planning of corresponding sample size requirements. PMID:1410963

Donner, A; Eliasziw, M

1992-08-01

257

A goodness-of-fit approach to inference procedures for the kappa statistic: confidence interval construction, significance-testing and sample size estimation.  

UK PubMed Central (United Kingdom)

We propose a new procedure for constructing a confidence interval about the kappa statistic in the case of two raters and a dichotomous outcome. The procedure is based on a chi-square goodness-of-fit test as applied to a model frequently used for clustered binary data. The procedure provides coverage levels that are accurate in samples of smaller size than those required for other procedures. The procedure also has use for significance-testing and the planning of corresponding sample size requirements.

Donner A; Eliasziw M

1992-08-01

258

The dose response functions of ionization chambers in photon dosimetry - Gaussian or non-Gaussian?  

UK PubMed Central (United Kingdom)

This study is concerned with the spatial resolution of air-filled ionization chambers in photon-beam dosimetry, i.e. with their dose response functions. These act as convolution kernels K(x,y), transforming true dose profiles D(x,y) into the measured signal profiles M(x,y). One-dimensional dose response functions have been experimentally determined for nine types of cylindrical ionization chambers both in their lateral and longitudinal directions, as well as across two plane-parallel chambers and for the single chambers of two 2D arrays. All these 1D dose response functions are closely described by Gaussian functions. The associated energy-dependent values of the standard deviations ? have been measured for 6 and 15 MV photons with an uncertainty of 0.02mm. At depths beyond secondary electron fluence build-up, there was no detectable depth dependence of the ? values. The general occurrence of Gaussian dose response functions, their extension beyond the geometrical boundaries of the chambers, and the energy dependence of their standard deviations can be understood by considering the underlying system of convolutions, which is the origin of the influences of secondary electron transport. Monte-Carlo simulations of the convolution kernels for a cylindrical, a square, and a flat ionization chamber and their Fourier analysis have been employed to show that the Gaussian convolution kernels are approximations to the true dose response functions, valid in the clinically relevant domain of the spatial frequency. This paper is conceived as the starting point for the deconvolution methods to be described in a further publication.

Looe HK; Stelljes TS; Foschepoth S; Harder D; Willborn K; Poppe B

2013-05-01

259

[Review on dose-response relationship between low level vibration and low back pain].  

UK PubMed Central (United Kingdom)

OBJECTIVES: Whole-body vibration (WBV) with high level acceleration is found in the workplaces of construction and mining, and has been reported to be associated with low back pain (LBP) experienced by operators of heavy vehicles as an occupational health problem. Because the work conditions with exposure to WBV include bending and twisting of the low back and other factors, the causal relationship between WBV and LBP has not yet been affirmed. A review suggesting the dose-response relationship between WBV with low acceleration and LBP has been published, although there is little evidence supporting the causal relationship. Therefore, we reviewed the dose-response relationship between WBV with low acceleration and LBP. Methods: We examined original articles which reported a dose-response relationship between WBV and LBP in addition to review articles with almost the same aims. RESULTS AND DISCUSSION: Studies which examined imaging findings such as CT and MRI, objective indicators of LBP, do not confirm the causal relationship. Although many studies demonstrated a positive relationship between working periods and incidence of LBP, there were very few reports which recognized a dose-response relationship for the vibration acceleration below 1.0 m/s(2) in which the 8-h energy-equivalent, combined frequency-weighted vibration of three diagonal, that is x, y and z, axes (root-sum-of-squares), Asum(8) was used as an index of vibration exposure. CONCLUSION: This paper reject the hypothesis of a dose-response relationship between WBV with low acceleration and LBP, concluding there is no evidence linking low level exposure to WBV with LBP for the Japan Society for Occupational Health to recommend 0.35 m/s(2)/as of Asum(8) as a tentative occupational exposure limits for WBV.

Okada A; Nakamura H

2013-01-01

260

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

UK PubMed Central (United Kingdom)

BACKGROUND: The consumption of dairy products may influence the risk of type 2 diabetes mellitus (T2DM), but inconsistent findings have been reported. Moreover, large variation in the types of dairy intake has not yet been fully explored. METHODS AND RESULTS: We conducted a systematic review and meta-analysis to clarify the dose-response association of dairy products intake and T2DM risk. We searched PubMed, EMBASE and Scopus for studies of dairy products intake and T2DM risk published up to the end of October 2012. Random-effects models were used to estimate summary relative risk (RR) statistics. Dose-response relations were evaluated using data from different dairy products in each study. We included 14 articles of cohort studies that reported RR estimates and 95% confidence intervals (95% CIs) of T2DM with dairy products intake. We found an inverse linear association of consumption of total dairy products (13 studies), low-fat dairy products (8 studies), cheese (7 studies) and yogurt (7 studies) and risk of T2DM. The pooled RRs were 0.94 (95% CI 0.91-0.97) and 0.88 (0.84-0.93) for 200 g/day total and low-fat dairy consumption, respectively. The pooled RRs were 0.80 (0.69-0.93) and 0.91 (0.82-1.00) for 30 g/d cheese and 50 g/d yogurt consumption, respectively. We also found a nonlinear association of total and low-fat dairy intake and T2DM risk, and the inverse association appeared to be strongest within 200 g/d intake. CONCLUSION: A modest increase in daily intake of dairy products such as low fat dairy, cheese and yogurt may contribute to the prevention of T2DM, which needs confirmation in randomized controlled trials.

Gao D; Ning N; Wang C; Wang Y; Li Q; Meng Z; Liu Y; Li Q

2013-01-01

 
 
 
 
261

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

Science.gov (United States)

Background The consumption of dairy products may influence the risk of type 2 diabetes mellitus (T2DM), but inconsistent findings have been reported. Moreover, large variation in the types of dairy intake has not yet been fully explored. Methods and Results We conducted a systematic review and meta-analysis to clarify the dose–response association of dairy products intake and T2DM risk. We searched PubMed, EMBASE and Scopus for studies of dairy products intake and T2DM risk published up to the end of October 2012. Random-effects models were used to estimate summary relative risk (RR) statistics. Dose-response relations were evaluated using data from different dairy products in each study. We included 14 articles of cohort studies that reported RR estimates and 95% confidence intervals (95% CIs) of T2DM with dairy products intake. We found an inverse linear association of consumption of total dairy products (13 studies), low-fat dairy products (8 studies), cheese (7 studies) and yogurt (7 studies) and risk of T2DM. The pooled RRs were 0.94 (95% CI 0.91–0.97) and 0.88 (0.84–0.93) for 200 g/day total and low-fat dairy consumption, respectively. The pooled RRs were 0.80 (0.69–0.93) and 0.91 (0.82–1.00) for 30 g/d cheese and 50 g/d yogurt consumption, respectively. We also found a nonlinear association of total and low-fat dairy intake and T2DM risk, and the inverse association appeared to be strongest within 200 g/d intake. Conclusion A modest increase in daily intake of dairy products such as low fat dairy, cheese and yogurt may contribute to the prevention of T2DM, which needs confirmation in randomized controlled trials.

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

2013-01-01

262

Pisces did not have increased heart failure: data-driven comparisons of binary proportions between levels of a categorical variable can result in incorrect statistical significance levels.  

UK PubMed Central (United Kingdom)

OBJECTIVE: We examined the impact on statistical inference when a chi(2) test is used to compare the proportion of successes in the level of a categorical variable that has the highest observed proportion of successes with the proportion of successes in all other levels of the categorical variable combined. STUDY DESIGN AND SETTING: Monte Carlo simulations and a case study examining the association between astrological sign and hospitalization for heart failure. RESULTS: A standard chi(2) test results in an inflation of the type I error rate, with the type I error rate increasing as the number of levels of the categorical variable increases. Using a standard chi(2) test, the hospitalization rate for Pisces was statistically significantly different from that of the other 11 astrological signs combined (P=0.026). After accounting for the fact that the selection of Pisces was based on it having the highest observed proportion of heart failure hospitalizations, subjects born under the sign of Pisces no longer had a significantly higher rate of heart failure hospitalization compared to the other residents of Ontario (P=0.152). CONCLUSIONS: Post hoc comparisons of the proportions of successes across different levels of a categorical variable can result in incorrect inferences.

Austin PC; Goldwasser MA

2008-03-01

263

STATISTICAL ESTIMATION OF CONTINUITY OF FORMATION OF SOCIALLY SIGNIFICANT HIERARCHY OF MOTIVES OF THE LEARNING OF SENIOR PUPILS BY MEANS OF MULTIMEDIA TECHNOLOGY OF TRAINING  

Directory of Open Access Journals (Sweden)

Full Text Available It is theoretically proved and experimentally possibility of maintenance of continuity of formation of socially significant hierarchy of motives of the learning of senior pupils by means of multimedia technology proves to be true at training to the physicist.The pedagogical category of continuity as one of important didactic principles is discussed. On the basis of the wide pedagogical experiment which has captured a number of educational institutions, efficiency of multimedia technology is shown at formation of hierarchy of motives of the learning of the schoolboys, having socially significant orientation.Introduction possibility in pedagogical researches of modern statistical measures of estimation is discussed and their efficiency with reference to a problem of continuity of formation of motives of the learning of senior pupils is shown.

Marina Yepifanova; Boris Zhelezovsky

2012-01-01

264

Placebo-controlled double-blind dose-response study of the non-purine-selective xanthine oxidase inhibitor febuxostat (TMX-67) in patients with hyperuricemia (including gout patients) in japan: late phase 2 clinical study.  

UK PubMed Central (United Kingdom)

BACKGROUND: Allopurinol has been widely used for the treatment of hyperuricemia, however, it may be associated with various adverse effects. Febuxostat has been identified as a potentially safe and efficacious alternative. OBJECTIVES: A multicenter study with randomized, placebo-controlled, double-blind, parallel, intergroup comparison was carried out to evaluate the dose-response relationship, efficacy, and safety of febuxostat in 202 patients with hyperuricemia (including patients with gout) in Japan. METHODS: The subjects were treated with febuxostat at fixed maintenance doses (20-80 mg/d) or a placebo for 16 weeks. The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less and the percent change in serum uric acid levels after 16 weeks of treatment were evaluated. RESULTS: The percentage of patients achieving serum uric acid levels 6.0 mg/dL or less at 16 weeks was 87.8% in the 80-mg/d dose group, 83.3% in the 60-mg/d group, 82.9% in the 40-mg/d group, 46.5% in the 20-mg/d group, and 2.6% in the placebo group (P < 0.001, Mantel-Haenszel test). A statistically significant dose-response relationship was found. The percent change in serum uric acid levels after 16 weeks of treatment differed significantly between each febuxostat dose group and the placebo group and increased in a dose-dependent manner above 40 mg/d. No deaths, events posing a clinical problem, or serious adverse reactions attributable to febuxostat were noted. Similar results were obtained regardless of gout history. CONCLUSIONS: Febuxostat can safely reduce serum uric acid levels to 6.0 mg/dL or less in 80% or more of patients with hyperuricemia (including gout) at doses of 40 mg/d or higher.

Naoyuki K; Shin F; Toshikazu H; Tatsuo H; Kenjiro K; Toshitaka N; Takanori U; Tetsuya Y; Hisashi Y; Yuji M

2011-06-01

265

Coffee and caffeine intake and breast cancer risk: an updated dose-response meta-analysis of 37 published studies.  

UK PubMed Central (United Kingdom)

OBJECTIVE: We conducted an updated meta-analysis to summarize the evidence from published studies regarding the association of coffee and caffeine intake with breast cancer risk. METHODS: Pertinent studies were identified by a search of PubMed and by reviewing the reference lists of retrieved articles. The fixed or random effect model was used based on heterogeneity test. The dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. RESULTS: 37 published articles, involving 59,018 breast cancer cases and 966,263 participants, were included in the meta-analysis. No significant association was found between breast cancer risk and coffee (RR=0.97, P=0.09), decaffeinated coffee (RR=0.98, P=0.55) and caffeine (RR=0.99, P=0.73), respectively. And the association was still not significant when combining coffee and caffeine (coffee/caffeine) (RR=0.97, P=0.09). However, an inverse association of coffee/caffeine with breast cancer risk was found for postmenopausal women (RR=0.94, P=0.02), and a strong and significant association of coffee with breast cancer risk was found for BRCA1 mutation carriers (RR=0.69, P<0.01). A linear dose-response relationship was found for breast cancer risk with coffee and caffeine, and the risk of breast cancer decreased by 2% (P=0.05) for every 2 cups/day increment in coffee intake, and 1% (P=0.52) for every 200mg/day increment in caffeine intake, respectively. CONCLUSIONS: Findings from this meta-analysis suggested that coffee/caffeine might be weakly associated with breast cancer risk for postmenopausal women, and the association for BRCA1 mutation carriers deserves further investigation.

Jiang W; Wu Y; Jiang X

2013-06-01

266

Evaluation of protein allergenic potential in mice: dose-response analyses.  

UK PubMed Central (United Kingdom)

BACKGROUND: With the increasing interest in novel foods derived from transgenic crop plants, there is a growing need for the development of approaches for the characterization of the allergenic potential of proteins. Whereas immunogenicity is a common property of foreign proteins, including food proteins, relatively few are significant dietary allergens with the inherent capacity to provoke IgE antibody production and immediate-type hypersensitivity responses. OBJECTIVE: In order to evaluate an approach for the measurement of the allergenic potential of proteins, detailed dose-response analyses of humoral immune responses induced following systemic exposure of BALB/c strain mice to proteins known to differ in terms of sensitizing activity have been conducted. RESULTS: Mice were exposed to a range of concentrations of ovalbumin, a major allergenic constituent of hen's egg, a purified peanut allergen, Arachis hypogea agglutinin, or to the milk allergen bovine serum albumin, and to materials considered to lack significant allergenicity: a crude potato protein extract and a purified potato protein, potato agglutinin. The specific IgE antibody was measured by homologous passive cutaneous anaphylaxis assay, and the specific IgG antibody was measured by enzyme-linked immunosorbent assay. Each of the five proteins was immunogenic in mice, inducing IgG antibody responses at all doses tested, although there was some variation with respect to the vigour of IgG responses. Marked differences in the capacity of these proteins to induce IgE responses were observed, however, with relatively high-titre IgE antibody provoked by all three allergens over the dose ranges examined, whereas the potato proteins stimulated low-titre IgE antibody at the highest dose (10%) only. Importantly, differences in IgE antibody production have been observed against a background of equivalent immunogenicity (IgG antibody responses). CONCLUSION: The data presented here suggest that the measurement of antibody (IgE) responses in BALB/c mice appears to identify allergens accurately and to distinguish them from those materials that apparently lack allergenicity.

Dearman RJ; Stone S; Caddick HT; Basketter DA; Kimber I

2003-11-01

267

Dose-response study of thimerosal-induced murine systemic autoimmunity  

International Nuclear Information System (INIS)

The organic compound ethylmercurithiosalicylate (thimerosal), which is primarily present in the tissues as ethylmercury, has caused illness and several deaths due to erroneous handling when used as a disinfectant or as a preservative in medical preparations. Lately, possible health effects of thimerosal in childhood vaccines have been much discussed. Thimerosal is a well-known sensitizing agent, although usually of no clinical relevance. In rare cases, thimerosal has caused systemic immune reactions including acrodynia. We have studied if thimerosal might induce the systemic autoimmune condition observed in genetically susceptible mice after exposure to inorganic mercury. A.SW mice were exposed to 1.25-40 mg thimerosal/l drinking water for 70 days. Antinucleolar antibodies, targeting the 34-kDa protein fibrillarin, developed in a dose-related pattern and first appeared after 10 days in the two highest dose groups. The lowest observed adverse effect level (LOAEL) for antifibrillarin antibodies was 2.5 mg thimerosal/l, corresponding to an absorbed dose of 147 ?g Hg/kg bw and a concentration of 21 and 1.9 ?g Hg/g in the kidney and lymph nodes, respectively. The same LOAEL was found for tissue immune-complex deposits. The total serum concentration of IgE, IgG1, and IgG2a showed a significant dose-related increase in thimerosal-treated mice, with a LOAEL of 5 mg thimerosal/l for IgG1 and IgE, and 20 mg thimerosal/l for IgG2a. The polyclonal B-cell activation showed a significant dose-response relationship with a LOAEL of 10 mg thimerosal/l. Therefore, thimerosal induces in genetically susceptible mice a systemic autoimmune syndrome very similar to that seen after treatment with inorganic mercury, although a higher absorbed dose of Hg is needed using thimerosal. The autoimmune syndrome induced by thimerosal is different from the weaker and more restricted autoimmune reaction observed after treatment with an equipotent dose of methylmercury.

2004-01-15

268

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

Science.gov (United States)

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 oven workers. PMID:23745771

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

2013-06-21

269

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

Science.gov (United States)

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

270

Dose response of tracheal epithelial cells to ionizing radiation in air-liquid interface cultures  

Energy Technology Data Exchange (ETDEWEB)

The dose-response relationships of tracheal epithelial cells to ionizing radiation was examined in air-liquid interface cultures, which were developed for the purpose of simulating in vivo conditions. The cultures investigated in this study were expected to be advantageous for the performance of irradiation experiments using short-range {alpha} rays. The level of dose response of air-liquid interface cultures to ionizing radiation proved to be the same as that for in vivo conditions. This result indicates that air-liquid interface cultures will prove most useful, to facilitate future studies for the investigation of the biological effects induced in tracheal epithelial cells by ionizing radiation, especially by {alpha}-rays. (orig.)

Fukutsu, K.; Yamada, Y.; Shimo, M. [National Inst. of Radiological Sciences, Chiba (Japan)

2002-03-01

271

Dose response of tracheal epithelial cells to ionizing radiation in air-liquid interface cultures  

International Nuclear Information System (INIS)

The dose-response relationships of tracheal epithelial cells to ionizing radiation was examined in air-liquid interface cultures, which were developed for the purpose of simulating in vivo conditions. The cultures investigated in this study were expected to be advantageous for the performance of irradiation experiments using short-range ? rays. The level of dose response of air-liquid interface cultures to ionizing radiation proved to be the same as that for in vivo conditions. This result indicates that air-liquid interface cultures will prove most useful, to facilitate future studies for the investigation of the biological effects induced in tracheal epithelial cells by ionizing radiation, especially by ?-rays. (orig.)

2002-01-01

272

Effects of chewing gum on stress and health: a replication and investigation of dose-response.  

Science.gov (United States)

Research suggests that chewing gum may be associated with reduced stress, depression and a reduced likelihood of having high cholesterol and blood pressure. The present study aimed to replicate these findings and extend them by examining dose-response. A web-based survey was completed by a sample of 388 workers from public sector organisations (68.5% female; mean age: 42?years, range 17-64?years). The results showed that chewing gum was associated in a linear dose-response manner with lower levels of perceived stress (both at work and life in general), anxiety and depression. Occasional gum chewers also reported a reduced risk of high cholesterol and blood pressure. Intervention studies are now required to extend these findings, and the mechanisms underlying the effects reported here need further investigation. PMID:22496105

Smith, Andrew

2012-04-11

273

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

Scientific Electronic Library Online (English)

Full Text Available Abstract in spanish OBJETIVOS: Caracterizar el empleo de las pruebas convencionales de significación estadística y las tendencias actuales que muestra su uso en tres revistas biomédicas del ámbito hispanohablante. MÉTODOS: Se examinaron todos los artículos originales descriptivos o explicativos que fueron publicados en el quinquenio de 1996­2000 en tres publicaciones: Revista Cubana de Medicina General Integral, Revista Panamericana de Salud Pública/Pan American Journal of Public (more) 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 Amer (more) ican 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.

Sarria Castro, Madelaine; Silva Ayçaguer, Luis Carlos

2004-05-01

274

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

Directory of Open Access Journals (Sweden)

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

Madelaine Sarria Castro; Luis Carlos Silva Ayçaguer

2004-01-01

275

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

Directory of Open Access Journals (Sweden)

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

Wong Wing-Cheong; Loh Marie; Eisenhaber Frank

2008-01-01

276

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

Energy Technology Data Exchange (ETDEWEB)

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

Mossman, K.L.

1986-01-01

277

Dose response of hydrazine - Deproteinated tooth enamel under blue light stimulation  

International Nuclear Information System (INIS)

The beta dose response and Optically Stimulated Luminescence (OSL) signal stability characteristics of human tooth enamel deproteinated by hydrazine reagent under blue photon stimulation are reported. Removal of the protein organic component of tooth enamel resulted in a higher OSL sensitivity and slower fading of OSL signals. The effect of chemical sample preparation on the enamel sample sensitivity is discussed and further steps to make this deproteinization treatment suitable for in vitro dose reconstruction studies are suggested.

2010-01-01

278

Human cytogenetic dosimetry: a dose-response relationship for alpha particle radiation from 241Am  

International Nuclear Information System (INIS)

Cytogenetic dosimetry estimates to guide treatment of persons internally contaminated with transuranic elements have not previously been possible because appropriate in vitro dose-response curves specifically for alpha particle irradiation of human lymphocytes do not exist. Using well-controlled cytogenetic methods for human lymphocyte culture, an experimentally derived dose-response curve for 241Am alpha particle (5.49 and 5.44 MeV) radiation of G0 lymphocytes was generated. Cells were exposed to 43.8, 87.7, 175.3 or 350.6 nCi/ml 241Am for 1.7 hr giving doses of 0.85, 1.71, 3.42 or 6.84 rad. Based on dicentric chromosome yield, the linear dose-response equation is Y = 4.90(+-0.42) x 10-2 X, with Y given as dicentrics per cell and X as dose in rads. The study also shows that the two-break asymmetrical exchanges in cells damaged by alpha particle radiation are overdispersed when compared to a Poisson distribution. An example is presented to show how the derived dose-response equation can be used to estimate the radiation dose for a person internally contaminated with an actinide. An experimentally derived RBE value of 118 at 0.85 rad is calculated for the efficiency of 241Am alpha particle induction of dicentric chromosomes in human G0 lymphocytes as compared with the efficiency of 60Co gamma radiation. The maximum theoretical value for the RBE for cytogenetic damage from alpha irradiation was determined to be 278 at 0.1 rad or less which is in marked contrast to previously reported RBE values of approx. 20. (author)

1979-01-01

279

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

Energy Technology Data Exchange (ETDEWEB)

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 approx.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.

Morris, M.D.; Jones, T.D.

1987-04-30

280

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

International Nuclear Information System (INIS)

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

1992-01-01

 
 
 
 
281

Hypothesis testing and the choice of the dose-response model.  

UK PubMed Central (United Kingdom)

The shape of the dose-response curve for exposure to ionising radiation is probably one of the most contentious issues in toxicology. The initial assumption was that there was a threshold to the appearance of a health detriment, including cancer, with the so-called linear-no-threshold (LNT) hypothesis first being introduced in the early 1960s. Since that time a number of models have been suggested, and present work in health physics, toxicology and epidemiology is concerned with questions about both the shape of the dose-response curve and whether or not a threshold exists. This paper presents an analysis of the robustness of the LNT hypothesis from a philosophy of science standpoint-arguing that claims about dose-response curve need to pay more attention to the assumptions and auxillary hypotheses behind choices, and that further mechanistic studies are required to unravel the effects of exposure to ionising radiation. It suggests that whereas LNT falls short of the requirements for a good scientific hypothesis, it is a reasonable model for regulating the carcinogenic and hereditary effects of radiation exposure.

Oughton D

2006-03-01

282

Hypothesis testing and the choice of the dose-response model.  

Science.gov (United States)

The shape of the dose-response curve for exposure to ionising radiation is probably one of the most contentious issues in toxicology. The initial assumption was that there was a threshold to the appearance of a health detriment, including cancer, with the so-called linear-no-threshold (LNT) hypothesis first being introduced in the early 1960s. Since that time a number of models have been suggested, and present work in health physics, toxicology and epidemiology is concerned with questions about both the shape of the dose-response curve and whether or not a threshold exists. This paper presents an analysis of the robustness of the LNT hypothesis from a philosophy of science standpoint-arguing that claims about dose-response curve need to pay more attention to the assumptions and auxillary hypotheses behind choices, and that further mechanistic studies are required to unravel the effects of exposure to ionising radiation. It suggests that whereas LNT falls short of the requirements for a good scientific hypothesis, it is a reasonable model for regulating the carcinogenic and hereditary effects of radiation exposure. PMID:16325358

Oughton, Deborah

2005-12-01

283

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

International Nuclear Information System (INIS)

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

1981-01-01

284

Radiation therapy for retinoblastoma. Results and dose-response analysis. Radiotherapy of Teikyo University (6th report)  

International Nuclear Information System (INIS)

We studied the treatment results for retinoblastoma following external beam radiotherapy (EBR), and analyzed the difference between the dose-response relationships in the posterior and anterior poles. We studied 35 patients (38 eyes) with retinoblastoma who were treated with radiotherapy with curative intent at Teikyo University's Ichihara Hospital between 1986 and 1997. The Reese-Elsworth Classification was I in 7 eyes, II in 17, III in 6, IV in 3, and V in 5. Radiation therapy was delivered mainly using the single lateral lens-sparing technique. The mean total dosage was 39.5±5.8 Gy (range, 21.8-50 Gy) at 3 Gy/fraction, 3 fractions/week. All tumors (88 tumors) treated with radiotherapy were included in the study of the dose-response analysis. The initial tumor-control was evaluated based on the results of the fundoscopic findings performed within 1 mo. after the completion of radiotherapy. The long-term tumor-control was evaluated based on the last fundoscopic findings. The mean follow-up period was 4 yr. 4 mo. (range, 5 mo.-10 yr 6 mo.). The 5- and 10- yr. overall survival rates (OSRs) were both 88.2±6.5%. The 5- and 10- yr. local control rates (LCRs) were both 55.5±9.1%. The 5- and 10-year LCRs of the posterior tumors were 70.4±10.4% and those of the anterior tumors were 23.0±14.0%; the differences between these rates were significant (p

2007-01-01

285

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)

2012-01-01

286

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

International Nuclear Information System (INIS)

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

2010-06-07

287

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

International Nuclear Information System (INIS)

[en] Purpose: Cerebral low-grade gliomas (LGG) in adults are mostly composed of astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. There is at present no consensus in the policy of treatment of these tumors. We sought to determine the efficacy of radiotherapy and the presence of a dose-response relationship for these tumors in two multicentric randomized trials conducted by the European Organization for Research and Treatment of Cancer (EORTC). The dose-response study is the subject of this article. Methods and Materials: For the dose-response trial, 379 adult patients with cerebral LGGs were randomized centrally at the EORTC Data Center to receive irradiation postoperatively (or postbiopsy) with either 45 Gy in 5 weeks or 59.4 Gy in 6.6 weeks with quality-controlled radiation therapy. All known parameters with possible influences on prognosis were prospectively recorded. Conventional treatment techniques were recommended. Results: With 343 (91%) eligible and evaluable patients followed up for at least 50 months with a median of 74 months, there is no significant difference in terms of survival (58% for the low-dose arm and 59% for the high-dose arm) or the progression free survival (47% and 50%) between the two arms of the trial. However, this prospective trial has revealed some important facets about the prognostic parameters: The T of the TNM classifications as proposed in the protocol appears to be one of the most important prognostic factors (p

1996-10-01

288

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.,

1987-05-11

289

Dose response of 1,2-dimethylhydrazine and methylazoxymethanol acetate in the F 344 rat.  

UK PubMed Central (United Kingdom)

Weanling male and female F 344 rats were given various doses of 1,2-dimethylhydrazine (DMH) or methylazoxymethyl acetate (MAMAc), and were then held for 46-64 weeks in an effort to determine a dose response and establish a dose level which would produce a low level of intestinal neoplasia with a minimal number of tumors in other organs. DMH proved superior to MAM in this respect, although liver lesions were still observed with both compounds at the lowest carcinogenic intestinal dose.

McConnell EE; Wilson RE; Moore JA; Haseman JK

1980-01-01

290

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

International Nuclear Information System (INIS)

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

2004-01-01

291

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

UK PubMed Central (United Kingdom)

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.

Marounek M; Volek Z; Dušková D; T?ma J; Taubner T

2013-09-01

292

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

Science.gov (United States)

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

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

2013-05-25

293

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

Directory of Open Access Journals (Sweden)

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

Santosh H. Shinde; T. Mukherjee

2011-01-01

294

Droplet-based microfluidics for dose-response assay of enzyme inhibitors by electrochemical method.  

Science.gov (United States)

A simple but robust droplet-based microfluidic system was developed for dose-response enzyme inhibition assay by combining concentration gradient generation method with electrochemical detection method. A slotted-vials array and a tapered tip capillary were used for reagents introduction and concentration gradient generation, and a polydimethylsiloxane (PDMS) microfluidic chip integrated with microelectrodes was used for droplet generation and electrochemical detection. Effects of oil flow rate and surfactant on electrochemical sensing were investigated. This system was validated by measuring dose-response curves of three types of acetylcholinesterase (AChE) inhibitors, including carbamate pesticide, organophosphorus pesticide, and therapeutic drugs regulating Alzheimer's disease. Carbaryl, chlorpyrifos, and tacrine were used as model analytes, respectively, and their IC50 (half maximal inhibitory concentration) values were determined. A whole enzyme inhibition assay was completed in 6min, and the total consumption of reagents was less than 5?L. This microfluidic system is applicable to many biochemical reactions, such as drug screening and kinetic studies, as long as one of the reactants or products is electrochemically active. PMID:24016585

Gu, Shuqing; Lu, Youlan; Ding, Yaping; Li, Li; Zhang, Fenfen; Wu, Qingsheng

2013-08-14

295

Fluoride dose-response of human and bovine enamel caries lesions under remineralizing conditions.  

UK PubMed Central (United Kingdom)

PURPOSE: To investigate the relative fluoride dose-response of human and bovine enamel caries lesions under remineralizing conditions and utilizing an established pH cycling model. METHODS: Early caries-like lesions were formed in human and bovine enamel, characterized using Vickers surface microhardness (VHN) and assigned to five dentifrice treatment groups: 0/250/1100 ppm fluoride as sodium fluoride (F as NaF) formulation 1; 1100 ppm F as NaF formulation 2; 1000 ppm F as monofluorophosphate (MFP) formulation 3. The daily pH cycling regimen comprised: 4x1-minute dentifrice slurry treatments; 1 x 4-hour acid challenge and intermittent remineralization in a 1:1-mixture of pooled human/artificial saliva. After 20 days, VHN of specimens were measured again and changes from lesion baseline calculated (REM). Subsequently, enamel fluoride uptake (EFU) was determined using the microdrill technique and specimens were demineralized again to determine their acid resistance (DEM). Data were analyzed using two-way ANOVA (factors: enamel, dentifrice). RESULTS: Both enamel type and dentifrice as well as their interaction affected REM and DEM. EFU was only affected by dentifrice. Human and bovine enamel showed a good fluoride dose-response for REM and correlated well. However, bovine enamel showed more remineralization than human enamel. There were good correlations between dentifrice-F concentration vs. REM and EFU, and between REM vs. EFU, regardless of enamel type.

Lippert F; Hara AT

2012-08-01

296

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.

1986-01-01

297

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

Energy Technology Data Exchange (ETDEWEB)

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.

Hong, Seong Eon; Ahn, Chi Yul [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

1986-12-15

298

Ceruletide intravenous dose-response study by a simplified scintigraphic technique  

Energy Technology Data Exchange (ETDEWEB)

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.

Krishnamurthy, G.T.; Turner, F.E.; Mangham, D.; Bobba, V.V.R.; White, S.A.; Langrell, K.

1985-04-01

299

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

UK PubMed Central (United Kingdom)

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<0.01). Participants who adhered per protocol decreased pain by 35 mm VAS (95% CI -26 to -44) from baseline to follow-up corresponding to a 70% reduction. In the dose-response analyses, participants with medium and high training adherence showed better pain relief than the control group and those with low adherence (p<0.0001). The decrease from baseline in the medium and high adherence groups was 37 mm VAS [28 to 46 mm] and 33 mm VAS [24 to 43 mm] respectively. Specific strength training reduces pain intensity in women with severe neck pain, and 1-2 training sessions per week for 20 weeks (?30 training sessions) appears sufficient for optimal pain relief.

Andersen CH; Andersen LL; Pedersen MT; Mortensen P; Karstad K; Mortensen OS; Zebis MK; Sjøgaard G

2013-03-01

300

Dose-response relationship between cigarette smoking and risk of ischemic stroke in young women.  

UK PubMed Central (United Kingdom)

BACKGROUND AND PURPOSE: Although cigarette smoking is known to be a risk factor for ischemic stroke, there are few data on the dose-response relationship between smoking and stroke risk in a young ethnically diverse population. METHODS: We used data from the Stroke Prevention in Young Women Study, a population-based case-control study of risk factors for ischemic stroke in women aged 15 to 49 years to examine the relationship between cigarette smoking and ischemic stroke. Historical data, including smoking history, was obtained through standardized interviews. Odds ratios (OR) were estimated using logistic regression. Cases (n=466) were women with stroke in the greater Baltimore-Washington area, and controls (n=604) were women free of a stroke history identified by random digit dialing. RESULTS: After multivariable adjustment, the OR comparing current smokers to never smokers was 2.6 (P<0.0001); no difference in stroke risk was observed between former smokers and never smokers. Adjusted OR increased with increasing number of cigarettes smoked per day (OR=2.2 for 1 to 10 cigs/d; 2.5 for 11 to 20 cigs/d; 4.3 for 21 to 39 cigs/d; 9.1 for 40 or more cigs/d). CONCLUSIONS: These results suggest a strong dose-response relationship between cigarette smoking and ischemic stroke risk in young women and reinforce the need for aggressive smoking cessation efforts in young adults.

Bhat VM; Cole JW; Sorkin JD; Wozniak MA; Malarcher AM; Giles WH; Stern BJ; Kittner SJ

2008-09-01

 
 
 
 
301

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

Directory of Open Access Journals (Sweden)

Full Text Available 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 frequency/severity of spinal pain, and the other, with frequency/severity of TMD symptoms as independent variable. All 616 participants were allocated to four groups, one control group without spinal pain and three spinal pain groups. The subjects in the subset were allocated to one control group without TMD symptoms and three TMD groups. Odds ratios (ORs) were calculated for presence of frequent TMD symptoms in the separate spinal pain groups as well as for frequent spinal pain in the separate TMD groups. Results The analysis showed increasing ORs for TMD with increasing frequency/severity of spinal pain. We also found increasing ORs for spinal pain with increasing frequency/severity of TMD symptoms. Conclusion This study shows a reciprocal dose-response-like relationship between spinal pain and TMD. The results indicate that these two conditions may share common risk factors or that they may influence each other. Studies on the temporal sequence between spinal pain and TMD are warranted.

Wiesinger Birgitta; Malker Hans; Englund Erling; Wänman Anders

2009-01-01

302

Influence of DNA repair on nonlinear dose-responses for mutation.  

UK PubMed Central (United Kingdom)

Recent evidence has challenged the default assumption that all DNA-reactive alkylating agents exhibit a linear dose-response. Emerging evidence suggests that the model alkylating agents methyl- and ethylmethanesulfonate and methylnitrosourea (MNU) and ethylnitrosourea observe a nonlinear dose-response with a no observed genotoxic effect level (NOGEL). Follow-up mechanistic studies are essential to understand the mechanism of cellular tolerance and biological relevance of such NOGELs. MNU is one of the most mutagenic simple alkylators. Therefore, understanding the mechanism of mutation induction, following low-dose MNU treatment, sets precedence for weaker mutagenic alkylating agents. Here, we tested MNU at 10-fold lower concentrations than a previous study and report a NOGEL of 0.0075 µg/ml (72.8nM) in human lymphoblastoid cells, quantified through the hypoxanthine (guanine) phosphoribosyltransferase assay (OECD 476). Mechanistic studies reveal that the NOGEL is dependent upon repair of O(6)-methylguanine (O(6)MeG) by the suicide enzyme O(6)MeG-DNA methyltransferase (MGMT). Inactivation of MGMT sensitizes cells to MNU-induced mutagenesis and shifts the NOGEL to the left on the dose axis.

Thomas AD; Jenkins GJ; Kaina B; Bodger OG; Tomaszowski KH; Lewis PD; Doak SH; Johnson GE

2013-03-01

303

Neutron dose response of tradescantia stamen hair pink mutations and RBE  

Energy Technology Data Exchange (ETDEWEB)

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

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

1998-03-01

304

Neutron dose response of tradescantia stamen hair pink mutations and RBE  

International Nuclear Information System (INIS)

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

1998-01-01

305

Cancer incidence within a cohort occupationally exposed to asbestos: a study of dose--response relationships.  

UK PubMed Central (United Kingdom)

OBJECTIVES: The aim of our study was to analyse the dose-response relationship between occupational asbestos exposure and risk of cancer. METHODS: Our study was a retrospective morbidity study based on 2024 subjects occupationally exposed to asbestos, conducted over the period 1 January 1978 to 31 December 2004. Analysis of the dose-response relationship between occupational asbestos exposure, as a time-dependant variable, and risk of cancer was performed using a Cox model. In order to account for the effect of latency, we conducted the analysis with a lag of 10 years. RESULTS: 285 cases of cancers were observed in our cohort. The relative risk of pleuro-peritoneal mesothelioma, lung cancer and colorectal cancer associated with asbestos exposure, adjusted for age as a time-dependant variable and for sex, was correlated with exposure intensity (or average exposure level, AEL). The risk of cancer, whatever the anatomical site, did not increase with the duration of exposure to asbestos. CONCLUSION: While confirming the established relationship between asbestos exposure and pleuropulmonary and peritoneal cancers, this study also suggests a causal relationship between asbestos exposure and colorectal cancer.

Clin B; Morlais F; Launoy G; Guizard AV; Dubois B; Bouvier V; Desoubeaux N; Marquignon MF; Raffaelli C; Paris C; Galateau-Salle F; Guittet L; Letourneux M

2011-11-01

306

Dose-response effects of beta-phenylethylamine on stereotyped behavior in pargyline-pretreated rats.  

UK PubMed Central (United Kingdom)

We studied the dose-response and the time-course effect of beta-phenylethylamine (4.0-64.0 mg/kg, ip) on stereotyped behavior and motor activity in male Sprague-Dawley rats pretreated 2 hr eariler with pargyline (0.25-8.0 mg/kg, iv). Stereotyped behavior, defined as repetitive, nongoal-directed head movements and sniffing, and changes in motor activity were observed immediately after injection of beta-phenylethylamine for a 1 hr period. With increasing doses of pargyline pretreatment, beta-phenylethylamine produced, in a dose-response relationship, progressively more stereotyped behavior accompanied by increased motor activity. Without pargyline pretreatment, only 64.0 mg/kg beta-phenylethylamine induced behavioral changes. Stereotyped behavior and increased motor activity had an onset at 4-6 min after the injection of beta-phenylethylamine, peak at 10-30 min, and gradual decline in the next 10-20 min. These results are discussed in terms of a possible relationship with the degree of inhibition of Type a and Type B monoamine oxidase acused by the different doses of pargyline.

Moja EA; Stoff DM; Gillin JC; Wyatt RJ

1976-12-01

307

Dose Response Association between Physical Activity and Biological, Demographic, and Perceptions of Health Variables.  

UK PubMed Central (United Kingdom)

Background : Few population-based studies have examined the association between physical activity (PA) and cardiovascular disease risk factors, demographic variables, and perceptions of health status, and we do not have a clear understanding of the dose-response relationship among these variables. Methods : Data from the 2003-2006 National Health and Nutrition Examination Survey was used to examine the dose-response relationship between objectively measured PA and metabolic syndrome (and its individual cardiovascular disease risk factors), demographic variables, and perceptions of health. After exclusions, 5,538 participants 18 years or older were included in the present study, with 2,538 participants providing fasting glucose and 2,527 providing fasting triglyceride data. PA was categorized into deciles. Results : Overall, the health benefits showed a general pattern of increase with each increasing levels of PA. Of the ten PA classifications examined, participants in the highest moderate-to-vigorous physical activity (MVPA) category (at least 71 min/day) had the lowest odds of developing metabolic syndrome. Conclusion : At a minimum, sedentary adults should strive to meet current PA guidelines (i.e., 150 min/week of MVPA), with additional positive benefits associated with engaging in three times this level of PA. © 2013 S. Karger GmbH, Freiburg.

Loprinzi PD; Lee H; Cardinal BJ

2013-01-01

308

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1994-06-01

309

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)

1994-01-01

310

Cryptosporidium parvum: Determination of ID50 and the dose-response relationship in experimentally challenged dairy calves.  

Science.gov (United States)

The objectives were to determine the median infective dose (ID50) of Cryptosporidium parvum and to describe the dose-response relationship including associated clinical illness in experimentally challenged dairy calves. Within the first 24h of life, 27 test calves were experimentally challenged with C. parvum oocysts and 3 control calves were sham dosed. Test calves received 1 of 8 possible doses (25, 50, 100, 500, 1×10(3), 1×10(4), 1×10(5), and 1×10(6) oocysts). All 27 test calves developed diarrhea. Fecal oocyst shedding occurred in 25 (92.6%) test calves and in 0 control calves. The 2 non-shedding test calves both received 25 oocysts. There was an inverse relationship between dose and time to onset of fecal oocyst shedding (P=0.005). There was no relationship found between dose and duration (P=0.2) or cessation (P=0.3) of fecal oocyst shedding. In addition, there was not a significant relationship between log-dose and the log-peak oocysts (P=0.2) or log-total oocysts (P=0.5) counted/g of feces across the dose groups. There was a positive dose-response relationship between log-dose and diarrhea (P=0.01). However, when controlling for other factors, such as onset and cessation of fecal oocyst shedding, dose was not a significant predictor of diarrhea (P=0.5). Onset and cessation of fecal oocyst shedding were found to be the best predictors of diarrhea (P=0.0006 and P=0.04, respectively). The ID50 for fecal oocyst shedding was 5.8 oocysts, for diarrhea was 9.7 oocysts, and for fecal oocyst shedding with diarrhea was 16.6 oocysts. Given that the ID50 of C. parvum is far less than would be excreted into the environment by a naturally infected calf, prevention and control of cryptosporidiosis is a formidable challenge. PMID:23680540

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

2013-04-20

311

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

DEFF Research Database (Denmark)

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

Lorenzen, Ellen; Einer-Jensen, Katja

2000-01-01

312

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

International Nuclear Information System (INIS)

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

2004-01-01

313

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

UK PubMed Central (United Kingdom)

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

Reynolds M; Fallone BG; Rathee S

2013-04-01

314

Airborne trichloramine (NCl(3)) levels and self-reported health symptoms in indoor swimming pool workers: dose-response relationships.  

UK PubMed Central (United Kingdom)

The hypothesis that attendance at indoor chlorinated swimming pool is a risk factor for irritative ocular and respiratory symptoms and bronchial asthma is well known in literature, although epidemiological evidence is still inconclusive. The aim of this study was to evaluate the association between airborne trichloramine (NCl(3)) levels and irritative symptoms in swimming pool employees in order to obtain detailed data regarding dose-response relationships and to identify the airborne NCl(3) exposure level, if any, without health effects. A total of 20 indoor swimming pools in the Emilia Romagna region of Italy were included in the study. Information about the health status of 128 employees was collected using a self-administered questionnaire. Exposure to airborne NCl(3) was evaluated in indoor swimming pools by a modified DPD/KI method. The results of the study evidenced a mean value of airborne NCl(3) of 0.65±0.20?mg/m(3) (ranging from 0.20 to 1.02?mg/m(3)). Both ocular and upper respiratory symptoms, in particular red eyes, runny nose, voice loss and cold symptoms, were declared more frequently by lifeguards and trainers when compared with employees working in other areas of the facility (office, cafe, and so on). Pool attendants exposed to airborne NCl(3) levels of >0.5?mg/m(3) experienced higher risks for runny nose (OR: 2.91; 95% CI: 1.22-6.93) red eyes (OR: 3.16; 95% CI: 1.46-6.82), voice loss (OR: 3.56; 95% CI: 1.60-7.95) and itchy eyes (OR: 2.23; 95% CI: 1.04-4.78) than other employees. Moreover, red eyes, itchy eyes, runny nose and voice loss are related to airborne NCl(3) levels, with strong dose-response relationships. In conclusion, this study shows that lifeguards and trainers experience ocular and respiratory irritative symptoms more frequently than employees not exposed. Irritative symptoms become significant starting from airborne NCl(3) levels of >0.5?mg/m(3), confirming that the WHO-recommended value can be considered protective in occupational exposure to airborne NCl(3) in indoor swimming pools.

Fantuzzi G; Righi E; Predieri G; Giacobazzi P; Petra B; Aggazzotti G

2013-01-01

315

Effects of whey proteins on glycaemia and insulinaemia to an oral glucose load in healthy adults; a dose-response study.  

UK PubMed Central (United Kingdom)

BACKGROUND/OBJECTIVES: Whey proteins have insulinogenic properties and the effect appears to be mediated from a postprandial plasma amino-acid (AA) response. The aim was to study the possible dose-response relationship between whey intake and glycaemic-, insulinaemic- and plasma AA responses. SUBJECTS/METHODS: Twelve healthy volunteers participated in the study. They were provided three whey protein drinks, containing 4.5, 9 or 18?g protein as breakfast meals in random order. All meals contained 25?g available carbohydrates (glucose). The same amount of glucose in water was used as reference. RESULTS: Linear dose-response relations were found between whey protein intake and postprandial glycaemia, insulinaemia and plasma AAs. The two highest doses, 18?g and 9?g, significantly reduced postprandial glycaemia (incremental area under the curve (iAUC) 0-120?min; P ? 0.05). The 18?g dose significantly increased the insulin response (iAUC 0-120?min; P ? 0.05). All measured plasma AAs (15 in total), except glutamic acid, responded in a dose-dependent way, and the 9 and 18?g doses resulted in significantly higher plasma levels of AAs compared with the reference. CONCLUSIONS: Whey protein affects glycaemia, insulinaemia and plasma AAs to a glucose load in a dose-dependent manner. Comparatively low doses of whey protein (9?g) reduced postprandial glycaemia significantly when added to a carbohydrate-rich meal.

Gunnerud UJ; Ostman EM; Björck IM

2013-07-01

316

Radiation-dose response of glycophorin A somatic mutation in erythrocytes associated with gene polymorphisms of p53 binding protein 1.  

UK PubMed Central (United Kingdom)

Information on individual variations in response to ionizing radiation is still quite limited. Previous studies of atomic-bomb survivors revealed that somatic mutations at the glycophorin A (GPA) gene locus in erythrocytes were significantly elevated with radiation exposure dose, and that the dose response was significantly higher in survivors with subsequent cancer development compared to those without cancer development. Noteworthy in these studies were great inter-individual differences in GPA mutant fraction even in persons with similar radiation doses. It is hypothesized that persistent GPA mutations in erythrocytes of atomic-bomb survivors are derived from those in long-lived hematopoietic stem cell (HSC) populations, and that individual genetic backgrounds, specifically related to DNA double-strand break repair, contribute to individual differences in HSC mutability following radiation exposure. Thus, we examined the relationship between radiation exposure, GPA mutant fraction in erythrocytes, and single nucleotide polymorphisms (SNPs) of the key gene involved in DNA double-strand break repair, p53 binding protein 1 (53BP1). 53BP1 SNPs and inferred haplotypes demonstrated a significant interaction with radiation dose, suggesting that radiation-dose response of GPA somatic mutation is partly dependent on 53BP1 genotype. It is also possible that 53BP1 plays a significant role in DNA double-strand break repair in HSCs following radiation exposure.

Yoshida K; Kusunoki Y; Cologne JB; Kyoizumi S; Maki M; Nakachi K; Hayashi T

2013-07-01

317

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

Directory of Open Access Journals (Sweden)

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

K Montazeri; M Fallah

2005-01-01

318

CHOICE OF INDICATOR DETERMINES THE SIGNIFICANCE AND RISK OBTAINED FROM THE STATISTICAL ASSOCIATION BETWEN FINE PARTICULATE MATTER MASS AND CARDIOVASCULAR MORTALITY  

Science.gov (United States)

Minor changes in the indicator used to measure fine PM, which cause only modest changes in Mass concentrations, can lead to dramatic changes in the statistical relationship of fine PM mass with cardiovascular mortality. An epidemiologic study in Phoenix (Mar et al., 2000), augme...

319

Dose-response relationship between selective serotonin re-uptake inhibitors and injurious falls: a study in nursing home residents with dementia  

Science.gov (United States)

AIM The contribution of selective serotonin re-uptake inhibitors (SSRIs) to injurious fall risk in patients with dementia has not been quantified precisely until now. Our objective was to determine whether a dose–response relationship exists for the use of SSRIs and injurious falls in a population of nursing home residents with dementia. METHODS Daily drug use and daily falls were recorded in 248 nursing home residents with dementia from 1 January 2006 until 1 January 2008. For each resident and for each day of the study period, data on drug use were abstracted from the prescription database, and information on falls and subsequent injuries was retrieved from a standardized incident report system, resulting in a dataset of 85 074 person-days. RESULTS We found a significant dose–response relationship between injurious falls and the use of SSRIs. The risk of an injurious fall increased significantly with 31% at 0.25 of the Defined Daily Dose (DDD) of a SSRI, 73% at 0.50 DDD, and 198% at 1.00 DDD (Hazard ratio = 2.98; 95% confidence interval 1.94, 4.57). The risk increased further in combination with a hypnotic or sedative. CONCLUSIONS Even at low doses, SSRIs are associated with increased risk of an injurious fall in nursing home residents with dementia. Higher doses increase the risk further with a three-fold risk at 1.00 DDD. New treatment protocols might be needed that take into account the dose–response relationship between SSRIs and injurious falls.

Sterke, Carolyn S; Ziere, Gijsbertus; van Beeck, Ed F; Looman, Caspar W N; van der Cammen, Tischa J M

2012-01-01

320

Dose-response relationship between selective serotonin re-uptake inhibitors and injurious falls: a study in nursing home residents with dementia.  

UK PubMed Central (United Kingdom)

AIM: The contribution of selective serotonin re-uptake inhibitors (SSRIs) to injurious fall risk in patients with dementia has not been quantified precisely until now. Our objective was to determine whether a dose-response relationship exists for the use of SSRIs and injurious falls in a population of nursing home residents with dementia. METHODS: Daily drug use and daily falls were recorded in 248 nursing home residents with dementia from 1 January 2006 until 1 January 2008. For each resident and for each day of the study period, data on drug use were abstracted from the prescription database, and information on falls and subsequent injuries was retrieved from a standardized incident report system, resulting in a dataset of 85,074 person-days. RESULTS: We found a significant dose-response relationship between injurious falls and the use of SSRIs. The risk of an injurious fall increased significantly with 31% at 0.25 of the Defined Daily Dose (DDD) of a SSRI, 73% at 0.50 DDD, and 198% at 1.00 DDD (Hazard ratio = 2.98; 95% confidence interval 1.94, 4.57). The risk increased further in combination with a hypnotic or sedative. CONCLUSIONS: Even at low doses, SSRIs are associated with increased risk of an injurious fall in nursing home residents with dementia. Higher doses increase the risk further with a three-fold risk at 1.00 DDD. New treatment protocols might be needed that take into account the dose-response relationship between SSRIs and injurious falls.

Sterke CS; Ziere G; van Beeck EF; Looman CW; van der Cammen TJ

2012-05-01

 
 
 
 
321

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

DEFF Research Database (Denmark)

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

Larsen, C.N.; Nielsen, S.

2006-01-01

322

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

Science.gov (United States)

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 (p37 mm VAS [28 to 46 mm] and 33 mm VAS [24 to 43 mm] respectively. Specific strength training reduces pain intensity in women with severe neck pain, and 1-2 training sessions per week for 20 weeks (?30 training sessions) appears sufficient for optimal pain relief. PMID:23478473

Andersen, Christoffer H; Andersen, Lars L; Pedersen, Mogens T; Mortensen, Peter; Karstad, Kristina; Mortensen, Ole S; Zebis, Mette K; Sjøgaard, Gisela

2013-03-01

323

Dose-Response Relationship between Dietary Polyphenols from Acorns and Parotid Gland Hypertrophy in Pigs  

Directory of Open Access Journals (Sweden)

Full Text Available Proline contents of parotid glands (PG) in pigs constantly increase after the inclusion of different amounts of ripe hulled acorns in the diet providing high polyphenols levels. The dose-response relationship was estimated on natural hydrolizable tannins (expressed as tannic acid equivalent TAE) amounts of 25.8 to 36.1 g TAE/kg DM in experimental diets. Macroscopic and histological morphometry of parotid glands greatly varied according to feed intake and dosages of TAE ingested. The PG response (hypertrophy grade) on acorns’ tannins content in the diet was positively correlated (R2 = 0.748): the response to the protein precipitating activity (PPA) of tannins consisted of a functional parotidomegaly (hypertrophy), 1.34 up to 3.55 folds than control PGs, following an oral dosage 0.596 up 1.72 TAE g·kg body weight·d-1 respectively, after one week exposure.

Maria Grazia Cappai; Petra Wolf; Walter Pinna; Josef Kamphues

2012-01-01

324

Dose-response fallacy in human reproductive studies of toxic exposures  

Energy Technology Data Exchange (ETDEWEB)

The manner in which exposure is defined can affect the findings of reproductive studies of toxic exposures. The individual end points potentially examined, such as fetal loss, subfertility, and congenital malformations observed at birth, are on a continuum by severity of effect: the most extreme effects of the three being infertility because no pregnancy is possible, and the least extreme, congenital malformations recognized at birth. End points observed at birth are survivors of a long and complex process. The process yielding one of these adverse end points may result from a number of factors, including level of exposure could result in early fetal loss, whereas a lower one might result in a congenital malformation observed at birth. If the probability of a less-severe end point falls due to increasing probability of more-severe end points with increasing exposure, then a nontraditional dose-response relationship may be observed in the study of one type of outcome.

Selevan, S.G.; Lemasters, G.K.

1987-01-01

325

Dose-response fallacy in human reproductive studies of toxic exposures  

Energy Technology Data Exchange (ETDEWEB)

The manner in which exposure is defined can affect the findings of reproductive studies of toxic exposures. The individual end points potentially examined, such as fetal loss, subfertility, and congenital malformations observed at birth, are on a continuum by severity of effect: The most extreme effect of the three being infertility because no pregnancy is possible, and the least extreme, congenital malformations recognized at birth. End points observed at birth are survivors of a long and complex process. The process yielding one of these adverse end points may result from a number of factors, including level of exposure. For example, a very high exposure could result in early fetal loss, whereas a lower one might result in a congenital malformation observed at birth. If the probability of a less severe end point falls due to increasing probability of more severe end points with increasing exposure, then a nontraditional dose-response relationship may be observed in the study of one type of outcome.

Selevan, S.G.; Lemasters, G.K.

1987-05-01

326

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

UK PubMed Central (United Kingdom)

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).

Israelsson A; Gustafsson H; Lund E

2013-04-01

327

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

International Nuclear Information System (INIS)

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

2012-01-01

328

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

Energy Technology Data Exchange (ETDEWEB)

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

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

2012-07-15

329

Comparison of Comet assay dose-response for ethyl methanesulfonate using freshly prepared versus cryopreserved tissues.  

UK PubMed Central (United Kingdom)

The National Toxicology Program (NTP) is using the Comet assay to evaluate genotoxic potential, and is investigating the integration of this assay into repeat-dose toxicity studies. To reduce sample-to-sample variability, address logistical concerns associated with evaluating multiple tissues from many animals, and accommodate sample collection at geographically distant testing facilities, tissue samples collected for Comet analysis by the NTP are routinely flash-frozen in liquid nitrogen and stored in a -80°C freezer until evaluation. To compare data obtained from frozen tissues to data from freshly isolated tissues, we conducted a dose-response study in male Sprague Dawley rats. Rats (5 per treatment group) were administered ethyl methanesulfonate (EMS; 0, 25, 50, 100, or 200 mg/kg) by gavage twice at an interval of 21 hr; blood, liver, stomach, and colon tissues were harvested 3 hr after the second treatment. Single-cell preparations from each of the four tissues were put into Hank's balanced salt solution with 10% fresh dimethyl sulfoxide. One aliquot of each tissue preparation was used for immediate analysis, while additional aliquots were flash-frozen in liquid nitrogen and stored in a -80°C freezer for 1 or 8 weeks. One set of 8-week frozen samples was shipped roundtrip via air courier from Research Triangle Park, NC to Rochester, NY prior to analysis. For all four tissues, results from frozen, nontransported samples showed a similar dose-response pattern for EMS-induced genotoxicity. We also demonstrated that for three tissues (blood, liver, stomach), air transport did not alter the sensitivity of the Comet assay for detecting DNA damage.

Recio L; Kissling GE; Hobbs CA; Witt KL

2012-03-01

330

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

DEFF Research Database (Denmark)

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

Kjellström, Tord; Grandjean, Philippe

2007-01-01

331

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

DEFF Research Database (Denmark)

We derive equations for the effective concentration giving 10% inhibition (EC10) with 95% confidence limits for probit (log-normal), Weibull, and logistic dose -responsemodels on the basis of experimentally derived median effective concentrations (EC50s) and the curve slope at the central point (50% inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response regressions for four test chemicals (tetraethylammonium bromide, musculamine, benzonitrile, and 4-4-(trifluoromethyl)phenoxy-phenol) with ranges of representative slopes at 50% response (0.54-2.62) and EC50s (2.20-357 mg/L) were selected. Reference EC50s and EC10s with 95% confidence limits using probit or Weibull models are calculated by nonlinear regression on the whole dataset using a dose - response regression program with variance weighting and proper inverse estimation. The Weibull model provides the best fit to the data for all four chemicals. Predicted EC10s (95% confidence limits) from our derived equations are quite accurate; for example, with 4-4-(trifluoromethyl)phenoxy-phenol and the probit model, we obtain 1.40 (1.22-1.61) mg/L versus 1.40 (1.20-1.64) mg/L obtained from the nonlinear regression program. The main advantage of the approach is that EC10 or ECx (where x = 1 - 99) can be predicted from well-determined responses around EC20 to EC80 without experimental data in the low- or high-response range. Problems with the estimation of confidence interval for EClow,x (concentration predicted to cause x% inhibition) from algal growth inhibition also are addressed. Large confidence intervals may be the result of experimental error and lack of a well-defined reference response value.

Christensen, Erik R.; Kusk, Kresten Ole

2009-01-01

332

Olestra dose response on fat-soluble and water-soluble nutrients in humans.  

Science.gov (United States)

Ninety normal healthy adults were given 0, 8, 20 or 32 g/d olestra for 8 wk as part of a diet that provided 1 +/- 0.2 of the recommended dietary allowance (RDA) of vitamins A, D, E and K, folate zinc, calcium and iron. In addition, a 20 microg/d supplement of vitamin D was supplied. The diet provided 15% of energy from protein, 35% from fat and 55% from carbohydrate. The purpose of the study was to determine the dose response of olestra on vitamins D, E and K, carotenoids, vitamin B12, folate and zinc. Circulating concentrations of retinol, carotenoids, tocopherols, 25-hydroxy- and 1,25-dihydroxyvitamin D metabolites, phylloquinone, des-gamma-carboxyprothrombin, prothrombin, folate and hematological parameters were measured biweekly, as were urine concentrations of zinc and gamma-carboxyglutamic acid (Gla). Clinical chemistry, urinalysis and vitamin B12 absorption were measured at wk 0 and 8. Olestra reduced serum concentrations of carotenoids, alpha-tocopherol, 25-hydroxyergocalciferol and phylloquinone in a dose-responsive manner. Olestra did not affect Gla excretion, plasma des-gamma-carboxyprothrombin or prothrombin concentrations, prothrombin time, vitamin B12 absorption, overall vitamin D status or the status of folate or zinc. Laboratory evaluations showed no health-related effects of olestra. Subjects in all groups reported common gastrointestinal symptoms such as loose stools, fecal urgency and flatulence, which were transient and generally mild to moderate in severity. These symptoms did not affect protocol compliance or the ability to measure the potential for olestra to affect nutrient availability. PMID:9237961

Schlagheck, T G; Riccardi, K A; Zorich, N L; Torri, S A; Dugan, L D; Peters, J C

1997-08-01

333

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

Energy Technology Data Exchange (ETDEWEB)

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

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

1984-02-01

334

Dose-response relationship for breast cancer induction at radiotherapy dose  

Directory of Open Access Journals (Sweden)

Full Text Available Abstract Purpose Cancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer. Materials and methods In this work a dose-response relationship for breast cancer is derived based on (i) the analysis of breast cancer induction after Hodgkin's disease, (ii) a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii) the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy, (iv) the breast cancer induction of the A-bomb survivor data. Results The fitted model parameters for an ?/? = 3 Gy were ? = 0.067Gy-1 and R = 0.62. The risk for breast cancer is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 20 Gy and drops off only slightly at larger doses. The predicted EAR for breast cancer after radiotherapy of Hodgkin's disease is 11.7/10000PY which can be compared to the findings of several epidemiological studies where EAR for breast cancer varies between 10.5 and 29.4/10000PY. The model was used to predict the impact of the reduction of radiation volume on breast cancer risk. It was estimated that mantle field irradiation is associated with a 3.2-fold increased risk compared with mediastinal irradiation alone, which is in agreement with a published value of 2.7. It was also shown that the modelled age dependency of breast cancer risk is in satisfying agreement with published data. Conclusions The dose-response relationship obtained in this report can be used for the prediction of radiation induced secondary breast cancer of radiotherapy patients.

Schneider Uwe; Sumila Marcin; Robotka Judith; Gruber Günther; Mack Andreas; Besserer Jürgen

2011-01-01

335

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

UK PubMed Central (United Kingdom)

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

Calabrese EJ

2013-09-01

336

Comparisons of dose-response parameters for radiation-induced acentric fragments and micronuclei observed in cytokinesis-arrested lymphocytes  

International Nuclear Information System (INIS)

We employed cytochalasin B to block cytokinesis in human lymphocytes exposed to 220 kV X-radiation. When 3 ?g/ml of cytochalasin B was used, most cells escaped the block whereas at 6 ?g/ml 90% of the mitogen-responsive cells became binucleate. Using the higher concentration of cytochalasin B, we observed a linear-quadratic (i.e. Y = ? + ?D + ?D2) dose dependency for X-ray-induced micronuclei (MN) in preparations from three donors. When dose-response parameters were compared with those for total acentrics scored in first division metaphases, we observed no significant differences in estimates of the background (?) or linear (?) coefficients, but a 2-fold reduction in the ? coefficient for MN. We interpret our data as providing evidence that radiation-induced micronuclei are derived from acentric fragments (AF); that virtually all AF are recovered as MN in binucleate interphase daughter cells at low radiation doses; and that for our data, the relative proportion of AF that will be observed as independent MN decreases by a constant factor of approximately one-half as radiation dose increases. (author)

1989-01-01

337

Comparisons of dose-response parameters for radiation-induced acentric fragments and micronuclei observed in cytokinesis-arrested lymphocytes  

Energy Technology Data Exchange (ETDEWEB)

We employed cytochalasin B to block cytokinesis in human lymphocytes exposed to 220 kV X-radiation. When 3 mug/ml of cytochalasin B was used, most cells escaped the block whereas at 6 mug/ml 90% of the mitogen-responsive cells became binucleate. Using the higher concentration of cytochalasin B, we observed a linear-quadratic (i.e. Y = gamma + alphaD + betaD{sup 2}) dose dependency for X-ray-induced micronuclei (MN) in preparations from three donors. When dose-response parameters were compared with those for total acentrics scored in first division metaphases, we observed no significant differences in estimates of the background (gamma) or linear (alpha) coefficients, but a 2-fold reduction in the beta coefficient for MN. We interpret our data as providing evidence that radiation-induced micronuclei are derived from acentric fragments (AF); that virtually all AF are recovered as MN in binucleate interphase daughter cells at low radiation doses; and that for our data, the relative proportion of AF that will be observed as independent MN decreases by a constant factor of approximately one-half as radiation dose increases. (author).

Littlefield, L.G. (Oak Ridge Associated Universities, Inc., TN (USA)); Sayer, A.M.; Frome, E.L. (Oak Ridge National Lab., TN (USA))

1989-07-01

338

The dose response relationship between intervertebral disc flexion-extension neutral zone metrics and injected genipin concentration.  

UK PubMed Central (United Kingdom)

Purpose: Quantify changes in the flexion - extension neutral zone of the intervertebral disc with injections of increasing genipin concentration.?Methods: Bovine motion segments were treated with varying concentrations of genipin using bilateral injections of constant volume. After overnight static compression loading of the treated segments, anterior- posterior offset loading was used to simulate flexion - extension motion. Range of motion, neutral zone length, neutral zone stiffness, and an instability score were measured.?Results: Injection of the disc annulus with increasing concentrations of genipin resulted in corresponding changes in flexion-extension neutral zone. A minimum concentration of 40 mM was needed to observe a significant change. The largest changes were observed with the 400 mM injection. Netural zone stability was the most sensitive of the metrics with a percent change of 48% at 40 mM and over 200% at 400 mM.?Conclusion: This study establishes the efficacy of using injection delivery to affect disc joint mechanics and quantifies the dose response between injected genipin and the flexion-extension stability of the disc.

Kirking BC; Toungate JK; Hedman TP

2013-01-01

339

The dose response relationship between intervertebral disc flexion-extension neutral zone metrics and injected genipin concentration.  

Science.gov (United States)

Purpose: Quantify changes in the flexion - extension neutral zone of the intervertebral disc with injections of increasing genipin concentration.?Methods: Bovine motion segments were treated with varying concentrations of genipin using bilateral injections of constant volume. After overnight static compression loading of the treated segments, anterior- posterior offset loading was used to simulate flexion - extension motion. Range of motion, neutral zone length, neutral zone stiffness, and an instability score were measured.?Results: Injection of the disc annulus with increasing concentrations of genipin resulted in corresponding changes in flexion-extension neutral zone. A minimum concentration of 40 mM was needed to observe a significant change. The largest changes were observed with the 400 mM injection. Netural zone stability was the most sensitive of the metrics with a percent change of 48% at 40 mM and over 200% at 400 mM.?Conclusion: This study establishes the efficacy of using injection delivery to affect disc joint mechanics and quantifies the dose response between injected genipin and the flexion-extension stability of the disc. PMID:23728539

Kirking, Bryan C; Toungate, Justin K; Hedman, Thomas P

2013-09-13

340

Dose-response effects of Elephantopus scaber methanolic extract on N-nitrosodiethylamine-induced hepatotoxicity in rats.  

UK PubMed Central (United Kingdom)

AIM: A decoction of Elephantopus scaber (Asteraceae) root is used to treat liver disorders in Indian and Chinese traditional medicine. The study was designed to examine the dose response effects of E. scaber methanolic extract on rats exposed to N-nitrosodiethylamine (NDEA) induced hepatotoxicity (0.02% NDEA in water five days per week, per oral) in preventive and curative models. METHODS: In preventive groups, NDEA was administered for six weeks. Daily doses of E. scaber methanolic extract (200 and 100 mg·kg-1) started one week before the onset of NDEA intoxication and continued for six weeks. In curative animals, NDEA was administered for six weeks followed by treatment with the methanolic n-hexane extract of E. scaber (200 and 100 mg·kg-1) for ten days. RESULTS: E. scaber extract treatment significantly (P ? 0.05) reduced the levels of AST, ALT, and MDA in both experimental groups. The extract also enhanced the antioxidant enzyme and protein levels in rats intoxicated with NDEA. Treatment with the extract dose dependently protected the liver from NDEA-induced hepatotoxicity with normal hepatocytes and uniform sinusoids, but in some areas showed degenerating hepatic cells in both treatment groups. CONCLUSION: E. scaber methanolic extract dose dependently prevented and reversed the hepatotoxicity induced by NDEA in both experimental models.

Linza A; Wills PJ; Ansil PN; Prabha SP; Nitha A; Latha B; Sheeba KO; Latha MS

2013-07-01

 
 
 
 
341

Control of Ichthyophthirius multifiliis using a combination of water filtration and sodium percarbonate: Dose-response studies  

UK PubMed Central (United Kingdom)

Morbidity and mortality caused by infections with the skin parasite Ichthyophthirius multifiliis Fouquet, 1876 is a major problem in freshwater fish farming in most climatic zones. In both traditional and re-circulated systems various chemicals have been applied to combat outbreaks with I. multifiliis. The present work provides a basis for establishing a preventive strategy against I. multifiliis in fish farms. Thus, water filtration can remove tomonts (and thereby prevent formation of tomocysts and theronts). When combined with the use of an environmentally neutral compound (sodium percarbonate, SPC) (releasing hydrogen peroxide) for eliminating infective theronts the infection can be kept at an acceptable level. SPC was tested and compared to formaldehyde (FA) -- a traditionally used chemical against Ich at various concentrations (8, 16, 32 and 64 mg/l), temperatures (11-13 and 21-22 °C) and exposure times. SPC was found to have higher efficacy compared to FA but temperature and concentration of the chemical had significant influences on parasite survival. For both chemicals negative correlations were seen between survival of theronts and exposure time, temperature and concentration. A dose-response study conducted on tomonts showed that tomonts were exceedingly more tolerant towards both chemicals. Micro-filtration studies demonstrated that it was possible to filter out 100% of the tomonts using a mesh size of 80 ?m. Therefore mechanical methods are recommended in order to eliminate tomonts whereby the subsequent production of tomocysts and theronts will be prevented.

Heinecke RasmusD; Buchmann Kurt

2009-03-01

342

No significant cost reduction. 1999 statistics of gas engine heat-and-power stations; Keine gravierenden Kostensenkungen. Richtpreisuebersicht MHKW-Anlagen 1999  

Energy Technology Data Exchange (ETDEWEB)

Since 1994/'95, the energy department of Frankfurt city hall publishes yearly statistics of producers' recommended prices for gas motor heat-and-power stations. The new statistics covers 178 modular systems by 28 producers and also incudes heating oil fuelled engines. CW will publish this section in a later issue. [German] Seit 1994/1995 wird vom Energiereferat der Stadt Frankfurt jaehrlich eine Richtpreisuebersicht fuer Motoren-Heizkraftwerke (MHKW) erstellt. Die Resonanz in Fachkreisen sowie die Notwendigkeit, fuer eigene Planungen ueber aktuelle Preise fuer Gasmotoren zu verfuegen, haben den Ersteller dazu bewogen, die Marktbeobachtung zu aktualisieren und weiterzufuehren. Insgesamt liegen der Auswertung fuer Erdgasmaschinen 178 Modul-Angebote von 28 Herstellern bzw. Packagern zugrunde. Seit der Richtpreisuebersicht 1997 wurde die Markterhebung auch auf Heizoelmotoren ausgedehnt. CW veroeffentlicht diesen Teil in einer spaeteren Ausgabe. (orig.)

Anon.

1999-10-01

343

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

UK PubMed Central (United Kingdom)

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 < 0.05). This exposure-response effect was also observed for most PAH metabolites (all p(trend) < 0.01), except for 4-hydroxyphenanthrene and 8-OHdG (p(trend) = 0.108). Furthermore, it was shown that only urinary 1-hydroxypyrene has a significant positive association with both 8-OHdG and 8-iso-PGF2? after a Bonferroni correction (p < 0.005). Our results indicated that urinary ?OH-PAHs and plasma BPDE-Alb adducts can result in significant dose-related increases in oxidative damage to DNA and lipids. Furthermore, when a multianalyte method is unavailable, our findings demonstrate that urinary 1-hydroxypyrene is a useful biomarker for evaluating total PAHs exposure and assessing oxidative damage in coke oven workers.

Kuang D; Zhang W; Deng Q; Zhang X; Huang K; Guan L; Hu D; Wu T; Guo H

2013-07-01

344

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

International Nuclear Information System (INIS)

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

2005-03-01

345

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

Directory of Open Access Journals (Sweden)

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

Islam Khairul; Haque Abedul; Karim Rezaul; Fajol Abul; Hossain Ekhtear; Salam Kazi; Ali Nurshad; Saud Zahangir; Rahman Matiar; Rahman Mashiur; Karim Rezaul; Sultana Papia; Hossain Mostaque; Akhand Anwarul; Mandal Abul; Miyataka Hideki; Himeno Seiichiro; Hossain Khaled

2011-01-01

346

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

Energy Technology Data Exchange (ETDEWEB)

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

Calabrese, Edward J. [Environmental Health Sciences, School of Public Health, Morrill I, N344, University of Massachusetts, Amherst, MA 01003 (United States)]. E-mail: edwardc@schoolph.umass.edu

2005-12-15

347

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 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.

2005-01-01

348

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

UK PubMed Central (United Kingdom)

PURPOSE: 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. METHODS: Dosimeter samples in cuvettes were irradiated to 5 Gy. The temperature for the different cuvettes during irradiation and post-irradiation storage was varied in the range of 3-30 degrees C in order to quantify the temperature dependence of the dosimeter response. The optical properties of the dosimeter samples were measured using a spectrophotometer before irradiation as well as at several times after irradiation to quantify the temporal variation of dose response (expressed as the optical density change induced by irradiation) as a function of storage temperature. RESULTS: The measurements show considerable temperature dependencies of dose response both during irradiation and storage. Fit to an Arrhenius equation revealed an activation energy of 1.4 +/- 0.2 eV for the variation in irradiation temperature, indicating a contribution from a thermally activated process. Variation in dose response at different storage temperatures showed an exponential increase with time followed by a decrease in optical density. Exponential Arrhenius fits to rate constants gave activation energies of 1.7 +/- 0.2 eV for the increase in dose response and 2.3 +/- 0.5 eV for the subsequent decrease, in this case dominated by thermally activated processes. CONCLUSIONS: Due to the exponential dependencies, stabilization of the dosimeter during irradiation at low temperatures (e.g., 5 degrees C) is preferable in clinical use to optimize the accuracy of the dose response. In addition, a low storage temperature is recommended in order to minimize the post-irradiation temporal change in dose response and thereby increase the post-irradiation stability of the dosimeter. The measurements in this study show that if the observed temperature and temporal dependencies are not considered, this could potentially deteriorate the accuracy of the dosimeter.

Skyt PS; Balling P; Petersen JB; Yates ES; Muren LP

2011-05-01

349

Observations and an interpretation of dose-response relationships for cellular transformation in terms of induced (T) repair  

Energy Technology Data Exchange (ETDEWEB)

Both radiation-induced lethality and transformation frequency have been observed to plateau or diminish abruptly at relatively low dose levels and then increase with increasing doses, but at a reduced incremental rate. Discontinuities in dose-response relationships are postulated to correspond to the induction of a repair system ('T' repair) not functional at lower doses, i.e. below the induction threshold dose (T{sub t}). Anomalies (discontinuities) in dose-response relationships and effects of dose fractionation previously noted are qualitatively explained in terms of this model. (author).

Calkins, J.; Einspenner, M.; Azzam, E.; Kunhi, M.; Sigut, D.; Hannan, M. (King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia))

1991-01-01

350

Observations and an interpretation of dose-response relationships for cellular transformation in terms of induced (T) repair  

International Nuclear Information System (INIS)

Both radiation-induced lethality and transformation frequency have been observed to plateau or diminish abruptly at relatively low dose levels and then increase with increasing doses, but at a reduced incremental rate. Discontinuities in dose-response relationships are postulated to correspond to the induction of a repair system ('T' repair) not functional at lower doses, i.e. below the induction threshold dose (Tt). Anomalies (discontinuities) in dose-response relationships and effects of dose fractionation previously noted are qualitatively explained in terms of this model. (author).

1991-01-01

351

The crooked shall be made straight: dose response relationships for carcinogenesis  

International Nuclear Information System (INIS)

Estimates of radiation-induced malignancies come principally from the A-bomb survivors and from medically exposed individuals, including second cancers in radiotherapy patients. The A-bomb survivors show an excess incidence of carcinomas which is linear with dose from about 10 cGy to 2.5 Gy. Above and below this dose range, there is considerable uncertainty concerning the shape of the dose response relationship. These two dose ranges will be discussed separately. Low dose extrapolations ICRP and NCRP suggest that cancer risks at doses lower than those at which direct epidemiological observations are possible should be obtained by a linear extrapolation from higher doses. This is labeled a 'prudent and conservative' assumption but is a subject of considerable controversy. Two factors, the existence of radiosensitive subgroups in the human population (such as AT heterozygotes), and the demonstration of a Bystander effect both exaggerate the consequences of small doses of radiation and imply that a linear extrapolation from high doses would underestimate low dose risks. High dose extrapolations In the context of radiotherapy, some normal tissues receive 70 Gy, while a larger volume receives a lower dose, but still far higher than the range for which data are available from the A-bomb survivors. The question is, what is the dose response for carcinogenesis in the range 10 to 70 Gy? At one extreme, it might be expected that the risk of inducing cancer would fall off rapidly at higher does due to cell killing. The other extreme possibility is that the risk of solid tumors levels off by about 10 Gy, but does not decline thereafter. For a few cancers, data are available from 2 Gy in A-bomb survivors to 70 Gy in radiotherapy patients, and it appears that the relative risk does not vary with dose. This implies that the volume of tissue irradiated is more important than the maximum dose. This result has far reaching implications for new technologies such as IMRT, which produce a dose distribution that conforms closely to the tumor volume, but at the price of an increased risk of induced cancer because a larger volume of normal tissue is exposed to lower doses

2003-01-01

352

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

UK PubMed Central (United Kingdom)

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)[middle dot]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 R(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™ EBT3 film model are well within ±2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also found that criteria of 3%?3 mm for an IMRT QA plan and 3%?2 mm for a brachytherapy QA plan are passing 95% gamma function points. CONCLUSIONS: In this paper, we demonstrate the use of functional argument to linearize the inherently nonlinear response of a radiochromic film based reference dosimetry system. In this way, relative dosimetry can be conveniently performed using radiochromic film dosimetry system without the need of establishing calibration curve.

Devic S; Tomic N; Aldelaijan S; Deblois F; Seuntjens J; Chan MF; Lewis D

2012-08-01

353

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

Energy Technology Data Exchange (ETDEWEB)

Purpose: Despite numerous advantages of radiochromic film dosimeter (high spatial resolution, near tissue equivalence, low energy dependence) to measure a relative dose distribution with film, one needs to first measure an absolute dose (following previously established reference dosimetry protocol) and then convert measured absolute dose values into relative doses. In this work, we present result of our efforts to obtain a functional form that would linearize the inherently nonlinear dose-response curve of the radiochromic film dosimetry system. Methods: Functional form [{zeta}= (-1){center_dot}netOD{sup (2/3)}/ln(netOD)] was derived from calibration curves of various previously established radiochromic film dosimetry systems. In order to test the invariance of the proposed functional form with respect to the film model used we tested it with three different GAFCHROMIC Trade-Mark-Sign film models (EBT, EBT2, and EBT3) irradiated to various doses and scanned on a same scanner. For one of the film models (EBT2), we tested the invariance of the functional form to the scanner model used by scanning irradiated film pieces with three different flatbed scanner models (Epson V700, 1680, and 10000XL). To test our hypothesis that the proposed functional argument linearizes the response of the radiochromic film dosimetry system, verification tests have been performed in clinical applications: percent depth dose measurements, IMRT quality assurance (QA), and brachytherapy QA. Results: Obtained R{sup 2} values indicate that the choice of the functional form of the new argument appropriately linearizes the dose response of the radiochromic film dosimetry system we used. The linear behavior was insensitive to both film model and flatbed scanner model used. Measured PDD values using the green channel response of the GAFCHROMIC Trade-Mark-Sign EBT3 film model are well within {+-}2% window of the local relative dose value when compared to the tabulated Cobalt-60 data. It was also found that criteria of 3%/3 mm for an IMRT QA plan and 3%/2 mm for a brachytherapy QA plan are passing 95% gamma function points. Conclusions: In this paper, we demonstrate the use of functional argument to linearize the inherently nonlinear response of a radiochromic film based reference dosimetry system. In this way, relative dosimetry can be conveniently performed using radiochromic film dosimetry system without the need of establishing calibration curve.

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

2012-08-15

354

Nano-silver induces dose-response effects on the nematode Caenorhabditis elegans.  

UK PubMed Central (United Kingdom)

Toxicity of nano-formulated silver to eukaryotes was assessed by exposing nematodes (Caenorhabditis elegans) to two types of silver nanoparticles (AgNPs): with average primary particle diameters of 1 nm (AgNP1) and 28nm (AgNP28, PVP coated), respectively. Tests were performed with and without presence of Escherichia coli to evaluate how the presence of a food bacterium affects the AgNP toxicity. A pre-exposure experiment was also conducted with nematodes pre-exposed to 0 and 1mgAgNPL(-1), respectively, for 20 h prior to exposure at higher concentrations of AgNP. Both AgNP1 and AgNP28 showed adverse dose-response effects and mortality on C. elegans. LC(50) for AgNP28 was lower than for AgNP1 and, hence, at the present test conditions the PVP-coated AgNP28 was more toxic than AgNP1. Including E. coli in the test medium as a food source increased AgNPs toxicity towards nematodes compared to when bacteria were not present. Pre-exposure to a low-level AgNP1 concentration made the nematodes slightly more sensitive to further exposure at higher concentrations compared to no pre-exposure, indicating that nematodes have no efficient physiological ability to counteract nano-silver toxicity by acclimation. The amount of dissolved Ag(+) was 0.18 to 0.21 mg L(-1) after 20 h at the highest AgNP1 (10 mg L(-1)) and AgNP28 (3 mg L(-1)) doses in the exposure medium, respectively. The upper limit of Ag(+) solubility cannot immediately explain the dose-response-related toxic effects of the AgNP nor the difference between AgNP1 and AgNP28. Higher toxicity of AgNP28 than AgNP1 may be explained by a combination of effects of coating, Ag-solubility and higher uptake rates due to agglomeration into ?m-size agglomerates in the exposure medium.

Ellegaard-Jensen L; Jensen KA; Johansen A

2012-06-01

355

Nano-silver induces dose-response effects on the nematode Caenorhabditis elegans.  

Science.gov (United States)

Toxicity of nano-formulated silver to eukaryotes was assessed by exposing nematodes (Caenorhabditis elegans) to two types of silver nanoparticles (AgNPs): with average primary particle diameters of 1 nm (AgNP1) and 28nm (AgNP28, PVP coated), respectively. Tests were performed with and without presence of Escherichia coli to evaluate how the presence of a food bacterium affects the AgNP toxicity. A pre-exposure experiment was also conducted with nematodes pre-exposed to 0 and 1mgAgNPL(-1), respectively, for 20 h prior to exposure at higher concentrations of AgNP. Both AgNP1 and AgNP28 showed adverse dose-response effects and mortality on C. elegans. LC(50) for AgNP28 was lower than for AgNP1 and, hence, at the present test conditions the PVP-coated AgNP28 was more toxic than AgNP1. Including E. coli in the test medium as a food source increased AgNPs toxicity towards nematodes compared to when bacteria were not present. Pre-exposure to a low-level AgNP1 concentration made the nematodes slightly more sensitive to further exposure at higher concentrations compared to no pre-exposure, indicating that nematodes have no efficient physiological ability to counteract nano-silver toxicity by acclimation. The amount of dissolved Ag(+) was 0.18 to 0.21 mg L(-1) after 20 h at the highest AgNP1 (10 mg L(-1)) and AgNP28 (3 mg L(-1)) doses in the exposure medium, respectively. The