Cvrčková, Fatima; Luštinec, Jiří; Žárský, Viktor
2015-01-01
We usually expect the dose-response curves of biological responses to quantifiable stimuli to be simple, either monotonic or exhibiting a single maximum or minimum. Deviations are often viewed as experimental noise. However, detailed measurements in plant primary tissue cultures (stem pith explants of kale and tobacco) exposed to varying doses of sucrose, cytokinins (BA or kinetin) or auxins (IAA or NAA) revealed that growth and several biochemical parameters exhibit multiple reproducible, statistically significant maxima over a wide range of exogenous substance concentrations. This results in complex, non-monotonic dose-response curves, reminiscent of previous reports of analogous observations in both metazoan and plant systems responding to diverse pharmacological treatments. These findings suggest the existence of a hitherto neglected class of biological phenomena resulting in dose-response curves exhibiting periodic patterns of maxima and minima, whose causes remain so far uncharacterized, partly due to insufficient sampling frequency used in many studies.
Bornkamp, Björn; Ickstadt, Katja
2009-03-01
In this article, we consider monotone nonparametric regression in a Bayesian framework. The monotone function is modeled as a mixture of shifted and scaled parametric probability distribution functions, and a general random probability measure is assumed as the prior for the mixing distribution. We investigate the choice of the underlying parametric distribution function and find that the two-sided power distribution function is well suited both from a computational and mathematical point of view. The model is motivated by traditional nonlinear models for dose-response analysis, and provides possibilities to elicitate informative prior distributions on different aspects of the curve. The method is compared with other recent approaches to monotone nonparametric regression in a simulation study and is illustrated on a data set from dose-response analysis.
Dose-response curves from incomplete data
International Nuclear Information System (INIS)
Groer, P.G.
1978-01-01
Frequently many different responses occur in populations (animal or human) exposed to ionizing radiation. To obtain a dose-response curve, the exposed population is first divided into sub-groups whose members received the same radiation dose. To estimate the response, the fraction of subjects in each sub-group that showed the particular response of interest is determined. These fractions are plotted against dose to give the dose-response curve. This procedure of plotting the fractions versus the radiation dose is not the correct way to estimate the time distribution for a particular response at the different dose levels. Other observed responses competed for the individuals in the exposed population and therefore prevented manifestation of the complete information on the response-time distribution for one specific response. Such data are called incomplete in the statistical literature. A procedure is described which uses the by now classical Kaplan-Meier estimator, to establish dose-response curves from incomplete data under the assumption that the different observed responses are statistically independent. It is demonstrated that there is insufficient information in the observed survival functions to estimate the time distribution for one particular response if the assumption of independence is dropped. In addition, it is not possible to determine from the data (i.e. type of response and when it occurred) whether or not the different response-time distributions are independent. However, it is possible to give sharp bounds between which the response has to lie. This implies that for incomplete data, only a 'dose-response band' can be established if independence of the competing responses cannot be assumed. Examples are given using actual data to illustrate the estimation procedures
Lagarde, Fabien; Beausoleil, Claire; Belcher, Scott M; Belzunces, Luc P; Emond, Claude; Guerbet, Michel; Rousselle, Christophe
2015-01-01
International audience; Experimental studies investigating the effects of endocrine disruptors frequently identify potential unconventional dose-response relationships called non-monotonic dose-response (NMDR) relationships. Standardized approaches for investigating NMDR relationships in a risk assessment context are missing. The aim of this work was to develop criteria for assessing the strength of NMDR relationships. A literature search was conducted to identify published studies that repor...
Zoeller, R Thomas; Vandenberg, Laura N
2015-05-15
The fundamental principle in regulatory toxicology is that all chemicals are toxic and that the severity of effect is proportional to the exposure level. An ancillary assumption is that there are no effects at exposures below the lowest observed adverse effect level (LOAEL), either because no effects exist or because they are not statistically resolvable, implying that they would not be adverse. Chemicals that interfere with hormones violate these principles in two important ways: dose-response relationships can be non-monotonic, which have been reported in hundreds of studies of endocrine disrupting chemicals (EDCs); and effects are often observed below the LOAEL, including all environmental epidemiological studies examining EDCs. In recognition of the importance of this issue, Lagarde et al. have published the first proposal to qualitatively assess non-monotonic dose response (NMDR) relationships for use in risk assessments. Their proposal represents a significant step forward in the evaluation of complex datasets for use in risk assessments. Here, we comment on three elements of the Lagarde proposal that we feel need to be assessed more critically and present our arguments: 1) the use of Klimisch scores to evaluate study quality, 2) the concept of evaluating study quality without topical experts' knowledge and opinions, and 3) the requirement of establishing the biological plausibility of an NMDR before consideration for use in risk assessment. We present evidence-based logical arguments that 1) the use of the Klimisch score should be abandoned for assessing study quality; 2) evaluating study quality requires experts in the specific field; and 3) an understanding of mechanisms should not be required to accept observable, statistically valid phenomena. It is our hope to contribute to the important and ongoing debate about the impact of NMDRs on risk assessment with positive suggestions.
Dose-response curve estimation: a semiparametric mixture approach.
Yuan, Ying; Yin, Guosheng
2011-12-01
In the estimation of a dose-response curve, parametric models are straightforward and efficient but subject to model misspecifications; nonparametric methods are robust but less efficient. As a compromise, we propose a semiparametric approach that combines the advantages of parametric and nonparametric curve estimates. In a mixture form, our estimator takes a weighted average of the parametric and nonparametric curve estimates, in which a higher weight is assigned to the estimate with a better model fit. When the parametric model assumption holds, the semiparametric curve estimate converges to the parametric estimate and thus achieves high efficiency; when the parametric model is misspecified, the semiparametric estimate converges to the nonparametric estimate and remains consistent. We also consider an adaptive weighting scheme to allow the weight to vary according to the local fit of the models. We conduct extensive simulation studies to investigate the performance of the proposed methods and illustrate them with two real examples. © 2011, The International Biometric Society.
DEFF Research Database (Denmark)
Beausoleil, Claire; Ormsby, Jean-Nicolas; Gies, Andreas
2013-01-01
A workshop was held in Berlin September 12–14th 2012 to assess the state of the science of the data supporting low dose effects and non-monotonic dose responses (“low dose hypothesis”) for chemicals with endocrine activity (endocrine disrupting chemicals or EDCs). This workshop consisted of lectu...
Maximum likelihood estimation for cytogenetic dose-response curves
International Nuclear Information System (INIS)
Frome, E.L; DuFrain, R.J.
1983-10-01
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[γd + g(t, tau)d 2 ], where t is the time and d is dose. The coefficient of the d 2 term is determined by the recovery function and the temporal mode of irradiation. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting models are intrinsically nonlinear in the parameters. A general purpose maximum likelihood estimation procedure is described and illustrated with numerical examples from both experimental designs. Poisson regression analysis is used for estimation, hypothesis testing, and regression diagnostics. Results are discussed in the context of exposure assessment procedures for both acute and chronic human radiation exposure
Maximum likelihood estimation for cytogenetic dose-response curves
International Nuclear Information System (INIS)
Frome, E.L.; DuFrain, R.J.
1986-01-01
In vitro dose-response curves are used to describe the relation between chromosome aberrations and radiation dose for human lymphocytes. The lymphocytes are exposed to low-LET radiation, and the resulting dicentric chromosome aberrations follow the Poisson distribution. The expected yield depends on both the magnitude and the temporal distribution of the dose. A general dose-response model that describes this relation has been presented by Kellerer and Rossi (1972, Current Topics on Radiation Research Quarterly 8, 85-158; 1978, Radiation Research 75, 471-488) using the theory of dual radiation action. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting dose-time-response models are intrinsically nonlinear in the parameters. A general-purpose maximum likelihood estimation procedure is described, and estimation for the nonlinear models is illustrated with numerical examples from both experimental designs. Poisson regression analysis is used for estimation, hypothesis testing, and regression diagnostics. Results are discussed in the context of exposure assessment procedures for both acute and chronic human radiation exposure
Maximum likelihood estimation for cytogenetic dose-response curves
Energy Technology Data Exchange (ETDEWEB)
Frome, E.L; DuFrain, R.J.
1983-10-01
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(..gamma..d + g(t, tau)d/sup 2/), where t is the time and d is dose. The coefficient of the d/sup 2/ term is determined by the recovery function and the temporal mode of irradiation. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting models are intrinsically nonlinear in the parameters. A general purpose maximum likelihood estimation procedure is described and illustrated with numerical examples from both experimental designs. Poisson regression analysis is used for estimation, hypothesis testing, and regression diagnostics. Results are discussed in the context of exposure assessment procedures for both acute and chronic human radiation exposure.
International Nuclear Information System (INIS)
Conolly, Rory B.; Gaylor, David W.; Lutz, Werner K.
2005-01-01
Carcinogen dose-response curves for both ionizing radiation and chemicals are typically assumed to be linear at environmentally relevant doses. This assumption is used to ensure protection of the public health in the absence of relevant dose-response data. A theoretical justification for the assumption has been provided by the argument that low dose linearity is expected when an exogenous agent adds to an ongoing endogenous process. Here, we use computational modeling to evaluate (1) how two biological adaptive processes, induction of DNA repair and cell cycle checkpoint control, may affect the shapes of dose-response curves for DNA-damaging carcinogens and (2) how the resulting dose-response behaviors may vary within a population. Each model incorporating an adaptive process was capable of generating not only monotonic dose-responses but also nonmonotonic (J-shaped) and threshold responses. Monte Carlo analysis suggested that all these dose-response behaviors could coexist within a population, as the spectrum of qualitative differences arose from quantitative changes in parameter values. While this analysis is largely theoretical, it suggests that (a) accurate prediction of the qualitative form of the dose-response requires a quantitative understanding of the mechanism (b) significant uncertainty is associated with human health risk prediction in the absence of such quantitative understanding and (c) a stronger experimental and regulatory focus on biological mechanisms and interindividual variability would allow flexibility in regulatory treatment of environmental carcinogens without compromising human health
Linear dose response curves in fungi and tradescantia
International Nuclear Information System (INIS)
Unrau, P.
1999-07-01
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
Linear dose response curves in fungi and tradescantia
Energy Technology Data Exchange (ETDEWEB)
Unrau, P. [Atomic Energy of Canada Ltd., Chalk River, Ontario (Canada)
1999-07-15
Tradescantia Clone 02 data suggests that linear non-threshold dose responses are expected to the lowest doses and dose rates of low linear energy transfer (LET) radiation. This is likely to be true for other living organisms even though Clone 02 is radiation sensitive. It is concluded that Clone 02 is partially defective in the RAD 6 pathway for the repair of DNA interstrand cross-links (ISCL) and other loss of coding damage (LCD), based on its cross sensitivities to EMS and ionizing radiation. Tradescantia Clone 02 data showing linear non-threshold induction of somatic genetic events in part reflects the repair deficiency of this Clone. More DNA damage is repaired by recombinational mechanisms in Clone 02 than would occur in a wild-type strain. Two important classes of DNA lesions are induced by ionizing radiation in DNA - double strand breaks (DSB) which are repaired by recombination mechanisms, and loss of coding information damage (LCD), which is repaired by error prone mechanisms but may also be a substrate for recombinational repair. Based on data from yeast, there are two different repair pathways which deal with these differing lesions with different somatic genetic consequences. From yeast, yield cross sections can be derived and applied to DNA damage and repair in Tradescantia. For Clone 02, per lesion, more visible genetic events are scored than in wild-type strains. In a radiation-derived sub-clone, Clone 0106, which is more variable than Clone 02, even more events occur per lesion. This derivative clone, plus breeding experiments, indicate that Clone 02 is heterozygous, or a 'carrier' for a mutant version of a gene in the Tradescantia RAD 6 repair pathway. Clone 02 is, therefore, much like a Fanconi's anemia carrier in a human population, while the Clone 0106 derivative is much like a homozygous Fanconi's anemia patient, with respect to its response to ionizing radiation damage. Two anomalies in its dose response curves for &apos
Dose response curves for effects of low-level radiation
International Nuclear Information System (INIS)
Myers, D.K.
1980-01-01
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)
Dose-response curves with semiochemicals are reported in many articles in insect chemical ecology regarding neurophysiology and behavioral bioassays. Most such curves are shown in figures where the x-axis has order of magnitude increases in dosages versus responses on the y-axis represented by point...
Franklin, Elda
1981-01-01
Reviews studies on the etiology of monotonism, the monotone being that type of uncertain or inaccurate singer who cannot vocally match pitches and who has trouble accurately reproducing even a familiar song. Neurological factors (amusia, right brain abnormalities), age, and sex differences are considered. (Author/SJL)
International Nuclear Information System (INIS)
Hoffmann, D.; Woda, C.; Mangini, A.
2003-01-01
The dose-response of the CO 2 - signal (g=2.0006) in foraminifera with ages between 19 and 300 ka is investigated. The sum of two exponential saturation functions is an adequate function to describe the dose-response curve up to an additional dose of 8000 Gy. It yields excellent dating results but requires an artificial doses of at least 5000 Gy. For small additional doses of about 500 Gy the single exponential saturation function can be used to calculate a reliable equivalent dose D E , although it does not describ the dose-response for higher doses. The CO 2 - -signal dose-response indicates that the signal has two components of which one is less stable than the other
Cytogenetics dosimetry: dose-response curve for low doses of X-ray
International Nuclear Information System (INIS)
Lara, Virginia E. Noval; Pineda Bolivar, William R.; Riano, Victor M. Pabon; Ureana, Cecilia Crane
2013-01-01
The purpose of this study was to conduct a preliminary study for the standardization in the future, the dose-response curve for low doses of X-rays, through the analysis of in vitro cultures of peripheral blood samples of 3 men and 3 women occupationally not exposed to artificial sources of ionizing radiation, age 18-40 years, where possible nonsmokers
Single-dose-response curves of murine gastrointestinal crypt stem cells
International Nuclear Information System (INIS)
Masuda, K.; Withers, H.R.; Mason, K.A.; Chen, K.Y.
1977-01-01
Dose-response curves for the reproductive capacity of crypt stem cells of murine colonic, jejunal, and gastric mucosae exposed in situ to multifractionated gamma ray exposures were analyzed and single-dose-survival curves of these cells were constructed. The following conclusions were drawn: (1) The single-dose-response curves bend downward over a dose range of approximately 200 to 1500 rad; (2) cell death seems to be due to nonrepairable damage at doses less than 250 rad for colon, and 220 rad for jejunum; (3) there are 21, 110, and 140 stem cells per crypt of gastric, colonic, and jejunal mucosa, respectively; and (4) jejunal stem cells are the most radiosensitive and gastric mucosal stem cells are the most resistant
Human evidence on the shape of the dose-response curves for radiation carcinogenesis
International Nuclear Information System (INIS)
Burkart, W.
1981-09-01
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.)
International Nuclear Information System (INIS)
Rungsimaphorn, B.; Rerkamnuaychoke, B.; Sudprasert, W.
2014-01-01
Establishing in-vitro dose calibration curves is important for reconstruction of radiation dose in the exposed individuals. The aim of this pioneering work in Thailand was to generate dose-response curves using conventional biological dosimetry: dicentric chromosome assay (DCA) and premature chromosome condensation (PCC) assay. The peripheral blood lymphocytes were irradiated with 137 Cs at a dose rate of 0.652 Gy/min to doses of 0.1, 0.25, 0.5, 0.75, 1, 2, 3, 4 and 5 Gy for DCA technique, and 5, 10, 15, 20 and 25 Gy for PCC technique. The blood samples were cultured and processed following the standard procedure given by the IAEA with slight modifications. At least 500-1,000 metaphases or 100 dicentrics/ PCC rings were analyzed using an automated metaphase finder system. The yield of dicentrics with dose was fitted to a linear quadratic model using Chromosome Aberration Calculation Software (CABAS, version 2.0), whereas the dose-response curve of PCC rings was fitted to a linear relationship. These curves will be useful for in-vitro dose reconstruction and can support the preparedness for radiological emergency in the country.
Dose-response curves for fish MFO induction: How do we interpret different maxima and slopes?
International Nuclear Information System (INIS)
Parrott, J.L.
1995-01-01
Induction of hepatic mixed function oxygenase (MFO) activity has been useful for screening effluents from pulp mills and oil refineries. Effluents and pure compounds can be assessed by direct fish exposure or by concentration with semipermeable membrane devices (SPMDs) and by measuring MFO in fish liver cell lines exposed to SPMD extracts. In these experiments, both fish and fish cells showed differences in slopes of dose-response curves, and in the maximal ethoxyresorufin-O-deethylase (EROD) activity. For example, TCDD elicits an EROD maxima of over 500 pmol/mg/min in PLHC-1 (Poeciliopsis lucida hepatocellular carcinoma cell line), while pulp mill and oil refinery effluent extracts showed maxima of 40 to 200 pmol/mg/min. Substituted phenanthrenes caused induction maxima of 100 pmol/mg/min. Similarly, in rainbow trout in vivo, TCDD and other chlorinated dioxins and furans induced up to 500 pmol/mg/min, whereas pulp mill and refinery effluents and substituted phenanthrenes produced EROD maxima of up to 100 pmol/mg/min. Differences in the slopes of dose-response curves were also common. In the current assessment of potencies, these diverse response curves are boiled-down to one number, the EC50 or other threshold-type of concentration. Comparisons of EC50s cannot express these differences and instead, ignore them. However, the authors realize there must be a better approach that takes into account these large differences in dose-response curve shape, slope and maxima. Interaction and discussions with modelers in the session will allow them to discuss various approaches to expressing the potencies of MFO inducers in fish
Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.
Carnicella, Sebastien; Yowell, Quinn V; Ron, Dorit
2011-01-01
Oral ethanol self-administration procedures in rats are useful preclinical tools for the evaluation of potential new pharmacotherapies as well as for the investigation into the etiology of alcohol abuse disorders and addiction. Determination of the effects of a potential treatment on a full ethanol dose-response curve should be essential to predict its clinical efficacy. Unfortunately, this approach has not been fully explored because of the aversive taste reaction to moderate to high doses of ethanol, which may interfere with consumption. In this study, we set out to determine whether a meaningful dose-response curve for oral ethanol self-administration can be obtained in rats. Long-Evans rats were trained to self-administer a 20% ethanol solution in an operant procedure following a history of excessive voluntary ethanol intake. After stabilization of ethanol self-administration, the concentration of the solution was varied from 2.5 to 60% (v/v), and operant and drinking behaviors, as well as blood ethanol concentration (BEC), were evaluated following the self-administration of a 20, 40, and 60% ethanol solution. Varying the concentration of ethanol from 2.5 to 60% after the development of excessive ethanol consumption led to a typical inverted U-shaped dose-response curve. Importantly, rats adapted their level and pattern of responding to changes in ethanol concentration to obtain a constant level of intake and BEC, suggesting that their operant behavior is mainly driven by the motivation to obtain a specific pharmacological effect of ethanol. This procedure can be a useful and straightforward tool for the evaluation of the effects of new potential pharmacotherapies for the treatment of alcohol abuse disorders. Copyright © 2010 by the Research Society on Alcoholism.
The shape of the cancer mortality dose-response curve for atomic bomb survivors
International Nuclear Information System (INIS)
Pierce, D.A.; Vaeth, M.
1989-10-01
The shape of the cancer mortality dose-response in the atomic bomb survivor data is analyzed in the context of linear-quadratic (LQ) models. Results are given for all cancers except leukemia as a group, for leukemia, and for combined inferences assuming common curvature. Since there is substantial information aside from these data suggesting a dose-response concave from above, the emphasis here is not on estimating the best-fitting dose-response curve, but rather on assessing the maximal extent of curvature under LQ models which is consistent with the data. Such inferences are substantially affected by imprecision in the dose estimates, and methods are applied which make explicit allowances for biases due to this. The primary means used here to express the extent of curvature is the factor by which linear risk estimates should be divided to arrive at appropriate low-dose risk estimates. In the past, influential committees have recommended ranges of 2-10 and of 1.5-3 for such a factor. Results here suggest that values greater than about 2 are at least moderately inconsistent with these data, within the context of LQ models. It is emphasized, however, that there is little direct information in these data regarding low-dose risks; the inferences here depend strongly on the link between low-dose and high-dose risks provided by the assumption of an LQ model. (author)
International Nuclear Information System (INIS)
Cristakou, H.D.
1983-01-01
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)
Biological dosimetry in radiological protection: dose response curves elaboration for 60Co and 137Cs
International Nuclear Information System (INIS)
Silva, Marcia Augusta da
1997-01-01
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 60 Co and 137 Cs 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 60 Co: Y = (3 46 +- 2.14)10 -4 cGy -1 + (3
Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.
2004-01-01
Exposure to heavy particles can affect the functioning of the central nervous system (CNS), particularly the dopaminergic system. In turn, the radiation-induced disruption of dopaminergic function affects a variety of behaviors that are dependent upon the integrity of this system, including motor behavior (upper body strength), amphetamine (dopamine)-mediated taste aversion learning, and operant conditioning (fixed-ratio bar pressing). Although the relationships between heavy particle irradiation and the effects of exposure depend, to some extent, upon the specific behavioral or neurochemical endpoint under consideration, a review of the available research leads to the hypothesis that the endpoints mediated by the CNS have certain characteristics in common. These include: (1) a threshold, below which there is no apparent effect; (2) the lack of a dose-response relationship, or an extremely steep dose-response curve, depending on the particular endpoint; and (3) the absence of recovery of function, such that the heavy particle-induced behavioral and neural changes are present when tested up to one year following exposure. The current report reviews the data relevant to the degree to which these characteristics are common to neurochemical and behavioral endpoints that are mediated by the effects of exposure to heavy particles on CNS activity.
International Nuclear Information System (INIS)
Sheehan, Daniel M.
2006-01-01
We tested the hypothesis that no threshold exists when estradiol acts through the same mechanism as an active endogenous estrogen. A Michaelis-Menten (MM) equation accounting for response saturation, background effects, and endogenous estrogen level fit a turtle sex-reversal data set with no threshold and estimated the endogenous dose. Additionally, 31 diverse literature dose-response data sets were analyzed by adding a term for nonhormonal background; good fits were obtained but endogenous dose estimations were not significant due to low resolving power. No thresholds were observed. Data sets were plotted using a normalized MM equation; all 178 data points were accommodated on a single graph. Response rates from ∼1% to >95% were well fit. The findings contradict the threshold assumption and low-dose safety. Calculating risk and assuming additivity of effects from multiple chemicals acting through the same mechanism rather than assuming a safe dose for nonthresholded curves is appropriate
Clinical application of Chamomilla recutita in phlebitis: dose response curve study.
Reis, Paula Elaine Diniz Dos; Carvalho, Emilia Campos de; Bueno, Paula Carolina Pires; Bastos, Jairo Kenupp
2011-01-01
This experimental and dose-response curve study aimed to carry out the quality control of the Chamomilla recutita sample, as well as to estimate the ideal dose, for anti-inflammatory effect, of the extract of its capitula, in patients with phlebitis due to peripheral intravenous infusion of antineoplastic chemotherapy and to evaluate the toxicity of this extract in human beings. The therapeutic efficacy, concerning the anti-inflammatory potential, of different doses of Chamomilla recutita extract were analyzed and compared in 25 patients. The time of regression of phlebitis was shorter for groups with 2.5% concentration (mean=29.2h, standard deviation = 8.98) and 5% concentration (mean = 38.8h, standard deviation = 17.47). Local toxicity was almost not observed. This research contributes to the innovation of the nursing clinical practice, since it suggests an alternative for the treatment of phlebitis through the clinical use of phytotherapeutic drugs.
Methods for extracting dose response curves from radiation therapy data. I. A unified approach
International Nuclear Information System (INIS)
Herring, D.F.
1980-01-01
This paper discusses an approach to fitting models to radiation therapy data in order to extract dose response curves for tumor local control and normal tissue damage. The approach is based on the method of maximum likelihood and is illustrated by several examples. A general linear logistic equation which leads to the Ellis nominal standard dose (NSD) equation is discussed; the fit of this equation to experimental data for mouse foot skin reactions produced by fractionated irradiation is described. A logistic equation based on the concept that normal tissue reactions are associated with the surviving fraction of cells is also discussed, and the fit of this equation to the same set of mouse foot skin reaction data is also described. These two examples illustrate the importance of choosing a model based on underlying mechanisms when one seeks to attach biological significance to a model's parameters
Mathematical modeling improves EC50 estimations from classical dose-response curves.
Nyman, Elin; Lindgren, Isa; Lövfors, William; Lundengård, Karin; Cervin, Ida; Sjöström, Theresia Arbring; Altimiras, Jordi; Cedersund, Gunnar
2015-03-01
The β-adrenergic response is impaired in failing hearts. When studying β-adrenergic function in vitro, the half-maximal effective concentration (EC50 ) is an important measure of ligand response. We previously measured the in vitro contraction force response of chicken heart tissue to increasing concentrations of adrenaline, and observed a decreasing response at high concentrations. The classical interpretation of such data is to assume a maximal response before the decrease, and to fit a sigmoid curve to the remaining data to determine EC50 . Instead, we have applied a mathematical modeling approach to interpret the full dose-response curve in a new way. The developed model predicts a non-steady-state caused by a short resting time between increased concentrations of agonist, which affect the dose-response characterization. Therefore, an improved estimate of EC50 may be calculated using steady-state simulations of the model. The model-based estimation of EC50 is further refined using additional time-resolved data to decrease the uncertainty of the prediction. The resulting model-based EC50 (180-525 nm) is higher than the classically interpreted EC50 (46-191 nm). Mathematical modeling thus makes it possible to re-interpret previously obtained datasets, and to make accurate estimates of EC50 even when steady-state measurements are not experimentally feasible. The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database, and may be accessed at http://jjj.bio.vu.nl/database/nyman. © 2015 FEBS.
Transformation-invariant and nonparametric monotone smooth estimation of ROC curves.
Du, Pang; Tang, Liansheng
2009-01-30
When a new diagnostic test is developed, it is of interest to evaluate its accuracy in distinguishing diseased subjects from non-diseased subjects. The accuracy of the test is often evaluated by receiver operating characteristic (ROC) curves. Smooth ROC estimates are often preferable for continuous test results when the underlying ROC curves are in fact continuous. Nonparametric and parametric methods have been proposed by various authors to obtain smooth ROC curve estimates. However, there are certain drawbacks with the existing methods. Parametric methods need specific model assumptions. Nonparametric methods do not always satisfy the inherent properties of the ROC curves, such as monotonicity and transformation invariance. In this paper we propose a monotone spline approach to obtain smooth monotone ROC curves. Our method ensures important inherent properties of the underlying ROC curves, which include monotonicity, transformation invariance, and boundary constraints. We compare the finite sample performance of the newly proposed ROC method with other ROC smoothing methods in large-scale simulation studies. We illustrate our method through a real life example. Copyright (c) 2008 John Wiley & Sons, Ltd.
International Nuclear Information System (INIS)
Chen Ying; Luo Yisheng; Cao Zhenshan; Liu Xiulin
2006-01-01
To estimate accurately biological dose of the victims exposed to high dose, the dose-response curves of chromosome aberration induced by 6-22 Gy 60 Co γ-ray were established. Human peripheral blood in vitro was irradiated, then lymphocytes were concentrated, cultured 52h, 68h and 72h and harvested. The frequencies of dicentrics (multi-centrics) and rings were counted and compared between different culture times. The dose-response curves and equations were established, as well as verified with high dose exposure accidents. The experiment showed that the culture time should be prolonged properly after high dose exposure, and no significant differences were observed between 52-72h culture. The dose-response curve of 6-22 Gy fitted to linear-square model Y=-2.269 + 0.776D - 7.868 x 10 -3 D 2 and is reliable through verification of the accident dose estimations. In this study, the dose-response curve and equation of chromosome dic + r after 6-22 Gy high dose irradiation were established firstly, and exact dose estimation can be achieved according to it. (authors)
Isochronous relaxation curves for type 304 stainless steel after monotonic and cyclic strain
International Nuclear Information System (INIS)
Swindeman, R.W.
1978-01-01
Relaxation tests to 100 hr were performed on type 304 stainless steel in the temperature range 480 to 650 0 C and were used to develop isochronous relaxation curves. Behavior after monotonic and cyclic strain was compared. Relaxation differed only slightly as a consequence of the type of previous strain, provided that plastic flow preceded the relaxation period. We observed that the short-time relaxation behavior did not manifest strong heat-to-heat variation in creep strength
Validation of dose-response calibration curve for X-Ray field of CRCN-NE/CNEN: preliminary results
International Nuclear Information System (INIS)
Silva, Laís Melo; Mendonç, Julyanne Conceição de Goes; Andrade, Aida Mayra Guedes de; Hwang, Suy F.; Mendes, Mariana Esposito; Lima, Fabiana F.; Melo, Ana Maria M.A.
2017-01-01
It is very important in accident investigations that accurate estimating of absorbed dose takes place, so that it contributes to medical decisions and overall assessment of long-term health consequences. Analysis of chromosome aberrations is the most developed method for biological monitoring, and frequencies of dicentric chromosomes are related to absorbed dose of human peripheral blood lymphocytes using calibration curves. International Atomic Energy Agency (IAEA) recommends that each biodosimetry laboratory sets its own calibration curves, given that there are intrinsic differences in protocols and dose interpretations when using calibration curves produced in other laboratories, which could add further uncertainties to dose estimations. The Laboratory for Biological Dosimetry CRCN-NE recently completed dose-response calibration curves for X ray field. Curves of chromosomes dicentrics and dicentrics plus rings were made using Dose Estimate. This study aimed to validate the calibration curves dose-response for X ray with three irradiated samples. Blood was obtained by venipuncture from healthy volunteer and three samples were irradiated by x-rays of 250 kVp with different absorbed doses (0,5Gy, 1Gy and 2Gy). The irradiation was performed at the CRCN-NE/CNEN Metrology Service with PANTAK X-ray equipment, model HF 320. The frequency of dicentric and centric rings chromosomes were determined in 500 metaphases per sample after cultivation of lymphocytes, and staining with Giemsa 5%. Results showed that the estimated absorbed doses are included in the confidence interval of 95% of real absorbed dose. These Dose-response calibration curves (dicentrics and dicentrics plus rings) seems valid, therefore other tests will be done with different volunteers. (author)
Validation of dose-response calibration curve for X-Ray field of CRCN-NE/CNEN: preliminary results
Energy Technology Data Exchange (ETDEWEB)
Silva, Laís Melo; Mendonç, Julyanne Conceição de Goes; Andrade, Aida Mayra Guedes de; Hwang, Suy F.; Mendes, Mariana Esposito; Lima, Fabiana F., E-mail: falima@cnen.gov.br, E-mail: mendes_sb@hotmail.com [Centro Regional de Ciências Nucleares, (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Melo, Ana Maria M.A., E-mail: july_cgm@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Vitória de Santo Antão, PE (Brazil). Centro Acadêmico de Vitória
2017-07-01
It is very important in accident investigations that accurate estimating of absorbed dose takes place, so that it contributes to medical decisions and overall assessment of long-term health consequences. Analysis of chromosome aberrations is the most developed method for biological monitoring, and frequencies of dicentric chromosomes are related to absorbed dose of human peripheral blood lymphocytes using calibration curves. International Atomic Energy Agency (IAEA) recommends that each biodosimetry laboratory sets its own calibration curves, given that there are intrinsic differences in protocols and dose interpretations when using calibration curves produced in other laboratories, which could add further uncertainties to dose estimations. The Laboratory for Biological Dosimetry CRCN-NE recently completed dose-response calibration curves for X ray field. Curves of chromosomes dicentrics and dicentrics plus rings were made using Dose Estimate. This study aimed to validate the calibration curves dose-response for X ray with three irradiated samples. Blood was obtained by venipuncture from healthy volunteer and three samples were irradiated by x-rays of 250 kVp with different absorbed doses (0,5Gy, 1Gy and 2Gy). The irradiation was performed at the CRCN-NE/CNEN Metrology Service with PANTAK X-ray equipment, model HF 320. The frequency of dicentric and centric rings chromosomes were determined in 500 metaphases per sample after cultivation of lymphocytes, and staining with Giemsa 5%. Results showed that the estimated absorbed doses are included in the confidence interval of 95% of real absorbed dose. These Dose-response calibration curves (dicentrics and dicentrics plus rings) seems valid, therefore other tests will be done with different volunteers. (author)
International Nuclear Information System (INIS)
Kars, Romee H.; Wallinga, Jakob
2009-01-01
We recently proposed a model that reconstructs the natural dose response curve for K-rich feldspars, using laboratory fading measurements and dose response as input parameters. The model is based on the relationship between recombination centre density and trap lifetime. In this study we test the working of the model by comparing modelled feldspar ages with known quartz OSL ages of the same samples and with anomalous fading-corrected feldspar ages. The modelled feldspar ages are in good agreement with quartz OSL ages and corrected feldspar ages, opening possibilities for future use of the model on samples without independent age constraints. Furthermore, we investigate the effects of trap competition on the build-up of IRSL signal using two new variations of the model. Results show that incorporating trap competition into the model reduces the agreement between feldspar IRSL ages and quartz OSL ages.
Biological dosimetry in radiation accidents. Dose-response curve by chromosomal aberrations analysis
International Nuclear Information System (INIS)
Hadjidekova, V.; Hristova, R.; Atanasova, P.; Popova, L.; Stainova, A.; Bulanova, M.; Georgieva, I.; Vukov, M.
2005-01-01
The aim of this paper is to obtain a dose-response relationship for chromosomal aberrations induced in human lymphocytes after in vitro irradiation. Peripheral blood samples of 7 different donors were used. The blood irradiation was done with Cs137 gamma-rays at different doses: 0.0, 0.05, 0.1, 0.25, 0.5, 0.75, 1.0, 1.5, 2.0 and 3.0 Gy. Lymphocyte cultures were established and maintain for 48 hours at 37 0 C in CO 2 incubator for chromosomal aberration analysis. The dose response relationship has been established based on dysenteric and ring chromosomes yield. The relationship can be described by the following equation: Y = 0.0274D + 0.0251 D 2 , where (Y) = dysenteric and ring chromosomes yield, (D) = radiation dose obtained. EXCEL software was established for calculation of the received dose by using this equation, as a whole body equivalent dose acute irradiation
A dose-response curve for biodosimetry from a 6 MV electron linear accelerator
Energy Technology Data Exchange (ETDEWEB)
Lemos-Pinto, M.M.P.; Cadena, M.; Santos, N.; Fernandes, T.S.; Borges, E.; Amaral, A., E-mail: marcelazoo@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Departamento de Energia Nuclear
2015-10-15
Biological dosimetry (biodosimetry) is based on the investigation of radiation-induced biological effects (biomarkers), mainly dicentric chromosomes, in order to correlate them with radiation dose. To interpret the dicentric score in terms of absorbed dose, a calibration curve is needed. Each curve should be constructed with respect to basic physical parameters, such as the type of ionizing radiation characterized by low or high linear energy transfer (LET) and dose rate. This study was designed to obtain dose calibration curves by scoring of dicentric chromosomes in peripheral blood lymphocytes irradiated in vitro with a 6 MV electron linear accelerator (Mevatron M, Siemens, USA). Two software programs, CABAS (Chromosomal Aberration Calculation Software) and Dose Estimate, were used to generate the curve. The two software programs are discussed; the results obtained were compared with each other and with other published low LET radiation curves. Both software programs resulted in identical linear and quadratic terms for the curve presented here, which was in good agreement with published curves for similar radiation quality and dose rates. (author)
A dose-response curve for biodosimetry from a 6 MV electron linear accelerator.
Lemos-Pinto, M M P; Cadena, M; Santos, N; Fernandes, T S; Borges, E; Amaral, A
2015-10-01
Biological dosimetry (biodosimetry) is based on the investigation of radiation-induced biological effects (biomarkers), mainly dicentric chromosomes, in order to correlate them with radiation dose. To interpret the dicentric score in terms of absorbed dose, a calibration curve is needed. Each curve should be constructed with respect to basic physical parameters, such as the type of ionizing radiation characterized by low or high linear energy transfer (LET) and dose rate. This study was designed to obtain dose calibration curves by scoring of dicentric chromosomes in peripheral blood lymphocytes irradiated in vitro with a 6 MV electron linear accelerator (Mevatron M, Siemens, USA). Two software programs, CABAS (Chromosomal Aberration Calculation Software) and Dose Estimate, were used to generate the curve. The two software programs are discussed; the results obtained were compared with each other and with other published low LET radiation curves. Both software programs resulted in identical linear and quadratic terms for the curve presented here, which was in good agreement with published curves for similar radiation quality and dose rates.
Confidence bounds for nonlinear dose-response relationships
DEFF Research Database (Denmark)
Baayen, C; Hougaard, P
2015-01-01
An important aim of drug trials is to characterize the dose-response relationship of a new compound. Such a relationship can often be described by a parametric (nonlinear) function that is monotone in dose. If such a model is fitted, it is useful to know the uncertainty of the fitted curve...... intervals for the dose-response curve. These confidence bounds have better coverage than Wald intervals and are more precise and generally faster than bootstrap methods. Moreover, if monotonicity is assumed, the profile likelihood approach takes this automatically into account. The approach is illustrated...
International Nuclear Information System (INIS)
Brandao, Jose Odinilson de C.; Souza, Priscilla L.G.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F.; Calixto, Merilane S.; Santos, Neide
2009-01-01
There is increasing concern about airline crew members (about one million worldwide) are exposed to measurable neutrons doses. Historically, cytogenetic biodosimetry assays have been based on quantifying asymmetrical chromosome alterations (dicentrics, centric rings and acentric fragments) in mytogen-stimulated T-lymphocytes in their first mitosis after radiation exposure. Increased levels of chromosome damage in peripheral blood lymphocytes are a sensitive indicator of radiation exposure and they are routinely exploited for assessing radiation absorbed dose after accidental or occupational exposure. Since radiological accidents are not common, not all nations feel that it is economically justified to maintain biodosimetry competence. However, dependable access to biological dosimetry capabilities is completely critical in event of an accident. In this paper the dose-response curve was measured for the induction of chromosomal alterations in peripheral blood lymphocytes after chronic exposure in vitro to neutron-gamma mixes field. Blood was obtained from one healthy donor and exposed to two neutron-gamma mixed field from sources 241 AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The evaluated absorbed doses were 0.2 Gy; 1.0 Gy and 2.5 Gy. The dicentric chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphase figures were analyzed for the presence of dicentrics by two experienced scorers after painted by giemsa 5%. Our preliminary results showed a linear dependence between radiations absorbed dose and dicentric chromosomes frequencies. Dose-response curve described in this paper will contribute to the construction of calibration curve that will be used in our laboratory for biological dosimetry. (author)
Energy Technology Data Exchange (ETDEWEB)
Brandao, Jose Odinilson de C.; Souza, Priscilla L.G.; Santos, Joelan A.L.; Vilela, Eudice C.; Lima, Fabiana F., E-mail: jodinilson@cnen.gov.b, E-mail: fflima@cnen.gov.b, E-mail: jasantos@cnen.gov.b [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Calixto, Merilane S.; Santos, Neide, E-mail: santos_neide@yahoo.com.b [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. de Genetica
2009-07-01
There is increasing concern about airline crew members (about one million worldwide) are exposed to measurable neutrons doses. Historically, cytogenetic biodosimetry assays have been based on quantifying asymmetrical chromosome alterations (dicentrics, centric rings and acentric fragments) in mytogen-stimulated T-lymphocytes in their first mitosis after radiation exposure. Increased levels of chromosome damage in peripheral blood lymphocytes are a sensitive indicator of radiation exposure and they are routinely exploited for assessing radiation absorbed dose after accidental or occupational exposure. Since radiological accidents are not common, not all nations feel that it is economically justified to maintain biodosimetry competence. However, dependable access to biological dosimetry capabilities is completely critical in event of an accident. In this paper the dose-response curve was measured for the induction of chromosomal alterations in peripheral blood lymphocytes after chronic exposure in vitro to neutron-gamma mixes field. Blood was obtained from one healthy donor and exposed to two neutron-gamma mixed field from sources {sup 241}AmBe (20 Ci) at the Neutron Calibration Laboratory (NCL-CRCN/NE-PE-Brazil). The evaluated absorbed doses were 0.2 Gy; 1.0 Gy and 2.5 Gy. The dicentric chromosomes were observed at metaphase, following colcemid accumulation and 1000 well-spread metaphase figures were analyzed for the presence of dicentrics by two experienced scorers after painted by giemsa 5%. Our preliminary results showed a linear dependence between radiations absorbed dose and dicentric chromosomes frequencies. Dose-response curve described in this paper will contribute to the construction of calibration curve that will be used in our laboratory for biological dosimetry. (author)
SU-E-T-96: Energy Dependence of the New GafChromic- EBT3 Film's Dose Response-Curve.
Chiu-Tsao, S; Massillon-Jl, G; Domingo-Muñoz, I; Chan, M
2012-06-01
To study and compare the dose response curves of the new GafChromic EBT3 film for megavoltage and kilovoltage x-ray beams, with different spatial resolution. Two sets of EBT3 films (lot#A101711-02) were exposed to each x-ray beam (6MV, 15MV and 50kV) at 8 dose values (50-3200cGy). The megavoltage beams were calibrated per AAPM TG-51 protocol while the kilovoltage beam was calibrated following the TG-61 using an ionization chamber calibrated at NIST. Each film piece was scanned three consecutive times in the center of Epson 10000XL flatbed scanner in transmission mode, landscape orientation, 48-bit color at two separate spatial resolutions of 75 and 300 dpi. The data were analyzed using ImageJ and, for each scanned image, a region of interest (ROI) of 2×2cm 2 at the field center was selected to obtain the mean pixel value with its standard deviation in the ROI. For each energy, dose value and spatial resolution, the average netOD and its associated uncertainty were determined. The Student's t-test was performed to evaluate the statistical differences between the netOD/dose values of the three energy modalities, with different color channels and spatial resolutions. The dose response curves for the three energy modalities were compared in three color channels with 75 and 300dpi. Weak energy dependence was found. For doses above 100cGy, no statistical differences were observed between 6 and 15MV beams, regardless of spatial resolution. However, statistical differences were observed between 50kV and the megavoltage beams. The degree of energy dependence (from MV to 50kV) was found to be function of color channel, dose level and spatial resolution. The dose response curves for GafChromic EBT3 films were found to be weakly dependent on the energy of the photon beams from 6MV to 50kV. The degree of energy dependence varies with color channel, dose and spatial resolution. GafChromic EBT3 films were supplied by Ashland Corp. This work was partially supported by DGAPA
Energy Technology Data Exchange (ETDEWEB)
Venkatachalam, P.; Paul, S.F.D.; Mohankumar, M.N.; Prabhu, B.K.; Gajendiran, N.; Jeevanram, R.K
2000-07-01
A translocation dose-response curve using a single pair of painted chromosomes was constructed. The translocation frequencies observed at different doses were compared to those obtained for dicentrics (DC) and micronuclei (MN). The translocation and DC frequency followed the Poisson distribution and MN showed over-dispersion. The translocation and DC frequencies were nearly the same for each dose point. Micronuclei showed a comparatively lower frequency. The alpha/beta ratio for translocations (0.916) and DC (0.974) were comparable, whereas the value for MN (1.526) was much higher. The equal frequencies of translocations and DC observed for a given dose indicated that genomic translocation frequency estimated using a single pair of painted chromosomes provides a reliable and easy method to measure translocation frequency. (autho000.
International Nuclear Information System (INIS)
Venkatachalam, P.; Paul, S.F.D.; Mohankumar, M.N.; Prabhu, B.K.; Gajendiran, N.; Jeevanram, R.K.
2000-01-01
A translocation dose-response curve using a single pair of painted chromosomes was constructed. The translocation frequencies observed at different doses were compared to those obtained for dicentrics (DC) and micronuclei (MN). The translocation and DC frequency followed the Poisson distribution and MN showed over-dispersion. The translocation and DC frequencies were nearly the same for each dose point. Micronuclei showed a comparatively lower frequency. The alpha/beta ratio for translocations (0.916) and DC (0.974) were comparable, whereas the value for MN (1.526) was much higher. The equal frequencies of translocations and DC observed for a given dose indicated that genomic translocation frequency estimated using a single pair of painted chromosomes provides a reliable and easy method to measure translocation frequency. (author)
International Nuclear Information System (INIS)
Chapot, M.S.; Roberts, H.M.; Duller, G.A.T.; Lai, Z.P.
2016-01-01
This study compares natural and laboratory generated thermally transferred optically stimulated luminescence (TT-OSL) dose response curves (DRCs) for fine-grain quartz extracts from the Luochuan loess section in central China. Both DRCs saturate at high doses relative to the quartz OSL signal; the natural TT-OSL DRC saturates at about 2200 Gy and laboratory DRCs saturate at about 2700 Gy. However, the natural and laboratory TT-OSL DRCs deviate from one another at circa 150 Gy resulting in TT-OSL equivalent dose underestimation relative to palaeodoses expected from dose rates and independent age control. The lifetime of the TT-OSL signal at 10 °C, calculated from values of trap parameters E and s, is compared against the value for lifetime of the TT-OSL signal in nature at average burial temperature as determined from the age underestimation caused by deviation of the natural and laboratory generated DRCs. These two independent assessments of TT-OSL signal lifetime at Luochuan give similar values, suggesting that laboratory measurements of thermal stability reflect natural burial lifetimes and can potentially be used to correct TT-OSL ages for the difference between natural and laboratory dose response curves. - Highlights: • Natural and laboratory TT-OSL DRCs deviate at ∼150 Gy but saturate at higher doses. • TT-OSL signal lifetime at 10 °C calculated from measured E and s values is ∼180 ka. • TT-OSL signal lifetime at Luochuan estimated from the DRCs' deviation is ∼175 ka. • Natural and laboratory TT-OSL DRC deviation may be caused by low thermal stability. • Laboratory measurements of signal lifetime may be able to correct old TT-OSL ages.
Biological effects in lymphocytes irradiated with 99mTc: determination of the curve dose-response
International Nuclear Information System (INIS)
Oliveira, Romero Marcilio Barros Matias de
2002-08-01
Biological dosimetry estimates the absorbed dose taking into account changes in biological parameters. The most used biological indicator of an exposition to ionizing radiation is the quantification of chromosomal aberrations of lymphocytes from irradiated individuals. The curves of dose versus induced biological effects, obtained through bionalyses, are used in used in retrospective evaluations of the dose, mainly in the case of accidents. In this research, a simple model for electrons and photons transports was idealized to simulate the irradiation of lymphocytes with 99m Tc, representing a system used for irradiation of blood cells. The objective of the work was to establish a curve of dose versus frequencies of chromosomal aberrations in lymphocytes of human blood. For the irradiation of blood samples micro spheres of human serum of albumin (HSAM) market with 99m Tc were used, allowing the irradiation of blood with different administered activities of 99m Tc, making possible the study the cytogenetical effects as a function of such activities. The conditions of irradiation in vivo using HSAM spheres marked with 99m Tc were simulated with MCNP 4C (Monte Carlo N-Particle) code to obtain the dose-response curve. Soft tissue composition was employed to simulate blood tissue and the analyses of the curve of dose versus biological effect showed a linear quadratic response of the unstable chromosomal aberrations. As a result, the response of dose versus chromosomal aberrations of blood irradiation with 99m Tc was best fitted by the curve Y=(8,99 ±2,06) x 1- -4 + (1,24 ±0,62) x 10 -2 D + (5,67 ± 0,64) x 10 -2 D 2 . (author)
Boobis, Alan; Flari, Villie; Gosling, John Paul; Hart, Andy; Craig, Peter; Rushton, Lesley; Idahosa-Taylor, Ehi
2013-07-01
The general approach to risk assessment of genotoxic carcinogens has been to advise reduction of exposure to "as low as reasonably achievable/practicable" (ALARA/P). However, whilst this remains the preferred risk management option, it does not provide guidance on the urgency or extent of risk management actions necessary. To address this, the "Margin of Exposure" (MOE) approach has been proposed. The MOE is the ratio between the point of departure for carcinogenesis and estimated human exposure. However, interpretation of the MOE requires implicit or explicit consideration of the shape of the dose-response curve at human relevant exposures. In a structured elicitation exercise, we captured expert opinion on available scientific evidence for low dose-response relationships for genotoxic carcinogens. This allowed assessment of: available evidence for the nature of dose-response relationships at human relevant exposures; the generality of judgments about such dose-response relationships; uncertainties affecting judgments on the nature of such dose-response relationships; and whether this last should differ for different classes of genotoxic carcinogens. Elicitation results reflected the variability in experts' views on the form of the dose-response curve for low dose exposure and major sources of uncertainty affecting the assumption of a linear relationship. Copyright © 2013 Elsevier Ltd. All rights reserved.
Energy Technology Data Exchange (ETDEWEB)
Lara, Virginia E. Noval; Pineda Bolivar, William R.; Riano, Victor M. Pabon, E-mail: venovall.15@hotmail.com, E-mail: wrpineda@misena.edu.co, E-mail: vmpabonr@udistrital.edu.co [Universidad Distrital Francisco Jose de Caldas (UD), Bogota (Colombia). Grupo de Investigacion en Ciencia y Tecnologia Nuclear; Ureana, Cecilia Crane, E-mail: cecicrane@yahoo.com [Instituto Nacional de Salud (INS), Bogota (Colombia). Laboratorio de Genetica
2013-07-01
The purpose of this study was to conduct a preliminary study for the standardization in the future, the dose-response curve for low doses of X-rays, through the analysis of in vitro cultures of peripheral blood samples of 3 men and 3 women occupationally not exposed to artificial sources of ionizing radiation, age 18-40 years, where possible nonsmokers.
International Nuclear Information System (INIS)
Mendonca, Julyanne C.G.; Mendes, Mariana E.; Hwang, Suy F.; Lima, Fabiana F.; Santos, Neide
2014-01-01
The cytogenetic study has the chromosomal alterations as biomarkers in absorbed dose estimation by the body of individuals involved in exposure to ionizing radiation by interpreting a dose response calibration curve. Since the development of the technique to the analysis of data, you can see protocol characteristics, leading the International Atomic Energy Agency indicate that any laboratory with intention to carry out biological dosimetry establish their own calibration curves. The Biological Dosimetry Laboratory of the Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN), Brazil, recently established the calibration curve related to gamma radiation ( 60 Co). Thus, this work aimed to start the validation of this calibration curve from samples of three different blood donors which were irradiated with an absorbed known single dose of 1 Gy. Samples were exposed to 60 Co source (Glaucoma 220) located in the Department of Nuclear Energy (DEN/UFPE). After fixation with methanol and acetic acid and 5% Giemsa staining, the frequency of chromosomal alterations (dicentric chromosomes, acentric rings and fragments) were established from reading of 500 metaphases per sample and doses were estimated using Dose Estimate program. The results showed that, using the dose-response curve calibration for dicentrics, the dose absorbed estimated for the three individuals ranged from 0.891 - 1,089Gy, taking into account the range of confidence of 95%. By using the dose-response curve for dicentrics added to rings and for the same interval of confidence the doses ranged from 0,849 - 1,081Gy. Thus, the estimative encompassed known absorbed dose the three individuals in confidence interval of 95%. These preliminary results seems to demonstrate that dicentric dose-response curves and dicentrics plus rings established by CRCN-NE / CNEN are valid for dose estimation in exposed individuals. This validation will continue with samples from different individuals at different doses
Paterna, Salvatore; Di Gaudio, Francesca; La Rocca, Vincenzo; Balistreri, Fabio; Greco, Massimiliano; Torres, Daniele; Lupo, Umberto; Rizzo, Giuseppina; di Pasquale, Pietro; Indelicato, Sergio; Cuttitta, Francesco; Butler, Javed; Parrinello, Gaspare
2015-10-01
14% for urine output; 29, 24, and 16% for total sodium excretion; 45, 34, and 20% for urinary osmolarity; and 27, 36, and 32% for total furosemide excretion in groups 1, 2, and 3, respectively. These findings were translated in an improvement in the furosemide dose-response curves in these patients. These results may serve as new pathophysiological basis for HSS use in the treatment of refractory CHF.
Energy Technology Data Exchange (ETDEWEB)
Jo, Wol Soon; Oh, Su Jung; Jeong, Soo Kyun; Yang, Kwang Mo [Dept. of Research center, Dong Nam Institute of Radiological and Medical Sciences, Busan (Korea, Republic of); Jeong, Min Ho [Dept. of Microbiology, Dong A University College of Medicine, Busan (Korea, Republic of)
2012-11-15
Recently, the increased threat of radiologically industrial accident such as radiation nondestructive inspection or destruction of nuclear accident by natural disaster such as Fukushima accident requires a greater capacity for cytogenetic biodosimetry, which is critical for clinical triage of potentially thousands of radiation-exposed individuals. Dicentric chromosome aberration analysis is the conventional means of assessing radiation exposure. Dose–response calibration curves for {sup 13}'7Cs gamma rays have been established for unstable chromosome aberrations in human peripheral blood lymphocytes in many laboratories of international biodosimetry network. In this study, therefore, we established dose– response calibration curves of our laboratory for {sup 137}Cs gamma raysaccording to the IAEA protocols for conducting the dicentric chromosome assay We established in vitro dose–response calibration curves for dicentric chromosome aberrations in human lymphocytes for{sup 13}'7Cs gamma rays in the 0 to 5 Gy range, using the maximum likelihood linear-quadratic model, Y = c+αD+βD2. The estimated coefficients of the fitted curves were within the 95% confidence intervals (CIs) and the curve fitting of dose–effect relationship data indicated a good fit to the linear-quadratic model. Hence, meaningful dose estimation from unknown sample can be determined accurately by using our laboratory’s calibration curve according to standard protocol.
International Nuclear Information System (INIS)
Mendonça, J.C.G.; Mendes, M.E.; Melo, A.M.M.A.; Silva, L.M.; Andrade, A.M.G.; Hwang, S.F.; Lima, F.F.
2017-01-01
Since the discovery of ionizing radiation, and consequently of its properties, there has been an increasing in its use, which in turn has raised concerns about the biological damage that it could cause in exposed individuals. As a result, cytogenetic dosimetry has emerged: a method that can be used as a complement or, in the absence of physical dosimetry, relating the frequency of chromosomal changes found in the blood of the exposed individual and the dose absorbed through dose-response calibration curves. This work aimed to verify the frequencies of the unstable chromosomal changes in human blood lymphocytes irradiated by X-rays of 250 kVp with different absorbed doses and later establish the dose-response calibration curves. The irradiation was performed at the CRCN-NE/CNEN-PE, Brazil metrology service on a PANTAK X-ray machine, model HF 320. The blood samples had their lymphocytes cultured in culture media and, after the processing, the metaphases were obtained. The chromosomal alterations analyzed were chromosomes dicentric, ring and isolated actinic fragments. There was an increase in frequencies of all chromosomal changes with increased absorbed dose. The calibration curves of dicentric and dicentric + rings presented good adjustments with the values of the coefficients Y = 0.0013 + 0.0271D + 0.0556D 2 (X 2 = 10.36 / GL = 6) and Y = 0.0013 + 0.0263D + 0.0640D 2 (X 2 = 7.43 / GL = 6), respectively. The establishment of these curves enables the Laboratory of Biological Dosimetry of the CRCN/NE/CNEN-PE to estimate the dose absorbed by occupationally exposed individuals and in cases of radiological accidents
International Nuclear Information System (INIS)
Gao Jinsheng; Zheng Siying; Bao Hong
1992-06-01
The dose-effect relationship of premature condensed chromosome fragments in human lymphocytes irradiated by 60 Co gamma ray was studied by PCC method (premature condensed chromosomes). In addition, The conventional cellular genetics method was also used in the study. The response curve of both methods can represented by two linear equations. The ratio of two slopes, K PCC /K M1 , is about 28. Comparing with conventional method, the PCC method has many advantages such as faster, simpler, more sensitive and accurate. The PCC method used in the studying of radiation damage is also discussed
International Nuclear Information System (INIS)
Wilkins, T.A.; Chadney, D.C.; Bryant, J.; Palmstroem, S.H.; Winder, R.L.
1977-01-01
Using the simple univalent antigen univalent-antibody equilibrium model the dose-response curve of a radioimmunoassay (RIA) may be expressed as a function of Y, X and the four physical parameters of the idealised system. A compact but powerful mini-computer program has been written in BASIC for rapid iterative non-linear least squares curve fitting and dose interpolation with this function. In its simplest form the program can be operated in an 8K byte mini-computer. The program has been extensively tested with data from 10 different assay systems (RIA and CPBA) for measurement of drugs and hormones ranging in molecular size from thyroxine to insulin. For each assay system the results have been analysed in terms of (a) curve fitting biases and (b) direct comparison with manual fitting. In all cases the quality of fitting was remarkably good in spite of the fact that the chemistry of each system departed significantly from one or more of the assumptions implicit in the model used. A mathematical analysis of departures from the model's principal assumption has provided an explanation for this somewhat unexpected observation. The essential features of this analysis are presented in this paper together with the statistical analyses of the performance of the program. From these and the results obtained to date in the routine quality control of these 10 assays, it is concluded that the method of curve fitting and dose interpolation presented in this paper is likely to be of general applicability. (orig.) [de
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Serna Berna, A.; Alcaraz, M.; Acevedo, C.; Vicente, V.; Fuente, I. de la; Canteras, M.
2006-07-01
The determination of the dose-response curve is a crucial step to use the Micronucleus assay in Lymphocytes as a biological dosimeters. The most widely used fitting function is the linear-quadratic function. The coefficients are fitted by calibration data provided by irradiations of blood from healthy donors. In our case we performed the calibration curve corresponding to gamma radiation from Cesium-137 (660 keV). Doses ranged from 0 to 16 Gy. The fitting procedure used was the iteratively re weighted least square algorithm implemented in a Matlab routine. The results of the analysis of our data show that the dose-effect curve does not follow a linear-quadratic curve at high radiation doses, diminishing the quadratic parameters as dose increases. This can be interpreted as a micronucleus saturation effect beyond a certain dose level. We conclude that the MN assay with lymphocytes can be well characterized as a biological dosimeters up to a maximum dose of 4.5 Gy. (Author)
Zuardi, Antonio W; Rodrigues, Natália P; Silva, Angélica L; Bernardo, Sandra A; Hallak, Jaime E C; Guimarães, Francisco S; Crippa, José A S
2017-01-01
The purpose of this study was to investigate whether the anxiolytic effect of cannabidiol (CBD) in humans follows the same pattern of an inverted U-shaped dose-effect curve observed in many animal studies. Sixty healthy subjects of both sexes aged between 18 and 35 years were randomly assigned to five groups that received placebo, clonazepam (1 mg), and CBD (100, 300, and 900 mg). The subjects were underwent a test of public speaking in a real situation (TPSRS) where each subject had to speak in front of a group formed by the remaining participants. Each subject completed the anxiety and sedation factors of the Visual Analog Mood Scale and had their blood pressure and heart rate recorded. These measures were obtained in five experimental sessions with 12 volunteers each. Each session had four steps at the following times (minutes) after administration of the drug/placebo, as time 0: -5 (baseline), 80 (pre-test), 153 (speech), and 216 (post-speech). Repeated-measures analyses of variance showed that the TPSRS increased the subjective measures of anxiety, heart rate, and blood pressure. Student-Newman-Keuls test comparisons among the groups in each phase showed significant attenuation in anxiety scores relative to the placebo group in the group treated with clonazepam during the speech phase, and in the clonazepam and CBD 300 mg groups in the post-speech phase. Clonazepam was more sedative than CBD 300 and 900 mg and induced a smaller increase in systolic and diastolic blood pressure than CBD 300 mg. The results confirmed that the acute administration of CBD induced anxiolytic effects with a dose-dependent inverted U-shaped curve in healthy subjects, since the subjective anxiety measures were reduced with CBD 300 mg, but not with CBD 100 and 900 mg, in the post-speech phase.
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Antonio W. Zuardi
2017-05-01
Full Text Available The purpose of this study was to investigate whether the anxiolytic effect of cannabidiol (CBD in humans follows the same pattern of an inverted U-shaped dose-effect curve observed in many animal studies. Sixty healthy subjects of both sexes aged between 18 and 35 years were randomly assigned to five groups that received placebo, clonazepam (1 mg, and CBD (100, 300, and 900 mg. The subjects were underwent a test of public speaking in a real situation (TPSRS where each subject had to speak in front of a group formed by the remaining participants. Each subject completed the anxiety and sedation factors of the Visual Analog Mood Scale and had their blood pressure and heart rate recorded. These measures were obtained in five experimental sessions with 12 volunteers each. Each session had four steps at the following times (minutes after administration of the drug/placebo, as time 0: -5 (baseline, 80 (pre-test, 153 (speech, and 216 (post-speech. Repeated-measures analyses of variance showed that the TPSRS increased the subjective measures of anxiety, heart rate, and blood pressure. Student-Newman-Keuls test comparisons among the groups in each phase showed significant attenuation in anxiety scores relative to the placebo group in the group treated with clonazepam during the speech phase, and in the clonazepam and CBD 300 mg groups in the post-speech phase. Clonazepam was more sedative than CBD 300 and 900 mg and induced a smaller increase in systolic and diastolic blood pressure than CBD 300 mg. The results confirmed that the acute administration of CBD induced anxiolytic effects with a dose-dependent inverted U-shaped curve in healthy subjects, since the subjective anxiety measures were reduced with CBD 300 mg, but not with CBD 100 and 900 mg, in the post-speech phase.
International Nuclear Information System (INIS)
Kaplan, R.W.
1978-01-01
Strain CV of Serratia marcescens mutates by UV with high frequency to 3 groups of mutants (w, h, s) differing in colour from the red wild-type. The mutational dose-response curve has a curvature corresponding to about 3 hits. It reaches a peak and declines at high doses. Inactivation curves have a broad shoulder and mostly, but not always, a break to a lesser slope at UV doses near the peak of mutations. Photo reactivation (PR) gives a dose reduction of about 2 for both inactivation and mutation including the break and peak. The dose curve with PR for w-mutations shows 1 hit-, the other types 2-hit curvature leading to a change of mutation spectrum with dose due to PR. The UV-sensitive mutant uvs21 of CV has a survival curve with a small shoulder and a long upward concavity without a break, and the mutation curve is of the one-hit type without a peak and decline. PR gives a dose reduction of 12 for inactivation and of 7.5 for mutation. The 3-hit mutation curve of CV is interpreted by assuming that 2 further hits are required to protect the 1-hit pre-mutations from being abolished by the repair lacking in uvs21. UV induction of SOS repair cannot be responsible for the 3-hit curvature because UVR of phages and induction of prophage are already saturated at rather low doses. As high-dose decline is not observed in uvs21, possibly the non-mutagenic repair lacking from uvs21 interferes with the mutation finishing processes at high doses in the repair-proficient strain CV. However, UV induction of this interference cannot be a one-hit process but requires a very large number of hits. (Auth.)
International Nuclear Information System (INIS)
Underbrink, A.G.; Kellerer, A.M.; Mills, R.E.; Sparrow, A.H.; Brookhaven National Lab., Upton, N.Y.
1976-01-01
Microdosimetric data indicate that the mean specific energy, xi, produced by individual charged particles from X rays and gamma rays is different for the two radiation qualities by nearly a factor of two. In order to test whether this influences the initial, linear component in the dose-effect relations, a comparison was made between dose-response curves for pink somatic mutations in Tradescantia clone 02 stamen hairs following X and gamma irradiations. Absorbed doses ranged from 2.66 to 300 rad. The results are in agreement with predictions made on the basis of microdosimetric data. At low doses gamma rays are substantially less effective than X rays. The RBE of gamma rays vs. X rays at low doses was approximately 0.6, a value lower than those usually reported in other experimental systems. (orig.) [de
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Mendes, Mariana E.; Mendonça, Julyanne C.G.; Andrade, Aida M.G.; Silva, Laís M.; Hwang, Suy; Melo, Ana M.M.A.; Santos, Neide; Lima, Fabiana F., E-mail: mendes_sb@hotmail.com [Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil)
2017-11-01
Biodosimetry represents a biological marker to the estimation of health risks after accidental overexposure to ionizing radiation. Chromosomal dicentric in peripheral blood lymphocytes have been the most reliable biomarker of exposure to IR during the last several decades. This technique could be used to support physical dosimetry or when it is impossible to achieve it. A reliable measurement of the absorbed dose is critical for medical decision, including the assessment of long-term health consequences. The aim of this research is to compare dose-response curves for dicentric aberration induced in human lymphocytes by {sup 60}Co and X-Rays. For both quality of radiation, the samples were exposed to at least eight different absorbed doses. The X-rays with dose rate of 0,275 Gy/min at Laboratory of Metrology (CRCN/NE - PE - Brazil) and the second one was exposed to cobalt source with dose rate of 0.055 Gy/min ({sup 60}Co Gammacell 220) located at Department of Nuclear Energy (UFPE-DEN-BRASIL). Mitotic metaphase cells were obtained by lymphocyte culture for chromosomal analysis and slides were stained with Giemsa 5%. The frequencies of dicentrics were counted in more than 18.000 metaphases for this comparison. After that, all frequencies and distributions of dicentrics were tested to analyze their conformity with Poisson distribution and then each quality of radiation were used for build the calibration curves using Dose Estimate program. These results showed that both curves followed the Poisson distribution and coefficients of each one are: YX-rays = 0,0013 (± 0,0006) + 0,0271 (± 0,0086)⁎D + 0,0556(±0,0050))⁎D{sup 2} and Y{sub Co-60} = 0,0014 (± 0,0010) + 0,0081 (± 0,0073))⁎D + 0,0451 (± 0,0046))⁎D{sup 2} (Y = frequency of dicentrics and D = absorbed dose). It was expected that there was no significant difference between this two types of radiation because both were low LET. We believed that dose rate have been a principal factor to produce this
Aurioles-López, Verónica; Polo-López, M. Inmaculada; Fernández-Ibáñez, Pilar; López-Malo, Aurelio; Bandala, Erick R.
2016-02-01
The inactivation of Fusarium solani in water was assessed by solar driven Fenton-like processes using three different iron salts: ferric acetylacetonate (Fe(acac)3), ferric chloride (FeCl3) and ferrous sulfate (FeSO4). The experimental conditions tested were [Fe] ≈ 5 mg L-1, [H2O2] ≈ 10 mg L-1 and [Fe] ≈ 10 mg L-1; [H2O2] ≈ 20 mg L-1 mild and high, respectively, and pH 3.0 and 5.0, under solar radiation. The highest inactivation rates were observed at high reaction conditions for the three iron salts tested at pH 5.0 with less than 3.0 kJ L-1 of accumulate energy (QUV) to achieve over 99.9% of F. solani inactivation. Fe(acac)3 was the best iron salt to accomplishing F. solani inactivation. The modified Fermi equation was used to fix the experimental inactivation, data showed it was helpful for modeling the process, adequately describing dose-response curves. Inactivation process using FeSO4 at pH 3.0 was modeled fairly with r2 = 0.98 and 0.99 (mild and high concentration, respectively). Fe(acac)3, FeCl3 and FeSO4 at high concentration (i.e. [Fe] ≈ 10 mg L-1; [H2O2] ≈ 20 mg L-1) and pH 5.0 showed the highest fitting values (r2 = 0.99). Iron salt type showed a remarkable influence on the Fenton-like inactivation process.
Dose-response meta-analysis of differences in means
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Alessio Crippa
2016-08-01
Full Text Available Abstract Background Meta-analytical methods are frequently used to combine dose-response findings expressed in terms of relative risks. However, no methodology has been established when results are summarized in terms of differences in means of quantitative outcomes. Methods We proposed a two-stage approach. A flexible dose-response model is estimated within each study (first stage taking into account the covariance of the data points (mean differences, standardized mean differences. Parameters describing the study-specific curves are then combined using a multivariate random-effects model (second stage to address heterogeneity across studies. Results The method is fairly general and can accommodate a variety of parametric functions. Compared to traditional non-linear models (e.g. E max, logistic, spline models do not assume any pre-specified dose-response curve. Spline models allow inclusion of studies with a small number of dose levels, and almost any shape, even non monotonic ones, can be estimated using only two parameters. We illustrated the method using dose-response data arising from five clinical trials on an antipsychotic drug, aripiprazole, and improvement in symptoms in shizoaffective patients. Using the Positive and Negative Syndrome Scale (PANSS, pooled results indicated a non-linear association with the maximum change in mean PANSS score equal to 10.40 (95 % confidence interval 7.48, 13.30 observed for 19.32 mg/day of aripiprazole. No substantial change in PANSS score was observed above this value. An estimated dose of 10.43 mg/day was found to produce 80 % of the maximum predicted response. Conclusion The described approach should be adopted to combine correlated differences in means of quantitative outcomes arising from multiple studies. Sensitivity analysis can be a useful tool to assess the robustness of the overall dose-response curve to different modelling strategies. A user-friendly R package has been developed to facilitate
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Mendonca, Julyanne C.G.; Mendes, Mariana E.; Hwang, Suy F.; Lima, Fabiana F. [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Santos, Neide, E-mail: july_cgm@yahoo.com.br [Universidade Federal de Pernambuco (CCB/UFPE), Recife, PE (Brazil). Departamento de Genetica
2014-07-01
The cytogenetic study has the chromosomal alterations as biomarkers in absorbed dose estimation by the body of individuals involved in exposure to ionizing radiation by interpreting a dose response calibration curve. Since the development of the technique to the analysis of data, you can see protocol characteristics, leading the International Atomic Energy Agency indicate that any laboratory with intention to carry out biological dosimetry establish their own calibration curves. The Biological Dosimetry Laboratory of the Centro Regional de Ciencias Nucleares (CRCN-NE/CNEN), Brazil, recently established the calibration curve related to gamma radiation ({sup 60}Co). Thus, this work aimed to start the validation of this calibration curve from samples of three different blood donors which were irradiated with an absorbed known single dose of 1 Gy. Samples were exposed to {sup 60}Co source (Glaucoma 220) located in the Department of Nuclear Energy (DEN/UFPE). After fixation with methanol and acetic acid and 5% Giemsa staining, the frequency of chromosomal alterations (dicentric chromosomes, acentric rings and fragments) were established from reading of 500 metaphases per sample and doses were estimated using Dose Estimate program. The results showed that, using the dose-response curve calibration for dicentrics, the dose absorbed estimated for the three individuals ranged from 0.891 - 1,089Gy, taking into account the range of confidence of 95%. By using the dose-response curve for dicentrics added to rings and for the same interval of confidence the doses ranged from 0,849 - 1,081Gy. Thus, the estimative encompassed known absorbed dose the three individuals in confidence interval of 95%. These preliminary results seems to demonstrate that dicentric dose-response curves and dicentrics plus rings established by CRCN-NE / CNEN are valid for dose estimation in exposed individuals. This validation will continue with samples from different individuals at different doses.
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Feng Liu
2017-10-01
Full Text Available Abstract Background It is important to quantify the dose response for a drug in phase 2a clinical trials so the optimal doses can then be selected for subsequent late phase trials. In a phase 2a clinical trial of new lead drug being developed for the treatment of rheumatoid arthritis (RA, a U-shaped dose response curve was observed. In the light of this result further research was undertaken to design an efficient phase 2a proof of concept (PoC trial for a follow-on compound using the lessons learnt from the lead compound. Methods The planned analysis for the Phase 2a trial for GSK123456 was a Bayesian Emax model which assumes the dose-response relationship follows a monotonic sigmoid “S” shaped curve. This model was found to be suboptimal to model the U-shaped dose response observed in the data from this trial and alternatives approaches were needed to be considered for the next compound for which a Normal dynamic linear model (NDLM is proposed. This paper compares the statistical properties of the Bayesian Emax model and NDLM model and both models are evaluated using simulation in the context of adaptive Phase 2a PoC design under a variety of assumed dose response curves: linear, Emax model, U-shaped model, and flat response. Results It is shown that the NDLM method is flexible and can handle a wide variety of dose-responses, including monotonic and non-monotonic relationships. In comparison to the NDLM model the Emax model excelled with higher probability of selecting ED90 and smaller average sample size, when the true dose response followed Emax like curve. In addition, the type I error, probability of incorrectly concluding a drug may work when it does not, is inflated with the Bayesian NDLM model in all scenarios which would represent a development risk to pharmaceutical company. The bias, which is the difference between the estimated effect from the Emax and NDLM models and the simulated value, is comparable if the true dose response
Liu, Feng; Walters, Stephen J; Julious, Steven A
2017-10-02
It is important to quantify the dose response for a drug in phase 2a clinical trials so the optimal doses can then be selected for subsequent late phase trials. In a phase 2a clinical trial of new lead drug being developed for the treatment of rheumatoid arthritis (RA), a U-shaped dose response curve was observed. In the light of this result further research was undertaken to design an efficient phase 2a proof of concept (PoC) trial for a follow-on compound using the lessons learnt from the lead compound. The planned analysis for the Phase 2a trial for GSK123456 was a Bayesian Emax model which assumes the dose-response relationship follows a monotonic sigmoid "S" shaped curve. This model was found to be suboptimal to model the U-shaped dose response observed in the data from this trial and alternatives approaches were needed to be considered for the next compound for which a Normal dynamic linear model (NDLM) is proposed. This paper compares the statistical properties of the Bayesian Emax model and NDLM model and both models are evaluated using simulation in the context of adaptive Phase 2a PoC design under a variety of assumed dose response curves: linear, Emax model, U-shaped model, and flat response. It is shown that the NDLM method is flexible and can handle a wide variety of dose-responses, including monotonic and non-monotonic relationships. In comparison to the NDLM model the Emax model excelled with higher probability of selecting ED90 and smaller average sample size, when the true dose response followed Emax like curve. In addition, the type I error, probability of incorrectly concluding a drug may work when it does not, is inflated with the Bayesian NDLM model in all scenarios which would represent a development risk to pharmaceutical company. The bias, which is the difference between the estimated effect from the Emax and NDLM models and the simulated value, is comparable if the true dose response follows a placebo like curve, an Emax like curve, or log
Heckman, James J; Pinto, Rodrigo
2018-01-01
This paper defines and analyzes a new monotonicity condition for the identification of counterfactuals and treatment effects in unordered discrete choice models with multiple treatments, heterogenous agents and discrete-valued instruments. Unordered monotonicity implies and is implied by additive separability of choice of treatment equations in terms of observed and unobserved variables. These results follow from properties of binary matrices developed in this paper. We investigate conditions under which unordered monotonicity arises as a consequence of choice behavior. We characterize IV estimators of counterfactuals as solutions to discrete mixture problems.
Dose/response relationships and policy formulation
International Nuclear Information System (INIS)
Robinson, P.D.
1981-01-01
The ICRP 26 cost/benefit approach to establishing operational radiation protection guidelines is discussed. The purpose is to aid the policy maker in the decision making process, using as a basis the dose-response curve
Yamada, Tomohide; Shojima, Nobuhiro; Yamauchi, Toshimasa; Kadowaki, Takashi
2016-01-01
Adequate sleep is important for good health, but it is not always easy to achieve because of social factors. Daytime napping is widely prevalent around the world. We performed a meta-analysis to investigate the association between napping (or excessive daytime sleepiness: EDS) and the risk of type 2 diabetes or metabolic syndrome, and to quantify the potential dose-response relation using cubic spline models. Electronic databases were searched for articles published up to 2016, with 288,883 Asian and Western subjects. Pooled analysis revealed that a long nap (≥60 min/day) and EDS were each significantly associated with an increased risk of type 2 diabetes versus no nap or no EDS (odds ratio 1.46 (95% CI 1.23–1.74, p nap and 2.00 (1.58–2.53) for EDS). In contrast, a short nap (nap time and the risk of diabetes or metabolic syndrome, with no effect of napping up to about 40 minutes/day, followed by a sharp increase in risk at longer nap times. In summary, longer napping is associated with an increased risk of metabolic disease. Further studies are needed to confirm the benefit of a short nap. PMID:27909305
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Shuai Chang
Full Text Available This study was designed to identify common HIV-1 mutation complexes affecting the slope of inhibition curve, and to propose a new parameter incorporating both the IC50 and the slope to evaluate phenotypic resistance.Utilizing site-directed mutagenesis, we constructed 22 HIV-1 common mutation complexes. IC50 and slope of 10 representative approved drugs and a novel agent against these mutations were measured to determine the resistance phenotypes. The values of new parameter incorporating both the IC50 and the slope of the inhibition curve were calculated, and the correlations between parameters were assessed.Depending on the class of drug, there were intrinsic differences in how the resistance mutations affected the drug parameters. All of the mutations resulted in large increases in the IC50s of nucleoside reverse transcriptase inhibitors. The effects of the mutations on the slope were the most apparent when examining their effects on the inhibition of non-nucleoside reverse transcriptase inhibitors and protease inhibitors. For example, some mutations, such as V82A, had no effect on IC50, but reduced the slope. We proposed a new concept, termed IIPatoxic, on the basis of IC50, slope and the maximum limiting concentrations of the drug. The IIPatoxic values of 10 approved drugs and 1 novel agent were calculated, and were closely related to the IIPmax values (r > 0.95, p < 0.001.This study confirms that resistance mutations cannot be accurately assessed by IC50 alone, because it tends to underestimate the degree of resistance. The slope parameter is of very importance in the measurement of drug resistance and the effect can be applied to more complex patterns of resistance. This is the most apparent when testing the effects of the mutations on protease inhibitors activity. We also propose a new index, IIPatoxic, which incorporates both the IC50 and the slope. This new index could complement current IIP indices, thereby enabling predict the
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Oliveira, Romero Marcilio Barros Matias de
2002-08-01
Biological dosimetry estimates the absorbed dose taking into account changes in biological parameters. The most used biological indicator of an exposition to ionizing radiation is the quantification of chromosomal aberrations of lymphocytes from irradiated individuals. The curves of dose versus induced biological effects, obtained through bionalyses, are used in used in retrospective evaluations of the dose, mainly in the case of accidents. In this research, a simple model for electrons and photons transports was idealized to simulate the irradiation of lymphocytes with {sup 99m} Tc, representing a system used for irradiation of blood cells. The objective of the work was to establish a curve of dose versus frequencies of chromosomal aberrations in lymphocytes of human blood. For the irradiation of blood samples micro spheres of human serum of albumin (HSAM) market with {sup 99m} Tc were used, allowing the irradiation of blood with different administered activities of {sup 99m} Tc, making possible the study the cytogenetical effects as a function of such activities. The conditions of irradiation in vivo using HSAM spheres marked with {sup 99m} Tc were simulated with MCNP 4C (Monte Carlo N-Particle) code to obtain the dose-response curve. Soft tissue composition was employed to simulate blood tissue and the analyses of the curve of dose versus biological effect showed a linear quadratic response of the unstable chromosomal aberrations. As a result, the response of dose versus chromosomal aberrations of blood irradiation with {sup 99m} Tc was best fitted by the curve Y=(8,99 {+-}2,06) x 1-{sup -4} + (1,24 {+-}0,62) x 10{sup -2} D + (5,67 {+-} 0,64) x 10{sup -2} D{sup 2}. (author)
Experimental data and dose-response models
International Nuclear Information System (INIS)
Ullrich, R.L.
1985-01-01
Dose-response relationships for radiation carcinogenesis have been of interest to biologists, modelers, and statisticians for many years. Despite his interest there are few instances in which there are sufficient experimental data to allow the fitting of various dose-response models. In those experimental systems for which data are available the dose-response curves for tumor induction for the various systems cannot be described by a single model. Dose-response models which have been observed following acute exposures to gamma rays include threshold, quadratic, and linear models. Data on sex, age, and environmental influences of dose suggest a strong role of host factors on the dose response. With decreasing dose rate the effectiveness of gamma ray irradiation tends to decrease in essentially every instance. In those cases in which the high dose rate dose response could be described by a quadratic model, the effect of dose rate is consistent with predictions based on radiation effects on the induction of initial events. Whether the underlying reasons for the observed dose-rate effect is a result of effects on the induction of initial events or is due to effects on the subsequent steps in the carcinogenic process is unknown. Information on the dose response for tumor induction for high LET (linear energy transfer) radiations such as neutrons is even more limited. The observed dose and dose rate data for tumor induction following neutron exposure are complex and do not appear to be consistent with predictions based on models for the induction of initial events
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André Luiz de Souza Lacerda
2004-01-01
. The herbicide glyphosate, inhibitor of the enzyme EPSPs, was used at rate 0.0; 11.3; 22.5; 45; 90; 180; 360; 720 and 1440 g.ha-1 a.i. Curves of dose-response were made by the adjustment of the equation of the collected data of green biomass using the log-logistic model: Y = C+D-C / 1 + Exp{b[log(x-log(RC50]}, calculated by the no linear statistical model through the SAS statistical program. After the determination of the dose-response curves for the species mentioned above the Bidens pilosa was considered the most susceptible weed to glyphosate, showing the houvest RC50 (31.86 g.ha-1 a.i.. The species Tridax procumbens, Digitaria insularis, Spermacoce latifolia, Ipomoea grandifolia and Commelina benghalensis obtained RC50 equal to 58.40; 128.50; 250.44; 615.49 and > 1440.00 g.ha-1 a.i., respectively, what means that the necessary amount of herbicide to reduce in 50% the green biomass was 1.83; 4.03; 7.86; 19.31 and >359.56 times higher in relation the Bidens pilosa.
Single toxin dose-response models revisited
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Demidenko, Eugene, E-mail: eugened@dartmouth.edu [Department of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Hanover, NH03756 (United States); Glaholt, SP, E-mail: sglaholt@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States); Kyker-Snowman, E, E-mail: ek2002@wildcats.unh.edu [Department of Natural Resources and the Environment, University of New Hampshire, Durham, NH03824 (United States); Shaw, JR, E-mail: joeshaw@indiana.edu [Indiana University, School of Public & Environmental Affairs, Bloomington, IN47405 (United States); Chen, CY, E-mail: Celia.Y.Chen@dartmouth.edu [Department of Biological Sciences, Dartmouth College, Hanover, NH03755 (United States)
2017-01-01
The goal of this paper is to offer a rigorous analysis of the sigmoid shape single toxin dose-response relationship. The toxin efficacy function is introduced and four special points, including maximum toxin efficacy and inflection points, on the dose-response curve are defined. The special points define three phases of the toxin effect on mortality: (1) toxin concentrations smaller than the first inflection point or (2) larger then the second inflection point imply low mortality rate, and (3) concentrations between the first and the second inflection points imply high mortality rate. Probabilistic interpretation and mathematical analysis for each of the four models, Hill, logit, probit, and Weibull is provided. Two general model extensions are introduced: (1) the multi-target hit model that accounts for the existence of several vital receptors affected by the toxin, and (2) model with a nonzero mortality at zero concentration to account for natural mortality. Special attention is given to statistical estimation in the framework of the generalized linear model with the binomial dependent variable as the mortality count in each experiment, contrary to the widespread nonlinear regression treating the mortality rate as continuous variable. The models are illustrated using standard EPA Daphnia acute (48 h) toxicity tests with mortality as a function of NiCl or CuSO{sub 4} toxin. - Highlights: • The paper offers a rigorous study of a sigmoid dose-response relationship. • The concentration with highest mortality rate is rigorously defined. • A table with four special points for five morality curves is presented. • Two new sigmoid dose-response models have been introduced. • The generalized linear model is advocated for estimation of sigmoid dose-response relationship.
Monotone piecewise bicubic interpolation
International Nuclear Information System (INIS)
Carlson, R.E.; Fritsch, F.N.
1985-01-01
In a 1980 paper the authors developed a univariate piecewise cubic interpolation algorithm which produces a monotone interpolant to monotone data. This paper is an extension of those results to monotone script C 1 piecewise bicubic interpolation to data on a rectangular mesh. Such an interpolant is determined by the first partial derivatives and first mixed partial (twist) at the mesh points. Necessary and sufficient conditions on these derivatives are derived such that the resulting bicubic polynomial is monotone on a single rectangular element. These conditions are then simplified to a set of sufficient conditions for monotonicity. The latter are translated to a system of linear inequalities, which form the basis for a monotone piecewise bicubic interpolation algorithm. 4 references, 6 figures, 2 tables
International Nuclear Information System (INIS)
Korshunov, A D
2003-01-01
Monotone Boolean functions are an important object in discrete mathematics and mathematical cybernetics. Topics related to these functions have been actively studied for several decades. Many results have been obtained, and many papers published. However, until now there has been no sufficiently complete monograph or survey of results of investigations concerning monotone Boolean functions. The object of this survey is to present the main results on monotone Boolean functions obtained during the last 50 years
Dose-Response Calculator for ArcGIS
Hanser, Steven E.; Aldridge, Cameron L.; Leu, Matthias; Nielsen, Scott E.
2011-01-01
The Dose-Response Calculator for ArcGIS is a tool that extends the Environmental Systems Research Institute (ESRI) ArcGIS 10 Desktop application to aid with the visualization of relationships between two raster GIS datasets. A dose-response curve is a line graph commonly used in medical research to examine the effects of different dosage rates of a drug or chemical (for example, carcinogen) on an outcome of interest (for example, cell mutations) (Russell and others, 1982). Dose-response curves have recently been used in ecological studies to examine the influence of an explanatory dose variable (for example, percentage of habitat cover, distance to disturbance) on a predicted response (for example, survival, probability of occurrence, abundance) (Aldridge and others, 2008). These dose curves have been created by calculating the predicted response value from a statistical model at different levels of the explanatory dose variable while holding values of other explanatory variables constant. Curves (plots) developed using the Dose-Response Calculator overcome the need to hold variables constant by using values extracted from the predicted response surface of a spatially explicit statistical model fit in a GIS, which include the variation of all explanatory variables, to visualize the univariate response to the dose variable. Application of the Dose-Response Calculator can be extended beyond the assessment of statistical model predictions and may be used to visualize the relationship between any two raster GIS datasets (see example in tool instructions). This tool generates tabular data for use in further exploration of dose-response relationships and a graph of the dose-response curve.
Dose response relationship and Alara
International Nuclear Information System (INIS)
Hubert, P.
1986-09-01
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
Dose-response relationships for carcinogens: a review
International Nuclear Information System (INIS)
Zeise, L.; Wilson, R.; Crouch, E.A.C.
1987-01-01
The authors review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Their major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so they pay special attention to experimentally observed and theoretically expected nonlinearities. There are few experimental examples of nonlinear dose-response relations in humans, but this may simply be due to the limitations in the data. The several examples in rodents, even though for high dose data, suggest that nonlinearity is common. In some cases such nonlinearities may be rationalized on the basis of the pharmacokinetics of the test compound or its metabolites
Statistical and low dose response
International Nuclear Information System (INIS)
Thorson, M.R.; Endres, G.W.R.
1981-01-01
The low dose response and the lower limit of detection of the Hanford dosimeter depend upon may factors, including the energy of the radiation, whether the exposure is to be a single radiation or mixed fields, annealing cycles, environmental factors, and how well various batches of TLD materials are matched in the system. A careful statistical study and sensitivity analysis were performed to determine how these factors influence the response of the dosimeter system. Estimates have been included in this study of the standard deviation of calculated dose for various mixed field exposures from 0 to 1000 mrem
Energy Technology Data Exchange (ETDEWEB)
Mendonça, J.C.G.; Mendes, M.E.; Melo, A.M.M.A., E-mail: july_cgm@yahoo.com.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Silva, L.M.; Andrade, A.M.G.; Hwang, S.F.; Lima, F.F. [Centro Regional de Ciências Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil). Lab. de Dosimetria Biológica
2017-07-01
Since the discovery of ionizing radiation, and consequently of its properties, there has been an increasing in its use, which in turn has raised concerns about the biological damage that it could cause in exposed individuals. As a result, cytogenetic dosimetry has emerged: a method that can be used as a complement or, in the absence of physical dosimetry, relating the frequency of chromosomal changes found in the blood of the exposed individual and the dose absorbed through dose-response calibration curves. This work aimed to verify the frequencies of the unstable chromosomal changes in human blood lymphocytes irradiated by X-rays of 250 kVp with different absorbed doses and later establish the dose-response calibration curves. The irradiation was performed at the CRCN-NE/CNEN-PE, Brazil metrology service on a PANTAK X-ray machine, model HF 320. The blood samples had their lymphocytes cultured in culture media and, after the processing, the metaphases were obtained. The chromosomal alterations analyzed were chromosomes dicentric, ring and isolated actinic fragments. There was an increase in frequencies of all chromosomal changes with increased absorbed dose. The calibration curves of dicentric and dicentric + rings presented good adjustments with the values of the coefficients Y = 0.0013 + 0.0271D + 0.0556D{sup 2} (X{sup 2} = 10.36 / GL = 6) and Y = 0.0013 + 0.0263D + 0.0640D{sup 2} (X{sup 2} = 7.43 / GL = 6), respectively. The establishment of these curves enables the Laboratory of Biological Dosimetry of the CRCN/NE/CNEN-PE to estimate the dose absorbed by occupationally exposed individuals and in cases of radiological accidents.
Bayesian Dose-Response Modeling in Sparse Data
Kim, Steven B.
This book discusses Bayesian dose-response modeling in small samples applied to two different settings. The first setting is early phase clinical trials, and the second setting is toxicology studies in cancer risk assessment. In early phase clinical trials, experimental units are humans who are actual patients. Prior to a clinical trial, opinions from multiple subject area experts are generally more informative than the opinion of a single expert, but we may face a dilemma when they have disagreeing prior opinions. In this regard, we consider compromising the disagreement and compare two different approaches for making a decision. In addition to combining multiple opinions, we also address balancing two levels of ethics in early phase clinical trials. The first level is individual-level ethics which reflects the perspective of trial participants. The second level is population-level ethics which reflects the perspective of future patients. We extensively compare two existing statistical methods which focus on each perspective and propose a new method which balances the two conflicting perspectives. In toxicology studies, experimental units are living animals. Here we focus on a potential non-monotonic dose-response relationship which is known as hormesis. Briefly, hormesis is a phenomenon which can be characterized by a beneficial effect at low doses and a harmful effect at high doses. In cancer risk assessments, the estimation of a parameter, which is known as a benchmark dose, can be highly sensitive to a class of assumptions, monotonicity or hormesis. In this regard, we propose a robust approach which considers both monotonicity and hormesis as a possibility. In addition, We discuss statistical hypothesis testing for hormesis and consider various experimental designs for detecting hormesis based on Bayesian decision theory. Past experiments have not been optimally designed for testing for hormesis, and some Bayesian optimal designs may not be optimal under a
A method to adjust radiation dose-response relationships for clinical risk factors
DEFF Research Database (Denmark)
Appelt, Ane Lindegaard; Vogelius, Ivan R
2012-01-01
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...
Czech Academy of Sciences Publication Activity Database
Jeřábek, Emil
2012-01-01
Roč. 58, č. 3 (2012), s. 177-187 ISSN 0942-5616 R&D Projects: GA AV ČR IAA100190902; GA MŠk(CZ) 1M0545 Institutional support: RVO:67985840 Keywords : proof complexity * monotone sequent calculus Subject RIV: BA - General Mathematics Impact factor: 0.376, year: 2012 http://onlinelibrary.wiley.com/doi/10.1002/malq.201020071/full
Radiation dose response of strand breaks in SINPV-DNA
International Nuclear Information System (INIS)
Zhang Chunxiang; Luo Daling; Li Mianfeng; Liu Xiaowei; Zeng Rong; Wang Xunzhang
1995-01-01
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
Matching by Monotonic Tone Mapping.
Kovacs, Gyorgy
2018-06-01
In this paper, a novel dissimilarity measure called Matching by Monotonic Tone Mapping (MMTM) is proposed. The MMTM technique allows matching under non-linear monotonic tone mappings and can be computed efficiently when the tone mappings are approximated by piecewise constant or piecewise linear functions. The proposed method is evaluated in various template matching scenarios involving simulated and real images, and compared to other measures developed to be invariant to monotonic intensity transformations. The results show that the MMTM technique is a highly competitive alternative of conventional measures in problems where possible tone mappings are close to monotonic.
BIMOND3, Monotone Bivariate Interpolation
International Nuclear Information System (INIS)
Fritsch, F.N.; Carlson, R.E.
2001-01-01
1 - Description of program or function: BIMOND is a FORTRAN-77 subroutine for piecewise bi-cubic interpolation to data on a rectangular mesh, which reproduces the monotonousness of the data. A driver program, BIMOND1, is provided which reads data, computes the interpolating surface parameters, and evaluates the function on a mesh suitable for plotting. 2 - Method of solution: Monotonic piecewise bi-cubic Hermite interpolation is used. 3 - Restrictions on the complexity of the problem: The current version of the program can treat data which are monotone in only one of the independent variables, but cannot handle piecewise monotone data
Dose Response of Alanine Detectors Irradiated with Carbon Ion Beams
DEFF Research Database (Denmark)
Herrmann, Rochus; Jäkel, Oliver; Palmans, Hugo
2011-01-01
Purpose: The dose response of the alanine detector shows a dependence on particle energy and type, when irradiated with ion beams. The purpose of this study is to investigate the response behaviour of the alanine detector in clinical carbon ion beams and compare the results with model predictions......-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 quasi mono energetic measurements. Deviations in depth-dose measurements are mainly attributed to uncertainties...
Optimal Monotone Drawings of Trees
He, Dayu; He, Xin
2016-01-01
A monotone drawing of a graph G is a straight-line drawing of G such that, for every pair of vertices u,w in G, there exists abpath P_{uw} in G that is monotone in some direction l_{uw}. (Namely, the order of the orthogonal projections of the vertices of P_{uw} on l_{uw} is the same as the order they appear in P_{uw}.) The problem of finding monotone drawings for trees has been studied in several recent papers. The main focus is to reduce the size of the drawing. Currently, the smallest drawi...
Dose-response analysis using R
DEFF Research Database (Denmark)
Ritz, Christian; Baty, Florent; Streibig, Jens Carl
2015-01-01
Dose-response analysis can be carried out using multi-purpose commercial statistical software, but except for a few special cases the analysis easily becomes cumbersome as relevant, non-standard output requires manual programming. The extension package drc for the statistical environment R provides...
Dose-response-a challenge for allelopathy?
Belz, Regina G; Hurle, Karl; Duke, Stephen O
2005-04-01
The response of an organism to a chemical depends, among other things, on the dose. Nonlinear dose-response relationships occur across a broad range of research fields, and are a well established tool to describe the basic mechanisms of phytotoxicity. The responses of plants to allelochemicals as biosynthesized phytotoxins, relate as well to nonlinearity and, thus, allelopathic effects can be adequately quantified by nonlinear mathematical modeling. The current paper applies the concept of nonlinearity to assorted aspects of allelopathy within several bioassays and reveals their analysis by nonlinear regression models. Procedures for a valid comparison of effective doses between different allelopathic interactions are presented for both, inhibitory and stimulatory effects. The dose-response applications measure and compare the responses produced by pure allelochemicals [scopoletin (7-hydroxy-6-methoxy-2H-1-benzopyran-2-one); DIBOA (2,4-dihydroxy-2H-1,4-benzoxaxin-3(4H)-one); BOA (benzoxazolin-2(3H)-one); MBOA (6-methoxy-benzoxazolin-2(3H)-one)], involved in allelopathy of grain crops, to demonstrate how some general principles of dose responses also relate to allelopathy. Hereupon, dose-response applications with living donor plants demonstrate the validity of these principles for density-dependent phytotoxicity of allelochemicals produced and released by living plants (Avena sativa L., Secale cereale L., Triticum L. spp.), and reveal the use of such experiments for initial considerations about basic principles of allelopathy. Results confirm that nonlinearity applies to allelopathy, and the study of allelopathic effects in dose-response experiments allows for new and challenging insights into allelopathic interactions.
Some hybrid models applicable to dose-response relationships
International Nuclear Information System (INIS)
Kumazawa, Shigeru
1992-01-01
A new type of models of dose-response relationships has been studied as an initial stage to explore a reliable extrapolation of the relationships decided by high dose data to the range of low dose covered by radiation protection. The approach is to use a 'hybrid scale' of linear and logarithmic scales; the first model is that the normalized surviving fraction (ρ S > 0) in a hybrid scale decreases linearly with dose in a linear scale, and the second is that the induction in a log scale increases linearly with the normalized dose (τ D > 0) in a hybrid scale. The hybrid scale may reflect an overall effectiveness of a complex system against adverse events caused by various agents. Some data of leukemia in the atomic bomb survivors and of rodent experiments were used to show the applicability of hybrid scale models. The results proved that proposed models fit these data not less than the popular linear-quadratic models, providing the possible interpretation of shapes of dose-response curves, e.g. shouldered survival curves varied by recovery time. (author)
Dose response relationship in anti-stress gene regulatory networks.
Zhang, Qiang; Andersen, Melvin E
2007-03-02
To maintain a stable intracellular environment, cells utilize complex and specialized defense systems against a variety of external perturbations, such as electrophilic stress, heat shock, and hypoxia, etc. Irrespective of the type of stress, many adaptive mechanisms contributing to cellular homeostasis appear to operate through gene regulatory networks that are organized into negative feedback loops. In general, the degree of deviation of the controlled variables, such as electrophiles, misfolded proteins, and O2, is first detected by specialized sensor molecules, then the signal is transduced to specific transcription factors. Transcription factors can regulate the expression of a suite of anti-stress genes, many of which encode enzymes functioning to counteract the perturbed variables. The objective of this study was to explore, using control theory and computational approaches, the theoretical basis that underlies the steady-state dose response relationship between cellular stressors and intracellular biochemical species (controlled variables, transcription factors, and gene products) in these gene regulatory networks. Our work indicated that the shape of dose response curves (linear, superlinear, or sublinear) depends on changes in the specific values of local response coefficients (gains) distributed in the feedback loop. Multimerization of anti-stress enzymes and transcription factors into homodimers, homotrimers, or even higher-order multimers, play a significant role in maintaining robust homeostasis. Moreover, our simulation noted that dose response curves for the controlled variables can transition sequentially through four distinct phases as stressor level increases: initial superlinear with lesser control, superlinear more highly controlled, linear uncontrolled, and sublinear catastrophic. Each phase relies on specific gain-changing events that come into play as stressor level increases. The low-dose region is intrinsically nonlinear, and depending on
Dose response relationship in anti-stress gene regulatory networks.
Directory of Open Access Journals (Sweden)
Qiang Zhang
2007-03-01
Full Text Available To maintain a stable intracellular environment, cells utilize complex and specialized defense systems against a variety of external perturbations, such as electrophilic stress, heat shock, and hypoxia, etc. Irrespective of the type of stress, many adaptive mechanisms contributing to cellular homeostasis appear to operate through gene regulatory networks that are organized into negative feedback loops. In general, the degree of deviation of the controlled variables, such as electrophiles, misfolded proteins, and O2, is first detected by specialized sensor molecules, then the signal is transduced to specific transcription factors. Transcription factors can regulate the expression of a suite of anti-stress genes, many of which encode enzymes functioning to counteract the perturbed variables. The objective of this study was to explore, using control theory and computational approaches, the theoretical basis that underlies the steady-state dose response relationship between cellular stressors and intracellular biochemical species (controlled variables, transcription factors, and gene products in these gene regulatory networks. Our work indicated that the shape of dose response curves (linear, superlinear, or sublinear depends on changes in the specific values of local response coefficients (gains distributed in the feedback loop. Multimerization of anti-stress enzymes and transcription factors into homodimers, homotrimers, or even higher-order multimers, play a significant role in maintaining robust homeostasis. Moreover, our simulation noted that dose response curves for the controlled variables can transition sequentially through four distinct phases as stressor level increases: initial superlinear with lesser control, superlinear more highly controlled, linear uncontrolled, and sublinear catastrophic. Each phase relies on specific gain-changing events that come into play as stressor level increases. The low-dose region is intrinsically nonlinear
Dose-response relationship in clinical oncology
International Nuclear Information System (INIS)
Gehan, E.A.
1984-01-01
The relationship of dose (and dose rate) to response and toxicity in clinical oncology is reviewed. The concepts expressed by some authors in dose-response studies in animal and human systems are reviewed briefly. Dose rate and tactics of conducting clinical studies are reviewed for both radiotherapy and various types of chemotherapeutic treatment. Examples are given from clinical studies in Hodgkin's disease, acute leukemia, and breast cancer that may prove useful in planning future clinical studies
International Nuclear Information System (INIS)
Metz, C.E.; Tokars, R.P.; Kronman, H.B.; Griem, M.L.
1982-01-01
A Therapeutic Operating Characteristic (TOC) curve for radiation therapy plots, for all possible treatment doses, the probability of tumor ablation as a function of the probability of radiation-induced complication. Application of this analysis to actual therapeutic situation requires that dose-response curves for ablation and for complication be estimated from clinical data. We describe an approach in which ''maximum likelihood estimates'' of these dose-response curves are made, and we apply this approach to data collected on responses to radiotherapy for carcinoma of the nasopharynx. TOC curves constructed from the estimated dose-response curves are subject to moderately large uncertainties because of the limitations of available data.These TOC curves suggest, however, that treatment doses greater than 1800 rem may substantially increase the probability of tumor ablation with little increase in the risk of radiation-induced cervical myelopathy, especially for T1 and T2 tumors
Monotonicity of social welfare optima
DEFF Research Database (Denmark)
Hougaard, Jens Leth; Østerdal, Lars Peter Raahave
2010-01-01
This paper considers the problem of maximizing social welfare subject to participation constraints. It is shown that for an income allocation method that maximizes a social welfare function there is a monotonic relationship between the incomes allocated to individual agents in a given coalition...
Skull base chordomas: analysis of dose-response characteristics
International Nuclear Information System (INIS)
Niemierko, Andrzej; Terahara, Atsuro; Goitein, Michael
1997-01-01
Objective: To extract dose-response characteristics from dose-volume histograms and corresponding actuarial survival statistics for 115 patients with skull base chordomas. Materials and Methods: We analyzed data for 115 patients with skull base chordoma treated with combined photon and proton conformal radiotherapy to doses in the range 66.6Gy - 79.2Gy. Data set for each patient included gender, histology, age, tumor volume, prescribed dose, overall treatment time, time to recurrence or time to last observation, target dose-volume histogram, and several dosimetric parameters (minimum/mean/median/maximum target dose, percent of the target volume receiving the prescribed dose, dose to 90% of the target volume, and the Equivalent Uniform Dose (EUD). Data were analyzed using the Kaplan-Meier survivor function estimate, the proportional hazards (Cox) model, and parametric modeling of the actuarial probability of recurrence. Parameters of dose-response characteristics were obtained using the maximum likelihood method. Results: Local failure developed in 42 (36%) of patients, with actuarial local control rates at 5 years of 59.2%. The proportional hazards model revealed significant dependence of gender on the probability of recurrence, with female patients having significantly poorer prognosis (hazard ratio of 2.3 with the p value of 0.008). The Wilcoxon and the log-rank tests of the corresponding Kaplan-Meier recurrence-free survival curves confirmed statistical significance of this effect. The Cox model with stratification by gender showed significance of tumor volume (p=0.01), the minimum target dose (p=0.02), and the EUD (p=0.02). Other parameters were not significant at the α level of significance of 0.05, including the prescribed dose (p=0.21). Parametric analysis using a combined model of tumor control probability (to account for non-uniformity of target dose distribution) and the Weibull failure time model (to account for censoring) allowed us to estimate
The Dose Response Relationship for Radiation Carcinogenesis
Hall, Eric
2008-03-01
Recent surveys show that the collective population radiation dose from medical procedures in the U.S. has increased by 750% in the past two decades. It would be impossible to imagine the practice of medicine today without diagnostic and therapeutic radiology, but nevertheless the widespread and rapidly increasing use of a modality which is a known human carcinogen is a cause for concern. To assess the magnitude of the problem it is necessary to establish the shape of the dose response relationship for radiation carcinogenesis. Information on radiation carcinogenesis comes from the A-bomb survivors, from occupationally exposed individuals and from radiotherapy patients. The A-bomb survivor data indicates a linear relationship between dose and the risk of solid cancers up to a dose of about 2.5 Sv. The lowest dose at which there is a significant excess cancer risk is debatable, but it would appear to be between 40 and 100 mSv. Data from the occupation exposure of nuclear workers shows an excess cancer risk at an average dose of 19.4 mSv. At the other end of the dose scale, data on second cancers in radiotherapy patients indicates that cancer risk does not continue to rise as a linear function of dose, but tends towards a plateau of 40 to 60 Gy, delivered in a fractionated regime. These data can be used to estimate the impact of diagnostic radiology at the low dose end of the dose response relationship, and the impact of new radiotherapy modalities at the high end of the dose response relationship. In the case of diagnostic radiology about 90% of the collective population dose comes from procedures (principally CT scans) which involve doses at which there is credible evidence of an excess cancer incidence. While the risk to the individual is small and justified in a symptomatic patient, the same is not true of some screening procedures is asymptomatic individuals, and in any case the huge number of procedures must add up to a potential public health problem. In the
DEFF Research Database (Denmark)
Appelt, A. L.; Ploen, J.; Vogelius, I. R.
2013-01-01
estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination...... of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect...... of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D-50,D-i, and the normalized dose-response gradient, gamma(50,i). Results: A highly...
Generalized monotone operators in Banach spaces
International Nuclear Information System (INIS)
Nanda, S.
1988-07-01
The concept of F-monotonicity was first introduced by Kato and this generalizes the notion of monotonicity introduced by Minty. The purpose of this paper is to define various types of F-monotonicities and discuss the relationships among them. (author). 6 refs
Dose-response characteristics of an amorphous silicon EPID
International Nuclear Information System (INIS)
Winkler, Peter; Hefner, Alfred; Georg, Dietmar
2005-01-01
Electronic portal imaging devices (EPIDs) were originally developed for the purpose of patient setup verification. Nowadays, they are increasingly used as dosimeters (e.g., for IMRT verification and linac-specific QA). A prerequisite for any clinical dosimetric application is a detailed understanding of the detector's dose-response behavior. The aim of this study is to investigate the dosimetric properties of an amorphous silicon EPID (Elekta IVIEWGT) with respect to three photon beam qualities: 6, 10, and 25 MV. The EPID showed an excellent temporal stability on short term as well as on long term scales. The stability throughout the day was strongly influenced by warming up, which took several hours and affected EPID response by 2.5%. Ghosting effects increased the sensitivity of the EPID. They became more pronounced with decreasing time intervals between two exposures as well as with increasing dose. Due to ghosting, changes in pixel sensitivity amounted up to 16% (locally) for the 25 MV photon beam. It was observed that the response characteristics of our EPID depended on dose as well as on dose rate. Doubling the dose rate increased the EPID sensitivity by 1.5%. This behavior was successfully attributed to a dose per frame effect, i.e., a nonlinear relationship between the EPID signal and the dose which was delivered to the panel between two successive readouts. The sensitivity was found to vary up to 10% in the range of 1 to 1000 monitor units. This variation was governed by two independent effects. For low doses, the EPID signal was reduced due to the linac's changing dose rate during startup. Furthermore, the detector reading was influenced by intrabeam variations of EPID sensitivity, namely, an increase of detector response during uniform exposure. For the beam qualities which were used, the response characteristics of the EPID did not depend on energy. Differences in relative dose-response curves resulted from energy dependent temporal output
Quantisation of monotonic twist maps
International Nuclear Information System (INIS)
Boasman, P.A.; Smilansky, U.
1993-08-01
Using an approach suggested by Moser, classical Hamiltonians are generated that provide an interpolating flow to the stroboscopic motion of maps with a monotonic twist condition. The quantum properties of these Hamiltonians are then studied in analogy with recent work on the semiclassical quantization of systems based on Poincare surfaces of section. For the generalized standard map, the correspondence with the usual classical and quantum results is shown, and the advantages of the quantum Moser Hamiltonian demonstrated. The same approach is then applied to the free motion of a particle on a 2-torus, and to the circle billiard. A natural quantization condition based on the eigenphases of the unitary time--development operator is applied, leaving the exact eigenvalues of the torus, but only the semiclassical eigenvalues for the billiard; an explanation for this failure is proposed. It is also seen how iterating the classical map commutes with the quantization. (authors)
Dose response of artificial irradiation of fluvial sediment sample for ESR dating
International Nuclear Information System (INIS)
Liu Chunru; Yin Gongming; Gao Lu; Li Jianping; Han Fei; Lin Min
2011-01-01
ESR dating samples need be irradiated to obtain dose response curve and the equivalent dose. The artificial dose rate is about 1 x 10 -1 -1 x 10 2 Gy/min, whereas the natural dose rate is about 3 Gy/ka. Therefore, one must be sure whether the much higher artificial dose rate is suitable for the ESR dating study. In this paper, we use different artificial dose rate to irradiate the same fluvial sample and measure the quartz Al centre ESR signal under the same conditions. The dose response curves are compared, in an attempt to gain a preliminary knowledge on that problem and build a good foundation for our ESR dating studies on fluvial samples. (authors)
International Nuclear Information System (INIS)
Mossman, K.L.
1983-01-01
A quantitative dose-response curve for salivary gland function in patients during radiotherapy is presented. Salivary-function data used in this study were obtained from four previously published reports. All patients were treated with 60 Co teletherapy to the head and neck using conventional treatment techniques. Salivary dysfunction was determined at specific dose levels by comparing salivary flow rates before therapy with flow rates at specific dose intervals during radiotherapy up to a total dose of 6000 cGy. Fifty percent salivary dysfunction occurred after 1000 cGy and eighty percent dysfunction was observed by the end of the therapy course (6000 cGy). The salivary-function curve was also compared to the previously published dose-response curve for taste function. Comparisons of the two curves indicate that salivary dysfunction precedes taste loss and that the shapes of the dose-response curves are different. A new term, tissue tolerance ratio, defined as the ratio of responses of two tissues given the same radiation dose, was used to make the comparisons between gustatory and salivary gland tissue effects. Measurements of salivary gland function and analysis of dose-response curves may be useful in evaluating chemical modifiers of radiation response
International Nuclear Information System (INIS)
Koana, Takao; Sakai, Kazuo; Okada, M.O.
2004-01-01
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)
Sünram-Lea, Sandra I; Owen, Lauren; Finnegan, Yvonne; Hu, Henglong
2011-08-01
It has been suggested that the memory enhancing effect of glucose follows an inverted U-shaped curve, with 25 g resulting in optimal facilitation in healthy young adults. The aim of this study was to further investigate the dose dependency of the glucose facilitation effect in this population across different memory domains and to assess moderation by interindividual differences in glucose regulation and weight. Following a double-blind, repeated measures design, 30 participants were administered drinks containing five different doses of glucose (0 g, 15 g, 25 g, 50 g, and 60 g) and were tested across a range of memory tasks. Glycaemic response and changes in mood state were assessed following drink administration. Analysis of the data showed that glucose administration did not affect mood, but significant glucose facilitation of several memory tasks was observed. However, dose-response curves differed depending on the memory task with only performance on the long-term memory tasks adhering largely to the previously observed inverted U-shaped dose-response curve. Moderation of the response profiles by interindividual differences in glucose regulation and weight was observed. The current data suggest that dose-response function and optimal dose might depend on cognitive domain and are moderated by interindividual differences in glucose regulation and weight.
Guidelines for Use of the Approximate Beta-Poisson Dose-Response Model.
Xie, Gang; Roiko, Anne; Stratton, Helen; Lemckert, Charles; Dunn, Peter K; Mengersen, Kerrie
2017-07-01
For dose-response analysis in quantitative microbial risk assessment (QMRA), the exact beta-Poisson model is a two-parameter mechanistic dose-response model with parameters α>0 and β>0, which involves the Kummer confluent hypergeometric function. Evaluation of a hypergeometric function is a computational challenge. Denoting PI(d) as the probability of infection at a given mean dose d, the widely used dose-response model PI(d)=1-(1+dβ)-α is an approximate formula for the exact beta-Poisson model. Notwithstanding the required conditions α1, issues related to the validity and approximation accuracy of this approximate formula have remained largely ignored in practice, partly because these conditions are too general to provide clear guidance. Consequently, this study proposes a probability measure Pr(0 (22α̂)0.50 for 0.020.99) . This validity measure and rule of thumb were validated by application to all the completed beta-Poisson models (related to 85 data sets) from the QMRA community portal (QMRA Wiki). The results showed that the higher the probability Pr(0 Poisson model dose-response curve. © 2016 Society for Risk Analysis.
Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake.
Demonty, Isabelle; Ras, Rouyanne T; van der Knaap, Henk C M; Duchateau, Guus S M J E; Meijer, Linsie; Zock, Peter L; Geleijnse, Johanna M; Trautwein, Elke A
2009-02-01
Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)-lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C-lowering efficacy of different phytosterol doses. Eighty-four trials including 141 trial arms were included. A nonlinear equation comprising 2 parameters (the maximal LDL-C lowering and an incremental dose step) was used to describe the dose-response curve. The overall pooled absolute (mmol/L) and relative (%) LDL-C-lowering effects of phytosterols were also assessed with a random effects model. The pooled LDL-C reduction was 0.34 mmol/L (95% CI: -0.36, -0.31) or 8.8% (95% CI: -9.4, -8.3) for a mean daily dose of 2.15 g phytosterols. The impacts of subject baseline characteristics, food formats, type of phytosterols, and study quality on the continuous dose-response curve were determined by regression or subgroup analyses. Higher baseline LDL-C concentrations resulted in greater absolute LDL-C reductions. No significant differences were found between dose-response curves established for plant sterols vs. stanols, fat-based vs. non fat-based food formats and dairy vs. nondairy foods. A larger effect was observed with solid foods than with liquid foods only at high phytosterol doses (>2 g/d). There was a strong tendency (P = 0.054) towards a slightly lower efficacy of single vs. multiple daily intakes of phytosterols. In conclusion, the dose-dependent LDL-C-lowering efficacy of phytosterols incorporated in various food formats was confirmed and equations of the continuous relationship were established to predict the effect of a given phytosterol dose. Further investigations are warranted to investigate the impact of solid vs. liquid food formats and frequency of intake on phytosterol efficacy.
On the size of monotone span programs
Nikov, V.S.; Nikova, S.I.; Preneel, B.; Blundo, C.; Cimato, S.
2005-01-01
Span programs provide a linear algebraic model of computation. Monotone span programs (MSP) correspond to linear secret sharing schemes. This paper studies the properties of monotone span programs related to their size. Using the results of van Dijk (connecting codes and MSPs) and a construction for
Edit Distance to Monotonicity in Sliding Windows
DEFF Research Database (Denmark)
Chan, Ho-Leung; Lam, Tak-Wah; Lee, Lap Kei
2011-01-01
Given a stream of items each associated with a numerical value, its edit distance to monotonicity is the minimum number of items to remove so that the remaining items are non-decreasing with respect to the numerical value. The space complexity of estimating the edit distance to monotonicity of a ...
International Nuclear Information System (INIS)
Iliakis, George; Okayasu, Ryuichi; Seaner, Robert
1988-01-01
The purpose of this work was to investigate a possible correlation between DNA elution dose-response and cell radiosensitivity. For this purpose neutral (pH 9.6) DNA filter elution dose-response curves were measured with radiosensitive xrs-5 and the parental Chinese hamster ovary (CHO) cells in the logarithmic and plateau phase of growth. No difference was observed between the two cell types in the DNA elution dose-response curves either in logarithmic or plateau phase, despite the dramatic differences in cell radiosensitivity. This observation indicates that the shape of the DNA elution dose-response curve and the shape of the cell survival curve are not causally related. It is proposed that the shoulder observed in the DNA elution dose-response curve reflects either partial release of DNA from chromatin, or cell cycle-specific alterations in the physicochemical properties of the DNA. (author)
Directory of Open Access Journals (Sweden)
Paulo Ricardo Nazário Viecili
2009-05-01
diferencias en la PA, el índice de variación (D% y el efecto hipotensor máximo (EHM% entre las sesiones. Los datos estaban expresados por promedio ± desviación estándar, y se utilizó la prueba t y correlación, tomando p BACKGROUND: The effect of exercise on blood pressure (BP is already known; however, the dose-response curve of the hypotensive effect of exercise in hypertensive individuals is yet to be clarified. OBJECTIVE: To evaluate the dose-response curve of the number of sessions that are necessary to cause a hypotensive effect in hypertensive individuals. METHODS: 88 individuals, aged 58 ± 11 years, divided in Experimental group (EG, with 48 that participated in a physical exercise program (PEP, which consisted of 40 minutes of aerobic exercises performed 3x/week, for 3 months, at 70% of the VO2max, and muscular exercises at 40% of the maximal voluntary contraction (MVC and Control Group (CG with 40 individuals that did not participate in the PEP. The systolic (SAP and diastolic (DAP arterial pressures were measured before each of the 36 sessions in the EG and assessed by ambulatory blood pressure monitoring (ABPM in the CG. Differences in BP, the variation rate (D% and the maximum hypotensive effect (MHE% were observed between sessions. The data were expressed as means ± SD; the t test and correlation were used, with p<0.05 being considered significant. RESULTS: There was no difference regarding BP values in the CG. The EG showed an important decrease of 15 mmHg in SAP and 7 mmHg in DAP, with a large part of this effect occurring as early as the first session and the majority up to the 5th session. There was a strong inverse correlation (R:-0.66 with the number of sessions. CONCLUSION: An important hypotensive effect was observed from the 1st session on and it was observed that the dose-response curve can be abrupt and decrescent, instead of flat.
X-ray dose response of calcite—A comprehensive analysis for optimal application in TL dosimetry
International Nuclear Information System (INIS)
Kalita, J.M.; Wary, G.
2016-01-01
Highlights: • Effect of annealing temperature on TL signal of calcite has been studied. • Specific annealing treatment for optimal dose response has been evaluated. • The dose response of natural calcite has been analyzed quantitatively. - Abstract: The effect of various annealing treatments on dosimetric characteristics of orange calcite (CaCO_3) mineral has been studied in detail. Quantitative analysis on the dose response shows that the 573 K annealed sample showed sublinear dose response from 10 mGy to 1 Gy. The fading and reproducibility of this sample are also good enough for dosimetric application. However, a specific annealing treatment after irradiation shows some significant improvements in the dosimetric characteristics of the sample. The 773 K pre-annealed sample, after X-ray irradiation post-annealing at 340 K for 6 min provides linear dose response from 10 mGy to 3.60 Gy, very less fading and good reproducibility. Moreover, this sample after post-annealing at 380 K for 6 min shows linear dose response from 10 mGy to 5.40 Gy when analyzed from the ∼408 K thermoluminescence (TL) glow peak. Analysis of TL glow curves confirmed that the 1.30 eV trap center in calcite crystal is the most effective trapping site for dosimetric application.
X-ray dose response of calcite—A comprehensive analysis for optimal application in TL dosimetry
Energy Technology Data Exchange (ETDEWEB)
Kalita, J.M., E-mail: jitukalita09@gmail.com; Wary, G.
2016-09-15
Highlights: • Effect of annealing temperature on TL signal of calcite has been studied. • Specific annealing treatment for optimal dose response has been evaluated. • The dose response of natural calcite has been analyzed quantitatively. - Abstract: The effect of various annealing treatments on dosimetric characteristics of orange calcite (CaCO{sub 3}) mineral has been studied in detail. Quantitative analysis on the dose response shows that the 573 K annealed sample showed sublinear dose response from 10 mGy to 1 Gy. The fading and reproducibility of this sample are also good enough for dosimetric application. However, a specific annealing treatment after irradiation shows some significant improvements in the dosimetric characteristics of the sample. The 773 K pre-annealed sample, after X-ray irradiation post-annealing at 340 K for 6 min provides linear dose response from 10 mGy to 3.60 Gy, very less fading and good reproducibility. Moreover, this sample after post-annealing at 380 K for 6 min shows linear dose response from 10 mGy to 5.40 Gy when analyzed from the ∼408 K thermoluminescence (TL) glow peak. Analysis of TL glow curves confirmed that the 1.30 eV trap center in calcite crystal is the most effective trapping site for dosimetric application.
Stewart, Catherine E; Moseley, Merrick J; Stephens, David A; Fielder, Alistair R
2004-09-01
Amblyopia is the commonest visual disorder of childhood. Yet the contributions of the two principal treatments (spectacle wear and occlusion) to outcome are unknown. This study was undertaken to investigate the dose-response relationship of amblyopia therapy. The study comprised three distinct phases: baseline, in which repeat measures of visual function were undertaken to confirm the initial visual deficit; refractive adaptation: an 18-week period of spectacle wear with six weekly measurements of logarithm of the minimum angle of resolution (logMAR) visual acuity; occlusion: in which participants were prescribed 6 hours of "patching" per day. In the latter phase, occlusion was objectively monitored and logMAR visual acuity recorded at 2-week intervals until any observed gains had ceased. Data were obtained from 94 participants (mean age, 5.1 +/- 1.4 years) with amblyopia associated with strabismus (n = 34), anisometropia (n = 23), and both anisometropia and strabismus (n = 37). Eighty-six underwent refractive adaptation. Average concordance with patching was 48%. The relationship between logMAR visual acuity gain and total occlusion dose was monotonic and linear. Increasing dose rate beyond 2 h/d hastened the response but did not improve outcome. More than 80% of the improvement during occlusion occurred within 6 weeks. Treatment outcome was significantly better for children younger than 4 years (n = 17) than in those older than 6 years (n = 24; P = 0.0014). Continuous objective monitoring of the amount of patching therapy received has provided insight into the dose-response relationship of occlusion therapy for amblyopia. Patching is most effective within the first few weeks of treatment, even for those in receipt of a relatively small dose. Further studies are needed to elucidate the neural basis for the dose-response functions. Copyright Association for Research in Vision and Ophthalmology
International Nuclear Information System (INIS)
Lashin, E.A.; Elaasar, E.M.; Moustafa, H.F.; Bakir, Y.Y.; Al Zenki, S.D.
1990-01-01
Dose response curves for lymphocyte chromosome aberration frequencies using X- and gamma radiation became an important and reliable indicator as biological dosimeter especially in radiation accidents and occupational over exposures. Nowadays electron beam therapy is frequently used for their advantages in cases of tumours under or near to the body surface. Dose-response curves for these electron beams are rarely published. Human peripheral blood lymphocytes were in vitro irradiated with various low and high doses (0.1 Gy to 4.9 Gy) of 18 MeV electron beams to utilize such a dose-response curve using chromosomal aberration frequencies as a biological indicator. Then we compared the biological curve with physically obtained curves normally used in planning for radiotherapy treatment. It is interesting to find a significant difference between both of them. The biological curve is generally higher in value and the aberrations induced by 93% of a dose is significantly higher and deeper in site than those aberrations induced by the 100% dose calculated physically. If the above observation is confirmed by detailed studies, it would be of importance to the radiotherapist to plan for isodose curves according to biological determinations. (author)
Wigchert, S.C.M.; Kuiper, E.; Boelhouwer, G.J.; Nefkens, G.H.L.; Verkley, J.A.C.; Zwanenburg, B.
1999-01-01
Striga and Orobanche seeds germinate in response to a host-derived germination stimulant. Dose-response curves of the synthetic strigolactone analogues GR 24 and Nijmegen 1 were determined, and their activities were compared to that of the naturally occurring stimulant sorgolactone. Typical
International Nuclear Information System (INIS)
Mossman, K.L.
1982-01-01
Quantitative radiation dose-response curves for normal gustatory tissue in man were studied. Taste function, expressed as taste loss, was evaluated in 84 patients who were given either photon or neutron radiotherapy for tumors in the head and neck region. Patients were treated to average tumor doses of 6600 cGy (photon) or 2200 cGy intervals for photon patients and 320-cGy intervals for neutron patients during radiotherapy. The dose-response curves for photons and neutrons were analyzed by fitting a four-parameter logistic equation to the data. Photon and neutron curves differed principally in their relative position along the dose axis. Comparison of the dose-response curves were made by determination of RBE. At 320 cGy, the lowest neutron dose at which taste measurements were made, RBE = 5.7. If this RBE is correct, then the therapeutic gain factor may be equal to or less than 1, indicating no biological advantage in using neutrons over photons for this normal tissue. These studies suggest measurements of taste function and evaluation of dose-response relationships may also be useful in quantitatively evaluating the efficacy of chemical modifiers of radiation response such as hypoxic cell radiosensitizers and radioprotectors
Assembled cross-species perchlorate dose-response data
U.S. Environmental Protection Agency — This data set contains dose-response data for perchlorate exposure in multiple species. These data were assembled from peer-reviewed studies. Species included in...
Model for dose-response with alternative change of sign
International Nuclear Information System (INIS)
Osovets, S.V.
1998-01-01
A new mathematical model of dose-response relationships is proposed, suitable for calculating stochastic effects of low level exposure. The corresponding differential equations are presented as well as their solution. (A.K.)
International Nuclear Information System (INIS)
Liniecki, J.; Bajerska, A.; Wyszynska, K.
1983-01-01
Dose-response relationships were established for yield of dicentrics and for a fraction of damaged metaphases in lymphocytes after γ-irradiation of rabbits' whole blood in vitro. These relationships were based on the scoring of cells only in their first post-stimulation division and they served as a reference system for comparison with results of 60 Co γ-irradiation in vivo, either of the whole or of predetermined parts of an animal's body. There was a statistically acceptable agreement between dose-response data established for dicentric yield after whole-body irradiation in vivo and the reference dose-response curve derived from exposure of rabbit's blood in vitro. For partial-body (1/2) irradiations there was a satisfactory agreement between the dose-response curves in vitro for dicentric yield and fraction of metaphases damaged on the one hand and the response in vivo when the latter was related to mean doses to circulating blood. However, there was a drastic disagreement with the dose responses in vitro when measured cytogenetic quantities were plotted versus mean doses to body mass. When the latter were substituted for by comparable doses to circulating blood the in vivo-in vitro agreement was acceptable after irradiation. (orig.)
International Nuclear Information System (INIS)
Appelt, Ane L.; Pløen, John; Vogelius, Ivan R.; Bentzen, Søren M.; Jakobsen, Anders
2013-01-01
Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D 50,i , and the normalized dose-response gradient, γ 50,i . Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D 50,TRG1 = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), γ 50,TRG1 = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D 50,TRG1 and 2 = 72.1 Gy (CI 65.3-94.0 Gy), γ 50,TRG1 and 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.
Mahalanobis distance and variable selection to optimize dose response
International Nuclear Information System (INIS)
Moore, D.H. II; Bennett, D.E.; Wyrobek, A.J.; Kranzler, D.
1979-01-01
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
Human cytogenetic dosimetry: a dose-response relationship for alpha particle radiation from 241Am
International Nuclear Information System (INIS)
DuFrain, R.J.; Littlefield, L.G.; Joiner, E.E.; Frome, E.L.
1979-01-01
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 241 Am alpha particle (5.49 and 5.44 MeV) radiation of G 0 lymphocytes was generated. Cells were exposed to 43.8, 87.7, 175.3 or 350.6 nCi/ml 241 Am 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 241 Am alpha particle induction of dicentric chromosomes in human G 0 lymphocytes as compared with the efficiency of 60 Co 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)
Dose response on the 110 °C thermoluminescence peak of un-heated, synthetic Merck quartz
Energy Technology Data Exchange (ETDEWEB)
Kaya Keleş, Şule, E-mail: sule.kaya@ankara.edu.tr; Meriç, Niyazi; Polymeris, George S.
2016-07-15
Studies on 110 °C TL peak have been carried out using natural quartz from different origins and synthetic quartz produced by different suppliers. The interest in quartz is due to its usage in dating and retrospective dosimetry as a main material; both synthetic and natural types of quartz yield the 110 °C TL peak in their glow curve. In most studies to understand the physical mechanism behind the TL system, synthetic quartz samples are used and there are many investigations about dose response, in both low and high radiation dose region. In these studies generally synthetic quartz samples produced by Sawyer Research Products are used and the studies showed that both heated and un-heated synthetic quartz samples have intense supra-linear responses. Supra-linearity was enhanced by applying a pre-irradiation while several models have been developed towards an explanation to these supra-linearity effects. In this study commercially available synthetic Merck quartz was used. Different combinations of optical filters were used to obtain dose response curves upto 266 Gy and the effect of pre-dose to these dose response curves was studied. Un-pre-dosed Merck quartz samples dose supra-linearity index is below 1 independently on the optical filters; so Merck quartz showed linear or sub-linear dose response.
Kang, Hyeon-Ah; Su, Ya-Hui; Chang, Hua-Hua
2018-03-08
A monotone relationship between a true score (τ) and a latent trait level (θ) has been a key assumption for many psychometric applications. The monotonicity property in dichotomous response models is evident as a result of a transformation via a test characteristic curve. Monotonicity in polytomous models, in contrast, is not immediately obvious because item response functions are determined by a set of response category curves, which are conceivably non-monotonic in θ. The purpose of the present note is to demonstrate strict monotonicity in ordered polytomous item response models. Five models that are widely used in operational assessments are considered for proof: the generalized partial credit model (Muraki, 1992, Applied Psychological Measurement, 16, 159), the nominal model (Bock, 1972, Psychometrika, 37, 29), the partial credit model (Masters, 1982, Psychometrika, 47, 147), the rating scale model (Andrich, 1978, Psychometrika, 43, 561), and the graded response model (Samejima, 1972, A general model for free-response data (Psychometric Monograph no. 18). Psychometric Society, Richmond). The study asserts that the item response functions in these models strictly increase in θ and thus there exists strict monotonicity between τ and θ under certain specified conditions. This conclusion validates the practice of customarily using τ in place of θ in applied settings and provides theoretical grounds for one-to-one transformations between the two scales. © 2018 The British Psychological Society.
Directory of Open Access Journals (Sweden)
Chakkrid Klin-eam
2009-01-01
Full Text Available We prove strong convergence theorems for finding a common element of the zero point set of a maximal monotone operator and the fixed point set of a hemirelatively nonexpansive mapping in a Banach space by using monotone hybrid iteration method. By using these results, we obtain new convergence results for resolvents of maximal monotone operators and hemirelatively nonexpansive mappings in a Banach space.
Theory of thermoluminescence gamma dose response: The unified interaction model
International Nuclear Information System (INIS)
Horowitz, Y.S.
2001-01-01
We describe the development of a comprehensive theory of thermoluminescence (TL) dose response, the unified interaction model (UNIM). The UNIM is based on both radiation absorption stage and recombination stage mechanisms and can describe dose response for heavy charged particles (in the framework of the extended track interaction model - ETIM) as well as for isotropically ionising gamma rays and electrons (in the framework of the TC/LC geminate recombination model) in a unified and self-consistent conceptual and mathematical formalism. A theory of optical absorption dose response is also incorporated in the UNIM to describe the radiation absorption stage. The UNIM is applied to the dose response supralinearity characteristics of LiF:Mg,Ti and is especially and uniquely successful in explaining the ionisation density dependence of the supralinearity of composite peak 5 in TLD-100. The UNIM is demonstrated to be capable of explaining either qualitatively or quantitatively all of the major features of TL dose response with many of the variable parameters of the model strongly constrained by ancilliary optical absorption and sensitisation measurements
Thermoluminescence dose response of quartz as a function of irradiation temperature
International Nuclear Information System (INIS)
Kitis, G.; Kaldoudi, E.; Charalambous, S.
1990-01-01
The thermoluminescence (TL) response of pure Norwegian quartz as a function of irradiation temperature (T irr ) and dose has been investigated. The TL response of the (150-230 o C) and (230-350 o C) glow curve intervals shows a strong dependence on T irr between 77 and 373 K in the dose range from 54 to 8.4 x 10 4 Gy. Both glow curve intervals also show temperature dependent dose response properties. The 150-230 o C interval is supralinear from the lowest dose (54 Gy). Its maximum supralinearity factor appears at T irr = 293 K. The 230-350 o C interval shows sublinear behaviour below T irr = + 193 K, while at T irr ≥ 273 K it shows the well known dose response curves. Its maximum supralinearity factor appears at T irr = 323 K. The linear response is extended up to 460 Gy at T irr = 273 K and falls to 80 Gy at T irr = 373 K. (author)
Energy Technology Data Exchange (ETDEWEB)
Schoellnberger, Helmut [Helmholtz Zentrum Muenchen, Department of Radiation Sciences, Institute of Radiation Protection, Neuherberg (Germany); Federal Office for Radiation Protection, Department of Radiation Protection and the Environment, Neuherberg (Germany); Eidemueller, Markus; Simonetto, Cristoforo; Kaiser, Jan Christian [Helmholtz Zentrum Muenchen, Department of Radiation Sciences, Institute of Radiation Protection, Neuherberg (Germany); Cullings, Harry M. [Radiation Effects Research Foundation, Department of Statistics, Hiroshima (Japan); Neff, Frauke [Staedtisches Klinikum Muenchen and Technical University of Munich, Institute of Pathology, Munich (Germany)
2018-03-15
The scientific community faces important discussions on the validity of the linear no-threshold (LNT) model for radiation-associated cardiovascular diseases at low and moderate doses. In the present study, mortalities from cerebrovascular diseases (CeVD) and heart diseases from the latest data on atomic bomb survivors were analyzed. The analysis was performed with several radio-biologically motivated linear and nonlinear dose-response models. For each detrimental health outcome one set of models was identified that all fitted the data about equally well. This set was used for multi-model inference (MMI), a statistical method of superposing 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. MMI provides a more accurate determination of the dose response and a more comprehensive characterization of uncertainties. It was found that for CeVD, the dose-response curve from MMI is located below the linear no-threshold model at low and medium doses (0-1.4 Gy). At higher doses MMI predicts a higher risk compared to the LNT model. A sublinear dose-response was also found for heart diseases (0-3 Gy). The analyses provide no conclusive answer to the question whether there is a radiation risk below 0.75 Gy for CeVD and 2.6 Gy for heart diseases. MMI suggests that the dose-response curves for CeVD and heart diseases in the Lifespan Study are sublinear at low and moderate doses. This has relevance for radiotherapy treatment planning and for international radiation protection practices in general. (orig.)
A Generalized QMRA Beta-Poisson Dose-Response Model.
Xie, Gang; Roiko, Anne; Stratton, Helen; Lemckert, Charles; Dunn, Peter K; Mengersen, Kerrie
2016-10-01
Quantitative microbial risk assessment (QMRA) is widely accepted for characterizing the microbial risks associated with food, water, and wastewater. Single-hit dose-response models are the most commonly used dose-response models in QMRA. Denoting PI(d) as the probability of infection at a given mean dose d, a three-parameter generalized QMRA beta-Poisson dose-response model, PI(d|α,β,r*), is proposed in which the minimum number of organisms required for causing infection, K min , is not fixed, but a random variable following a geometric distribution with parameter 0Poisson model, PI(d|α,β), is a special case of the generalized model with K min = 1 (which implies r*=1). The generalized beta-Poisson model is based on a conceptual model with greater detail in the dose-response mechanism. Since a maximum likelihood solution is not easily available, a likelihood-free approximate Bayesian computation (ABC) algorithm is employed for parameter estimation. By fitting the generalized model to four experimental data sets from the literature, this study reveals that the posterior median r* estimates produced fall short of meeting the required condition of r* = 1 for single-hit assumption. However, three out of four data sets fitted by the generalized models could not achieve an improvement in goodness of fit. These combined results imply that, at least in some cases, a single-hit assumption for characterizing the dose-response process may not be appropriate, but that the more complex models may be difficult to support especially if the sample size is small. The three-parameter generalized model provides a possibility to investigate the mechanism of a dose-response process in greater detail than is possible under a single-hit model. © 2016 Society for Risk Analysis.
Multipartite classical and quantum secrecy monotones
International Nuclear Information System (INIS)
Cerf, N.J.; Massar, S.; Schneider, S.
2002-01-01
In order to study multipartite quantum cryptography, we introduce quantities which vanish on product probability distributions, and which can only decrease if the parties carry out local operations or public classical communication. These 'secrecy monotones' therefore measure how much secret correlation is shared by the parties. In the bipartite case we show that the mutual information is a secrecy monotone. In the multipartite case we describe two different generalizations of the mutual information, both of which are secrecy monotones. The existence of two distinct secrecy monotones allows us to show that in multipartite quantum cryptography the parties must make irreversible choices about which multipartite correlations they want to obtain. Secrecy monotones can be extended to the quantum domain and are then defined on density matrices. We illustrate this generalization by considering tripartite quantum cryptography based on the Greenberger-Horne-Zeilinger state. We show that before carrying out measurements on the state, the parties must make an irreversible decision about what probability distribution they want to obtain
Buonanno, Paolo; Fergusson, Leopoldo; Vargas, Juan Fernando
2014-01-01
We document the existence of a Crime Kuznets Curve in US states since the 1970s. As income levels have risen, crime has followed an inverted U-shaped pattern, first increasing and then dropping. The Crime Kuznets Curve is not explained by income inequality. In fact, we show that during the sample period inequality has risen monotonically with income, ruling out the traditional Kuznets Curve. Our finding is robust to adding a large set of controls that are used in the literature to explain the...
Dose-response of photographic emulsions under gamma irradiation
International Nuclear Information System (INIS)
Tran Dai Nghiep; Do Thi Nguyet Minh; Le Van Vinh
2003-01-01
Photographic emulsion is irradiated under gamma rays irradiation of 137 Cs in the IAEA/WHO secondary standard dosimetry laboratory. Dose-response of the film is established. The sensitivity of the film is determined. The dose-rate effect is studied. (author)
Dose-response relation between physical activity and sick leave
Proper, K.I.; Heuvel, S.G. van den; Vroome, E.M. de; Hildebrandt, V.H.; Beek, A.J. van der
2006-01-01
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
Dose-response relationship with radiotherapy: an evidence?
International Nuclear Information System (INIS)
Chauvet, B.; Rauglaudre, G. de; Mineur, L.; Alfonsi, M.; Reboul, F.
2003-01-01
The dose-response relationship is a fundamental basis of radiobiology. Despite many clinical data, difficulties remain to demonstrate a relation between dose and local control: relative role of treatment associated with radiation therapy (surgery, chemotherapy, hormonal therapy), tumor heterogeneity, few prospective randomized studies, uncertainty of local control assessment. Three different situations are discussed: tumors with high local control probabilities for which dose effect is demonstrated by randomized studies (breast cancer) or sound retrospective data (soft tissues sarcomas), tumors with intermediate local control probabilities for which dose effect seems to be important according to retrospective studies and ongoing or published phase III trials (prostate cancer), tumors with low local control probabilities for which dose effect appears to be modest beyond standard doses, and inferior to the benefit of concurrent chemotherapy (lung and oesophageal cancer). For head and neck tumors, the dose-response relationship has been explored through hyperfractionation and accelerated radiation therapy and a dose effect has been demonstrated but must be compared to the benefit of concurrent chemotherapy. Last but not least, the development of conformal radiotherapy allow the exploration of the dose response relationship for tumors such as hepatocellular carcinomas traditionally excluded from the field of conventional radiation therapy. In conclusion, the dose-response relationship remains a sound basis of radiation therapy for many tumors and is a parameter to take into account for further randomized studies. (author)
Dose Response Model of Biological Reaction to Low Dose Rate Gamma Radiation
International Nuclear Information System (INIS)
Magae, J.; Furikawa, C.; Hoshi, Y.; Kawakami, Y.; Ogata, H.
2004-01-01
It is necessary to use reproducible and stable indicators to evaluate biological responses to long term irradiation at low dose-rate. They should be simple and quantitative enough to produce the results statistically accurate, because we have to analyze the subtle changes of biological responses around background level at low dose. For these purposes we chose micronucleus formation of U2OS, a human osteosarcoma cell line, as indicators of biological responses. Cells were exposed to gamma ray in irradiation rom bearing 50,000 Ci 60Co. After irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, and cytoplasm and nucleus were stained with DAPI and prospidium iodide, respectively. the number of binuclear cells bearing micronuclei was counted under a fluorescence microscope. Dose rate in the irradiation room was measured with PLD. Dose response of PLD is linear between 1 mGy to 10 Gy, and standard deviation of triplicate count was several percent of mean value. We fitted statistically dose response curves to the data, and they were plotted on the coordinate of linearly scale response and dose. The results followed to the straight line passing through the origin of the coordinate axes between 0.1-5 Gy, and dose and does rate effectiveness factor (DDREF) was less than 2 when cells were irradiated for 1-10 min. Difference of the percent binuclear cells bearing micronucleus between irradiated cells and control cells was not statistically significant at the dose above 0.1 Gy when 5,000 binuclear cells were analyzed. In contrast, dose response curves never followed LNT, when cells were irradiated for 7 to 124 days. Difference of the percent binuclear cells bearing micronucleus between irradiated cells and control cells was not statistically significant at the dose below 6 Gy, when cells were continuously irradiated for 124 days. These results suggest that dose response curve of biological reaction is remarkably affected by exposure
Radiation Dose-Response Relationships and Risk Assessment
International Nuclear Information System (INIS)
Strom, Daniel J.
2005-01-01
The notion of a dose-response relationship was probably invented shortly after the discovery of poisons, the invention of alcoholic beverages, and the bringing of fire into a confined space in the forgotten depths of ancient prehistory. The amount of poison or medicine ingested can easily be observed to affect the behavior, health, or sickness outcome. Threshold effects, such as death, could be easily understood for intoxicants, medicine, and poisons. As Paracelsus (1493-1541), the 'father' of modern toxicology said, 'It is the dose that makes the poison.' Perhaps less obvious is the fact that implicit in such dose-response relationships is also the notion of dose rate. Usually, the dose is administered fairly acutely, in a single injection, pill, or swallow; a few puffs on a pipe; or a meal of eating or drinking. The same amount of intoxicants, medicine, or poisons administered over a week or month might have little or no observable effect. Thus, before the discovery of ionizing radiation in the late 19th century, toxicology ('the science of poisons') and pharmacology had deeply ingrained notions of dose-response relationships. This chapter demonstrates that the notion of a dose-response relationship for ionizing radiation is hopelessly simplistic from a scientific standpoint. While useful from a policy or regulatory standpoint, dose-response relationships cannot possibly convey enough information to describe the problem from a quantitative view of radiation biology, nor can they address societal values. Three sections of this chapter address the concepts, observations, and theories that contribute to the scientific input to the practice of managing risks from exposure to ionizing radiation. The presentation begins with irradiation regimes, followed by responses to high and low doses of ionizing radiation, and a discussion of how all of this can inform radiation risk management. The knowledge that is really needed for prediction of individual risk is presented
Somatic cell genetics of uranium miners and plutonium workers. A biological dose-response indicator
International Nuclear Information System (INIS)
Brandom, W.F.; Bloom, A.D.; Bistline, R.W.; Saccomanno, G.
1978-01-01
Two populations of underground uranium miners and plutonium workers work in the state of Colorado, United States of America. We have explored the prevalence of structural chromosome aberrations in peripheral blood lymphocytes as a possible biological indicator of absorbed radiation late-effects in these populations. The uranium miners are divided into four exposure groups expressed in Working Level Months (WLM), the plutonium workers into six groups with estimated 239 Pu burdens expressed in nCi. Comparison of chromosome aberration frequency data between controls, miners, and plutonium workers demonstrate: (1) a cytogenetic response to occupational ionizing radiation at low estimated doses; and (2) an increasing monotonic dose-response in the prevalence of complex (all exchange) or total aberrations in all exposure groups in these populations. We also compared trends in the prevalence of aberrations per exposure unit (WLM and nCi) in each exposure subgroup for each population. In the uranium miners, the effects per WLM seem to decrease monotonically with increasing dose, whereas in the Pu workers the change per nCi appears abrupt, with all exposure groups over 1.3 nCi (minimum detectable level) having essentially similar rates. The calculations of aberrations per respective current maximum permissible dose (120 WLM and 40 nCi) for the two populations yield 4.8 X 10 -2 /100 cells for uranium miners and 90.6 X 10 -2 /100 cells for Pu workers. Factors which may have influenced this apparent 20-fold increase in the effectiveness of plutonium in the production of complex aberrations (9-fold increase in total aberrations) are discussed. (author)
Directory of Open Access Journals (Sweden)
Ross H Johnstone
2017-03-01
Full Text Available Dose-response (or ‘concentration-effect’ relationships commonly occur in biological and pharmacological systems and are well characterised by Hill curves. These curves are described by an equation with two parameters: the inhibitory concentration 50% (IC50; and the Hill coefficient. Typically just the ‘best fit’ parameter values are reported in the literature. Here we introduce a Python-based software tool, PyHillFit , and describe the underlying Bayesian inference methods that it uses, to infer probability distributions for these parameters as well as the level of experimental observation noise. The tool also allows for hierarchical fitting, characterising the effect of inter-experiment variability. We demonstrate the use of the tool on a recently published dataset on multiple ion channel inhibition by multiple drug compounds. We compare the maximum likelihood, Bayesian and hierarchical Bayesian approaches. We then show how uncertainty in dose-response inputs can be characterised and propagated into a cardiac action potential simulation to give a probability distribution on model outputs.
Radiation dose response of N channel MOSFET submitted to filtered X-ray photon beam
Gonçalves Filho, Luiz C.; Monte, David S.; Barros, Fabio R.; Santos, Luiz A. P.
2018-01-01
MOSFET can operate as a radiation detector mainly in high-energy photon beams, which are normally used in cancer treatments. In general, such an electronic device can work as a dosimeter from threshold voltage shift measurements. The purpose of this article is to show a new way for measuring the dose-response of MOSFETs when they are under X-ray beams generated from 100kV potential range, which is normally used in diagnostic radiology. Basically, the method consists of measuring the MOSFET drain current as a function of the radiation dose. For this the type of device, it has to be biased with a high value resistor aiming to see a substantial change in the drain current after it has been irradiated with an amount of radiation dose. Two types of N channel device were used in the experiment: a signal transistor and a power transistor. The delivered dose to the device was varied and the electrical curves were plotted. Also, a sensitivity analysis of the power MOSFET response was made, by varying the tube potential of about 20%. The results show that both types of devices have responses very similar, the shift in the electrical curve is proportional to the radiation dose. Unlike the power MOSFET, the signal transistor does not provide a linear function between the dose rate and its drain current. We also have observed that the variation in the tube potential of the X-ray equipment produces a very similar dose-response.
Monotonicity and bounds on Bessel functions
Directory of Open Access Journals (Sweden)
Larry Landau
2000-07-01
Full Text Available survey my recent results on monotonicity with respect to order of general Bessel functions, which follow from a new identity and lead to best possible uniform bounds. Application may be made to the "spreading of the wave packet" for a free quantum particle on a lattice and to estimates for perturbative expansions.
New concurrent iterative methods with monotonic convergence
Energy Technology Data Exchange (ETDEWEB)
Yao, Qingchuan [Michigan State Univ., East Lansing, MI (United States)
1996-12-31
This paper proposes the new concurrent iterative methods without using any derivatives for finding all zeros of polynomials simultaneously. The new methods are of monotonic convergence for both simple and multiple real-zeros of polynomials and are quadratically convergent. The corresponding accelerated concurrent iterative methods are obtained too. The new methods are good candidates for the application in solving symmetric eigenproblems.
SU-F-J-147: Magnetic Field Dose Response Considerations for a Linac Monitor Chamber
Energy Technology Data Exchange (ETDEWEB)
Reynolds, M; Fallone, B [Cross Cancer Institute, Edmonton, AB (Canada)
2016-06-15
Purpose: The impact of magnetic fields on the readings of a linac monitor chamber have not yet been investigated. Herein we examine the total dose response as well as any deviations in the beam parameters of flatness and symmetry when a Varian monitor chamber is irradiated within an applied magnetic field. This work has direct application to the development of Linac-MR systems worldwide. Methods: A Varian monitor chamber was modeled in the Monte Carlo code PENELOPE and irradiated in the presence of a magnetic field with a phase space generated from a model of a Linac-MR prototype system. The magnetic field strength was stepped from 0 to 3.0T in both parallel and perpendicular directions with respect to the normal surface of the phase space. Dose to each of the four regions in the monitor chamber were scored separately for every magnetic field adaptation to evaluate the effect of the magnetic field on flatness and symmetry. Results: When the magnetic field is perpendicular to the phase space normal we see a change in dose response with a maximal deviation (10–25% depending on the chamber region) near 0.75T. In the direction of electron deflection we expectedly see opposite responses in chamber regions leading to a measured asymmetry. With a magnetic field parallel to the phase space normal we see no measured asymmetries, however there is a monotonic rise in dose response leveling off at about +12% near 2.5T. Conclusion: Attention must be given to correct for the strength and direction of the magnetic field at the location of the linac monitor chamber in hybrid Linac-MR devices. Elsewise the dose sampled by these chambers may not represent the actual dose expected at isocentre; additionally there may be a need to correct for the symmetry of the beam recorded by the monitor chamber. Fallone is a co-founder and CEO of MagnetTx Oncology Solutions (under discussions to license Alberta bi-planar linac MR for commercialization).
The non-monotonic shear-thinning flow of two strongly cohesive concentrated suspensions
Buscall, Richard; Kusuma, Tiara E.; Stickland, Anthony D.; Rubasingha, Sayuri; Scales, Peter J.; Teo, Hui-En; Worrall, Graham L.
2014-01-01
The behaviour in simple shear of two concentrated and strongly cohesive mineral suspensions showing highly non-monotonic flow curves is described. Two rheometric test modes were employed, controlled stress and controlled shear-rate. In controlled stress mode the materials showed runaway flow above a yield stress, which, for one of the suspensions, varied substantially in value and seemingly at random from one run to the next, such that the up flow-curve appeared to be quite irreproducible. Th...
International Nuclear Information System (INIS)
Koana, T.; Takashima, Y.; Okada, M. O.; Ikehata, M.; Miyakoshi, J.; Sakai, K.
2004-01-01
The dose-response relationship of ionizing radiation and its stochastic effects has been thought to be linear without any thresholds. The basic data for this model was obtained from mutational assays in the male germ cells of fruits fly Drosophila melanogaster. However, carcinogenic activity should be examined more appropriately in somatic cells than in germ cells. Here, the dose-response relationship of X- ray irradiation and somatic mutation is examined in Drosophila. A threshold at approximately 1Gy was observed in the DNA repair proficient flies. In the repair deficient siblings, the threshold was smaller and the inclination of the dose-response curve was much 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) 35 refs
Theoretical and experimental study of non-monotonous effects
International Nuclear Information System (INIS)
Delforge, J.
1977-01-01
In recent years, the study of the effects of low dose rates has expanded considerably, especially in connection with current problems concerning the environment and health physics. After having made a precise definition of the different types of non-monotonous effect which may be encountered, for each the main experimental results known are indicated, as well as the principal consequences which may be expected. One example is the case of radiotherapy, where there is a chance of finding irradiation conditions such that the ratio of destructive action on malignant cells to healthy cells is significantly improved. In the second part of the report, the appearance of these phenomena, especially at low dose rates are explained. For this purpose, the theory of transformation systems of P. Delattre is used as a theoretical framework. With the help of a specific example, it is shown that non-monotonous effects are frequently encountered, especially when the overall effect observed is actually the sum of several different elementary effects (e.g. in survival curves, where death may be due to several different causes), or when the objects studied possess inherent kinetics not limited to restoration phenomena alone (e.g. cellular cycle) [fr
The risk of chronic myeloid leukemia: Can the dose-response curve be U-shaped?
Czech Academy of Sciences Publication Activity Database
Radivoyevitch, T.; Kozubek, Stanislav; Sachs, R. K.
2002-01-01
Roč. 157, č. 1 (2002), s. 106-109 ISSN 0033-7587 R&D Projects: GA ČR GA202/01/0197; GA ČR GA301/01/0186; GA AV ČR IBS5004010 Keywords : radiation risk * chronic myeloid leukemia * chromosome translocation Subject RIV: BO - Biophysics Impact factor: 2.768, year: 2002
Dual Effects of Phytoestrogens Result in U-Shaped Dose-Response Curves
DEFF Research Database (Denmark)
Almstrup, Kristian; Fernández, Mariana F.; Petersen, Jørgen Holm
2002-01-01
Endocrine disruptors can affect the endocrine system without directly interacting with receptors, for example, by interfering with the synthesis or metabolism of steroid hormones. The aromatase that converts testosterone to 17beta-estradiol is a possible target. In this paper we describe an assay...
A note on monotone real circuits
Czech Academy of Sciences Publication Activity Database
Hrubeš, Pavel; Pudlák, Pavel
2018-01-01
Roč. 131, March (2018), s. 15-19 ISSN 0020-0190 EU Projects: European Commission(XE) 339691 - FEALORA Institutional support: RVO:67985840 Keywords : computational complexity * monotone real circuit * Karchmer-Wigderson game Subject RIV: BA - General Mathematics OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 0.748, year: 2016 http ://www.sciencedirect.com/science/article/pii/S0020019017301965?via%3Dihub
A note on monotone real circuits
Czech Academy of Sciences Publication Activity Database
Hrubeš, Pavel; Pudlák, Pavel
2018-01-01
Roč. 131, March (2018), s. 15-19 ISSN 0020-0190 EU Projects: European Commission(XE) 339691 - FEALORA Institutional support: RVO:67985840 Keywords : computational complexity * monotone real circuit * Karchmer-Wigderson game Subject RIV: BA - General Mathematics OBOR OECD: Computer sciences, information science, bioinformathics (hardware development to be 2.2, social aspect to be 5.8) Impact factor: 0.748, year: 2016 http://www.sciencedirect.com/science/article/pii/S0020019017301965?via%3Dihub
The dose-response analysis between BMI and common chronic diseases in northeast China.
Yu, Jianxing; Tao, Yuchun; Dou, Jing; Ye, Junsen; Yu, Yaqin; Jin, Lina
2018-03-09
High body mass index (BMI) predisposes to several chronic diseases, but a large-scale systematic and detailed study of dose-response relationship between BMI and chronic diseases has not been reported previously. In this study, we aimed to investigate the relationship between BMI and 3 chronic diseases (hypertension, dyslipidemia and MetS) in northeast China. A sample of 16412 participants aged 18~79 years old were included in Jilin province in 2012. The lambda-mu-sigma (LMS) method was applied to examine the trend of BMI by age, and the restricted cubic splines were used to investigate the non-linear associations (dose-response curve) between BMI and chronic diseases. It was pointed out that BMI increased rapidly when young, then kept steady in middle age, and finally declined slowly in old age, and accordingly age was divided into 3 segments, which were different by gender. The odds ratios (ORs) of BMI for the chronic diseases increased relatively slowly when young, then increased dramatically in middle-age and old population, especially for men. Further, the ORs of BMI among non-smokers were lower than those among smokers, and the same trend was shown to be more apparent among drinkers and non-drinkers. The risk of BMI for common chronic diseases increased dramatically in middle-aged, especially for men with drinking and smoking habits.
Directory of Open Access Journals (Sweden)
Rui-Ru Ji
2009-09-01
Full Text Available The dose response curve is the gold standard for measuring the effect of a drug treatment, but is rarely used in genomic scale transcriptional profiling due to perceived obstacles of cost and analysis. One barrier to examining transcriptional dose responses is that existing methods for microarray data analysis can identify patterns, but provide no quantitative pharmacological information. We developed analytical methods that identify transcripts responsive to dose, calculate classical pharmacological parameters such as the EC50, and enable an in-depth analysis of coordinated dose-dependent treatment effects. The approach was applied to a transcriptional profiling study that evaluated four kinase inhibitors (imatinib, nilotinib, dasatinib and PD0325901 across a six-logarithm dose range, using 12 arrays per compound. The transcript responses proved a powerful means to characterize and compare the compounds: the distribution of EC50 values for the transcriptome was linked to specific targets, dose-dependent effects on cellular processes were identified using automated pathway analysis, and a connection was seen between EC50s in standard cellular assays and transcriptional EC50s. Our approach greatly enriches the information that can be obtained from standard transcriptional profiling technology. Moreover, these methods are automated, robust to non-optimized assays, and could be applied to other sources of quantitative data.
Droplet-based microfluidics for dose-response assay of enzyme inhibitors by electrochemical method.
Gu, Shuqing; Lu, Youlan; Ding, Yaping; Li, Li; Zhang, Fenfen; Wu, Qingsheng
2013-09-24
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 6 min, and the total consumption of reagents was less than 5 μL. 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. Copyright © 2013 Elsevier B.V. All rights reserved.
International Nuclear Information System (INIS)
Suwinski, R.; Maciejewski, B.; Withers, H.R.
1998-01-01
The aim of this study is to assign dose-response relationship for subclinical neck metastases of squamous cell head and neck cancer based on extensive survey of 24 data sets collected from the literature. Neck relapse rates (NRR) without and after elective (ENI) or preoperative irradiation were estimated for each site and stage of primary tumor and the reduction in neck relapse rate was calculated. An average NRR without ENI was 22% (12-35% ) and only 2.5% (0-1 0%) after the ENI with total dose of 46- 50 Gy which gives high reduction rate in the risk of neck recurrences being on the average 89% and 42% (0-46%) after preoperative irradiation using 22-30 Gy. Dose response curve for elective and preoperative irradiation have shown that 50 Gy in 2 Gy fraction reduces the incidence of neck relapses in the NO patients by more than 90% and only by less than 50% after total doses lower than 30 Gy. No correlation between the risk of neck metastases without ENI and the reduction in neck relapses after ENI was found. (authors)
A study on dose response of NIPAM-based dosimeter used in radiotherapy
International Nuclear Information System (INIS)
Hsieh, B.T.; Wu, J.; Chang, Y.J.; Han, R.P.; Hsieh, L.L.; Chang, C.J.
2011-01-01
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)
Stepsize Restrictions for Boundedness and Monotonicity of Multistep Methods
Hundsdorfer, W.; Mozartova, A.; Spijker, M. N.
2011-01-01
In this paper nonlinear monotonicity and boundedness properties are analyzed for linear multistep methods. We focus on methods which satisfy a weaker boundedness condition than strict monotonicity for arbitrary starting values. In this way, many
The Radiation Dose-Response of the Human Spinal Cord
International Nuclear Information System (INIS)
Schultheiss, Timothy E.
2008-01-01
Purpose: To characterize the radiation dose-response of the human spinal cord. Methods and Materials: Because no single institution has sufficient data to establish a dose-response function for the human spinal cord, published reports were combined. Requisite data were dose and fractionation, number of patients at risk, number of myelopathy cases, and survival experience of the population. Eight data points for cervical myelopathy were obtained from five reports. Using maximum likelihood estimation correcting for the survival experience of the population, estimates were obtained for the median tolerance dose, slope parameter, and α/β ratio in a logistic dose-response function. An adequate fit to thoracic data was not possible. Hyperbaric oxygen treatments involving the cervical cord were also analyzed. Results: The estimate of the median tolerance dose (cervical cord) was 69.4 Gy (95% confidence interval, 66.4-72.6). The α/β = 0.87 Gy. At 45 Gy, the (extrapolated) probability of myelopathy is 0.03%; and at 50 Gy, 0.2%. The dose for a 5% myelopathy rate is 59.3 Gy. Graphical analysis indicates that the sensitivity of the thoracic cord is less than that of the cervical cord. There appears to be a sensitizing effect from hyperbaric oxygen treatment. Conclusions: The estimate of α/β is smaller than usually quoted, but values this small were found in some studies. Using α/β = 0.87 Gy, one would expect a considerable advantage by decreasing the dose/fraction to less than 2 Gy. These results were obtained from only single fractions/day and should not be applied uncritically to hyperfractionation
Dose response relationship in local radiotherapy for hepatocellular carcinoma
International Nuclear Information System (INIS)
Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok
2001-01-01
In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was 48.2±7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at 4-8 weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. An objective response was observed in 106 of 158 patients, giving a response rate of 67. 1%. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only 29.2% showed objective response in patients treated with dose less than 40 Gy, while 68.6% and 77.1 % showed major response in patients with 40-50 Gy and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver
Testing Manifest Monotonicity Using Order-Constrained Statistical Inference
Tijmstra, Jesper; Hessen, David J.; van der Heijden, Peter G. M.; Sijtsma, Klaas
2013-01-01
Most dichotomous item response models share the assumption of latent monotonicity, which states that the probability of a positive response to an item is a nondecreasing function of a latent variable intended to be measured. Latent monotonicity cannot be evaluated directly, but it implies manifest monotonicity across a variety of observed scores,…
Tang, Leilei; Guérard, Melanie; Zeller, Andreas
2014-01-01
Mutagenic and clastogenic effects of some DNA damaging agents such as methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) have been demonstrated to exhibit a nonlinear or even "thresholded" dose-response in vitro and in vivo. DNA repair seems to be mainly responsible for these thresholds. To this end, we assessed several mutagenic alkylators in the Ames test with four different strains of Salmonella typhimurium: the alkyl transferases proficient strain TA1535 (Ogt+/Ada+), as well as the alkyl transferases deficient strains YG7100 (Ogt+/Ada-), YG7104 (Ogt-/Ada+) and YG7108 (Ogt-/Ada-). The known genotoxins EMS, MMS, temozolomide (TMZ), ethylnitrosourea (ENU) and methylnitrosourea (MNU) were tested in as many as 22 concentration levels. Dose-response curves were statistically fitted by the PROAST benchmark dose model and the Lutz-Lutz "hockeystick" model. These dose-response curves suggest efficient DNA-repair for lesions inflicted by all agents in strain TA1535. In the absence of Ogt, Ada is predominantly repairing methylations but not ethylations. It is concluded that the capacity of alkyl-transferases to successfully repair DNA lesions up to certain dose levels contributes to genotoxicity thresholds. Copyright © 2013 Wiley Periodicals, Inc.
International Nuclear Information System (INIS)
Radford, I.R.
1990-01-01
The suggestion by Okayasu and Iliakis (1989) that the non-linear dose-response curve, obtained with the non-denaturing filter elution technique for mammalian cells exposed to low-LET radiation, is the result of a technical artefact, was not confirmed. (author)
Dose-response models for the radiation-induction of skin tumours in mice
International Nuclear Information System (INIS)
Papworth, D.G.; Hulse, E.V.
1983-01-01
Extensive data on radiation-induced skin tumours in mice were examined using 8 models, all based on the concept that incidences of radiation-induced tumours depend on a combination of two radiation effects: a tumour induction process and the loss of reproductive integrity by the potential tumour cells. Models with and without a threshold were used, in spite of theoretical objections to threshold models. No model fitted well both the epidermal and the dermal tumour data and models which proved to be statistically satisfactory for some of the data were rejected for biological reasons. It is concluded that, for skin tumours, dose-response curves depending on a combination of cancer induction and loss of cellular reproductive integrity are distorted by some special, relatively radio-resistant, factor which we have previously postulated as being involved in radiation skin carcinogenesis. (author)
DEFF Research Database (Denmark)
Christensen, Erik R.; Kusk, Kresten Ole; Nyholm, Niels
2009-01-01
We derive equations for the effective concentration giving 10% inhibition (EC10) with 95% confidence limits for probit (log-normal), Weibull, and logistic dose -responsemodels on the basis of experimentally derived median effective concentrations (EC50s) and the curve slope at the central point (50......% inhibition). For illustration, data from closed, freshwater algal assays are analyzed using the green alga Pseudokirchneriella subcapitata with growth rate as the response parameter. Dose-response regressions for four test chemicals (tetraethylammonium bromide, musculamine, benzonitrile, and 4...... 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...
International Nuclear Information System (INIS)
Wrenn, M.E.; Taylor, G.N.; Stevens, W.
1986-01-01
In the completed 226 Ra portion of a 30-year-long experiment to determine the relative radiotoxicity of injected 226 Ra and 239 Pu, 42 of 116 animals injected with 226 Ra developed 63 bone sarcomas; none were observed in 44 controls. Average alpha plus beta dose to the skeleton to death was calculated on the basis of mathematical functions developed from sequential measurements of radium and radon retention in each dog. Bone sarcomas were identified radiographically or clinically, with subsequent histopathological confirmation and classification. Most primary bone tumors were classified as osteosarcomas if osteoid arose from a malignant stroma. The dose-response curve over the six lowest injected dose levels fits well to a linear, no-threshold, least squares fit, through a control incidence of 0.8%, and with a slope of 0.042% incidence per rad. 19 refs., 5 figs., 2 tabs
Alternans by non-monotonic conduction velocity restitution, bistability and memory
International Nuclear Information System (INIS)
Kim, Tae Yun; Hong, Jin Hee; Heo, Ryoun; Lee, Kyoung J
2013-01-01
Conduction velocity (CV) restitution is a key property that characterizes any medium supporting traveling waves. It reflects not only the dynamics of the individual constituents but also the coupling mechanism that mediates their interaction. Recent studies have suggested that cardiac tissues, which have a non-monotonic CV-restitution property, can support alternans, a period-2 oscillatory response of periodically paced cardiac tissue. This study finds that single-hump, non-monotonic, CV-restitution curves are a common feature of in vitro cultures of rat cardiac cells. We also find that the Fenton–Karma model, one of the well-established mathematical models of cardiac tissue, supports a very similar non-monotonic CV restitution in a physiologically relevant parameter regime. Surprisingly, the mathematical model as well as the cell cultures support bistability and show cardiac memory that tends to work against the generation of an alternans. Bistability was realized by adopting two different stimulation protocols, ‘S1S2’, which produces a period-1 wave train, and ‘alternans-pacing’, which favors a concordant alternans. Thus, we conclude that the single-hump non-monotonicity in the CV-restitution curve is not sufficient to guarantee a cardiac alternans, since cardiac memory interferes and the way the system is paced matters. (paper)
Neuromuscular dose-response studies: determining sample size.
Kopman, A F; Lien, C A; Naguib, M
2011-02-01
Investigators planning dose-response studies of neuromuscular blockers have rarely used a priori power analysis to determine the minimal sample size their protocols require. Institutional Review Boards and peer-reviewed journals now generally ask for this information. This study outlines a proposed method for meeting these requirements. The slopes of the dose-response relationships of eight neuromuscular blocking agents were determined using regression analysis. These values were substituted for γ in the Hill equation. When this is done, the coefficient of variation (COV) around the mean value of the ED₅₀ for each drug is easily calculated. Using these values, we performed an a priori one-sample two-tailed t-test of the means to determine the required sample size when the allowable error in the ED₅₀ was varied from ±10-20%. The COV averaged 22% (range 15-27%). We used a COV value of 25% in determining the sample size. If the allowable error in finding the mean ED₅₀ is ±15%, a sample size of 24 is needed to achieve a power of 80%. Increasing 'accuracy' beyond this point requires increasing greater sample sizes (e.g. an 'n' of 37 for a ±12% error). On the basis of the results of this retrospective analysis, a total sample size of not less than 24 subjects should be adequate for determining a neuromuscular blocking drug's clinical potency with a reasonable degree of assurance.
TESS-based dose-response using pediatric clonidine exposures
International Nuclear Information System (INIS)
Benson, Blaine E.; Spyker, Daniel A.; Troutman, William G.; Watson, William A.
2006-01-01
Objective: The toxic and lethal doses of clonidine in children are unclear. This study was designed to determine whether data from the American Association of Poison Control Centers Toxic Exposure Surveillance System (TESS) could be utilized to determine a dose-response relationship for pediatric clonidine exposure. Methods: 3458 single-substance clonidine exposures in children <6 years of age reported to TESS from January 2000 through December 2003 were examined. Dose ingested, age, and medical outcome were available for 1550 cases. Respiratory arrest cases (n = 8) were classified as the most severe of the medical outcome categories (Arrest, Major, Moderate, Mild, and No effect). Exposures reported as a 'taste or lick' (n = 51) were included as a dose of 1/10 of the dosage form involved. Dose ranged from 0.4 to 1980 (median 13) μg/kg. Weight was imputed based on a quadratic estimate of weight for age. Dose certainty was coded as exact (26% of cases) or not exact (74%). Medical outcome (response) was examined via logistic regression using SAS JMP (release 5.1). Results: The logistic model describing medical outcome (P < 0.0001) included Log dose/kg (P 0.0000) and Certainty (P = 0.045). Conclusion: TESS data can provide the basis for a statistically sound description of dose-response for pediatric clonidine poisoning exposures
TESS-based dose-response using pediatric clonidine exposures.
Benson, Blaine E; Spyker, Daniel A; Troutman, William G; Watson, William A
2006-06-01
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. 3,458 single-substance clonidine exposures in children TESS from January 2000 through December 2003 were examined. Dose ingested, age, and medical outcome were available for 1550 cases. Respiratory arrest cases (n = 8) were classified as the most severe of the medical outcome categories (Arrest, Major, Moderate, Mild, and No effect). Exposures reported as a "taste or lick" (n = 51) were included as a dose of 1/10 of the dosage form involved. Dose ranged from 0.4 to 1980 (median 13) microg/kg. Weight was imputed based on a quadratic estimate of weight for age. Dose certainty was coded as exact (26% of cases) or not exact (74%). Medical outcome (response) was examined via logistic regression using SAS JMP (release 5.1). The logistic model describing medical outcome (P TESS data can provide the basis for a statistically sound description of dose-response for pediatric clonidine poisoning exposures.
Monotone Comparative Statics for the Industry Composition
DEFF Research Database (Denmark)
Laugesen, Anders Rosenstand; Bache, Peter Arendorf
2015-01-01
We let heterogeneous firms face decisions on a number of complementary activities in a monopolistically-competitive industry. The endogenous level of competition and selection regarding entry and exit of firms introduces a wedge between monotone comparative statics (MCS) at the firm level and MCS...... for the industry composition. The latter phenomenon is defined as first-order stochastic dominance shifts in the equilibrium distributions of all activities across active firms. We provide sufficient conditions for MCS at both levels of analysis and show that we may have either type of MCS without the other...
International Nuclear Information System (INIS)
Oniya, E.O.; Polymeris, G.S.; Tsirliganis, N.C.; Kitis, G.
2012-01-01
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 C 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 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 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: ► 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.
The Monotonicity Puzzle: An Experimental Investigation of Incentive Structures
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Jeannette Brosig
2010-05-01
Full Text Available Non-monotone incentive structures, which - according to theory - are able to induce optimal behavior, are often regarded as empirically less relevant for labor relationships. We compare the performance of a theoretically optimal non-monotone contract with a monotone one under controlled laboratory conditions. Implementing some features relevant to real-world employment relationships, our paper demonstrates that, in fact, the frequency of income-maximizing decisions made by agents is higher under the monotone contract. Although this observed behavior does not change the superiority of the non-monotone contract for principals, they do not choose this contract type in a significant way. This is what we call the monotonicity puzzle. Detailed investigations of decisions provide a clue for solving the puzzle and a possible explanation for the popularity of monotone contracts.
International Nuclear Information System (INIS)
Levegruen, Sabine; Jackson, Andrew; Zelefsky, Michael J.; Venkatraman, Ennapadam S.; Skwarchuk, Mark W.; Schlegel, Wolfgang; Fuks, Zvi; Leibel, Steven A.; Ling, C. Clifton
2002-01-01
Background and purpose: We fit phenomenological tumor control probability (TCP) models to biopsy outcome after three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer patients to quantify the local dose-response of prostate cancer. Materials and methods: We analyzed the outcome after photon beam 3D-CRT of 103 patients with stage T1c-T3 prostate cancer treated at Memorial Sloan-Kettering Cancer Center (MSKCC) (prescribed target doses between 64.8 and 81 Gy) who had a prostate biopsy performed ≥2.5 years after end of treatment. A univariate logistic regression model based on D mean (mean dose in the planning target volume of each patient) was fit to the whole data set and separately to subgroups characterized by low and high values of tumor-related prognostic factors T-stage ( 6), and pre-treatment prostate-specific antigen (PSA) (≤10 ng/ml vs. >10 ng/ml). In addition, we evaluated five different classifications of the patients into three risk groups, based on all possible combinations of two or three prognostic factors, and fit bivariate logistic regression models with D mean and the risk group category to all patients. Dose-response curves were characterized by TCD 50 , the dose to control 50% of the tumors, and γ 50 , the normalized slope of the dose-response curve at TCD 50 . Results: D mean correlates significantly with biopsy outcome in all patient subgroups and larger values of TCD 50 are observed for patients with unfavorable compared to favorable prognostic factors. For example, TCD 50 for high T-stage patients is 7 Gy higher than for low T-stage patients. For all evaluated risk group definitions, D mean and the risk group category are independent predictors of biopsy outcome in bivariate analysis. The fit values of TCD 50 show a clear separation of 9-10.6 Gy between low and high risk patients. The corresponding dose-response curves are steeper (γ 50 =3.4-5.2) than those obtained when all patients are analyzed together (γ 50 =2
Proposal of a probabilistic dose-response model
International Nuclear Information System (INIS)
Barrachina, M.
1997-01-01
A biologically updated dose-response model is presented as an alternative to the linear-quadratic model currently in use for cancer risk assessment. The new model is based on the probability functions for misrepair and/or unrepair of DNA lesions, in terms of the radiation damage production rate in the cell (supposedly, a stem cell) and its repair-rate constant. The model makes use, interpreting it on the basis of misrepair probabilities, of the ''dose and dose-rate effectiveness factor'' of ICRP, and provides the way for a continuous extrapolation between the high and low dose-rate regions, ratifying the ''linear non-threshold hypothesis'' as the main option. Anyhow, the model throws some doubts about the additive property of the dose. (author)
Repair and dose-response at low doses
International Nuclear Information System (INIS)
Totter, J.R.; Weinberg, A.M.
1977-04-01
The DNA of each individual is subject to formation of some 2-4 x 10 14 ion pairs during the first 30 years of life from background radiation. If a single hit is sufficient to cause cancer, as is implicit in the linear, no-threshold theories, it is unclear why all individuals do not succumb to cancer, unless repair mechanisms operate to remove the damage. We describe a simple model in which the exposed population displays a distribution of repair thresholds. The dose-response at low dose is shown to depend on the shape of the threshold distribution at low thresholds. If the probability of zero threshold is zero, the response at low dose is quadratic. The model is used to resolve a longstanding discrepancy between observed incidence of leukemia at Nagasaki and the predictions of the usual linear hypothesis
Alcohol and cirrhosis: dose--response or threshold effect?
DEFF Research Database (Denmark)
Kamper-Jørgensen, Mads; Grønbaek, Morten; Tolstrup, Janne
2004-01-01
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. METHODS: A cohort of 6152...... alcohol misusing men and women aged 15-83 were interviewed about drinking pattern and social issues and followed for 84,257 person-years. Outcome was alcoholic cirrhosis mortality. Data was analyzed by means of Cox-regression models. RESULTS: In this large prospective cohort study of alcohol misusers...... there was a 27 fold increased mortality from alcoholic cirrhosis in men and a 35 fold increased mortality from alcoholic cirrhosis in women compared to the Danish population. Number of drinks per day was not significantly associated with death from alcoholic cirrhosis, since there was no additional risk of death...
Multifraction dose response of growing and resting phase hair follicles
International Nuclear Information System (INIS)
Vegesna, V.; Withers, H.R.
1987-01-01
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
Dose-response relationships for radium-induced bone sarcomas
International Nuclear Information System (INIS)
Rowland, R.E.; Stehney, A.F.; Lucas, H.F. Jr.
1981-01-01
The incidence of bone sarcomas among 3055 female radium-dial workers who entered the dial industry before 1950 was used to determine dose-response relationships for the induction of bone sarcomas by radium. Two subpopulations were analyzed: all measured cases who survived at last five years after the start of employment and all cases who survived at least two years after first measurement. The first constituted a group based on year of entry; it contained 1468 women who experienced 42 bone sarcomas; the expected number was 0.4. The second comprised a group based on first measurement; it contained 1257 women who experienced 13 bone sarcomas; the expected number was 0.2. The dose-response function, I = (C + αD + #betta#D 2 )e/sup -#betta#D/, and simplifications of this general form, were fit to each data set. Two functions, I = (C + αD + #betta#D 2 )e/sup -#betta#D/ and I = (C + #betta#D 2 )e/sup -#betta#D/, fit the data for year of entry (p greater than or equal to 0.05); both these functions and I = (C + αD) fit the data for first measurement. The function I = (C + #betta#D 2 )e/sup -#betta#D/ was used to predict the number of bone sarcomas in all other pre-1950 radium cases (medical, laboratory, and other exposure); fewer were actually observed than the fit of this function to the female dial workers predicted
The dose-response relationship for UV-tumorigenesis
International Nuclear Information System (INIS)
Gruijl, F.R. de.
1982-01-01
The main objective of the investigations was to extend the knowledge on experimental UV-carcinogenesis and to use the experimental results as guidelines for developing a dose-response model for UV-carcinogenesis. The animal experiments carried out were all long-term ones. It was decided that - in anticipation of the data to be obtained - a model for such an assessment should be developed using the experimental results available at the start of the present study (1977). This initial study is presented. The results of two animal experiments are presented, which show that UV radiation is capable of inducing a systemic effect that enhances the de novo formation of UV induced tumors. The results of the main experiment are presented. In this experiment groups of mice were subjected to daily exposure to a certain dose of UV radiation in order to find the dose-response relationship. The relation between the daily dose and the duration of the treatment till the appearance of tumors (for instance, as measured by the yield) was ascertained for tumors of different sizes. It appears that the growth of a tumor is dose-independent, and, therefore, only the initiation of a tumor is dose-dependent. Finally an experiment is presented in which it was measured that, if a mouse is subjected to daily UV exposure, the transmission of the epidermis in the shortwave UV region decreases continuously. This decrease is due to hyperplasia of the epidermis, i.e., thickening of the epidermis by an increase in the number of cells per unit surface area. (Auth.)
Generalized convexity, generalized monotonicity recent results
Martinez-Legaz, Juan-Enrique; Volle, Michel
1998-01-01
A function is convex if its epigraph is convex. This geometrical structure has very strong implications in terms of continuity and differentiability. Separation theorems lead to optimality conditions and duality for convex problems. A function is quasiconvex if its lower level sets are convex. Here again, the geo metrical structure of the level sets implies some continuity and differentiability properties for quasiconvex functions. Optimality conditions and duality can be derived for optimization problems involving such functions as well. Over a period of about fifty years, quasiconvex and other generalized convex functions have been considered in a variety of fields including economies, man agement science, engineering, probability and applied sciences in accordance with the need of particular applications. During the last twenty-five years, an increase of research activities in this field has been witnessed. More recently generalized monotonicity of maps has been studied. It relates to generalized conve...
Wang, Yan; Xu, Chang; Du, Li Qing; Cao, Jia; Liu, Jian Xiang; Su, Xu; Zhao, Hui; Fan, Fei-Yue; Wang, Bing; Katsube, Takanori; Fan, Sai Jun; Liu, Qiang
2013-01-01
Dose- and time-response curves were combined to assess the potential of the comet assay in radiation biodosimetry. The neutral comet assay was used to detect DNA double-strand breaks in lymphocytes caused by γ-ray irradiation. A clear dose-response relationship with DNA double-strand breaks using the comet assay was found at different times after irradiation (p < 0.001). A time-response relationship was also found within 72 h after irradiation (p < 0.001). The curves for DNA double-strand breaks and DNA repair in vitro of human lymphocytes presented a nice model, and a smooth, three-dimensional plane model was obtained when the two curves were combined. PMID:24240807
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Qiang Liu
2013-11-01
Full Text Available Dose- and time-response curves were combined to assess the potential of the comet assay in radiation biodosimetry. The neutral comet assay was used to detect DNA double-strand breaks in lymphocytes caused by γ-ray irradiation. A clear dose-response relationship with DNA double-strand breaks using the comet assay was found at different times after irradiation (p < 0.001. A time-response relationship was also found within 72 h after irradiation (p < 0.001. The curves for DNA double-strand breaks and DNA repair in vitro of human lymphocytes presented a nice model, and a smooth, three-dimensional plane model was obtained when the two curves were combined.
Non-monotonic dose dependence of the Ge- and Ti-centres in quartz
International Nuclear Information System (INIS)
Woda, C.; Wagner, G.A.
2007-01-01
The dose response of the Ge- and Ti-centres in quartz is studied over a large dose range. After an initial signal increase in the low dose range, both defects show a pronounced decrease in signal intensities for high doses. The model by Euler and Kahan [1987. Radiation effects and anelastic loss in germanium-doped quartz. Phys. Rev. B 35 (9), 4351-4359], in which the signal drop is explained by an enhanced trapping of holes at the electron trapping site, is critically discussed. A generalization of the model is then developed, following similar considerations by Lawless et al. [2005. A model for non-monotonic dose dependence of thermoluminescence (TL). J. Phys. Condens. Matter 17, 737-753], who explained a signal drop in TL by an enhanced recombination rate with electrons at the recombination centre. Finally, an alternative model for the signal decay is given, based on the competition between single and double electron capture at the electron trapping site. From the critical discussion of the different models it is concluded that the double electron capture mechanism is the most probable effect for the dose response
Energy Technology Data Exchange (ETDEWEB)
Berrington de Gonzalez, Amy, E-mail: berringtona@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Gilbert, Ethel; Curtis, Rochelle; Inskip, Peter; Kleinerman, Ruth; Morton, Lindsay; Rajaraman, Preetha; Little, Mark P. [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)
2013-06-01
Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studies of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of ≥60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques.
DEFF Research Database (Denmark)
Carlsen, B C; Fischer, Louise Arup; Sosted, H
2009-01-01
with nickel sulphate, methyldibromo glutaronitrile (MDBGN) and p-phenylenediamine (PPD) in dilution series. The ratio between the doses eliciting a response in 50% of patients in the two groups was used as the measure for relative sensitivity. RESULTS: The dose-response curves of the polysensitized group...... for MDBGN and PPD were shifted to the right, and for nickel sulphate shifted to the left, compared with the single/double-sensitized group. The relative sensitivity for each of the three allergens and a combined relative sensitivity for all three allergens were not significantly different when comparing...
Type monotonic allocation schemes for multi-glove games
Brânzei, R.; Solymosi, T.; Tijs, S.H.
2007-01-01
Multiglove markets and corresponding games are considered.For this class of games we introduce the notion of type monotonic allocation scheme.Allocation rules for multiglove markets based on weight systems are introduced and characterized.These allocation rules generate type monotonic allocation schemes for multiglove games and are also helpful in proving that each core element of the corresponding game is extendable to a type monotonic allocation scheme.The T-value turns out to generate a ty...
Dose-response relationship in local radiotherapy for hepatocellular carcinoma
International Nuclear Information System (INIS)
Park, Hee Chul; Seong, Jinsil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Suh, Chang Ok
2002-01-01
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
Stability of dynamical systems on the role of monotonic and non-monotonic Lyapunov functions
Michel, Anthony N; Liu, Derong
2015-01-01
The second edition of this textbook provides a single source for the analysis of system models represented by continuous-time and discrete-time, finite-dimensional and infinite-dimensional, and continuous and discontinuous dynamical systems. For these system models, it presents results which comprise the classical Lyapunov stability theory involving monotonic Lyapunov functions, as well as corresponding contemporary stability results involving non-monotonicLyapunov functions.Specific examples from several diverse areas are given to demonstrate the applicability of the developed theory to many important classes of systems, including digital control systems, nonlinear regulator systems, pulse-width-modulated feedback control systems, and artificial neural networks. The authors cover the following four general topics: - Representation and modeling of dynamical systems of the types described above - Presentation of Lyapunov and Lagrange stability theory for dynamical sy...
Stepsize Restrictions for Boundedness and Monotonicity of Multistep Methods
Hundsdorfer, W.
2011-04-29
In this paper nonlinear monotonicity and boundedness properties are analyzed for linear multistep methods. We focus on methods which satisfy a weaker boundedness condition than strict monotonicity for arbitrary starting values. In this way, many linear multistep methods of practical interest are included in the theory. Moreover, it will be shown that for such methods monotonicity can still be valid with suitable Runge-Kutta starting procedures. Restrictions on the stepsizes are derived that are not only sufficient but also necessary for these boundedness and monotonicity properties. © 2011 Springer Science+Business Media, LLC.
Biophysical Monitoring and dose response characteristics of irradiated hemoglobin
International Nuclear Information System (INIS)
Elshemey, W.M; Selim, N.S.; Desouky, O.
2003-01-01
The present work aims to move a step forward towards a deeper understanding of the scattering of x-ray, from lyophilized biological samples. Comparative study has been performed using LAXS and UV-visible spectrophotometry for monitoring the dose response characteristics of the hemoglobin molecule of irradiated blood. Blood samples were irradiated at doses ranging from 5 up to 100 Gy. Diluted hemoglobin solution was scanned in the UV- visible range (200-700 nm), and lyophilized hemoglobin was prepared for LAXS measurement. The radiation-induced changes in the hemoglobin structure have been evaluated. The LAXS profile of hemoglobin molecule is characterized by the presence of two peaks in the forward direction of scattering. These peaks were found to be sensitive to the variations in the molecular structure of a given sample. The obtained results suggest that the 1 s t peak, recorded at 4.65 o , is sensitive to the tertiary and quaternary structure of the globin part, while the major peak, recorded at 10.5 o , appeared to be related to its primary and secondary structure
Optimal dose-response relationships in voice therapy.
Roy, Nelson
2012-10-01
Like other areas of speech-language pathology, the behavioural management of voice disorders lacks precision regarding optimal dose-response relationships. In voice therapy, dosing can presumably vary from no measurable effect (i.e., no observable benefit or adverse effect), to ideal dose (maximum benefit with no adverse effects), to doses that produce toxic or harmful effects on voice production. Practicing specific vocal exercises will inevitably increase vocal load. At ideal doses, these exercises may be non-toxic and beneficial, while at intermediate or high doses, the same exercises may actually be toxic or damaging to vocal fold tissues. In pharmacology, toxicity is a critical concept, yet it is rarely considered in voice therapy, with little known regarding "effective" concentrations of specific voice therapies vs "toxic" concentrations. The potential for vocal fold tissue damage related to overdosing on specific vocal exercises has been under-studied. In this commentary, the issue of dosing will be explored within the context of voice therapy, with particular emphasis placed on possible "overdosing".
Monotone measures of ergodicity for Markov chains
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J. Keilson
1998-01-01
Full Text Available The following paper, first written in 1974, was never published other than as part of an internal research series. Its lack of publication is unrelated to the merits of the paper and the paper is of current importance by virtue of its relation to the relaxation time. A systematic discussion is provided of the approach of a finite Markov chain to ergodicity by proving the monotonicity of an important set of norms, each measures of egodicity, whether or not time reversibility is present. The paper is of particular interest because the discussion of the relaxation time of a finite Markov chain [2] has only been clean for time reversible chains, a small subset of the chains of interest. This restriction is not present here. Indeed, a new relaxation time quoted quantifies the relaxation time for all finite ergodic chains (cf. the discussion of Q1(t below Equation (1.7]. This relaxation time was developed by Keilson with A. Roy in his thesis [6], yet to be published.
Directory of Open Access Journals (Sweden)
Sencer Buzrul
2017-09-01
Full Text Available Modeling of microbial inactivation by high hydrostatic pressure (HHP requires a plot of the log microbial count or survival ratio versus time data under a constant pressure and temperature. However, at low pressure and temperature values, very long holding times are needed to obtain measurable inactivation. Since the time has a significant effect on the cost of HHP processing it may be reasonable to fix the time at an appropriate value and quantify the inactivation with respect to pressure. Such a plot is called dose-response curve and it may be more beneficial than the traditional inactivation modeling since short holding times with different pressure values can be selected and used for the modeling of HHP inactivation. For this purpose, 49 dose-response curves (with at least 4 log10 reduction and ≥5 data points including the atmospheric pressure value (P = 0.1 MPa, and with holding time ≤10 min for HHP inactivation of microorganisms obtained from published studies were fitted with four different models, namely the Discrete model, Shoulder model, Fermi equation, and Weibull model, and the pressure value needed for 5 log10 (P5 inactivation was calculated for all the models above. The Shoulder model and Fermi equation produced exactly the same parameter and P5 values, while the Discrete model produced similar or sometimes the exact same parameter values as the Fermi equation. The Weibull model produced the worst fit (had the lowest adjusted determination coefficient (R2adj and highest mean square error (MSE values, while the Fermi equation had the best fit (the highest R2adj and lowest MSE values. Parameters of the models and also P5 values of each model can be useful for the further experimental design of HHP processing and also for the comparison of the pressure resistance of different microorganisms. Further experiments can be done to verify the P5 values at given conditions. The procedure given in this study can also be extended for
Logarithmically completely monotonic functions involving the Generalized Gamma Function
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Faton Merovci
2010-12-01
Full Text Available By a simple approach, two classes of functions involving generalization Euler's gamma function and originating from certain problems of traffic flow are proved to be logarithmically completely monotonic and a class of functions involving the psi function is showed to be completely monotonic.
Logarithmically completely monotonic functions involving the Generalized Gamma Function
Faton Merovci; Valmir Krasniqi
2010-01-01
By a simple approach, two classes of functions involving generalization Euler's gamma function and originating from certain problems of traffic flow are proved to be logarithmically completely monotonic and a class of functions involving the psi function is showed to be completely monotonic.
Testing manifest monotonicity using order-constrained statistical inference
Tijmstra, J.; Hessen, D.J.; van der Heijden, P.G.M.; Sijtsma, K.
2013-01-01
Most dichotomous item response models share the assumption of latent monotonicity, which states that the probability of a positive response to an item is a nondecreasing function of a latent variable intended to be measured. Latent monotonicity cannot be evaluated directly, but it implies manifest
Shared dosimetry error in epidemiological dose-response analyses
International Nuclear Information System (INIS)
Stram, Daniel O.; Preston, Dale L.; Sokolnikov, Mikhail; Napier, Bruce; Kopecky, Kenneth J.; Boice, John; Beck, Harold; Till, John; Bouville, Andre; Zeeb, Hajo
2015-01-01
Radiation dose reconstruction systems for large-scale epidemiological studies are sophisticated both in providing estimates of dose and in representing dosimetry uncertainty. For example, a computer program was used by the Hanford Thyroid Disease Study to provide 100 realizations of possible dose to study participants. The variation in realizations reflected the range of possible dose for each cohort member consistent with the data on dose determinates in the cohort. Another example is the Mayak Worker Dosimetry System 2013 which estimates both external and internal exposures and provides multiple realizations of 'possible' dose history to workers given dose determinants. This paper takes up the problem of dealing with complex dosimetry systems that provide multiple realizations of dose in an epidemiologic analysis. In this paper we derive expected scores and the information matrix for a model used widely in radiation epidemiology, namely the linear excess relative risk (ERR) model that allows for a linear dose response (risk in relation to radiation) and distinguishes between modifiers of background rates and of the excess risk due to exposure. We show that treating the mean dose for each individual (calculated by averaging over the realizations) as if it was true dose (ignoring both shared and unshared dosimetry errors) gives asymptotically unbiased estimates (i.e. the score has expectation zero) and valid tests of the null hypothesis that the ERR slope β is zero. Although the score is unbiased the information matrix (and hence the standard errors of the estimate of β) is biased for β≠0 when ignoring errors in dose estimates, and we show how to adjust the information matrix to remove this bias, using the multiple realizations of dose. The use of these methods in the context of several studies including, the Mayak Worker Cohort, and the U.S. Atomic Veterans Study, is discussed
Dose-response relationship in the treatment of gastrointestinal disorders.
Weihrauch, T R; Demol, P
1989-08-01
Numerous clinical studies have been performed to establish efficacy and safety of drugs in gastroenterological disorders. Only in a few if any of these studies, however, the rationale for the optimal dose and the dose regimens, respectively, have been addressed. Adequate and well-controlled dose finding studies play a key role in the clinical assessment of new drugs and in the evaluation of new indications. Hereby the range from the minimal effective dose to the maximal effective and well tolerated dose can be assessed and thus the optimal dose-range and dosage regimen be determined. Meaningful pharmacodynamic studies can be performed in the gastrointestinal tract also in healthy volunteers provided that a method with a high predictability for the desired therapeutic effect is available such as measurement of gastric acid secretion and its inhibition by a drug. Dose finding studies in gastroenterology can be carried out under two main aspects: First, to assess the pharmacodynamic and therapeutic effect of a compound on the gastrointestinal tract (e.g. anti-ulcer drug). Second, to evaluate the side effects of a drug on the gastrointestinal tract (e.g. gastric mucosal damage by non-steroidal anti-inflammatory drugs). For the evaluation of new drugs in gastrointestinal therapy a number of methods are available which yield accurate and reproducible data. While careful clinical-pharmacological dose-response studies using these methods have been carried out already more than a decade ago, it is surprising that therapeutic dose finding studies have become available only during the past few years. For scientific as well as for ethical reasons more trials which determine the optimal therapeutic dose are warranted.
Chronic periodontitis and smoking. Prevalence and dose-response relationship.
Khan, Shahrukh; Khalid, Taimur; Awan, Kamran H
2016-08-01
To determine the prevalence and dose-response relationship of chronic periodontitis among smokers in Pakistan. This is a cross-sectional study among participants seeking dental care in Karachi Medical and Dental College, Karachi, Pakistan. A total of 443 participants with a mean age of 44.3 (±6.5) participated in the study from April 2011 to December 2011. Males comprised 64.7%, and females comprised 35.2%. Participants were interviewed on social demographics and oral habits. Participants with shallow pockets (3.5-5.5 mm) and deep pockets (greater than 5.5 mm) were considered suffering from chronic periodontitis. The characteristics of participants were assessed using frequency distribution for categorical variables and mean (standard deviation) for continuous variables. Among 443 participants, smokers were distributed as 55.1% and non-smokers as 44.9%. Smoking was found to be significantly related to young adults (p less than 0.007), male gender (p less than 0.001), and lower education level (p less than 0.01). Overall prevalence of chronic periodontitis among smokers was estimated at 81.6%. Heavy smoking was found to have significantly high prevalence (p less than 0.001) and severity (p less than 0.001) of periodontitis as compared with moderate and light smokers. The multivariate unadjusted model depicted 3.5 times higher risk of chronic periodontitis among smokers (p less than 0.001). Chronic periodontitis had a high prevalence among smokers. Heavy smoking was found to have a higher risk for having periodontitis.
Ma Shao Gang; Song Yi Xin
2002-01-01
Objective: To study the dose response characteristics and the influence factors such as gantry angle, field size and acquisition mode on the dosimetric response curves, when using a scanning liquid ion-chamber electronic portal imaging device (EPID) for dose verification. Methods: All experiments were carried out on a Varian 600 C/D accelerator (6 MV X-ray) equipped with a Varian PortalVision sup T sup M MK2 type EPID. To obtain the dose response curve, the relationship between the incident radiation intensity to the detector and the pixel value output from the EPID were established. Firstly, the different dose rates of 6 MV X-rays were obtained by varying SSD. Secondly, three digital portal images were acquired for each dose rate using the EPID and averaged to avoid the influence of the dose rate fluctuations of the accelerator. The pixel values of all images were read using self-designed image analysis software, and and average for a region consisting of 11 x 11 pixels around the center was taken as the res...
Using plant biomonitors and flux modelling to develop O3 dose-response relationships in Catalonia
International Nuclear Information System (INIS)
Filella, Iolanda; Pen-tilde uelas, Josep; Ribas, Angela
2005-01-01
We used tobacco Bel-W3 biomonitoring data and ozone flux modelling (WINDEP model) with the aim of developing the absorbed dose-response relationship, and comparing this approach with the most commonly used AOT40 (the sum of hourly ozone concentrations above a cut-off of 40 ppb during daylight hours, when global radiation exceeds 50 W m -2 ) in the estimation of exposure-damage curves. Leaf damage values were more related to OAD 15days,potential (potential ozone absorbed dose calculated over 15 consecutive days) than to AOT40 in all the studied stations. An OAD 15days,potential of 180 mg m -2 was found to be the threshold for damage to the most sensitive species in this region under well watered conditions. The results show the applicability of the flux approach for risk assessment at the local scale, the improvement of the ozone damage estimation when the potential absorbed dose is modelled and used instead of just the ozone exposure, and finally, the possibilities opened by the use of biomonitoring networks. - Modelling of biomonitors ozone absorbed dose improves damage estimation in comparison with exposure indices such as AOT40
Dose-response relationships and threshold levels in skin and respiratory allergy
Arts, J.H.E.; Mommers, C.; Heer, C.de
2006-01-01
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
International Nuclear Information System (INIS)
Kim, J. S.; Yang, M.; Kim, J.; Lee, D.; Kim, J. C.; Shin, T.; Kim, S. H.; Moon, C.
2012-01-01
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)
Strong monotonicity in mixed-state entanglement manipulation
International Nuclear Information System (INIS)
Ishizaka, Satoshi
2006-01-01
A strong entanglement monotone, which never increases under local operations and classical communications (LOCC), restricts quantum entanglement manipulation more strongly than the usual monotone since the usual one does not increase on average under LOCC. We propose strong monotones in mixed-state entanglement manipulation under LOCC. These are related to the decomposability and one-positivity of an operator constructed from a quantum state, and reveal geometrical characteristics of entangled states. These are lower bounded by the negativity or generalized robustness of entanglement
Monotonicity-based electrical impedance tomography for lung imaging
Zhou, Liangdong; Harrach, Bastian; Seo, Jin Keun
2018-04-01
This paper presents a monotonicity-based spatiotemporal conductivity imaging method for continuous regional lung monitoring using electrical impedance tomography (EIT). The EIT data (i.e. the boundary current-voltage data) can be decomposed into pulmonary, cardiac and other parts using their different periodic natures. The time-differential current-voltage operator corresponding to the lung ventilation can be viewed as either semi-positive or semi-negative definite owing to monotonic conductivity changes within the lung regions. We used these monotonicity constraints to improve the quality of lung EIT imaging. We tested the proposed methods in numerical simulations, phantom experiments and human experiments.
The alanine detector in BNCT dosimetry: dose response in thermal and epithermal neutron fields.
Schmitz, T; Bassler, N; Blaickner, M; Ziegner, M; Hsiao, M C; Liu, Y H; Koivunoro, H; Auterinen, I; Serén, T; Kotiluoto, P; Palmans, H; Sharpe, P; Langguth, P; Hampel, G
2015-01-01
The response of alanine solid state dosimeters to ionizing radiation strongly depends on particle type and energy. Due to nuclear interactions, neutron fields usually also consist of secondary particles such as photons and protons of diverse energies. Various experiments have been carried out in three different neutron beams to explore the alanine dose response behavior and to validate model predictions. Additionally, application in medical neutron fields for boron neutron capture therapy is discussed. Alanine detectors have been irradiated in the thermal neutron field of the research reactor TRIGA Mainz, Germany, in five experimental conditions, generating different secondary particle spectra. Further irradiations have been made in the epithermal neutron beams at the research reactors FiR 1 in Helsinki, Finland, and Tsing Hua open pool reactor in HsinChu, Taiwan ROC. Readout has been performed with electron spin resonance spectrometry with reference to an absorbed dose standard in a (60)Co gamma ray beam. Absorbed doses and dose components have been calculated using the Monte Carlo codes fluka and mcnp. The relative effectiveness (RE), linking absorbed dose and detector response, has been calculated using the Hansen & Olsen alanine response model. The measured dose response of the alanine detector in the different experiments has been evaluated and compared to model predictions. Therefore, a relative effectiveness has been calculated for each dose component, accounting for its dependence on particle type and energy. Agreement within 5% between model and measurement has been achieved for most irradiated detectors. Significant differences have been observed in response behavior between thermal and epithermal neutron fields, especially regarding dose composition and depth dose curves. The calculated dose components could be verified with the experimental results in the different primary and secondary particle fields. The alanine detector can be used without
Thor, Maria; Owosho, Adepitan A; Clark, Haley D; Oh, Jung Hun; Riaz, Nadeem; Hovan, Allan; Tsai, Jillian; Thomas, Steven D; Yom, Sae Hee K; Wu, Jonn S; Huryn, Joseph M; Moiseenko, Vitali; Lee, Nancy Y; Estilo, Cherry L; Deasy, Joseph O
2017-02-01
To study internal and external generalizability of temporal dose-response relationships for xerostomia after intensity-modulated radiotherapy (IMRT) for head and neck cancer, and to investigate potential amendments of the QUANTEC guidelines. Objective xerostomia was assessed in 121 patients (n Cohort1 =55; n Cohort2 =66) treated to 70Gy@2Gy in 2006-2015. Univariate and multivariate analyses (UVA, MVA with 1000 bootstrap populations) were conducted in Cohort1, and generalizability of the best-performing MVA model was investigated in Cohort2 (performance: AUC, p-values, and Hosmer-Lemeshow p-values (p HL )). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmean contra , Dmean ipsi ) were estimated from the generated dose-response curves. The observed xerostomia rate was 38%/47% (3months) and 19%/23% (11-12months) in Cohort1/Cohort2. Risk of xerostomia at 3months increased for higher Dmean contra and Dmean ipsi (Cohort1: 0.17·Dmean contra +0.11·Dmean ipsi -8.13; AUC=0.90±0.05; p=0.0002±0.002; p HL =0.22±0.23; Cohort2: AUC=0.81; pxerostomia following IMRT. Our results also suggest decreasing Dmean contra to below 20Gy, while keeping Dmean ipsi to around 25Gy. Long-term xerostomia was less frequent, and no dose-response relationship was established for this follow-up time. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Dose-response relationship of γ-H2AX foci induction in human lymphocytes after X-rays exposure
International Nuclear Information System (INIS)
Mandina, Tania; Roch-Lefevre, Sandrine H.; Voisin, Pascale; Gonzalez, Jorge E.; Lamadrid, Ana I.; Romero, Ivonne; Garcia, Omar; Voisin, Philippe; Roy, Laurence
2011-01-01
Biological dosimeters are recommended for dose estimation in case of human overexposure to ionising radiation. Rapid measurement of γ-H2AX foci as a marker of DNA double-strand breaks (DSB) induction has been recently tested with this purpose. Here we reported a dose-response relationship after X-ray irradiation at different times post-exposure. Blood samples were obtained from several healthy donors and exposed to doses between 0 and 2 Gy. After irradiation, blood samples were incubated at 37 deg. C during 0.5 h, 5 h, and 8 h. Scoring of cells and γ-H2AX foci was performed by software. The dose-response curves for different incubation times were as follows: Y (0.5h) = 11.66D + 0.15 (R 2 = 0.99), Y (5h) = 2.44D + 0.15 (R 2 = 0.99), Y (8h) = 1.57D + 0.22 (R 2 = 0.99). At 0.5 h post-exposure, the dose-response relationship for X-irradiated lymphocytes was similar to the one obtained after gamma-irradiation using the same protocol. On the other hand, the results were not similar after 8 h due to different kinetics after gamma- and X-irradiation. Our results confirm the possibilities of using γ-H2AX foci method for dose estimation in a period from 0.5 h up to 8 h post X-irradiation and support the hypothesis of differences in γ-H2AX foci kinetics after gamma- and X-irradiation in vitro.
Energy Technology Data Exchange (ETDEWEB)
Adamus-Górka, Magdalena; Mavroidis, Panayiotis, E-mail: panayiotis.mavroidis@ki.se; Lind, Bengt K.; Brahme, Anders [Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm S-17176 (Sweden)
2011-05-18
Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ{sup 2}-distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint.
International Nuclear Information System (INIS)
Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Lind, Bengt K.; Brahme, Anders
2011-01-01
Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ 2 -distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint
Dose-response relationship of {gamma}-H2AX foci induction in human lymphocytes after X-rays exposure
Energy Technology Data Exchange (ETDEWEB)
Mandina, Tania [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Roch-Lefevre, Sandrine H.; Voisin, Pascale [Institut de Radioprotection et de Surete Nucleaire (IRSN), DRPH, SRBE, LDB, BP17, 92262 Fontenay-aux-Roses (France); Gonzalez, Jorge E.; Lamadrid, Ana I.; Romero, Ivonne [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Garcia, Omar, E-mail: omar@cphr.edu.cu [Centro de Proteccion e Higiene de las Radiaciones, Calle 20 No. 4113 e/41y 47 Miramar, AP 6195 C. Habana (Cuba); Voisin, Philippe; Roy, Laurence [Institut de Radioprotection et de Surete Nucleaire (IRSN), DRPH, SRBE, LDB, BP17, 92262 Fontenay-aux-Roses (France)
2011-09-15
Biological dosimeters are recommended for dose estimation in case of human overexposure to ionising radiation. Rapid measurement of {gamma}-H2AX foci as a marker of DNA double-strand breaks (DSB) induction has been recently tested with this purpose. Here we reported a dose-response relationship after X-ray irradiation at different times post-exposure. Blood samples were obtained from several healthy donors and exposed to doses between 0 and 2 Gy. After irradiation, blood samples were incubated at 37 deg. C during 0.5 h, 5 h, and 8 h. Scoring of cells and {gamma}-H2AX foci was performed by software. The dose-response curves for different incubation times were as follows: Y{sub (0.5h)} = 11.66D + 0.15 (R{sup 2} = 0.99), Y{sub (5h)} = 2.44D + 0.15 (R{sup 2} = 0.99), Y{sub (8h)} = 1.57D + 0.22 (R{sup 2} = 0.99). At 0.5 h post-exposure, the dose-response relationship for X-irradiated lymphocytes was similar to the one obtained after gamma-irradiation using the same protocol. On the other hand, the results were not similar after 8 h due to different kinetics after gamma- and X-irradiation. Our results confirm the possibilities of using {gamma}-H2AX foci method for dose estimation in a period from 0.5 h up to 8 h post X-irradiation and support the hypothesis of differences in {gamma}-H2AX foci kinetics after gamma- and X-irradiation in vitro.
Risk-Sensitive Control with Near Monotone Cost
International Nuclear Information System (INIS)
Biswas, Anup; Borkar, V. S.; Suresh Kumar, K.
2010-01-01
The infinite horizon risk-sensitive control problem for non-degenerate controlled diffusions is analyzed under a 'near monotonicity' condition on the running cost that penalizes large excursions of the process.
An Examination of Cooper's Test for Monotonic Trend
Hsu, Louis
1977-01-01
A statistic for testing monotonic trend that has been presented in the literature is shown not to be the binomial random variable it is contended to be, but rather it is linearly related to Kendall's tau statistic. (JKS)
A Survey on Operator Monotonicity, Operator Convexity, and Operator Means
Directory of Open Access Journals (Sweden)
Pattrawut Chansangiam
2015-01-01
Full Text Available This paper is an expository devoted to an important class of real-valued functions introduced by Löwner, namely, operator monotone functions. This concept is closely related to operator convex/concave functions. Various characterizations for such functions are given from the viewpoint of differential analysis in terms of matrix of divided differences. From the viewpoint of operator inequalities, various characterizations and the relationship between operator monotonicity and operator convexity are given by Hansen and Pedersen. In the viewpoint of measure theory, operator monotone functions on the nonnegative reals admit meaningful integral representations with respect to Borel measures on the unit interval. Furthermore, Kubo-Ando theory asserts the correspondence between operator monotone functions and operator means.
Completely monotonic functions related to logarithmic derivatives of entire functions
DEFF Research Database (Denmark)
Pedersen, Henrik Laurberg
2011-01-01
The logarithmic derivative l(x) of an entire function of genus p and having only non-positive zeros is represented in terms of a Stieltjes function. As a consequence, (-1)p(xml(x))(m+p) is a completely monotonic function for all m ≥ 0. This generalizes earlier results on complete monotonicity...... of functions related to Euler's psi-function. Applications to Barnes' multiple gamma functions are given....
Monotonic Loading of Circular Surface Footings on Clay
DEFF Research Database (Denmark)
Ibsen, Lars Bo; Barari, Amin
2011-01-01
Appropriate modeling of offshore foundations under monotonic loading is a significant challenge in geotechnical engineering. This paper reports experimental and numerical analyses, specifically investigating the response of circular surface footings during monotonic loading and elastoplastic...... behavior during reloading. By using the findings presented in this paper, it is possible to extend the model to simulate the vertical-load displacement response of offshore bucket foundations....
Low dose response analysis through a cytogenetic end-point
International Nuclear Information System (INIS)
Bojtor, I.; Koeteles, G.J.
1998-01-01
The effects of low doses were studied on human lymphocytes of various individuals. The frequency of micronuclei in cytokinesis-blocked cultured lymphocytes was taken as end-point. The probability distribution of radiation-induced increment was statistically proved and identified as to be asymmetric when the blood samples had been irradiated with doses of 0.01-0.05 Gy of X-rays, similarly to that in unirradiated control population. On the contrary, at or above 1 Gy the corresponding normal curve could be accepted only reflecting an approximately symmetrical scatter of the increments about their mean value. It was found that the slope as well as the closeness of correlation of the variables considerably changed when lower and lower dose ranges had been selected. Below approximately 0.2 Gy even an unrelatedness was found betwen the absorbed dose and the increment
Dose-response relationships of acute exposure to sulfur dioxide
International Nuclear Information System (INIS)
Englehardt, F.R.; Holliday, M.G.
1981-01-01
Acute toxicity effects of sulphur dioxide are reviewed, and the derivation of a dose-lethality curve (presented as LC 50 vs. time) for human exposure to sulphur dioxide is attempted for periods ranging from ten seconds to two hours. As an aid to assessment of the hazards involved in operating heavy water manufacturing facilities, the fact that sulphur dioxide would be produced by the combustion of hydrogen sulphide was briefly considered in an appendix. It is suggested that sulphuric acid, a much more toxic substance than sulphur dioxide, may also be formed in such an event. It is concluded, therefore, that an overall hazard evaluation may have to address the contributory effects of sulphuric acid. (author)
Moduli and Characteristics of Monotonicity in Some Banach Lattices
Directory of Open Access Journals (Sweden)
Miroslav Krbec
2010-01-01
Full Text Available First the characteristic of monotonicity of any Banach lattice X is expressed in terms of the left limit of the modulus of monotonicity of X at the point 1. It is also shown that for Köthe spaces the classical characteristic of monotonicity is the same as the characteristic of monotonicity corresponding to another modulus of monotonicity δ^m,E. The characteristic of monotonicity of Orlicz function spaces and Orlicz sequence spaces equipped with the Luxemburg norm are calculated. In the first case the characteristic is expressed in terms of the generating Orlicz function only, but in the sequence case the formula is not so direct. Three examples show why in the sequence case so direct formula is rather impossible. Some other auxiliary and complemented results are also presented. By the results of Betiuk-Pilarska and Prus (2008 which establish that Banach lattices X with ε0,m(X<1 and weak orthogonality property have the weak fixed point property, our results are related to the fixed point theory (Kirk and Sims (2001.
Specific non-monotonous interactions increase persistence of ecological networks.
Yan, Chuan; Zhang, Zhibin
2014-03-22
The relationship between stability and biodiversity has long been debated in ecology due to opposing empirical observations and theoretical predictions. Species interaction strength is often assumed to be monotonically related to population density, but the effects on stability of ecological networks of non-monotonous interactions that change signs have not been investigated previously. We demonstrate that for four kinds of non-monotonous interactions, shifting signs to negative or neutral interactions at high population density increases persistence (a measure of stability) of ecological networks, while for the other two kinds of non-monotonous interactions shifting signs to positive interactions at high population density decreases persistence of networks. Our results reveal a novel mechanism of network stabilization caused by specific non-monotonous interaction types through either increasing stable equilibrium points or reducing unstable equilibrium points (or both). These specific non-monotonous interactions may be important in maintaining stable and complex ecological networks, as well as other networks such as genes, neurons, the internet and human societies.
2002-01-01
The Atlas of Stress-Strain Curves, Second Edition is substantially bigger in page dimensions, number of pages, and total number of curves than the previous edition. It contains over 1,400 curves, almost three times as many as in the 1987 edition. The curves are normalized in appearance to aid making comparisons among materials. All diagrams include metric (SI) units, and many also include U.S. customary units. All curves are captioned in a consistent format with valuable information including (as available) standard designation, the primary source of the curve, mechanical properties (including hardening exponent and strength coefficient), condition of sample, strain rate, test temperature, and alloy composition. Curve types include monotonic and cyclic stress-strain, isochronous stress-strain, and tangent modulus. Curves are logically arranged and indexed for fast retrieval of information. The book also includes an introduction that provides background information on methods of stress-strain determination, on...
Teratogenic radiation effects: Phenomena, dose-response relationships and risk levels
International Nuclear Information System (INIS)
Konermann, G.
1991-01-01
The report in hand informs about a study performed within the framework of the research project 'Animal experiments with albino mice for establishing a model for the detection and assessment of radiation-induced, developmental risks in man due to low-dose irradiation'. The subjects investigated in this study are: (1) Dose-response relationships for postnatal developmental disturbances of the brain as a result of prenatal X-ray treatment. (2) Biokinetics, distribution patterns and effects of inorganically and organically bonded radioiodine (I-125) during the phase of development of the brain. For investigation of the first-mentioned subject, computerized microphotograph analysis was applied for detecting and assessing disturbances of the alignment of axons, as well as deviations from normal cross-sectional data of the Cortex layer, and cerebral commissures as final locations of neurogenetic damage. With all parameters studied, the slope of the relevant curves was found to decrease as a function of age of the fetus at the time of exposure. In addition, time factor effects were investigated. For the parameter cross-sectional area of the Cortex, a clear decrease of effect was found, but for all other parameters, reactions were ambiguous. The study into the second subject was done with cell cultures, showing that the I-125 bonded to the cell nucleus has a much stronger radiotoxic effect than I-125 bonded to the cytoplasma. This difference in effect was studied in mice after incorporation of equal doses administered by way of (I-125)-sodium iodide or (I-125)-iododesoxyuridine. Long-term effects on Cortex cross-sectional areas, cerebral commissures or the texture of axons were quantified by microphotograph analysis. Acute cell death and initial disturbances of the neuronal cell growth were evident after incorporation of (I-125)-IdUR, but not detectable after administration of (I-125)-NaI. (orig./MG) [de
Comparison of dose response functions for EBT3 model GafChromic™ film dosimetry system.
Aldelaijan, Saad; Devic, Slobodan
2018-05-01
Different dose response functions of EBT3 model GafChromic™ film dosimetry system have been compared in terms of sensitivity as well as uncertainty vs. error analysis. We also made an assessment of the necessity of scanning film pieces before and after irradiation. Pieces of EBT3 film model were irradiated to different dose values in Solid Water (SW) phantom. Based on images scanned in both reflection and transmission mode before and after irradiation, twelve different response functions were calculated. For every response function, a reference radiochromic film dosimetry system was established by generating calibration curve and by performing the error vs. uncertainty analysis. Response functions using pixel values from the green channel demonstrated the highest sensitivity in both transmission and reflection mode. All functions were successfully fitted with rational functional form, and provided an overall one-sigma uncertainty of better than 2% for doses above 2 Gy. Use of pre-scanned images to calculate response functions resulted in negligible improvement in dose measurement accuracy. Although reflection scanning mode provides higher sensitivity and could lead to a more widespread use of radiochromic film dosimetry, it has fairly limited dose range and slightly increased uncertainty when compared to transmission scan based response functions. Double-scanning technique, either in transmission or reflection mode, shows negligible improvement in dose accuracy as well as a negligible increase in dose uncertainty. Normalized pixel value of the images scanned in transmission mode shows linear response in a dose range of up to 11 Gy. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
Toward a unified approach to dose-response modeling in ecotoxicology.
Ritz, Christian
2010-01-01
This study reviews dose-response models that are used in ecotoxicology. The focus lies on clarification of differences and similarities between models, and as a side effect, their different guises in ecotoxicology are unravelled. A look at frequently used dose-response models reveals major discrepancies, among other things in naming conventions. Therefore, there is a need for a unified view on dose-response modeling in order to improve the understanding of it and to facilitate communication and comparison of findings across studies, thus realizing its full potential. This study attempts to establish a general framework that encompasses most dose-response models that are of interest to ecotoxicologists in practice. The framework includes commonly used models such as the log-logistic and Weibull models, but also features entire suites of models as found in various guidance documents. An outline on how the proposed framework can be implemented in statistical software systems is also provided.
Dose response of alanine and methyl alanine towards gamma and in-situ alpha irradiation
International Nuclear Information System (INIS)
Mohapatra, M.; Rajeswari, B.; Bhide, M.K.; Rane, Vinayak; Kadam, R.M.
2017-01-01
In situ alpha and external gamma dose response of two ESR (electron spin resonance) dosimetric materials namely alanine and methyl alanine were investigated. It was observed that alanine dosimeter had a better dose response in comparison to methyl alanine for the in-situ alpha irradiation by using 239 Pu powder. On the other hand, in case of gamma radiation, methyl alanine was found to have the sensitivity as twice that of alanine. (author)
A neural network for the Bragg synthetic curves recognition
International Nuclear Information System (INIS)
Reynoso V, M.R.; Vega C, J.J.; Fernandez A, J.; Belmont M, E.; Policroniades R, R.; Moreno B, E.
1996-01-01
A ionization chamber was employed named Bragg curve spectroscopy. The Bragg peak amplitude is a monotone growing function of Z, which permits to identify elements through their measurement. A better technique for this measurement is to improve the use of neural networks with the purpose of the identification of the Bragg curve. (Author)
Simplest bifurcation diagrams for monotone families of vector fields on a torus
Baesens, C.; MacKay, R. S.
2018-06-01
In part 1, we prove that the bifurcation diagram for a monotone two-parameter family of vector fields on a torus has to be at least as complicated as the conjectured simplest one proposed in Baesens et al (1991 Physica D 49 387–475). To achieve this, we define ‘simplest’ by sequentially minimising the numbers of equilibria, Bogdanov–Takens points, closed curves of centre and of neutral saddle, intersections of curves of centre and neutral saddle, Reeb components, other invariant annuli, arcs of rotational homoclinic bifurcation of horizontal homotopy type, necklace points, contractible periodic orbits, points of neutral horizontal homoclinic bifurcation and half-plane fan points. We obtain two types of simplest case, including that initially proposed. In part 2, we analyse the bifurcation diagram for an explicit monotone family of vector fields on a torus and prove that it has at most two equilibria, precisely four Bogdanov–Takens points, no closed curves of centre nor closed curves of neutral saddle, at most two Reeb components, precisely four arcs of rotational homoclinic connection of ‘horizontal’ homotopy type, eight horizontal saddle-node loop points, two necklace points, four points of neutral horizontal homoclinic connection, and two half-plane fan points, and there is no simultaneous existence of centre and neutral saddle, nor contractible homoclinic connection to a neutral saddle. Furthermore, we prove that all saddle-nodes, Bogdanov–Takens points, non-neutral and neutral horizontal homoclinic bifurcations are non-degenerate and the Hopf condition is satisfied for all centres. We also find it has four points of degenerate Hopf bifurcation. It thus provides an example of a family satisfying all the assumptions of part 1 except the one of at most one contractible periodic orbit.
Information flow in layered networks of non-monotonic units
Schittler Neves, Fabio; Martim Schubert, Benno; Erichsen, Rubem, Jr.
2015-07-01
Layered neural networks are feedforward structures that yield robust parallel and distributed pattern recognition. Even though much attention has been paid to pattern retrieval properties in such systems, many aspects of their dynamics are not yet well characterized or understood. In this work we study, at different temperatures, the memory activity and information flows through layered networks in which the elements are the simplest binary odd non-monotonic function. Our results show that, considering a standard Hebbian learning approach, the network information content has its maximum always at the monotonic limit, even though the maximum memory capacity can be found at non-monotonic values for small enough temperatures. Furthermore, we show that such systems exhibit rich macroscopic dynamics, including not only fixed point solutions of its iterative map, but also cyclic and chaotic attractors that also carry information.
Information flow in layered networks of non-monotonic units
International Nuclear Information System (INIS)
Neves, Fabio Schittler; Schubert, Benno Martim; Erichsen, Rubem Jr
2015-01-01
Layered neural networks are feedforward structures that yield robust parallel and distributed pattern recognition. Even though much attention has been paid to pattern retrieval properties in such systems, many aspects of their dynamics are not yet well characterized or understood. In this work we study, at different temperatures, the memory activity and information flows through layered networks in which the elements are the simplest binary odd non-monotonic function. Our results show that, considering a standard Hebbian learning approach, the network information content has its maximum always at the monotonic limit, even though the maximum memory capacity can be found at non-monotonic values for small enough temperatures. Furthermore, we show that such systems exhibit rich macroscopic dynamics, including not only fixed point solutions of its iterative map, but also cyclic and chaotic attractors that also carry information. (paper)
Estimating monotonic rates from biological data using local linear regression.
Olito, Colin; White, Craig R; Marshall, Dustin J; Barneche, Diego R
2017-03-01
Accessing many fundamental questions in biology begins with empirical estimation of simple monotonic rates of underlying biological processes. Across a variety of disciplines, ranging from physiology to biogeochemistry, these rates are routinely estimated from non-linear and noisy time series data using linear regression and ad hoc manual truncation of non-linearities. Here, we introduce the R package LoLinR, a flexible toolkit to implement local linear regression techniques to objectively and reproducibly estimate monotonic biological rates from non-linear time series data, and demonstrate possible applications using metabolic rate data. LoLinR provides methods to easily and reliably estimate monotonic rates from time series data in a way that is statistically robust, facilitates reproducible research and is applicable to a wide variety of research disciplines in the biological sciences. © 2017. Published by The Company of Biologists Ltd.
Scaling laws for dislocation microstructures in monotonic and cyclic deformation of fcc metals
International Nuclear Information System (INIS)
Kubin, L.P.; Sauzay, M.
2011-01-01
This work reviews and critically discusses the current understanding of two scaling laws, which are ubiquitous in the modeling of monotonic plastic deformation in face-centered cubic metals. A compilation of the available data allows extending the domain of application of these scaling laws to cyclic deformation. The strengthening relation tells that the flow stress is proportional to the square root of the average dislocation density, whereas the similitude relation assumes that the flow stress is inversely proportional to the characteristic wavelength of dislocation patterns. The strengthening relation arises from short-range reactions of non-coplanar segments and applies all through the first three stages of the monotonic stress vs. strain curves. The value of the proportionality coefficient is calculated and simulated in good agreement with the bulk of experimental measurements published since the beginning of the 1960's. The physical origin of what is called similitude is not understood and the related coefficient is not predictable. Its value is determined from a review of the experimental literature. The generalization of these scaling laws to cyclic deformation is carried out on the base of a large collection of experimental results on single and polycrystals of various materials and on different microstructures. Surprisingly, for persistent slip bands (PSBs), both the strengthening and similitude coefficients appear to be more than two times smaller than the corresponding monotonic values, whereas their ratio is the same as in monotonic deformation. The similitude relation is also checked in cell structures and in labyrinth structures. Under low cyclic stresses, the strengthening coefficient is found even lower than in PSBs. A tentative explanation is proposed for the differences observed between cyclic and monotonic deformation. Finally, the influence of cross-slip on the temperature dependence of the saturation stress of PSBs is discussed in some detail
Iterates of piecewise monotone mappings on an interval
Preston, Chris
1988-01-01
Piecewise monotone mappings on an interval provide simple examples of discrete dynamical systems whose behaviour can be very complicated. These notes are concerned with the properties of the iterates of such mappings. The material presented can be understood by anyone who has had a basic course in (one-dimensional) real analysis. The account concentrates on the topological (as opposed to the measure theoretical) aspects of the theory of piecewise monotone mappings. As well as offering an elementary introduction to this theory, these notes also contain a more advanced treatment of the problem of classifying such mappings up to topological conjugacy.
Schmid, E; Wagner, F M; Romm, H; Walsh, L; Roos, H
2009-02-01
The biological effectiveness of neutrons from the neutron therapy facility MEDAPP (mean neutron energy 1.9 MeV) at the new research reactor FRM II at Garching, Germany, has been analyzed, at different depths in a polyethylene phantom. Whole blood samples were exposed to the MEDAPP beam in special irradiation chambers to total doses of 0.14-3.52 Gy at 2-cm depth, and 0.18-3.04 Gy at 6-cm depth of the phantom. The neutron and gamma-ray absorbed dose rates were measured to be 0.55 Gy min(-1) and 0.27 Gy min(-1) at 2-cm depth, while they were 0.28 and 0.25 Gy min(-1) at 6-cm depth. Although the irradiation conditions at the MEDAPP beam and the RENT beam of the former FRM I research reactor were not identical, neutrons from both facilities gave a similar linear-quadratic dose-response relationship for dicentric chromosomes at a depth of 2 cm. Different dose-response curves for dicentrics were obtained for the MEDAPP beam at 2 and 6 cm depth, suggesting a significantly lower biological effectiveness of the radiation with increasing depth. No obvious differences in the dose-response curves for dicentric chromosomes estimated under interactive or additive prediction between neutrons or gamma-rays and the experimentally obtained dose-response curves could be determined. Relative to (60)Co gamma-rays, the values for the relative biological effectiveness at the MEDAPP beam decrease from 5.9 at 0.14 Gy to 1.6 at 3.52 Gy at 2-cm depth, and from 4.1 at 0.18 Gy to 1.5 at 3.04 Gy at 6-cm depth. Using the best possible conditions of consistency, i.e., using blood samples from the same donor and the same measurement techniques for about two decades, avoiding the inter-individual variations in sensitivity or the differences in methodology usually associated with inter-laboratory comparisons, a linear-quadratic dose-response relationship for the mixed neutron and gamma-ray MEDAPP field as well as for its fission neutron part was obtained. Therefore, the debate on whether the fission
Eits, R.M.; Kwakkel, R.P.; Verstegen, M.W.A.; Hartog, den L.A.
2005-01-01
1. An empirical model of exponential form was developed, different versions of which can be used to predict growth rate, feed conversion and carcase and breast meat yield of broiler chickens as a function of dietary balanced protein ( DBP) content. The model was developed to support decision- making
National Research Council Canada - National Science Library
Sommerville, Douglas R
2005-01-01
... (involving acute inhalation exposures to G-type nerve agents) were reviewed and analyzed. For all three studies, slightly more than one standard deviation separated an effective concentration (ECxx...
International Nuclear Information System (INIS)
Gao Jinsheng; Zheng Siying; Cai Feng
1993-08-01
The micronucleus technique of cytokines block has been proposed as a new method to measure chromosome damage in cytogenetic. The cytokines is blocked by using cytochalasin B (Cyt-B), and micronuclei are scored in cytokines-blocked (CB) cells. This can easily be done owing to the appearance of binucleate cells and large numbers accumulated by adding 3.0 μg/ml cytochalasin B at 44 hours and scoring at 72 hours. The results show that the optimum concentration of Cyt-B is 3.0 μg/ml. the Cyt-B itself can not induce the increase of micronuclei. The micronucleus frequency of normal individuals in vivo, there is an approximately linear relationship between the frequency of induced micronuclei and irradiation dose. The formula is Y 0.36 D + 2.74 (γ 2 = 0.995 P<0.01). Because the cytokines block method is simple and reliable, it is effective for assaying chromosome damage caused by genetic toxic materials
Westerhof, W.; Estevez-Uscanga, O.; Meens, J.; Kammeyer, A.; Durocq, M.; Cario, I.
1990-01-01
In 54 healthy volunteers we assessed predictors of sensitivity to ultraviolet (UV) light, including Fitzpatrick's sun reactive skin types and constitutional skin color, and compared these with one another and with responses of the skin to UV irradiation, as determined experimentally by a minimal
Julien, Elizabeth; Boobis, Alan R; Olin, Stephen S
2009-09-01
The ILSI Research Foundation convened a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categories of bioactive agents-food allergens, nutrients, pathogenic microorganisms, and environmental chemicals. This effort generated a common analytical framework-the Key Events Dose-Response Framework (KEDRF)-for systematically examining key events that occur between the initial dose of a bioactive agent and the effect of concern. Individual key events are considered with regard to factors that influence the dose-response relationship and factors that underlie variability in that relationship. This approach illuminates the connection between the processes occurring at the level of fundamental biology and the outcomes observed at the individual and population levels. Thus, it promotes an evidence-based approach for using mechanistic data to reduce reliance on default assumptions, to quantify variability, and to better characterize biological thresholds. This paper provides an overview of the KEDRF and introduces a series of four companion papers that illustrate initial application of the approach to a range of bioactive agents.
The regularized monotonicity method: detecting irregular indefinite inclusions
DEFF Research Database (Denmark)
Garde, Henrik; Staboulis, Stratos
2018-01-01
inclusions, where the conductivity distribution has both more and less conductive parts relative to the background conductivity; one such method is the monotonicity method of Harrach, Seo, and Ullrich. We formulate the method for irregular indefinite inclusions, meaning that we make no regularity assumptions...
Generalized monotonicity from global minimization in fourth-order ODEs
M.A. Peletier (Mark)
2000-01-01
textabstractWe consider solutions of the stationary Extended Fisher-Kolmogorov equation with general potential that are global minimizers of an associated variational problem. We present results that relate the global minimization property to a generalized concept of monotonicity of the solutions.
Monotone difference schemes for weakly coupled elliptic and parabolic systems
P. Matus (Piotr); F.J. Gaspar Lorenz (Franscisco); L. M. Hieu (Le Minh); V.T.K. Tuyen (Vo Thi Kim)
2017-01-01
textabstractThe present paper is devoted to the development of the theory of monotone difference schemes, approximating the so-called weakly coupled system of linear elliptic and quasilinear parabolic equations. Similarly to the scalar case, the canonical form of the vector-difference schemes is
Pathwise duals of monotone and additive Markov processes
Czech Academy of Sciences Publication Activity Database
Sturm, A.; Swart, Jan M.
-, - (2018) ISSN 0894-9840 R&D Projects: GA ČR GAP201/12/2613 Institutional support: RVO:67985556 Keywords : pathwise duality * monotone Markov process * additive Markov process * interacting particle system Subject RIV: BA - General Mathematics Impact factor: 0.854, year: 2016 http://library.utia.cas.cz/separaty/2016/SI/swart-0465436.pdf
Statistical analysis of sediment toxicity by additive monotone regression splines
Boer, de W.J.; Besten, den P.J.; Braak, ter C.J.F.
2002-01-01
Modeling nonlinearity and thresholds in dose-effect relations is a major challenge, particularly in noisy data sets. Here we show the utility of nonlinear regression with additive monotone regression splines. These splines lead almost automatically to the estimation of thresholds. We applied this
Interval Routing and Minor-Monotone Graph Parameters
Bakker, E.M.; Bodlaender, H.L.; Tan, R.B.; Leeuwen, J. van
2006-01-01
We survey a number of minor-monotone graph parameters and their relationship to the complexity of routing on graphs. In particular we compare the interval routing parameters κslir(G) and κsir(G) with Colin de Verdi`ere’s graph invariant μ(G) and its variants λ(G) and κ(G). We show that for all the
On monotonic solutions of an integral equation of Abel type
International Nuclear Information System (INIS)
Darwish, Mohamed Abdalla
2007-08-01
We present an existence theorem of monotonic solutions for a quadratic integral equation of Abel type in C[0, 1]. The famous Chandrasekhar's integral equation is considered as a special case. The concept of measure of noncompactness and a fi xed point theorem due to Darbo are the main tools in carrying out our proof. (author)
Rational functions with maximal radius of absolute monotonicity
Loczi, Lajos; Ketcheson, David I.
2014-01-01
-Kutta methods for initial value problems and the radius of absolute monotonicity governs the numerical preservation of properties like positivity and maximum-norm contractivity. We construct a function with p=2 and R>2s, disproving a conjecture of van de Griend
POLARIZED LINE FORMATION IN NON-MONOTONIC VELOCITY FIELDS
Energy Technology Data Exchange (ETDEWEB)
Sampoorna, M.; Nagendra, K. N., E-mail: sampoorna@iiap.res.in, E-mail: knn@iiap.res.in [Indian Institute of Astrophysics, Koramangala, Bengaluru 560034 (India)
2016-12-10
For a correct interpretation of the observed spectro-polarimetric data from astrophysical objects such as the Sun, it is necessary to solve the polarized line transfer problems taking into account a realistic temperature structure, the dynamical state of the atmosphere, a realistic scattering mechanism (namely, the partial frequency redistribution—PRD), and the magnetic fields. In a recent paper, we studied the effects of monotonic vertical velocity fields on linearly polarized line profiles formed in isothermal atmospheres with and without magnetic fields. However, in general the velocity fields that prevail in dynamical atmospheres of astrophysical objects are non-monotonic. Stellar atmospheres with shocks, multi-component supernova atmospheres, and various kinds of wave motions in solar and stellar atmospheres are examples of non-monotonic velocity fields. Here we present studies on the effect of non-relativistic non-monotonic vertical velocity fields on the linearly polarized line profiles formed in semi-empirical atmospheres. We consider a two-level atom model and PRD scattering mechanism. We solve the polarized transfer equation in the comoving frame (CMF) of the fluid using a polarized accelerated lambda iteration method that has been appropriately modified for the problem at hand. We present numerical tests to validate the CMF method and also discuss the accuracy and numerical instabilities associated with it.
Modelling Embedded Systems by Non-Monotonic Refinement
Mader, Angelika H.; Marincic, J.; Wupper, H.
2008-01-01
This paper addresses the process of modelling embedded sys- tems for formal verification. We propose a modelling process built on non-monotonic refinement and a number of guidelines. The outcome of the modelling process is a model, together with a correctness argument that justifies our modelling
Investigation of vacuum pumping on the dose response of the MAGAS normoxic polymer gel dosimeter
International Nuclear Information System (INIS)
Venning, AJ.; Canberra Hospital, Canberra; University of Sydney, Sydney; Mather, ML.; Baldock, C.
2005-01-01
The effect of vacuum pumping on the dose response of the MAGAS polymer gel dosimeter has been investigated. A delay of several days post-manufacture before irradiation was previously necessary due to the slow oxygen scavenging of ascorbic acid. The MAGAS polymer gel dosimeter was vacuum pumped before gelation to remove dissolved oxygen. The MAGAS polymer gel dosimeter was poured into glass screw-top vials, which were irradiated at various times, post-manufacture to a range of doses. Magnetic resonance imaging techniques were used to determine the R2-dose response and /?2-dose sensitivity of the MAGAS polymer gel. The results were compared with a control batch of MAGAS polymer gel that was not vacuum pumped. It was shown that vacuum pumping on the MAGAS polymer gel solution immediately prior to sealing in glass screw-top vials initially increases the R2-dose response and R2-dose sensitivity of the dosimeter. An increase in the .R2-dose response and i?2-dose sensitivity was observed with increasing time between manufacture and irradiation. Over the range of post-manufacture irradiation times investigated, the greatest i?2-dose response and if 2 -dose sensitivity occurred at 96 hours
International Nuclear Information System (INIS)
Calabrese, Edward J.
2013-01-01
The most common quantitative feature of the hormetic-biphasic dose response is its modest stimulatory response which at maximum is only 30–60% greater than control values, an observation that is consistently independent of biological model, level of organization (i.e., cell, organ or individual), endpoint measured, chemical/physical agent studied, or mechanism. This quantitative feature suggests an underlying “upstream” mechanism common across biological systems, therefore basic and general. Hormetic dose response relationships represent an estimate of the peak performance of integrative biological processes that are allometrically based. Hormetic responses reflect both direct stimulatory or overcompensation responses to damage induced by relatively low doses of chemical or physical agents. The integration of the hormetic dose response within an allometric framework provides, for the first time, an explanation for both the generality and the quantitative features of the hormetic dose response. -- Highlights: •The hormetic stimulation is at maximum 30–60% greater than control responses. •Hormesis is a measure of biological performance and plasticity. •The hormetic response is evolutionary based and highly generalizable. -- This paper provides a biologically based explanation for the generalizability/quantitative features of the hormetic dose response, representing a fundamental contribution to the field
Energy Technology Data Exchange (ETDEWEB)
Lyon, M F; Cox, B D
1975-09-01
The induction by X-rays of translocations in spermatogonia was studied by cytological means in spermatocytes derived from them. In the rabbit and guinea-pig, hump-shaped dose-response curves were obtained, with a linear relationship at the low doses. The shapes of the curves were similar to those reported for the mouse, except that the maximum occurred at 600-700 rad in the mouse as opposed to 300 rad in the guinea-pig and rabbit. Unlike the guinea-pig and rabbit, the golden hamster showed a hump dose-response curve without a definite peak value and with little decrease in yield at high radiation doses. Over the low dose range 100-300 rad, the slopes of the curves of translocation yield were in the order: mouse (highest), rabbit, guinea-pig and hamster. Data on sterile periods suggested that the amount of spermatogonial killing in the rabbit and guinea-pig was as great or greater than in the mouse, and that in the golden hamster it was most severe. It is suggested that the differing shapes of the dose-response curves can be explained by a lower sensitivity to translocation induction in the test species and, also especially in the golden hamster, a greater sensitivity to cell killing. The possibility of extrapolating from these data to other species is discussed.
An adaptive two-stage dose-response design method for establishing proof of concept.
Franchetti, Yoko; Anderson, Stewart J; Sampson, Allan R
2013-01-01
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.
International Nuclear Information System (INIS)
Kim, Jin Kyu; Kim, Yeon Ku; Song, Hi Sup
1999-01-01
This study was carried out to investigate the radiation dose-response of micronucleus frequencies in Tradescantia pollen mother cells. The number of micronuclei increased in the tetrads as a result of chromosome deletion after irradiation. The maximal frequency of micronucleus showed a good dose-response relationship in the range of dose 0∼50 cGy. On the basis of the relationship, a dose of 1 cGy resulted in two additional micronuclei in 100 tetrads. The radiation dose-response relationship of micronucleus occurrence is prerequisite to biological monitoring of radiation and can be modified for biological risk assessment of toxicants, and to safety test of water or soil integrity
International Nuclear Information System (INIS)
Mendiola C, M.T.; Morales, R.P.
2000-01-01
The Unicellular electrophoresis in gel technique is a useful tool in the determination of simple ruptures and labile sites to the alkali in DNA of eucariontes cells. The determination of the induction kinetics of damage and repair of DNA can give more information. The objective of this work was to determine whether the analysis of the area under the damage/repair induction kinetics curve in comets percent or the comets frequency in the two peaks of maximum induction is adequate for determining the dose-response relationship. The mice were exposed at the doses of 0.5, 1.0, 2.0 Gy. (Author)
A Unified Probabilistic Framework for Dose-Response Assessment of Human Health Effects.
Chiu, Weihsueh A; Slob, Wout
2015-12-01
When chemical health hazards have been identified, probabilistic dose-response assessment ("hazard characterization") quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. We developed a unified framework for probabilistic dose-response assessment. We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose-response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, "effect metrics" can be specified to define "toxicologically equivalent" sizes for this underlying individual response; and d) dose-response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose-response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Probabilistically derived exposure limits are based on estimating a "target human dose" (HDMI), which requires risk management-informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%-10% effect sizes. Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions.
Addressing model uncertainty in dose-response: The case of chloroform
International Nuclear Information System (INIS)
Evans, J.S.
1994-01-01
This paper discusses the issues involved in addressing model uncertainty in the analysis of dose-response relationships. A method for addressing model uncertainty is described and applied to characterize the uncertainty in estimates of the carcinogenic potency of chloroform. The approach, which is rooted in Bayesian concepts of subjective probability, uses probability trees and formally-elicited expert judgments to address model uncertainty. It is argued that a similar approach could be used to improve the characterization of model uncertainty in the dose-response relationships for health effects from ionizing radiation
Mejias, Jorge F; Payeur, Alexandre; Selin, Erik; Maler, Leonard; Longtin, André
2014-01-01
The control of input-to-output mappings, or gain control, is one of the main strategies used by neural networks for the processing and gating of information. Using a spiking neural network model, we studied the gain control induced by a form of inhibitory feedforward circuitry-also known as "open-loop feedback"-, which has been experimentally observed in a cerebellum-like structure in weakly electric fish. We found, both analytically and numerically, that this network displays three different regimes of gain control: subtractive, divisive, and non-monotonic. Subtractive gain control was obtained when noise is very low in the network. Also, it was possible to change from divisive to non-monotonic gain control by simply modulating the strength of the feedforward inhibition, which may be achieved via long-term synaptic plasticity. The particular case of divisive gain control has been previously observed in vivo in weakly electric fish. These gain control regimes were robust to the presence of temporal delays in the inhibitory feedforward pathway, which were found to linearize the input-to-output mappings (or f-I curves) via a novel variability-increasing mechanism. Our findings highlight the feedforward-induced gain control analyzed here as a highly versatile mechanism of information gating in the brain.
Directory of Open Access Journals (Sweden)
Jorge F Mejias
2014-02-01
Full Text Available The control of input-to-output mappings, or gain control, is one of the main strategies used by neural networks for the processing and gating of information. Using a spiking neural network model, we studied the gain control induced by a form of inhibitory feedforward circuitry — also known as ’open-loop feedback’ —, which has been experimentally observed in a cerebellum-like structure in weakly electric fish. We found, both analytically and numerically, that this network displays three different regimes of gain control: subtractive, divisive, and non-monotonic. Subtractive gain control was obtained when noise is very low in the network. Also, it was possible to change from divisive to non-monotonic gain control by simply modulating the strength of the feedforward inhibition, which may be achieved via long-term synaptic plasticity. The particular case of divisive gain control has been previously observed in vivo in weakly electric fish. These gain control regimes were robust to the presence of temporal delays in the inhibitory feedforward pathway, which were found to linearize the input-to-output mappings (or f-I curves via a novel variability-increasing mechanism. Our findings highlight the feedforward-induced gain control analyzed here as a highly versatile mechanism of information gating in the brain.
Denjoy minimal sets and Birkhoff periodic orbits for non-exact monotone twist maps
Qin, Wen-Xin; Wang, Ya-Nan
2018-06-01
A non-exact monotone twist map φbarF is a composition of an exact monotone twist map φ bar with a generating function H and a vertical translation VF with VF ((x , y)) = (x , y - F). We show in this paper that for each ω ∈ R, there exists a critical value Fd (ω) ≥ 0 depending on H and ω such that for 0 ≤ F ≤Fd (ω), the non-exact twist map φbarF has an invariant Denjoy minimal set with irrational rotation number ω lying on a Lipschitz graph, or Birkhoff (p , q)-periodic orbits for rational ω = p / q. Like the Aubry-Mather theory, we also construct heteroclinic orbits connecting Birkhoff periodic orbits, and show that quasi-periodic orbits in these Denjoy minimal sets can be approximated by periodic orbits. In particular, we demonstrate that at the critical value F =Fd (ω), the Denjoy minimal set is not uniformly hyperbolic and can be approximated by smooth curves.
Assessing the Health of LiFePO4 Traction Batteries through Monotonic Echo State Networks
Anseán, David; Otero, José; Couso, Inés
2017-01-01
A soft sensor is presented that approximates certain health parameters of automotive rechargeable batteries from on-vehicle measurements of current and voltage. The sensor is based on a model of the open circuit voltage curve. This last model is implemented through monotonic neural networks and estimate over-potentials arising from the evolution in time of the Lithium concentration in the electrodes of the battery. The proposed soft sensor is able to exploit the information contained in operational records of the vehicle better than the alternatives, this being particularly true when the charge or discharge currents are between moderate and high. The accuracy of the neural model has been compared to different alternatives, including data-driven statistical models, first principle-based models, fuzzy observers and other recurrent neural networks with different topologies. It is concluded that monotonic echo state networks can outperform well established first-principle models. The algorithms have been validated with automotive Li-FePO4 cells. PMID:29267219
Assessing the Health of LiFePO4 Traction Batteries through Monotonic Echo State Networks
Directory of Open Access Journals (Sweden)
Luciano Sánchez
2017-12-01
Full Text Available A soft sensor is presented that approximates certain health parameters of automotive rechargeable batteries from on-vehicle measurements of current and voltage. The sensor is based on a model of the open circuit voltage curve. This last model is implemented through monotonic neural networks and estimate over-potentials arising from the evolution in time of the Lithium concentration in the electrodes of the battery. The proposed soft sensor is able to exploit the information contained in operational records of the vehicle better than the alternatives, this being particularly true when the charge or discharge currents are between moderate and high. The accuracy of the neural model has been compared to different alternatives, including data-driven statistical models, first principle-based models, fuzzy observers and other recurrent neural networks with different topologies. It is concluded that monotonic echo state networks can outperform well established first-principle models. The algorithms have been validated with automotive Li-FePO4 cells.
Directory of Open Access Journals (Sweden)
Hugo A. Rondón-Quintana
2012-12-01
Full Text Available The influence of compaction temperature on resistance under mono-tonic loading (Marshall of Crumb-Rubber Modified (CRM Hot-Mix As-phalt (HMA was evaluated. The emphasis of this study was the applica-tion in Bogotá D.C. (Colombia. In this city the compaction temperature of HMA mixtures decreases, compared to the optimum, in about 30°C. Two asphalt cements (AC 60-70 and AC 80-100 were modified. Two particle sizes distribution curve were used. The compaction temperatures used were 120, 130, 140 and 150°C. The decrease of the compaction tempera-ture produces a small decrease in resistance under monotonic loading of the modified mixtures tested. Mixtures without CRM undergo a lineal decrease in its resistance of up to 34%.
Directory of Open Access Journals (Sweden)
Hugo A. Rondón-Quintana
2012-12-01
Full Text Available The influence of compaction temperature on resistance under monotonic loading (Marshall of Crumb-Rubber Modified (CRM Hot-Mix Asphalt (HMA was evaluated. The emphasis of this study was the application in Bogotá D.C. (Colombia. In this city the compaction temperature of HMA mixtures decreases, compared to the optimum, in about 30°C. Two asphalt cements (AC 60-70 and AC 80-100 were modified. Two particle sizes distribution curve were used. The compaction temperatures used were 120, 130, 140 and 150°C. The decrease of the compaction temperature produces a small decrease in resistance under monotonic loading of the modified mixtures tested. Mixtures without CRM undergo a lineal decrease in its resistance of up to 34%.
Monotonicity properties of keff with shape change and with nesting
International Nuclear Information System (INIS)
Arzhanov, V.
2002-01-01
It was found that, contrary to expectations based on physical intuition, k eff can both increase and decrease when changing the shape of an initially regular critical system, while preserving its volume. Physical intuition would only allow for a decrease of k eff when the surface/volume ratio increases. The unexpected behaviour of increasing k eff was found through numerical investigation. For a convincing demonstration of the possibility of the non-monotonic behaviour, a simple geometrical proof was constructed. This latter proof, in turn, is based on the assumption that k eff can only increase (or stay constant) in the case of nesting, i.e. when adding extra volume to a system. Since we found no formal proof of the nesting theorem for the general case, we close the paper by a simple formal proof of the monotonic behaviour of k eff by nesting
A Hybrid Approach to Proving Memory Reference Monotonicity
Oancea, Cosmin E.
2013-01-01
Array references indexed by non-linear expressions or subscript arrays represent a major obstacle to compiler analysis and to automatic parallelization. Most previous proposed solutions either enhance the static analysis repertoire to recognize more patterns, to infer array-value properties, and to refine the mathematical support, or apply expensive run time analysis of memory reference traces to disambiguate these accesses. This paper presents an automated solution based on static construction of access summaries, in which the reference non-linearity problem can be solved for a large number of reference patterns by extracting arbitrarily-shaped predicates that can (in)validate the reference monotonicity property and thus (dis)prove loop independence. Experiments on six benchmarks show that our general technique for dynamic validation of the monotonicity property can cover a large class of codes, incurs minimal run-time overhead and obtains good speedups. © 2013 Springer-Verlag.
Rational functions with maximal radius of absolute monotonicity
Loczi, Lajos
2014-05-19
We study the radius of absolute monotonicity R of rational functions with numerator and denominator of degree s that approximate the exponential function to order p. Such functions arise in the application of implicit s-stage, order p Runge-Kutta methods for initial value problems and the radius of absolute monotonicity governs the numerical preservation of properties like positivity and maximum-norm contractivity. We construct a function with p=2 and R>2s, disproving a conjecture of van de Griend and Kraaijevanger. We determine the maximum attainable radius for functions in several one-parameter families of rational functions. Moreover, we prove earlier conjectured optimal radii in some families with 2 or 3 parameters via uniqueness arguments for systems of polynomial inequalities. Our results also prove the optimality of some strong stability preserving implicit and singly diagonally implicit Runge-Kutta methods. Whereas previous results in this area were primarily numerical, we give all constants as exact algebraic numbers.
Computation of Optimal Monotonicity Preserving General Linear Methods
Ketcheson, David I.
2009-07-01
Monotonicity preserving numerical methods for ordinary differential equations prevent the growth of propagated errors and preserve convex boundedness properties of the solution. We formulate the problem of finding optimal monotonicity preserving general linear methods for linear autonomous equations, and propose an efficient algorithm for its solution. This algorithm reliably finds optimal methods even among classes involving very high order accuracy and that use many steps and/or stages. The optimality of some recently proposed methods is verified, and many more efficient methods are found. We use similar algorithms to find optimal strong stability preserving linear multistep methods of both explicit and implicit type, including methods for hyperbolic PDEs that use downwind-biased operators.
Monotonicity and Logarithmic Concavity of Two Functions Involving Exponential Function
Liu, Ai-Qi; Li, Guo-Fu; Guo, Bai-Ni; Qi, Feng
2008-01-01
The function 1 divided by "x"[superscript 2] minus "e"[superscript"-x"] divided by (1 minus "e"[superscript"-x"])[superscript 2] for "x" greater than 0 is proved to be strictly decreasing. As an application of this monotonicity, the logarithmic concavity of the function "t" divided by "e"[superscript "at"] minus "e"[superscript"(a-1)""t"] for "a"…
Estimation of Poisson-Dirichlet Parameters with Monotone Missing Data
Directory of Open Access Journals (Sweden)
Xueqin Zhou
2017-01-01
Full Text Available This article considers the estimation of the unknown numerical parameters and the density of the base measure in a Poisson-Dirichlet process prior with grouped monotone missing data. The numerical parameters are estimated by the method of maximum likelihood estimates and the density function is estimated by kernel method. A set of simulations was conducted, which shows that the estimates perform well.
Sampling from a Discrete Distribution While Preserving Monotonicity.
1982-02-01
in a table beforehand, this procedure, known as the inverse transform method, requires n storage spaces and EX comparisons on average, which may prove...limitations that deserve attention: a. In general, the alias method does not preserve a monotone relationship between U and X as does the inverse transform method...uses the inverse transform approach but with more information computed beforehand, as in the alias method. The proposed method is not new having been
On a strong law of large numbers for monotone measures
Czech Academy of Sciences Publication Activity Database
Agahi, H.; Mohammadpour, A.; Mesiar, Radko; Ouyang, Y.
2013-01-01
Roč. 83, č. 4 (2013), s. 1213-1218 ISSN 0167-7152 R&D Projects: GA ČR GAP402/11/0378 Institutional support: RVO:67985556 Keywords : capacity * Choquet integral * strong law of large numbers Subject RIV: BA - General Mathematics Impact factor: 0.531, year: 2013 http://library.utia.cas.cz/separaty/2013/E/mesiar-on a strong law of large numbers for monotone measures.pdf
Monotonous braking of high energy hadrons in nuclear matter
International Nuclear Information System (INIS)
Strugalski, Z.
1979-01-01
Propagation of high energy hadrons in nuclear matter is discussed. The possibility of the existence of the monotonous energy losses of hadrons in nuclear matter is considered. In favour of this hypothesis experimental facts such as pion-nucleus interactions (proton emission spectra, proton multiplicity distributions in these interactions) and other data are presented. The investigated phenomenon in the framework of the hypothesis is characterized in more detail
Dose-response relations for stricture in the proximal oesophagus from head and neck radiotherapy
International Nuclear Information System (INIS)
Alevronta, Eleftheria; Ahlberg, Alexander; Mavroidis, Panayiotis; Al-Abany, Massoud; Friesland, Signe; Tilikidis, Aris; Laurell, Goeran; Lind, Bengt K.
2010-01-01
Background and purpose: Determination of the dose-response relations for oesophageal stricture after radiotherapy of the head and neck. Material and methods: In this study 33 patients who developed oesophageal stricture and 39 patients as controls are included. The patients received radiation therapy for head and neck cancer at Karolinska University Hospital, Stockholm, Sweden. For each patient the 3D dose distribution delivered to the upper 5 cm of the oesophagus was analysed. The analysis was conducted for two periods, 1992-2000 and 2001-2005, due to the different irradiation techniques used. The fitting has been done using the relative seriality model. Results: For the treatment period 1992-2005, the mean doses were 49.8 and 33.4 Gy, respectively, for the cases and the controls. For the period 1992-2000, the mean doses for the cases and the controls were 49.9 and 45.9 Gy and for the period 2001-2005 were 49.8 and 21.4 Gy. For the period 2001-2005 the best estimates of the dose-response parameters are D 50 = 61.5 Gy (52.9-84.9 Gy), γ = 1.4 (0.8-2.6) and s = 0.1 (0.01-0.3). Conclusions: Radiation-induced strictures were found to have a dose response relation and volume dependence (low relative seriality) for the treatment period 2001-2005. However, no dose response relation was found for the complete material.
Koshy, Gibby; Delpisheh, Ali; Brabin, Bernard J.
2011-01-01
The combined dose response effects of pregnancy cigarette smoke exposure on childhood overweight, obesity and short stature have not been reported. A community based cross-sectional survey of 3038 children aged 5-11 years from 15 primary schools in Merseyside, UK. Self-completed parental
Dose response of subcutaneous GLP-1 infusion in patients with type 2 diabetes
DEFF Research Database (Denmark)
Torekov, Signe Sørensen; Kipnes, M S; Harley, R E
2011-01-01
To evaluate the dose-response relationship of the recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes, with respect to reductions in fasting, postprandial and 11-h serum glucose profiles....
Froehlich, Tanya E.; Epstein, Jeffery N.; Nick, Todd G.; Melguizo Castro, Maria S.; Stein, Mark A.; Brinkman, William B.; Graham, Amanda J.; Langberg, Joshua M.; Kahn, Robert S.
2011-01-01
Objective: Because of significant individual variability in attention-deficit/hyperactivity disorder (ADHD) medication response, there is increasing interest in identifying genetic predictors of treatment effects. This study examined the role of four catecholamine-related candidate genes in moderating methylphenidate (MPH) dose-response. Method:…
IsoGeneGUI : Multiple approaches for dose-response analysis of microarray data using R
Otava, Martin; Sengupta, Rudradev; Shkedy, Ziv; Lin, Dan; Pramana, Setia; Verbeke, Tobias; Haldermans, Philippe; Hothorn, Ludwig A.; Gerhard, Daniel; Kuiper, Rebecca M.; Klinglmueller, Florian; Kasim, Adetayo
2017-01-01
The analysis of transcriptomic experiments with ordered covariates, such as dose-response data, has become a central topic in bioinformatics, in particular in omics studies. Consequently, multiple R packages on CRAN and Bioconductor are designed to analyse microarray data from various perspectives
QUANTITATION OF MOLECULAR ENDPOINTS FOR THE DOSE-RESPONSE COMPONENT OF CANCER RISK ASSESSMENT
Cancer risk assessment involves the steps of hazard identification, dose-response assessment, exposure assessment and risk characterization. The rapid advances in the use of molecular biology approaches has had an impact on all four components, but the greatest overall current...
Faraone, Stephen V.; Spencer, Thomas J.; Kollins, Scott H.; Glatt, Stephen J.; Goodman, David
2012-01-01
Objective: To explore dose-response effects of lisdexamfetamine dimesylate (LDX) treatment for ADHD. Method: This was a 4-week, randomized, double-blinded, placebo-controlled, parallel-group, forced-dose titration study in adult participants, aged 18 to 55 years, meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed., text rev.)…
Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms
DEFF Research Database (Denmark)
Urbain, Paul; Jakobsen, Jette
2015-01-01
The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour...
News Impact Curve for Stochastic Volatility Models
Makoto Takahashi; Yasuhiro Omori; Toshiaki Watanabe
2012-01-01
This paper proposes a new method to compute the news impact curve for stochastic volatility (SV) models. The new method incorporates the joint movement of return and volatility, which has been ignored by the extant literature, by simply adding a couple of steps to the Bayesian MCMC estimation procedures for SV models. This simple procedure is versatile and applicable to various SV type models. Contrary to the monotonic news impact functions in the extant literature, the new method gives a U-s...
Lugo, Alessandra; Bosetti, Cristina; Peveri, Giulia; Rota, Matteo; Bagnardi, Vincenzo; Gallus, Silvano
2017-11-01
Only a limited number of meta-analyses providing risk curve functions of dose-response relationships between various smoking-related variables and cancer-specific risk are available. To identify all relevant original publications on the issue, we will conduct a series of comprehensive systematic reviews based on three subsequent literature searches: (1) an umbrella review, to identify meta-analyses, pooled analyses and systematic reviews published before 28 April 2017 on the association between cigarette smoking and the risk of 28 (namely all) malignant neoplasms; (2) for each cancer site, an updated review of original publications on the association between cigarette smoking and cancer risk, starting from the last available comprehensive review identified through the umbrella review; and (3) a review of all original articles on the association between cigarette smoking and site-specific cancer risk included in the publications identified through the umbrella review and the updated reviews. The primary outcomes of interest will be (1) the excess incidence/mortality of various cancers for smokers compared with never smokers; and (2) the dose-response curves describing the association between smoking intensity, duration and time since stopping and incidence/mortality for various cancers. For each cancer site, we will perform a meta-analysis by pooling study-specific estimates for smoking status. We will also estimate the dose-response curves for other smoking-related variables through random-effects meta-regression models based on a non-linear dose-response relationship framework. Ethics approval is not required for this study. Main results will be published in peer-reviewed journals and will also be included in a publicly available website. We will provide therefore the most complete and updated estimates on the association between various measures of cigarette smoking and site-specific cancer risk. This will allow us to obtain precise estimates on the cancer burden
International Nuclear Information System (INIS)
Gordon, J; Snyder, K; Zhong, H; Chetty, I
2014-01-01
Purpose: Dose-response models that can reliably predict radiation pneumonitis (RP) to guide radiation therapy (RT) for lung cancer presently do not exist. A model is proposed that incorporates non-local radiationinduced bystander effect (RIBE). Methods: A single sigmoid response function, derived from published data for whole lung irradiation, relates RP probability to cumulative lung damage, regardless of fractionation scheme. Lung damage is assumed to be caused by direct local radiation damage, quantified via the linear-quadratic (LQ) model, and RIBE. Based on published data, RIBE is assumed to be activated when per-fraction dose rises above ∼0.6 Gy, but is constant with dose above that threshold. Integral RIBE damage is assumed proportional to lung volume irradiated above ∼0.6 Gy per fraction. Key model parameters include LQ α and β, and two RIBE parameters: the single-fraction probability δ of damage, and a proportionality parameter κ that relates the potential for RIBE damage to irradiated lung volume. All parameters are tentatively fitted from published data, the RIBE parameters from published RP rates for conventionally fractionated RT (CFRT) and stereotactic body RT (SBRT). Results: The model predicts dose-response curves that are consistent with clinical experience. It provides a tentative explanation for why V20 (33 fractions), V13 (20 fractions) and V5 (<10 fractions) are observed to be correlated with RP. It also provides a plausible explanation for the success of SBRT — RIBE damage increases with the number of fractions, so penalizes CFRT relative to SBRT. Conclusion: The proposed model is relatively simple, extrapolates from published data, plausibly explains several clinical observations, and produces dose-response curves that are consistent with clinical experience. While capable of elaboration, its ability to explain doseresponse experience with different fractionation schemes using a small number of assumptions and parameters is an
Energy Technology Data Exchange (ETDEWEB)
Gordon, J; Snyder, K; Zhong, H; Chetty, I [Henry Ford Health System, Dept. Radiation Oncology, Detroit, MI (United States)
2014-06-01
Purpose: Dose-response models that can reliably predict radiation pneumonitis (RP) to guide radiation therapy (RT) for lung cancer presently do not exist. A model is proposed that incorporates non-local radiationinduced bystander effect (RIBE). Methods: A single sigmoid response function, derived from published data for whole lung irradiation, relates RP probability to cumulative lung damage, regardless of fractionation scheme. Lung damage is assumed to be caused by direct local radiation damage, quantified via the linear-quadratic (LQ) model, and RIBE. Based on published data, RIBE is assumed to be activated when per-fraction dose rises above ∼0.6 Gy, but is constant with dose above that threshold. Integral RIBE damage is assumed proportional to lung volume irradiated above ∼0.6 Gy per fraction. Key model parameters include LQ α and β, and two RIBE parameters: the single-fraction probability δ of damage, and a proportionality parameter κ that relates the potential for RIBE damage to irradiated lung volume. All parameters are tentatively fitted from published data, the RIBE parameters from published RP rates for conventionally fractionated RT (CFRT) and stereotactic body RT (SBRT). Results: The model predicts dose-response curves that are consistent with clinical experience. It provides a tentative explanation for why V20 (33 fractions), V13 (20 fractions) and V5 (<10 fractions) are observed to be correlated with RP. It also provides a plausible explanation for the success of SBRT — RIBE damage increases with the number of fractions, so penalizes CFRT relative to SBRT. Conclusion: The proposed model is relatively simple, extrapolates from published data, plausibly explains several clinical observations, and produces dose-response curves that are consistent with clinical experience. While capable of elaboration, its ability to explain doseresponse experience with different fractionation schemes using a small number of assumptions and parameters is an
Dose-response relationships for environmentally mediated infectious disease transmission models.
Directory of Open Access Journals (Sweden)
Andrew F Brouwer
2017-04-01
Full Text Available Environmentally mediated infectious disease transmission models provide a mechanistic approach to examining environmental interventions for outbreaks, such as water treatment or surface decontamination. The shift from the classical SIR framework to one incorporating the environment requires codifying the relationship between exposure to environmental pathogens and infection, i.e. the dose-response relationship. Much of the work characterizing the functional forms of dose-response relationships has used statistical fit to experimental data. However, there has been little research examining the consequences of the choice of functional form in the context of transmission dynamics. To this end, we identify four properties of dose-response functions that should be considered when selecting a functional form: low-dose linearity, scalability, concavity, and whether it is a single-hit model. We find that i middle- and high-dose data do not constrain the low-dose response, and different dose-response forms that are equally plausible given the data can lead to significant differences in simulated outbreak dynamics; ii the choice of how to aggregate continuous exposure into discrete doses can impact the modeled force of infection; iii low-dose linear, concave functions allow the basic reproduction number to control global dynamics; and iv identifiability analysis offers a way to manage multiple sources of uncertainty and leverage environmental monitoring to make inference about infectivity. By applying an environmentally mediated infectious disease model to the 1993 Milwaukee Cryptosporidium outbreak, we demonstrate that environmental monitoring allows for inference regarding the infectivity of the pathogen and thus improves our ability to identify outbreak characteristics such as pathogen strain.
International Nuclear Information System (INIS)
Calabrese, Edward J.
2004-01-01
The conference attracts approximately 500 scientists researching in the area of non-linear low dose effects. These scientists represent a wide range of biological/medical fields and technical disciplines. Observations that biphasic dose responses are frequently reported in each of these areas but that the recognition of similar dose response relationships across disciplines is very rarely appreciated and exploited. By bringing scientist of such diverse backgrounds together who are working on the common area of non-linear dose response relationships this will enhance our understanding of the occurrence, origin, mechanism, significance and practical applications of such dose response relationships
Directory of Open Access Journals (Sweden)
Feng Qi
2014-10-01
Full Text Available The authors find the absolute monotonicity and complete monotonicity of some functions involving trigonometric functions and related to estimates the lower bounds of the first eigenvalue of Laplace operator on Riemannian manifolds.
Directory of Open Access Journals (Sweden)
Chowdhury Molhammad SR
2000-01-01
Full Text Available Results are obtained on existence theorems of generalized bi-quasi-variational inequalities for quasi-semi-monotone and bi-quasi-semi-monotone operators in both compact and non-compact settings. We shall use the concept of escaping sequences introduced by Border (Fixed Point Theorem with Applications to Economics and Game Theory, Cambridge University Press, Cambridge, 1985 to obtain results in non-compact settings. Existence theorems on non-compact generalized bi-complementarity problems for quasi-semi-monotone and bi-quasi-semi-monotone operators are also obtained. Moreover, as applications of some results of this paper on generalized bi-quasi-variational inequalities, we shall obtain existence of solutions for some kind of minimization problems with quasi- semi-monotone and bi-quasi-semi-monotone operators.
International Nuclear Information System (INIS)
O'Connor, V.A.; Lepper, K.; Morken, T.O.; Thorstad, D.J.; Podoll, A.; Giles, M.J.
2011-01-01
The Martian landscape is currently dominated by eolian processes, and eolian dunes are a direct geomorphic expression of the dynamic interaction between the atmosphere and the lithosphere of planets. The timing, frequency, and spatial extent of dune mobility directly reflects changing climatic conditions, therefore, sedimentary depositional ages are important for understanding the paleoclimatic and geomorphologic history of features and processes present on the surface of the Earth or Mars. Optical dating is an established terrestrial dosimetric dating technique that is being developed for this task on Mars. Gypsum and anhydrite are two of the most stable and abundant sulfate species found on the Earth, and they have been discovered in Martian sediments along with various magnesium sulfates and jarosite. In this study, the optical dating properties of various Ca-, Mg-, and Fe-bearing sulfates were documented to help evaluate the influence they may have on in-situ optical dating in eolian environments on Mars. Single-aliquot regenerative-dose (SAR) experimental procedures have been adapted to characterize the radiation dose response and signal stability of the Martian sulfate analogs. Jarosite was dosimetrically inert in our experiments. The radiation dose response of the Ca- and Mg-sulfates was monotonically increasing in all cases with characteristic doses ranging from ∼100 to ∼1000 Gy. Short-term signal fading also varied considerably in the Ca- and Mg-sulfates ranging from ∼0% to ∼40% per decade for these materials. These results suggest that the OSL properties of Ca- and Mg-sulfates will need to be considered when developing protocols for in-situ optical dating on Mars, but more enticingly, our results foreshadow the potential for gypsum to be developed as a geochronometer for Mars or the Earth. - Highlights: → The radiation dose response and OSL signal stability of Ca- and Mg-sulfates was highly variable. → OSL properties of Ca- and Mg
A non-parametric test for partial monotonicity in multiple regression
van Beek, M.; Daniëls, H.A.M.
Partial positive (negative) monotonicity in a dataset is the property that an increase in an independent variable, ceteris paribus, generates an increase (decrease) in the dependent variable. A test for partial monotonicity in datasets could (1) increase model performance if monotonicity may be
In some symmetric spaces monotonicity properties can be reduced to the cone of rearrangements
Czech Academy of Sciences Publication Activity Database
Hudzik, H.; Kaczmarek, R.; Krbec, Miroslav
2016-01-01
Roč. 90, č. 1 (2016), s. 249-261 ISSN 0001-9054 Institutional support: RVO:67985840 Keywords : symmetric spaces * K-monotone symmetric Banach spaces * strict monotonicity * lower local uniform monotonicity Subject RIV: BA - General Mathematics Impact factor: 0.826, year: 2016 http://link.springer.com/article/10.1007%2Fs00010-015-0379-6
Directory of Open Access Journals (Sweden)
Cheng-Ting Shih
Full Text Available Polymer gels are regarded as a potential dosimeter for independent validation of absorbed doses in clinical radiotherapy. Several imaging modalities have been used to convert radiation-induced polymerization to absorbed doses from a macro-scale viewpoint. This study developed a novel dose conversion mechanism by texture analysis of scanning electron microscopy (SEM images. The modified N-isopropyl-acrylamide (NIPAM gels were prepared under normoxic conditions, and were administered radiation doses from 5 to 20 Gy. After freeze drying, the gel samples were sliced for SEM scanning with 50×, 500×, and 3500× magnifications. Four texture indices were calculated based on the gray level co-occurrence matrix (GLCM. The results showed that entropy and homogeneity were more suitable than contrast and energy as dose indices for higher linearity and sensitivity of the dose response curves. After parameter optimization, an R (2 value of 0.993 can be achieved for homogeneity using 500× magnified SEM images with 27 pixel offsets and no outlier exclusion. For dose verification, the percentage errors between the prescribed dose and the measured dose for 5, 10, 15, and 20 Gy were -7.60%, 5.80%, 2.53%, and -0.95%, respectively. We conclude that texture analysis can be applied to the SEM images of gel dosimeters to accurately convert micro-scale structural features to absorbed doses. The proposed method may extend the feasibility of applying gel dosimeters in the fields of diagnostic radiology and radiation protection.
International Nuclear Information System (INIS)
Raabe, O.G.
1986-01-01
The three-dimensional lognormal cumulative probability power function was used to provide a unifying dose-response description of the lifetime cancer risk for chronic exposure of experimental animals and people, for risk evaluation, and for scaling between species. Bone tumor fatilities, primarily from alpha irradiation of the skeleton in lifetime studies of beagles injected with 226 Ra, were shown to be well described by this function. This function described cancer risk in lifetime studies as a curved smooth surface depending on radiation exposure rate and elapsed time, such that the principal risk at low dose rates occurred near the end of the normal life span without significant life shortening. Essentially identical functions with the median value of the power function displaced with respect to appropriate RBE values were shown to describe bone-cancer induction primarily from alpha irradiation of the skeleton in lifetime beagle studies with injected 226 Ra, 228 Th, 239 Pu and 241 Am, and with inhaled 238 Pu. Application of this model to human exposures to 226 Ra yielded a response ratio of 3.6; that is, the time required for development of bone cancer in people was 3.6 times longer than for beagles at the same average skeletal dose rate. It was suggested that similar techniques were appropriate to other carcinogens and other critical organs. 20 refs., 8 figs., 3 tabs
Non-monotonic behaviour in relaxation dynamics of image restoration
International Nuclear Information System (INIS)
Ozeki, Tomoko; Okada, Masato
2003-01-01
We have investigated the relaxation dynamics of image restoration through a Bayesian approach. The relaxation dynamics is much faster at zero temperature than at the Nishimori temperature where the pixel-wise error rate is minimized in equilibrium. At low temperature, we observed non-monotonic development of the overlap. We suggest that the optimal performance is realized through premature termination in the relaxation processes in the case of the infinite-range model. We also performed Markov chain Monte Carlo simulations to clarify the underlying mechanism of non-trivial behaviour at low temperature by checking the local field distributions of each pixel
An iterative method for nonlinear demiclosed monotone-type operators
International Nuclear Information System (INIS)
Chidume, C.E.
1991-01-01
It is proved that a well known fixed point iteration scheme which has been used for approximating solutions of certain nonlinear demiclosed monotone-type operator equations in Hilbert spaces remains applicable in real Banach spaces with property (U, α, m+1, m). These Banach spaces include the L p -spaces, p is an element of [2,∞]. An application of our results to the approximation of a solution of a certain linear operator equation in this general setting is also given. (author). 19 refs
Childhood adversity specificity and dose-response effect in non-affective first-episode psychosis
DEFF Research Database (Denmark)
Trauelsen, Anne Marie; Bendall, Sarah; Jansen, Jens Einar
2015-01-01
BACKGROUND: Reviews conclude that childhood and adolescence sexual, physical, emotional abuse and emotional and physical neglect are all risk factors for psychosis. However, studies suggest only some adversities are associated with psychosis. Dose-response effects of several adversities on risk......% of the control group. Childhood and adolescent sexual, physical, emotional abuse, and physical and emotional neglect, separation and institutionalization were about four to 17 times higher for the FEP group (all p... of psychosis have not been consistently found. The current study aimed to explore adversity specificity and dose-response effects of adversities on risk of psychosis. METHOD: Participants were 101 persons with first-episode psychosis (FEP) diagnosed with ICD-10 F20 - F29 (except F21) and 101 non-clinical...
Energy Technology Data Exchange (ETDEWEB)
Shinde, S.H. [Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)]. E-mail: shs_barc@yahoo.com; Mukherjee, T. [Radiation Safety Systems Division, Chemistry Group, Bhabha Atomic Research Centre, Mumbai 400 085 (India)
2007-02-15
Aspartame tablets were studied for gamma dose response, using spectrophotometric read-out method. The optimum concentration for ferrous ions was 2x10{sup -4}moldm{sup -3} and xylenol orange with 2.5x10{sup -1}moldm{sup -3} of sulphuric acid for the optimum acidity in FX solution. Wavelength of maximum absorbance is 548nm. Post-irradiation stability is appreciable i.e. for not less than one month. Dose response is non-linear with third order polynomial fit, in the dose range of 1000-10000Gy. This system of aspartame was further used for carrying out relative percentage dose profile measurement in Gamma Cell-220. Results obtained were inter-compared with that of a glutamine dosimeter, which showed that maximum difference between the values of aspartame and glutamine systems is within +/-10%.
Epidemiological methods for assessing dose-response and dose-effect relationships
DEFF Research Database (Denmark)
Kjellström, Tord; Grandjean, Philippe
2007-01-01
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......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...... 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...
International Nuclear Information System (INIS)
Shinde, S.H.; Mukherjee, T.
2007-01-01
Aspartame tablets were studied for gamma dose response, using spectrophotometric read-out method. The optimum concentration for ferrous ions was 2x10 -4 moldm -3 and xylenol orange with 2.5x10 -1 moldm -3 of sulphuric acid for the optimum acidity in FX solution. Wavelength of maximum absorbance is 548nm. Post-irradiation stability is appreciable i.e. for not less than one month. Dose response is non-linear with third order polynomial fit, in the dose range of 1000-10000Gy. This system of aspartame was further used for carrying out relative percentage dose profile measurement in Gamma Cell-220. Results obtained were inter-compared with that of a glutamine dosimeter, which showed that maximum difference between the values of aspartame and glutamine systems is within +/-10%
Dose response of tracheal epithelial cells to ionizing radiation in air-liquid interface cultures
International Nuclear Information System (INIS)
Fukutsu, K.; Yamada, Y.; Shimo, M.
2002-01-01
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 α 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 α-rays. (orig.)
Dose-response association between leisure time physical activity and work ability
DEFF Research Database (Denmark)
Calatayud, Joaquin; Jakobsen, Markus D.; Sundstrup, Emil
2015-01-01
INTRODUCTION: Regular physical activity is important for longevity and health, but knowledge about the optimal dose of physical activity for maintaining good work ability is unknown. This study investigates the association between intensity and duration of physical activity during leisure time......, lifestyle and chronic disease showed that the duration of high-intensity physical activity during leisure was positively associated with work ability, in a dose-response fashion (p physical activity per week had on average 8 points higher work ability...... than those not performing such activities. The duration of low-intensity leisure-time physical activity was not associated with work ability (p = 0.5668). CONCLUSIONS: The duration of high-intensity physical activity during leisure time is associated in a dose-response fashion with work ability...
Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 Diabetics
Nesse, Willem; Linde, Annemiek; Abbas, Frank; Spijkervet, Frederik Karst Lucien; Dijkstra, Pieter Ubele; de Brabander, Eric Carl; Gerstenbluth, Izzy; Vissink, Arjan
Nesse W, Linde A, Abbas F, Spijkervet FKL, Dijkstra PU, de Brabander EC, Gerstenbluth I, Vissink A. Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 diabetics. J Clin Periodontol 2009; 36: 295-300. doi: 10.1111/j.1600-051X.2009.01377.x. A dose-response
DEFF Research Database (Denmark)
Diez, Patricia; Vogelius, Ivan S; Bentzen, Søren M
2010-01-01
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).......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)....
A comparison of dose-response models for death from hematological depression
International Nuclear Information System (INIS)
Morris, M.D.; Jones, T.D.
1987-01-01
Many radiation-induced lethality experiments that have been published for various mammalian species have been compiled into a database suitable to study interspecific variability of radiosensitivity, dose-rate dependence of sensitivity, dose-response behavior within each experiment, etc. The data compiled were restricted to continuous and nearly continuous exposures to photon radiations having source energies above 100 keV. Also, photon source energy, exposure geometry, and body weight considerations were used to select studies where the dose to hematopoietic marrow was nearly uniform, i.e., < +- 20%. The data base reflects 13 mammalian test species ranging from mouse to cattle. Some 211 studies were compiled but only 105 were documented in adequate detail to be useful in development and evaluation of dose-response models of interest to practical human exposures. Of the 105 studies, 70 were for various rodent species, and 35 were for nonrodent groups ranging from standard laboratory primates (body weight ∼5 kg) to cattle (body weight 375 kg). This paper considers seven different dose-response models which are tested for validity against those 105 studies. The dose-response models included: a right-skewed extreme value, a left-skewed extreme value model, log-logistic, log-probit, logistic, probit, and Weibull models. In general, the log transformed models did not improve model performance and the extreme value models did not seem consistent with the preponderance of the data. Overall, the probit and the logistic models seemed preferable over the Weibull model. 30 refs., 8 tabs
Dose response of hydrazine - Deproteinated tooth enamel under blue light stimulation
Energy Technology Data Exchange (ETDEWEB)
Yuece, Ulkue Rabia, E-mail: ulkuyuce@hotmail.co [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Meric, Niyazi, E-mail: meric@ankara.edu.t [Ankara University, Faculty of Engineering, Department of Engineering Physics, 06100, Tandogan - Ankara (Turkey); Atakol, Orhan, E-mail: atakol@science.ankara.edu.t [Ankara University, Science Faculty, Department of Chemistry, 06100, Tandogan - Ankara (Turkey); Yasar, Fusun, E-mail: ab121310@adalet.gov.t [Council of Forensic Medicine, Ankara Branch, Ankara (Turkey)
2010-08-15
The beta dose response and Optically Stimulated Luminescence (OSL) signal stability characteristics of human tooth enamel deproteinated by hydrazine reagent under blue photon stimulation are reported. Removal of the protein organic component of tooth enamel resulted in a higher OSL sensitivity and slower fading of OSL signals. The effect of chemical sample preparation on the enamel sample sensitivity is discussed and further steps to make this deproteinization treatment suitable for in vitro dose reconstruction studies are suggested.
Dose response of hydrazine - Deproteinated tooth enamel under blue light stimulation
International Nuclear Information System (INIS)
Yuece, Ulkue Rabia; Meric, Niyazi; Atakol, Orhan; Yasar, Fusun
2010-01-01
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.
I-131 Dose Response for Incident Thyroid Cancers in Ukraine Related to the Chornobyl Accident
Brenner, Alina V.; Tronko, Mykola D.; Hatch, Maureen; Bogdanova, Tetyana I.; Oliynik, Valery A.; Lubin, Jay H.; Zablotska, Lydia B.; Tereschenko, Valery P.; McConnell, Robert J.; Zamotaeva, Galina A.; O?Kane, Patrick; Bouville, Andre C.; Chaykovskaya, Ludmila V.; Greenebaum, Ellen; Paster, Ihor P.
2011-01-01
Background: Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case?control studies, and studies of prevalent cancers. Objective: To address this limitation, we evaluated the dose?response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study. Methods: The cohort consists of individuals < 18 years of age on 26 April 1986 who ...
Analysis of Dose Response for Circulatory Disease After Radiotherapy for Benign Disease
Energy Technology Data Exchange (ETDEWEB)
Little, Mark P., E-mail: mark.little@nih.gov [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Kleinerman, Ruth A. [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States); Stovall, Marilyn; Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mabuchi, Kiyohiko [Radiation Epidemiology Branch, National Cancer Institute, Executive Plaza South, Rockville, Maryland (United States)
2012-12-01
Purpose: To assess the shape of the dose-response for various circulatory disease endpoints, and modifiers by age and time since exposure. Methods and Materials: This was an analysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by circulatory disease endpoint (ischemic heart, cerebrovascular, other circulatory disease). Results: There were significant excess risks for all circulatory disease, with an excess relative risk Gy{sup -1} of 0.082 (95% CI 0.031-0.140), and ischemic heart disease, with an excess relative risk Gy{sup -1} of 0.102 (95% CI 0.039-0.174) (both p = 0.01), and indications of excess risk for stroke. There were no statistically significant (p > 0.2) differences between risks by endpoint, and few indications of curvature in the dose-response. There were significant (p < 0.001) modifications of relative risk by time since exposure, the magnitude of which did not vary between endpoints (p > 0.2). Risk modifications were similar if analysis was restricted to patients receiving radiation, although the relative risks were slightly larger and the risk of stroke failed to be significant. The slopes of the dose-response were generally consistent with those observed in the Japanese atomic bomb survivors and in occupationally and medically exposed groups. Conclusions: There were excess risks for a variety of circulatory diseases in this dataset, with significant modification of risk by time since exposure. The consistency of the dose-response slopes with those observed in radiotherapeutically treated groups at much higher dose, as well as in lower dose-exposed cohorts such as the Japanese atomic bomb survivors and nuclear workers, implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.
Diethylene glycol-induced toxicities show marked threshold dose response in rats
Energy Technology Data Exchange (ETDEWEB)
Landry, Greg M., E-mail: Landry.Greg@mayo.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Dunning, Cody L., E-mail: cdunni@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Abreo, Fleurette, E-mail: fabreo@lsuhsc.edu [Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Latimer, Brian, E-mail: blatim@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Orchard, Elysse, E-mail: eorcha@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States); Division of Animal Resources, Louisiana State University Health Sciences Center, Shreveport, LA (United States); McMartin, Kenneth E., E-mail: kmcmar@lsuhsc.edu [Department of Pharmacology, Toxicology, & Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA (United States)
2015-02-01
Diethylene glycol (DEG) exposure poses risks to human health because of widespread industrial use and accidental exposures from contaminated products. To enhance the understanding of the mechanistic role of metabolites in DEG toxicity, this study used a dose response paradigm to determine a rat model that would best mimic DEG exposure in humans. Wistar and Fischer-344 (F-344) rats were treated by oral gavage with 0, 2, 5, or 10 g/kg DEG and blood, kidney and liver tissues were collected at 48 h. Both rat strains treated with 10 g/kg DEG had equivalent degrees of metabolic acidosis, renal toxicity (increased BUN and creatinine and cortical necrosis) and liver toxicity (increased serum enzyme levels, centrilobular necrosis and severe glycogen depletion). There was no liver or kidney toxicity at the lower DEG doses (2 and 5 g/kg) regardless of strain, demonstrating a steep threshold dose response. Kidney diglycolic acid (DGA), the presumed nephrotoxic metabolite of DEG, was markedly elevated in both rat strains administered 10 g/kg DEG, but no DGA was present at 2 or 5 g/kg, asserting its necessary role in DEG-induced toxicity. These results indicate that mechanistically in order to produce toxicity, metabolism to and significant target organ accumulation of DGA are required and that both strains would be useful for DEG risk assessments. - Highlights: • DEG produces a steep threshold dose response for kidney injury in rats. • Wistar and F-344 rats do not differ in response to DEG-induced renal injury. • The dose response for renal injury closely mirrors that for renal DGA accumulation. • Results demonstrate the importance of DGA accumulation in producing kidney injury.
Gustatory tissue injury in man: radiation dose response relationships and mechanisms of taste loss
International Nuclear Information System (INIS)
Mossman, K.L.
1986-01-01
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. (author)
Basic dose response of fluorescent screen-based portal imaging device
International Nuclear Information System (INIS)
Yeo, In Hwan; Yonannes, Yonas; Zhu, Yunping
1999-01-01
The purpose of this study is to investigate fundamental aspects of the dose response of fluorescent screen-based electronic portal imaging devices (EPIDs). We acquired scanned signal across portal planes as we varied the radiation that entered the EPID by changing the thickness and anatomy of the phantom as well as the air gap between the phantom and the EPID. In addition, we simulated the relative contribution of the scintillation light signal in the EPID system. We have shown that the dose profile across portal planes is a function of the air gap and phantom thickness. We have also found that depending on the density change within the phantom geometry, errors associated with dose response based on the EPID scan can be as high as 7%. We also found that scintillation light scattering within the EPID system is an important source of error. This study revealed and demonstrated fundamental characteristics of dose response of EPID, as relative to that of ion chambers. This study showed that EPID based on fluorescent screen cannot be an accurate dosimetry system
Directory of Open Access Journals (Sweden)
Hemantkumar Chavan
2017-01-01
Full Text Available Arsenite is a known carcinogen and its exposure has been implicated in a variety of noncarcinogenic health concerns. Increased oxidative stress is thought to be the primary cause of arsenite toxicity and the toxic effect is thought to be linear with detrimental effects reported at all concentrations of arsenite. But the paradigm of linear dose response in arsenite toxicity is shifting. In the present study we demonstrate that arsenite effects on mitochondrial respiration in primary hepatocytes follow a nonlinear dose response. In vitro exposure of primary hepatocytes to an environmentally relevant, moderate level of arsenite results in increased oxidant production that appears to arise from changes in the expression and activity of respiratory Complex I of the mitochondrial proton circuit. In primary hepatocytes the excess oxidant production appears to elicit adaptive responses that promote resistance to oxidative stress and a propensity to increased proliferation. Taken together, these results suggest a nonlinear dose-response characteristic of arsenite with low-dose arsenite promoting adaptive responses in a process known as mitohormesis, with transient increase in ROS levels acting as transducers of arsenite-induced mitohormesis.
Dose-response model of Rocky Mountain spotted fever (RMSF) for human.
Tamrakar, Sushil B; Haas, Charles N
2011-10-01
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 (ID₅₀) exposed human population, N₅₀, is 23 organisms with 95% confidence limits of 1 to 89 organisms. Similarly, ID₁₀ and ID₂₀ 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. © 2011 Society for Risk Analysis.
Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships
Blumberg, Jeffrey B.; Vita, Joseph A.; Chen, C. -Y. Oliver
2015-01-01
Pure fruit juices provide nutritional value with evidence suggesting some of their benefits on biomarkers of cardiovascular disease risk may be derived from their constituent polyphenols, particularly flavonoids. However, few data from clinical trials are available on the dose-response relationship of fruit juice flavonoids to these outcomes. Utilizing the results of clinical trials testing single doses, we have analyzed data from studies of 100% Concord grape juice by placing its flavonoid content in the context of results from randomized clinical trials of other polyphenol-rich foods and beverages describing the same outcomes but covering a broader range of intake. We selected established biomarkers determined by similar methods for measuring flow-mediated vasodilation (FMD), blood pressure, platelet aggregation, and the resistance of low density lipoprotein cholesterol (LDL) to oxidation. Despite differences among the clinical trials in the treatment, subjects, and duration, correlations were observed between the dose and FMD. Inverse dose-response relationships, albeit with lower correlation coefficients, were also noted for the other outcomes. These results suggest a clear relationship between consumption of even modest serving sizes of Concord grape juice, flavonoid intake, and effects on risk factors for cardiovascular disease. This approach to dose-response relationships may prove useful for testing other individual foods and beverages. PMID:26633488
International Nuclear Information System (INIS)
Albert, R.E.
1981-01-01
This chapter examines low-level dose-response relationships in terms of the two-stage mouse tumorigenesis model. Analyzes the feasibility of the linear non-threshold dose-response model which was first adopted for use in the assessment of cancer risks from ionizing radiation and more recently from chemical carcinogens. Finds that both the interaction of B(a)P with epidermal DNA of the mouse skin and the dose-response relationship for the initiation stage of mouse skin tumorigenesis showed a linear non-threshold dose-response relationship. Concludes that low level exposure to environmental carcinogens has a linear non-threshold dose-response relationship with the carcinogen acting as an initiator and the promoting action being supplied by the factors that are responsible for the background cancer rate in the target tissue
Stäuble, C G; Stäuble, R B; Schaller, S J; Unterbuchner, C; Fink, H; Blobner, M
2015-08-01
Similar to volatile anaesthetics, propofol may influence neuromuscular transmission. We hypothesised that the administration of propofol influenced the potency of rocuronium depending on the duration of the administration. After consent, patients scheduled for elective surgery randomly received rocuronium either after induction of anaesthesia with propofol (2 min of propofol, n = 36) or after 30 min of propofol infusion (30 min of propofol, n = 36). Remifentanil was given in both groups. Neuromuscular monitoring was performed by calibrated electromyography. The dose-response relationship of rocuronium was determined with a single-bolus technique (0.07, 0.1, 0.15, 0.2, 0.3 and 0.45 mg/kg rocuronium). The primary endpoints were the ED50 and ED95 of rocuronium after 2 and 30 min propofol. Data are presented as means with (95% confidence interval). The trial is registered with the Eudra-CT: 2009-012815-16. A total of 72 patients were included. Time to maximal neuromuscular blockade was significantly shorter in patients after 30 min of propofol [3.3 min (2.9-3.7)] compared with patients anaesthetised with 2 min of propofol [4.6 min (4.0-5.2)]. After 30 min of propofol, the slope of the dose-response curve was significantly steeper (30 min of propofol: 4.34 [3.62-5.05]; 2 min of propofol: [3.34 (2.72-3.96)], resulting in lower ED95 values of rocuronium (30 min of propofol: 0.287 mg/kg [0.221-0.368]; 2 min of propofol [0.391 mg/kg (0.296-0.520)]. The ED50 were not different between groups. The potency of rocuronium was significantly enhanced after propofol infusion for 30 min. Estimates of potency those are usually determined during steady-state anaesthesia might underestimate rocuronium requirements for endotracheal intubation at the time of induction. © 2015 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.
Experimental quantum control landscapes: Inherent monotonicity and artificial structure
International Nuclear Information System (INIS)
Roslund, Jonathan; Rabitz, Herschel
2009-01-01
Unconstrained searches over quantum control landscapes are theoretically predicted to generally exhibit trap-free monotonic behavior. This paper makes an explicit experimental demonstration of this intrinsic monotonicity for two controlled quantum systems: frequency unfiltered and filtered second-harmonic generation (SHG). For unfiltered SHG, the landscape is randomly sampled and interpolation of the data is found to be devoid of landscape traps up to the level of data noise. In the case of narrow-band-filtered SHG, trajectories are taken on the landscape to reveal a lack of traps. Although the filtered SHG landscape is trap free, it exhibits a rich local structure. A perturbation analysis around the top of these landscapes provides a basis to understand their topology. Despite the inherent trap-free nature of the landscapes, practical constraints placed on the controls can lead to the appearance of artificial structure arising from the resultant forced sampling of the landscape. This circumstance and the likely lack of knowledge about the detailed local landscape structure in most quantum control applications suggests that the a priori identification of globally successful (un)constrained curvilinear control variables may be a challenging task.
Positivity and monotonicity properties of C0-semigroups. Pt. 1
International Nuclear Information System (INIS)
Bratteli, O.; Kishimoto, A.; Robinson, D.W.
1980-01-01
If exp(-tH), exp(-tK), are self-adjoint, positivity preserving, contraction semigroups on a Hilbert space H = L 2 (X;dμ) we write esup(-tH) >= esup(-tK) >= 0 whenever exp(-tH) - exp(-tK) is positivity preserving for all t >= 0 and then we characterize the class of positive functions for which (*) always implies esup(-tf(H)) >= esup(-tf(K)) >= 0. This class consists of the f epsilon Csup(infinitely)(0, infinitely) with (-1)sup(n)fsup((n + 1))(x) >= 0, x epsilon(0, infinitely), n = 0, 1, 2, ... In particular it contains the class of monotone operator functions. Furthermore if exp(-tH) is Lsup(P)(X;dμ) contractive for all p epsilon[1, infinitely] and all t > 0 (or, equivalently, for p = infinitely and t > 0) then exp(-tf(H)) has the same property. Various applications to monotonicity properties of Green's functions are given. (orig.)
The Monotonic Lagrangian Grid for Rapid Air-Traffic Evaluation
Kaplan, Carolyn; Dahm, Johann; Oran, Elaine; Alexandrov, Natalia; Boris, Jay
2010-01-01
The Air Traffic Monotonic Lagrangian Grid (ATMLG) is presented as a tool to evaluate new air traffic system concepts. The model, based on an algorithm called the Monotonic Lagrangian Grid (MLG), can quickly sort, track, and update positions of many aircraft, both on the ground (at airports) and in the air. The underlying data structure is based on the MLG, which is used for sorting and ordering positions and other data needed to describe N moving bodies and their interactions. Aircraft that are close to each other in physical space are always near neighbors in the MLG data arrays, resulting in a fast nearest-neighbor interaction algorithm that scales as N. Recent upgrades to ATMLG include adding blank place-holders within the MLG data structure, which makes it possible to dynamically change the MLG size and also improves the quality of the MLG grid. Additional upgrades include adding FAA flight plan data, such as way-points and arrival and departure times from the Enhanced Traffic Management System (ETMS), and combining the MLG with the state-of-the-art strategic and tactical conflict detection and resolution algorithms from the NASA-developed Stratway software. In this paper, we present results from our early efforts to couple ATMLG with the Stratway software, and we demonstrate that it can be used to quickly simulate air traffic flow for a very large ETMS dataset.
Kathren, R L
1996-05-01
This paper traces the evolution of the linear nonthreshold dose-response model and its acceptance as a paradigm in radiation protection practice and risk analysis. Deterministic effects such as skin burns and even deep tissue trauma were associated with excessive exposure to x rays shortly after their discovery, and carcinogenicity was observed as early as 1902. Still, it was not until 1925 that the first protective limits were suggested. For three decades these limits were based on the concept of a tolerance dose which, if not exceeded, would result in no demonstrable harm to the individual and implicitly assumed a threshold dose below which radiation effects would be absent. After World War II, largely because of genetic concerns related to atmospheric weapons testing, radiation protection dose limits were expressed in terms of a risk based maximum permissible dose which clearly implied no threshold. The 1927 discovery by Muller of x-ray induced genetic mutations in fruit flies, linear with dose and with no apparent threshold, was an important underpinning of the standards. The linear nonthreshold dose-response model was originally used to provide an upper limit estimate of the risk, with zero being the lower limit, of low level irradiation since the dose-response curve could not be determined at low dose levels. Evidence to the contrary such as hormesis and the classic studies of the radium dial painters notwithstanding, the linear nonthreshold model gained greater acceptance and in the centennial year of the discovery of x rays stands as a paradigm although serious questions are beginning to be raised regarding its general applicability. The work includes a brief digression describing the work of x-ray protection pioneer William Rollins and concludes with a recommendation for application of a de minimis dose level in radiation protection.
International Nuclear Information System (INIS)
Lutz, W.K.; Gaylor, D.W.; Conolly, R.B.; Lutz, R.W.
2005-01-01
Nonlinear and threshold-like shapes of dose-response curves are often observed in tests for carcinogenicity. Here, we present three examples where an apparent threshold is spurious and can be misleading for low dose extrapolation and human cancer risk assessment. Case 1: For experiments that are not replicated, such as rodent bioassays for carcinogenicity, random variation can lead to misinterpretation of the result. This situation was simulated by 20 random binomial samplings of 50 animals per group, assuming a true linear dose response from 5% to 25% tumor incidence at arbitrary dose levels 0, 0.5, 1, 2, and 4. Linearity was suggested only by 8 of the 20 simulations. Four simulations did not reveal the carcinogenicity at all. Three exhibited thresholds, two showed a nonmonotonic behavior with a decrease at low dose, followed by a significant increase at high dose ('hormesis'). Case 2: Logarithmic representation of the dose axis transforms a straight line into a sublinear (up-bent) curve, which can be misinterpreted to indicate a threshold. This is most pronounced if the dose scale includes a wide low dose range. Linear regression of net tumor incidences and intersection with the dose axis results in an apparent threshold, even with an underlying true linear dose-incidence relationship. Case 3: Nonlinear shapes of dose-cancer incidence curves are rarely seen with epidemiological data in humans. The discrepancy to data in rodents may in part be explained by a wider span of individual susceptibilities for tumor induction in humans due to more diverse genetic background and modulation by co-carcinogenic lifestyle factors. Linear extrapolation of a human cancer risk could therefore be appropriate even if animal bioassays show nonlinearity
Multipartite entangled quantum states: Transformation, Entanglement monotones and Application
Cui, Wei
Entanglement is one of the fundamental features of quantum information science. Though bipartite entanglement has been analyzed thoroughly in theory and shown to be an important resource in quantum computation and communication protocols, the theory of entanglement shared between more than two parties, which is called multipartite entanglement, is still not complete. Specifically, the classification of multipartite entanglement and the transformation property between different multipartite states by local operators and classical communications (LOCC) are two fundamental questions in the theory of multipartite entanglement. In this thesis, we present results related to the LOCC transformation between multipartite entangled states. Firstly, we investigate the bounds on the LOCC transformation probability between multipartite states, especially the GHZ class states. By analyzing the involvement of 3-tangle and other entanglement measures under weak two-outcome measurement, we derive explicit upper and lower bound on the transformation probability between GHZ class states. After that, we also analyze the transformation between N-party W type states, which is a special class of multipartite entangled states that has an explicit unique expression and a set of analytical entanglement monotones. We present a necessary and sufficient condition for a known upper bound of transformation probability between two N-party W type states to be achieved. We also further investigate a novel entanglement transformation protocol, the random distillation, which transforms multipartite entanglement into bipartite entanglement ii shared by a non-deterministic pair of parties. We find upper bounds for the random distillation protocol for general N-party W type states and find the condition for the upper bounds to be achieved. What is surprising is that the upper bounds correspond to entanglement monotones that can be increased by Separable Operators (SEP), which gives the first set of
Sampling dynamics: an alternative to payoff-monotone selection dynamics
DEFF Research Database (Denmark)
Berkemer, Rainer
payoff-monotone nor payoff-positive which has interesting consequences. This can be demonstrated by application to the travelers dilemma, a deliberately constructed social dilemma. The game has just one symmetric Nash equilibrium which is Pareto inefficient. Especially when the travelers have many......'' of the standard game theory result. Both, analytical tools and agent based simulation are used to investigate the dynamic stability of sampling equilibria in a generalized travelers dilemma. Two parameters are of interest: the number of strategy options (m) available to each traveler and an experience parameter...... (k), which indicates the number of samples an agent would evaluate before fixing his decision. The special case (k=1) can be treated analytically. The stationary points of the dynamics must be sampling equilibria and one can calculate that for m>3 there will be an interior solution in addition...
Modeling non-monotonic properties under propositional argumentation
Wang, Geng; Lin, Zuoquan
2013-03-01
In the field of knowledge representation, argumentation is usually considered as an abstract framework for nonclassical logic. In this paper, however, we'd like to present a propositional argumentation framework, which can be used to closer simulate a real-world argumentation. We thereby argue that under a dialectical argumentation game, we can allow non-monotonic reasoning even under classical logic. We introduce two methods together for gaining nonmonotonicity, one by giving plausibility for arguments, the other by adding "exceptions" which is similar to defaults. Furthermore, we will give out an alternative definition for propositional argumentation using argumentative models, which is highly related to the previous reasoning method, but with a simple algorithm for calculation.
Monotonic childhoods: representations of otherness in research writing
Directory of Open Access Journals (Sweden)
Denise Marcos Bussoletti
2011-12-01
Full Text Available This paper is part of a doctoral thesis entitled “Monotonic childhoods – a rhapsody of hope”. It follows the perspective of a critical psychosocial and cultural study, and aims at discussing the other’s representation in research writing, electing childhood as an allegorical and refl ective place. It takes into consideration, by means of analysis, the drawings and poems of children from the Terezin ghetto during the Second World War. The work is mostly based on Serge Moscovici’s Social Representation Theory, but it is also in constant dialogue with other theories and knowledge fi elds, especially Walter Benjamin’s and Mikhail Bakhtin’s contributions. At the end, the paper supports the thesis that conceives poetics as one of the translation axes of childhood cultures.
Convex analysis and monotone operator theory in Hilbert spaces
Bauschke, Heinz H
2017-01-01
This reference text, now in its second edition, offers a modern unifying presentation of three basic areas of nonlinear analysis: convex analysis, monotone operator theory, and the fixed point theory of nonexpansive operators. Taking a unique comprehensive approach, the theory is developed from the ground up, with the rich connections and interactions between the areas as the central focus, and it is illustrated by a large number of examples. The Hilbert space setting of the material offers a wide range of applications while avoiding the technical difficulties of general Banach spaces. The authors have also drawn upon recent advances and modern tools to simplify the proofs of key results making the book more accessible to a broader range of scholars and users. Combining a strong emphasis on applications with exceptionally lucid writing and an abundance of exercises, this text is of great value to a large audience including pure and applied mathematicians as well as researchers in engineering, data science, ma...
Expert system for failures detection and non-monotonic reasoning
International Nuclear Information System (INIS)
Assis, Abilio de; Schirru, Roberto
1997-01-01
This paper presents the development of a shell denominated TIGER that has the purpose to serve as environment to the development of expert systems in diagnosis of faults in industrial complex plants. A model of knowledge representation and an inference engine based on non monotonic reasoning has been developed in order to provide flexibility in the representation of complex plants as well as performance to satisfy restrictions of real time. The TIGER is able to provide both the occurred fault and a hierarchical view of the several reasons that caused the fault to happen. As a validation of the developed shell a monitoring system of the critical safety functions of Angra-1 has been developed. 7 refs., 7 figs., 2 tabs
International Nuclear Information System (INIS)
Filyushkin, I.V.; Bragin, Yu.N.; Khandogina, E.K.
1989-01-01
Presented are the results of an investigation of the dose-response relationship for the yield of chromosome aberrations in peripheral blood lymphocytes of persons with some hereditary diseases which represent the high risk group with respect to the increased incidence of malignant tumors and decreased life span. Despite substantially different absolute radiosensitivities of chromosomes, the variations of the alpha/beta ratio determining the extrapolation of experimental dose-response relationships to low doses did not prove to be too high, the mean deviation from the control being 15%. This points to the possible practical use of the dose-response relationships averaged over the human population as a whole
Monotonicity of fitness landscapes and mutation rate control.
Belavkin, Roman V; Channon, Alastair; Aston, Elizabeth; Aston, John; Krašovec, Rok; Knight, Christopher G
2016-12-01
A common view in evolutionary biology is that mutation rates are minimised. However, studies in combinatorial optimisation and search have shown a clear advantage of using variable mutation rates as a control parameter to optimise the performance of evolutionary algorithms. Much biological theory in this area is based on Ronald Fisher's work, who used Euclidean geometry to study the relation between mutation size and expected fitness of the offspring in infinite phenotypic spaces. Here we reconsider this theory based on the alternative geometry of discrete and finite spaces of DNA sequences. First, we consider the geometric case of fitness being isomorphic to distance from an optimum, and show how problems of optimal mutation rate control can be solved exactly or approximately depending on additional constraints of the problem. Then we consider the general case of fitness communicating only partial information about the distance. We define weak monotonicity of fitness landscapes and prove that this property holds in all landscapes that are continuous and open at the optimum. This theoretical result motivates our hypothesis that optimal mutation rate functions in such landscapes will increase when fitness decreases in some neighbourhood of an optimum, resembling the control functions derived in the geometric case. We test this hypothesis experimentally by analysing approximately optimal mutation rate control functions in 115 complete landscapes of binding scores between DNA sequences and transcription factors. Our findings support the hypothesis and find that the increase of mutation rate is more rapid in landscapes that are less monotonic (more rugged). We discuss the relevance of these findings to living organisms.
Fractional poisson--a simple dose-response model for human norovirus.
Messner, Michael J; Berger, Philip; Nappier, Sharon P
2014-10-01
This study utilizes old and new Norovirus (NoV) human challenge data to model the dose-response relationship for human NoV infection. The combined data set is used to update estimates from a previously published beta-Poisson dose-response model that includes parameters for virus aggregation and for a beta-distribution that describes variable susceptibility among hosts. The quality of the beta-Poisson model is examined and a simpler model is proposed. The new model (fractional Poisson) characterizes hosts as either perfectly susceptible or perfectly immune, requiring a single parameter (the fraction of perfectly susceptible hosts) in place of the two-parameter beta-distribution. A second parameter is included to account for virus aggregation in the same fashion as it is added to the beta-Poisson model. Infection probability is simply the product of the probability of nonzero exposure (at least one virus or aggregate is ingested) and the fraction of susceptible hosts. The model is computationally simple and appears to be well suited to the data from the NoV human challenge studies. The model's deviance is similar to that of the beta-Poisson, but with one parameter, rather than two. As a result, the Akaike information criterion favors the fractional Poisson over the beta-Poisson model. At low, environmentally relevant exposure levels (Poisson model; however, caution is advised because no subjects were challenged at such a low dose. New low-dose data would be of great value to further clarify the NoV dose-response relationship and to support improved risk assessment for environmentally relevant exposures. © 2014 Society for Risk Analysis Published 2014. This article is a U.S. Government work and is in the public domain for the U.S.A.
Resto, Pedro J; Bhat, Abhishek; Stava, Eric; Lor, Chong; Merriam, Elliot; Diaz-Rivera, Ruben E; Pearce, Robert; Blick, Robert; Williams, Justin C
2017-11-01
Surface tension passive pumping is a way to actuate flow without the need for pumps, tubing or valves by using the pressure inside small drop to move liquid via a microfluidic channel. These types of tubeless devices have typically been used in cell biology. Herein we present the use of tubeless devices as a fluid exchange platform for patch clamp electrophysiology. Inertia from high-speed droplets and jets is used to create flow and perform on-the-fly mixing of solutions. These are then flowed over GABA transfected HEK cells under patch in order to perform a dose response analysis. TIRF imaging and electrical recordings are used to study the fluid exchange properties of the microfluidic device, resulting in 0-90% fluid exchange times of hundreds of milliseconds. COMSOL is used to model flow and fluid exchange within the device. Patch-clamping experiments show the ability to use high-speed passive pumping and its derivatives for studying peak dose responses, but not for studying ion channel kinetics. Our system results in fluid exchange times slower than when using a standard 12-barrel application system and is not as stable as traditional methods, but it offers a new platform with added functionality. Surface tension passive pumping and tubeless devices can be used in a limited fashion for electrophysiology. Users may obtain peak dose responses but the system, in its current form, is not capable of fluid exchange fast enough to study the kinetics of most ion channels. Copyright © 2017 Elsevier B.V. All rights reserved.
Dose response of bone-targeted enzyme replacement for murine hypophosphatasia.
Yadav, Manisha C; Lemire, Isabelle; Leonard, Pierre; Boileau, Guy; Blond, Laurent; Beliveau, Martin; Cory, Esther; Sah, Robert L; Whyte, Michael P; Crine, Philippe; Millán, José Luis
2011-08-01
Hypophosphatasia (HPP) features rickets or osteomalacia from tissue-nonspecific alkaline phosphatase (TNSALP) deficiency due to deactivating mutations within the ALPL gene. Enzyme replacement therapy with a bone-targeted, recombinant TNSALP (sALP-FcD(10), renamed ENB-0040) prevents manifestations of HPP when initiated at birth in TNSALP knockout (Akp2(-/-)) mice. Here, we evaluated the dose-response relationship of ENB-0040 to various phenotypic traits of Akp2(-/-) mice receiving daily subcutaneous (SC) injections of ENB-0040 from birth at 0.5, 2.0, or 8.2mg/kg for 43days. Radiographs, μCT, and histomorphometric analyses documented better bone mineralization with increasing doses of ENB-0040. We found a clear, positive correlation between ENB-0040 dose and prevention of mineralization defects of the feet, rib cage, lower limbs, and jaw bones. According to a dose-response model, the ED(80) (the dose that prevents bone defects in 80% of mice) was 3.2, 2.8 and 2.9mg/kg/day for these sites, respectively. Long bones seemed to respond to lower daily doses of ENB-0040. There was also a positive relationship between ENB-0040 dose and survival. Median survival, body weight, and bone length all improved with increasing doses of ENB-0040. Urinary PP(i) concentrations remained elevated in all treatment groups, indicating that while this parameter is a good biochemical marker for diagnosing HPP in patients, it may not be a good follow up marker for evaluating response to treatment when administering bone-targeted TNSALP to mice. These dose-response relationships strongly support the pharmacological efficacy of ENB-0040 for HPP, and provide the experimental basis for the therapeutic range of ENB-0040 chosen for clinical trials. Copyright © 2011 Elsevier Inc. All rights reserved.
International Nuclear Information System (INIS)
Karger, C.P.; Hartmann, G.H.
2001-01-01
Background: Dose response experiments aim to determine the complication probability as a function of dose. Adjusting the parameters of the frequently used dose response model P(D)=1/[1+(D 50 /D) k ] to the experimental data, 2 intuitive quantities are obtained: The tolerance dose D 50 and the slope parameter k. For mathematical reasons, however, standard statistic software uses a different set of parameters. Therefore, the resulting fit parameters of the statistic software as well as their standard errors have to be transformed to obtain D 50 and k as well as their standard errors. Material and Methods: The influence of the number of dose levels on the uncertainty of the fit parameters is studied by a simulation for a fixed number of animals. For experiments with small animal numbers, statistical artifacts may prevent the determination of the standard errors of the fit parameters. Consequences on the design of dose response experiments are investigated. Results: Explicit formulas are presented, which allow to calculate the parameters D 50 and k as well as their standard errors from the output of standard statistic software. The simulation shows, that the standard errors of the resulting parameters are independent of the number of dose levels, as long as the total number of animals involved in the experiment, remains constant. Conclusion: Statistical artifacts in experiments containing small animal numbers may be prevented by an adequate design of the experiment. For this, it is suggested to select a higher number of dose levels, rather than using a higher number of animals per dose level. (orig.) [de
External beam radiotherapy for painful osseous metastases: pooled data dose response analysis
International Nuclear Information System (INIS)
Ben-Josef, Edgar; Shamsa, Falah; Youssef, Emad; Porter, Arthur T.
1999-01-01
Purpose: Although the effectiveness of external beam irradiation in palliation of pain from osseous metastases is well established, the optimal fractionation schedule has not been determined. Clinical studies to date have failed to demonstrate an advantage for higher doses. To further address this issue, we conducted a pooled dose response analysis using data from published Phase III clinical trials. Methods and Materials: Complete response (CR) was used as an endpoint because it was felt to be least susceptible to inconsistencies in assessment.The biological effective dose (BED) was calculated for each schedule using the linear-quadratic model and an α/β of 10. Using SAS version 6.12, the data were fitted using a weighted linear regression, a logistic model, and the spline technique. Finally, BED was categorized, and odds ratios for each level were calculated. Results: CR was assessed early and late in 383 and 1,007 patients, respectively. Linear regression on the early-response data yielded a poor fit and a nonsignificant dose coefficient. With the late-response data, there was an excellent fit (R-square = 0.842) and a highly significant dose coefficient (p = 0.0002). Fitting early CR to a logistic model, we could not establish a significant dose response relationship. However, with the late-response data there was an excellent fit and the dose coefficient was significantly different from zero (0.017 ± 0.00524; p = 0.0012). Application of the spline technique or removal of an outlier resulted in an improved fit (p 0.048 and p = 0.0001, respectively). Using BED of < 14.4 Gy as a reference level, the odds ratios for late CR were 2.29-3.32 (BED of 19.5-51.4 Gy, respectively). Conclusion: Our results demonstrate a clear dose-response for pain relief. Further testing of high intensity regiments is warranted
Effect of Enamel Caries Lesion Baseline Severity on Fluoride Dose-Response
Directory of Open Access Journals (Sweden)
Frank Lippert
2017-01-01
Full Text Available This study aimed to investigate the effect of enamel caries lesion baseline severity on fluoride dose-response under pH cycling conditions. Early caries lesions were created in human enamel specimens at four different severities (8, 16, 24, and 36 h. Lesions were allocated to treatment groups (0, 83, and 367 ppm fluoride as sodium fluoride based on Vickers surface microhardness (VHN and pH cycled for 5 d. The cycling model comprised 3 × 1 min fluoride treatments sandwiched between 2 × 60 min demineralization challenges with specimens stored in artificial saliva in between. VHN was measured again and changes versus lesion baseline were calculated (ΔVHN. Data were analyzed using two-way ANOVA (p<0.05. Increased demineralization times led to increased surface softening. The lesion severity×fluoride concentration interaction was significant (p<0.001. Fluoride dose-response was observed in all groups. Lesions initially demineralized for 16 and 8 h showed similar overall rehardening (ΔVHN and more than 24 and 36 h lesions, which were similar. The 8 h lesions showed the greatest fluoride response differential (367 versus 0 ppm F which diminished with increasing lesion baseline severity. The extent of rehardening as a result of the 0 ppm F treatment increased with increasing lesion baseline severity, whereas it decreased for the fluoride treatments. In conclusion, lesion baseline severity impacts the extent of the fluoride dose-response.
Low-Active Male Adolescents: A Dose Response to High-Intensity Interval Training.
Logan, Greig Robert Melrose; Harris, Nigel; Duncan, Scott; Plank, Lindsay D; Merien, Fabrice; Schofield, Grant
2016-03-01
High-intensity interval training (HIIT) is a potential alternative to traditionally recommended steady state exercise for providing health benefits in adolescents, yet its dose-response relationship in this cohort remains unclear, as does its translatability to real-world, nonclinical settings. The present study adopts a novel dose-response design to investigate the effects of undertaking 8 wk of HIIT on the cardiometabolic health of low-active male adolescents. Twenty-six male adolescents (age 16 ± 1 yr), identified as low active by nonparticipation in structured sport and physical education classes, were randomly assigned to one of five treatment groups. Corresponding with their group numbers (1-5), participants completed a number of HIIT "sets," which consisted of 4 repeated bouts of 20-s near-maximal exertion interspersed with 10-s passive recovery. Participants performed two HIIT sessions and one resistance training session each week for 8 wk. Baseline and follow-up health measures consisted of peak oxygen uptake (V˙O2peak) with an incremental ramp test to volitional exhaustion; body composition (including visceral fat mass, body fat, and lean tissue mass) with dual-energy x-ray absorptiometry; and lipid profile, glucose, insulin, and interleukin-6 from blood analysis. All health outcomes were analyzed as percentage changes, and data were modeled using a quadratic function to explore dose-response relationships. Significant improvements were observed for V˙O2peak (∼6%), body fat percentage (∼4%), visceral fat mass (∼10%), and waist circumference-to-height ratio (∼3%), but there was no clear effect of dose across groups. Low-active adolescent males performing a single HIIT set twice weekly, in addition to one resistance training session, gained meaningful improvements in fitness and body composition. Performing additional HIIT sets provided no additional improvements to those of the lowest dose in this study.
Dose-response functions and corrosion mapping for a small geographical area
International Nuclear Information System (INIS)
Haagenrud, S.E.; Henriksen, J.F.; Gram, F.
1985-01-01
Detailed corrosion and environmental measurements have been used to develop dose response (D/R) functions for carbon steel, zinc, copper, and aluminum for a 26 x 31 km urban/rural area with approximately homogeneous climate. The D/R functions, expressed in terms of SO 2 and time of wetness, were of the same type for all four metals. The SO 2 contribution to the total corrosion dominates in the centers of towns and around an industrial plant. Corrosion maps for the whole area were established
The Environmental Kuznets Curve. An empirical analysis for OECD countries
Energy Technology Data Exchange (ETDEWEB)
Georgiev, E.
2008-09-15
This paper tests the Environmental Kuznets Curve hypothesis for four local (SOx, NOx, CO, VOC) and two global (CO2, GHG) air pollutants. Using a new panel data set of thirty OECD countries, the paper finds that the postulated inverted U-shaped relationship between income and pollution does not hold for all gases. A meaningful Environmental Kuznets Curve exists only for CO, VOC and NOx, where for CO2 the curve is monotonically increasing. For GHG there is indication of an inverted U-shaped relationship between income and pollution, but still most countries are on the increasing path of the curve and hence the future development of the curve is uncertain. For SOx it was found that emissions follow an U-shaped curve. Based on the empirical results, the paper concludes that the Environmental Kuznets Curve does not hold for all gases, it is rather an empirical artefact than a regularity.
The Environmental Kuznets Curve. An empirical analysis for OECD countries
International Nuclear Information System (INIS)
Georgiev, E.
2008-09-01
This paper tests the Environmental Kuznets Curve hypothesis for four local (SOx, NOx, CO, VOC) and two global (CO2, GHG) air pollutants. Using a new panel data set of thirty OECD countries, the paper finds that the postulated inverted U-shaped relationship between income and pollution does not hold for all gases. A meaningful Environmental Kuznets Curve exists only for CO, VOC and NOx, where for CO2 the curve is monotonically increasing. For GHG there is indication of an inverted U-shaped relationship between income and pollution, but still most countries are on the increasing path of the curve and hence the future development of the curve is uncertain. For SOx it was found that emissions follow an U-shaped curve. Based on the empirical results, the paper concludes that the Environmental Kuznets Curve does not hold for all gases, it is rather an empirical artefact than a regularity.
Ding, Kuan-Fu; Petricoin, Emanuel F; Finlay, Darren; Yin, Hongwei; Hendricks, William P D; Sereduk, Chris; Kiefer, Jeffrey; Sekulic, Aleksandar; LoRusso, Patricia M; Vuori, Kristiina; Trent, Jeffrey M; Schork, Nicholas J
2018-01-12
Cancer cell lines are often used in high throughput drug screens (HTS) to explore the relationship between cell line characteristics and responsiveness to different therapies. Many current analysis methods infer relationships by focusing on one aspect of cell line drug-specific dose-response curves (DRCs), the concentration causing 50% inhibition of a phenotypic endpoint (IC 50 ). Such methods may overlook DRC features and do not simultaneously leverage information about drug response patterns across cell lines, potentially increasing false positive and negative rates in drug response associations. We consider the application of two methods, each rooted in nonlinear mixed effects (NLME) models, that test the relationship relationships between estimated cell line DRCs and factors that might mitigate response. Both methods leverage estimation and testing techniques that consider the simultaneous analysis of different cell lines to draw inferences about any one cell line. One of the methods is designed to provide an omnibus test of the differences between cell line DRCs that is not focused on any one aspect of the DRC (such as the IC 50 value). We simulated different settings and compared the different methods on the simulated data. We also compared the proposed methods against traditional IC 50 -based methods using 40 melanoma cell lines whose transcriptomes, proteomes, and, importantly, BRAF and related mutation profiles were available. Ultimately, we find that the NLME-based methods are more robust, powerful and, for the omnibus test, more flexible, than traditional methods. Their application to the melanoma cell lines reveals insights into factors that may be clinically useful.
Log-supermodularity of weight functions and the loading monotonicity of weighted insurance premiums
Hristo S. Sendov; Ying Wang; Ricardas Zitikis
2010-01-01
The paper is motivated by a problem concerning the monotonicity of insurance premiums with respect to their loading parameter: the larger the parameter, the larger the insurance premium is expected to be. This property, usually called loading monotonicity, is satisfied by premiums that appear in the literature. The increased interest in constructing new insurance premiums has raised a question as to what weight functions would produce loading-monotonic premiums. In this paper we demonstrate a...
Non-linear dose response of a few plant taxa to acute gamma radiation
International Nuclear Information System (INIS)
George, J.T.; Patel, B.B.; Pius, J.; Narula, B.; Shankhadarwar, S.; Rane, V.A.; Venu-Babu, P.; Eapen, S.; Singhal, R.K.
2014-01-01
Micronuclei induction serves as an essential biomarker of radiation stress in a living system, and the simplicity of its detection technique has made it a widely used indicator of radiation damage. The present study was conducted to reveal the cytological dose-response of a few plant taxa, viz., Allium cepa var. aggregatum Linn., Allium sativum Linn., Chlorophytum comosum (Thunb.) Jacques and Eichhornia crassipes (Mart.) Solms, to low LET gamma radiation with special emphasis on the pattern of micronuclei induced across low and high dose regimes. A tri-phasic non-linear dose-response pattern was observed in the four taxa studied, characterized by a low dose linear segment, a plateau and a high dose linear segment. Despite a similar response trend, the critical doses where the phase transitions occurred varied amongst the plant taxa, giving an indication to their relative radiosensitivities. E. crassipes and A. sativum, with their lower critical doses for slope modifications of phase transitions, were concluded as being more radiosensitive as compared to C. comosum and A. cepa, which had relatively higher critical doses. (author)
Dose response evaluation of a low-density normoxic polymer gel dosimeter using MRI
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Haraldsson, P [Medical Radiation Physics, Department of Clinical Sciences, Lund University, Malmoe University Hospital, SE-205 02 Malmoe (Sweden); Department of Radiation Physics, Finsen Centre, Copenhagen University Hospital, DK-2100 Copenhagen (Denmark); Karlsson, A [Medical Radiation Physics, Department of Clinical Sciences, Lund University, Malmoe University Hospital, SE-205 02 Malmoe (Sweden); Wieslander, E [Medical Radiation Physics, Department of Clinical Sciences, Lund University Hospital, SE-221 85 Lund (Sweden); Gustavsson, H [Medical Radiation Physics, Department of Clinical Sciences, Lund University, Malmoe University Hospital, SE-205 02 Malmoe (Sweden); Baeck, S A J [Medical Radiation Physics, Department of Clinical Sciences, Lund University, Malmoe University Hospital, SE-205 02 Malmoe (Sweden)
2006-02-21
A low-density ({approx}0.6 g cm{sup -3}) normoxic polymer gel, containing the antioxidant tetrakis (hydroxymethyl) phosponium (THP), has been investigated with respect to basic absorbed dose response characteristics. The low density was obtained by mixing the gel with expanded polystyrene spheres. The depth dose data for 6 and 18 MV photons were compared with Monte Carlo calculations. A large volume phantom was irradiated in order to study the 3D dose distribution from a 6 MV field. Evaluation of the gel was carried out using magnetic resonance imaging. An approximately linear response was obtained for 1/T2 versus dose in the dose range of 2 to 8 Gy. A small decrease in the dose response was observed for increasing concentrations of THP. A good agreement between measured and Monte Carlo calculated data was obained, both for test tubes and the larger 3D phantom. It was shown that a normoxic polymer gel with a reduced density could be obtained by adding expanded polystyrene spheres. In order to get reliable results, it is very important to have a uniform distribution of the gel and expanded polystyrene spheres in the phantom volume.
Dose response evaluation of a low-density normoxic polymer gel dosimeter using MRI
Haraldsson, P.; Karlsson, A.; Wieslander, E.; Gustavsson, H.; Bäck, S. Å. J.
2006-02-01
A low-density (~0.6 g cm-3) normoxic polymer gel, containing the antioxidant tetrakis (hydroxymethyl) phosponium (THP), has been investigated with respect to basic absorbed dose response characteristics. The low density was obtained by mixing the gel with expanded polystyrene spheres. The depth dose data for 6 and 18 MV photons were compared with Monte Carlo calculations. A large volume phantom was irradiated in order to study the 3D dose distribution from a 6 MV field. Evaluation of the gel was carried out using magnetic resonance imaging. An approximately linear response was obtained for 1/T2 versus dose in the dose range of 2 to 8 Gy. A small decrease in the dose response was observed for increasing concentrations of THP. A good agreement between measured and Monte Carlo calculated data was obained, both for test tubes and the larger 3D phantom. It was shown that a normoxic polymer gel with a reduced density could be obtained by adding expanded polystyrene spheres. In order to get reliable results, it is very important to have a uniform distribution of the gel and expanded polystyrene spheres in the phantom volume.
Fenner-Crisp, Penelope A
2012-12-01
Contaminants are undesirable constituents in food. They may be formed during production of a processed food, present as a component in a source material, deliberately added to substitute for the proper substance, or the consequence of poor food-handling practices. Contaminants may be chemicals or pathogens. Chemicals generally degrade over time and become of less concern as a health threat. Pathogens have the ability to multiply, potentially resulting in an increased threat level. Formal structures have been lacking for systematically generating and evaluating hazard and exposure data for bioactive agents when problem situations arise. We need to know what the potential risk may be to determine whether intervention to reduce or eliminate contact with the contaminant is warranted. We need tools to aid us in assembling and assessing all available relevant information in an expeditious and scientifically sound manner. One such tool is the International Life Sciences Institute (ILSI) Key Events Dose-Response Framework (KEDRF). Developed as an extension of the WHO's International Program on Chemical Safety/ILSI mode of action/human relevance framework, it allows risk assessors to understand not only how a contaminant exerts its toxicity but also the dose response(s) for each key event and the ultimate outcome, including whether a threshold exists. This presentation will illustrate use of the KEDRF with case studies included in its development (chloroform and Listeriaonocytogenes) after its publication in the peer-reviewed scientific literature (chromium VI) and in a work in progress (3-monochloro-1, 2-propanediol).
I-131 dose response for incident thyroid cancers in Ukraine related to the Chornobyl accident.
Brenner, Alina V; Tronko, Mykola D; Hatch, Maureen; Bogdanova, Tetyana I; Oliynik, Valery A; Lubin, Jay H; Zablotska, Lydia B; Tereschenko, Valery P; McConnell, Robert J; Zamotaeva, Galina A; O'Kane, Patrick; Bouville, Andre C; Chaykovskaya, Ludmila V; Greenebaum, Ellen; Paster, Ihor P; Shpak, Victor M; Ron, Elaine
2011-07-01
Current knowledge about Chornobyl-related thyroid cancer risks comes from ecological studies based on grouped doses, case-control studies, and studies of prevalent cancers. To address this limitation, we evaluated the dose-response relationship for incident thyroid cancers using measurement-based individual iodine-131 (I-131) thyroid dose estimates in a prospective analytic cohort study. The cohort consists of individuals radioactivity measurements taken within 2 months after the accident, environmental transport models, and interview data. Excess radiation risks were estimated using Poisson regression models. Sixty-five incident thyroid cancers were diagnosed during the second through fourth screenings and 73,004 person-years (PY) of observation. The dose-response relationship was consistent with linearity on relative and absolute scales, although the excess relative risk (ERR) model described data better than did the excess absolute risk (EAR) model. The ERR per gray was 1.91 [95% confidence interval (CI), 0.43-6.34], and the EAR per 10⁴ PY/Gy was 2.21 (95% CI, 0.04-5.78). The ERR per gray varied significantly by oblast of residence but not by time since exposure, use of iodine prophylaxis, iodine status, sex, age, or tumor size. I-131-related thyroid cancer risks persisted for two decades after exposure, with no evidence of decrease during the observation period. The radiation risks, although smaller, are compatible with those of retrospective and ecological post-Chornobyl studies.
Does a dose-response relation exist between spinal pain and temporomandibular disorders?
Directory of Open Access Journals (Sweden)
Englund Erling
2009-03-01
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.
Directory of Open Access Journals (Sweden)
Paul D. Loprinzi
2013-08-01
Full Text Available 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.
International Nuclear Information System (INIS)
1975-01-01
The International Atomic Energy Agency hosted a two day Symposium from 2-3 December 1974 at its Headquarters, organized by the 'International Academy for Environmental Safety and the Forum fur Wissenschaft, Wirtschaft und Politik' on the subject 'Scientific Basis for the Establishment of Threshold. Levels and Dose Response Relationships of Carcinogenesis'. Following an introductory paper by the Radiation Biology Section of the Agency on 'Radiation Carcinogenesis - Dose Response Relationship, Threshold and Risk Estimates', a series of papers dealt with this problem in chemical carcinogenesis.It was suggested that more experiments should be done using non-human primates for tests of carcinogens, especially chemicals. Preliminary experiments using monkeys with a potent carcinogen - nitrosoamine - indicate that there could possibly be a dose where no effect can be observed during the 5 year period of study. It was also pointed out that the overall cost/benefit and risk/ benefit relationships should be taken into consideration in determining limits for chemicals which are potentially carcinogenic but are used routinely by the public and industries; these considerations have been weighed in setting exposure limits for radiation
A System of Generalized Variational Inclusions Involving a New Monotone Mapping in Banach Spaces
Directory of Open Access Journals (Sweden)
Jinlin Guan
2013-01-01
Full Text Available We introduce a new monotone mapping in Banach spaces, which is an extension of the -monotone mapping studied by Nazemi (2012, and we generalize the variational inclusion involving the -monotone mapping. Based on the new monotone mapping, we propose a new proximal mapping which combines the proximal mapping studied by Nazemi (2012 with the mapping studied by Lan et al. (2011 and show its Lipschitz continuity. Based on the new proximal mapping, we give an iterative algorithm. Furthermore, we prove the convergence of iterative sequences generated by the algorithm under some appropriate conditions. Our results improve and extend corresponding ones announced by many others.
Obliquely Propagating Non-Monotonic Double Layer in a Hot Magnetized Plasma
International Nuclear Information System (INIS)
Kim, T.H.; Kim, S.S.; Hwang, J.H.; Kim, H.Y.
2005-01-01
Obliquely propagating non-monotonic double layer is investigated in a hot magnetized plasma, which consists of a positively charged hot ion fluid and trapped, as well as free electrons. A model equation (modified Korteweg-de Vries equation) is derived by the usual reductive perturbation method from a set of basic hydrodynamic equations. A time stationary obliquely propagating non-monotonic double layer solution is obtained in a hot magnetized-plasma. This solution is an analytic extension of the monotonic double layer and the solitary hole. The effects of obliqueness, external magnetic field and ion temperature on the properties of the non-monotonic double layer are discussed
Poppinga, D; Meyners, J; Delfs, B; Muru, A; Harder, D; Poppe, B; Looe, H K
2015-12-21
This study aims at the experimental determination of the detector-specific 1D lateral dose response function K(x) and of its associated rotational symmetric counterpart K(r) for a set of high-resolution detectors presently used in narrow-beam photon dosimetry. A combination of slit-beam, radiochromic film, and deconvolution techniques served to accomplish this task for four detectors with diameters of their sensitive volumes ranging from 1 to 2.2 mm. The particular aim of the experiment was to examine the existence of significant negative portions of some of these response functions predicted by a recent Monte-Carlo-simulation (Looe et al 2015 Phys. Med. Biol. 60 6585-607). In a 6 MV photon slit beam formed by the Siemens Artiste collimation system and a 0.5 mm wide slit between 10 cm thick lead blocks serving as the tertiary collimator, the true cross-beam dose profile D(x) at 3 cm depth in a large water phantom was measured with radiochromic film EBT3, and the detector-affected cross-beam signal profiles M(x) were recorded with a silicon diode, a synthetic diamond detector, a miniaturized scintillation detector, and a small ionization chamber. For each detector, the deconvolution of the convolution integral M(x) = K(x) ∗ D(x) served to obtain its specific 1D lateral dose response function K(x), and K(r) was calculated from it. Fourier transformations and back transformations were performed using function approximations by weighted sums of Gaussian functions and their analytical transformation. The 1D lateral dose response functions K(x) of the four types of detectors and their associated rotational symmetric counterparts K(r) were obtained. Significant negative curve portions of K(x) and K(r) were observed in the case of the silicon diode and the diamond detector, confirming the Monte-Carlo-based prediction (Looe et al 2015 Phys. Med. Biol. 60 6585-607). They are typical for the perturbation of the secondary electron field by a detector with
SU-F-J-86: Method to Include Tissue Dose Response Effect in Deformable Image Registration
Energy Technology Data Exchange (ETDEWEB)
Zhu, J; Liang, J; Chen, S; Qin, A; Yan, D [Beaumont Health Systeml, Royal Oak, MI (United States)
2016-06-15
Purpose: Organ changes shape and size during radiation treatment due to both mechanical stress and radiation dose response. However, the dose response induced deformation has not been considered in conventional deformable image registration (DIR). A novel DIR approach is proposed to include both tissue elasticity and radiation dose induced organ deformation. Methods: Assuming that organ sub-volume shrinkage was proportional to the radiation dose induced cell killing/absorption, the dose induced organ volume change was simulated applying virtual temperature on each sub-volume. Hence, both stress and heterogeneity temperature induced organ deformation. Thermal stress finite element method with organ surface boundary condition was used to solve deformation. Initial boundary correspondence on organ surface was created from conventional DIR. Boundary condition was updated by an iterative optimization scheme to minimize elastic deformation energy. The registration was validated on a numerical phantom. Treatment dose was constructed applying both the conventional DIR and the proposed method using daily CBCT image obtained from HN treatment. Results: Phantom study showed 2.7% maximal discrepancy with respect to the actual displacement. Compared with conventional DIR, subvolume displacement difference in a right parotid had the mean±SD (Min, Max) to be 1.1±0.9(−0.4∼4.8), −0.1±0.9(−2.9∼2.4) and −0.1±0.9(−3.4∼1.9)mm in RL/PA/SI directions respectively. Mean parotid dose and V30 constructed including the dose response induced shrinkage were 6.3% and 12.0% higher than those from the conventional DIR. Conclusion: Heterogeneous dose distribution in normal organ causes non-uniform sub-volume shrinkage. Sub-volume in high dose region has a larger shrinkage than the one in low dose region, therefore causing more sub-volumes to move into the high dose area during the treatment course. This leads to an unfavorable dose-volume relationship for the normal organ
Effect of processing time delay on the dose response of Kodak EDR2 film.
Childress, Nathan L; Rosen, Isaac I
2004-08-01
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 10 x 10 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 3 x 3 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 10 x 10 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
SU-F-J-59: Assessment of Dose Response Distribution in Individual Human Tumor
Energy Technology Data Exchange (ETDEWEB)
Yan, D [William Beaumont Hospital, Royal Oak, MI (United States); Chen, S; Krauss, D; Chen, P [Beaumont Health System, Royal Oak, Michigan (United States); Wilson, G [Beaumont Health System, Royal Oak, MI (United States)
2016-06-15
Purpose: To fulfill precision radiotherapy via adaptive dose painting by number, voxel-by-voxel dose response or radio-sensitivity in individual human tumor needs to be determined in early treatment to guide treatment adaptation. In this study, multiple FDG PET images obtained pre- and weekly during the treatment course were utilized to determine the distribution/spectrum of dose response parameters in individual human tumors. Methods: FDG PET/CT images of 18 HN cancer patients were used in the study. Spatial parametric image of tumor metabolic ratio (dSUV) was created following voxel by voxel deformable image registration. Each voxel value in dSUV was a function of pre-treatment baseline SUV and treatment delivered dose, and used as a surrogate of tumor survival fraction (SF). Regression fitting with break points was performed using the LQ-model with tumor proliferation for the control and failure group of tumors separately. The distribution and spectrum of radiation sensitivity and growth in individual tumors were determined and evaluated. Results: Spectrum of tumor dose-sensitivity and proliferation in the controlled group was broad with α in tumor survival LQ-model from 0.17 to 0.8. It was proportional to the baseline SUV. Tlag was about 21∼25 days, and Tpot about 0.56∼1.67 days respectively. Commonly tumor voxels with high radio-sensitivity or larger α had small Tlag and Tpot. For the failure group, the radio-sensitivity α was low within 0.05 to 0.3, but did not show clear Tlag. In addition, tumor voxel radio-sensitivity could be estimated during the early treatment weeks. Conclusion: Dose response distribution with respect to radio-sensitivity and growth in individual human tumor can be determined using FDG PET imaging based tumor metabolic ratio measured in early treatment course. The discover is critical and provides a potential quantitative objective to implement tumor specific precision radiotherapy via adaptive dose painting by number.
Surfactants non-monotonically modify the onset of Faraday waves
Strickland, Stephen; Shearer, Michael; Daniels, Karen
2017-11-01
When a water-filled container is vertically vibrated, subharmonic Faraday waves emerge once the driving from the vibrations exceeds viscous dissipation. In the presence of an insoluble surfactant, a viscous boundary layer forms at the contaminated surface to balance the Marangoni and Boussinesq stresses. For linear gravity-capillary waves in an undriven fluid, the surfactant-induced boundary layer increases the amount of viscous dissipation. In our analysis and experiments, we consider whether similar effects occur for nonlinear Faraday (gravity-capillary) waves. Assuming a finite-depth, infinite-breadth, low-viscosity fluid, we derive an analytic expression for the onset acceleration up to second order in ɛ =√{ 1 / Re } . This expression allows us to include fluid depth and driving frequency as parameters, in addition to the Marangoni and Boussinesq numbers. For millimetric fluid depths and driving frequencies of 30 to 120 Hz, our analysis recovers prior numerical results and agrees with our measurements of NBD-PC surfactant on DI water. In both case, the onset acceleration increases non-monotonically as a function of Marangoni and Boussinesq numbers. For shallower systems, our model predicts that surfactants could decrease the onset acceleration. DMS-0968258.
Dynamical zeta functions for piecewise monotone maps of the interval
Ruelle, David
2004-01-01
Consider a space M, a map f:M\\to M, and a function g:M \\to {\\mathbb C}. The formal power series \\zeta (z) = \\exp \\sum ^\\infty _{m=1} \\frac {z^m}{m} \\sum _{x \\in \\mathrm {Fix}\\,f^m} \\prod ^{m-1}_{k=0} g (f^kx) yields an example of a dynamical zeta function. Such functions have unexpected analytic properties and interesting relations to the theory of dynamical systems, statistical mechanics, and the spectral theory of certain operators (transfer operators). The first part of this monograph presents a general introduction to this subject. The second part is a detailed study of the zeta functions associated with piecewise monotone maps of the interval [0,1]. In particular, Ruelle gives a proof of a generalized form of the Baladi-Keller theorem relating the poles of \\zeta (z) and the eigenvalues of the transfer operator. He also proves a theorem expressing the largest eigenvalue of the transfer operator in terms of the ergodic properties of (M,f,g).
The resource theory of quantum reference frames: manipulations and monotones
International Nuclear Information System (INIS)
Gour, Gilad; Spekkens, Robert W
2008-01-01
Every restriction on quantum operations defines a resource theory, determining how quantum states that cannot be prepared under the restriction may be manipulated and used to circumvent the restriction. A superselection rule (SSR) is a restriction that arises through the lack of a classical reference frame and the states that circumvent it (the resource) are quantum reference frames. We consider the resource theories that arise from three types of SSRs, associated respectively with lacking: (i) a phase reference, (ii) a frame for chirality, and (iii) a frame for spatial orientation. Focusing on pure unipartite quantum states (and in some cases restricting our attention even further to subsets of these), we explore single-copy and asymptotic manipulations. In particular, we identify the necessary and sufficient conditions for a deterministic transformation between two resource states to be possible and, when these conditions are not met, the maximum probability with which the transformation can be achieved. We also determine when a particular transformation can be achieved reversibly in the limit of arbitrarily many copies and find the maximum rate of conversion. A comparison of the three resource theories demonstrates that the extent to which resources can be interconverted decreases as the strength of the restriction increases. Along the way, we introduce several measures of frameness and prove that these are monotonically non-increasing under various classes of operations that are permitted by the SSR
The Marotto Theorem on planar monotone or competitive maps
International Nuclear Information System (INIS)
Yu Huang
2004-01-01
In 1978, Marotto generalized Li-Yorke's results on the criterion for chaos from one-dimensional discrete dynamical systems to n-dimensional discrete dynamical systems, showing that the existence of a non-degenerate snap-back repeller implies chaos in the sense of Li-Yorke. This theorem is very useful in predicting and analyzing discrete chaos in multi-dimensional dynamical systems. Yet, besides it is well known that there exists an error in the conditions of the original Marotto Theorem, and several authors had tried to correct it in different way, Chen, Hsu and Zhou pointed out that the verification of 'non-degeneracy' of a snap-back repeller is the most difficult in general and expected, 'almost beyond reasonable doubt', that the existence of only degenerate snap-back repeller still implies chaotic, which was posed as a conjecture by them. In this paper, we shall give necessary and sufficient conditions of chaos in the sense of Li-Yorke for planar monotone or competitive discrete dynamical systems and solve Chen-Hsu-Zhou Conjecture for such kinds of systems
The Monotonic Lagrangian Grid for Fast Air-Traffic Evaluation
Alexandrov, Natalia; Kaplan, Carolyn; Oran, Elaine; Boris, Jay
2010-01-01
This paper describes the continued development of a dynamic air-traffic model, ATMLG, intended for rapid evaluation of rules and methods to control and optimize transport systems. The underlying data structure is based on the Monotonic Lagrangian Grid (MLG), which is used for sorting and ordering positions and other data needed to describe N moving bodies, and their interactions. In ATMLG, the MLG is combined with algorithms for collision avoidance and updating aircraft trajectories. Aircraft that are close to each other in physical space are always near neighbors in the MLG data arrays, resulting in a fast nearest-neighbor interaction algorithm that scales as N. In this paper, we use ATMLG to examine how the ability to maintain a required separation between aircraft decreases as the number of aircraft in the volume increases. This requires keeping track of the primary and subsequent collision avoidance maneuvers necessary to maintain a five mile separation distance between all aircraft. Simulation results show that the number of collision avoidance moves increases exponentially with the number of aircraft in the volume.
Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure
Johnston, Sara C.; Lin, Kenny L.; Twenhafel, Nancy A.; Raymond, Jo Lynne W.; Shamblin, Joshua D.; Wollen, Suzanne E.; Wlazlowski, Carly B.; Wilkinson, Eric R.; Botto, Miriam A.; Goff, Arthur J.
2015-01-01
Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies. PMID:26413900
Dose response effect of cement dust on respiratory muscles competence in cement mill workers.
Meo, Sultan A; Azeem, Muhammad A; Qureshi, Aijaz A; Ghori, G Moinudin; Al-Drees, Abdul Majeed; Feisal Subhan, Mirza Muhammad
2006-12-01
Electromyography (EMG) of respiratory muscles is a reliable method of assessing the ventilatory muscle function, but still its use has not been fully utilized to determine the occupational and environmental hazards on respiratory muscles. Therefore, EMG of intercostal muscles was performed to determine the dose response effect of cement dust on respiratory muscles competence. Matched cross-sectional study of EMG in 50 non-smoking cement mill workers with an age range of 20 - 60 years, who worked without the benefit of cement dust control ventilation or respiratory protective devices. EMG was performed by using surface electrodes and chart recorder. Significant reduction was observed in number of peaks (p competence and stratification of results shows a dose-effect of years of exposure in cement mill.
Mass shootings: a meta-analysis of the dose-response relationship.
Wilson, Laura C
2014-12-01
A meta-analysis was conducted to examine the dose-response theory as it relates to posttraumatic stress symptoms (PTSSs) following mass shootings. It was hypothesized that greater exposure to a mass shooting would be associated with greater PTSSs. Trauma exposure in the current study was broadly defined as the extent to which a person experienced or learned about a mass shooting. The meta-analysis identified 11 qualifying studies that included 13 independent effect sizes from a total of 8,047 participants. The overall weighted mean effect size, based on a random effects model, was r = .19, p shooting on the relationship between exposure and PTSSs. Because so few studies satisfied the inclusion criteria, the present study also documents that this area of the literature is underresearched. Copyright © 2014 International Society for Traumatic Stress Studies.
SO/sub 2/ dose-response sensitivity classification data for crops and natural vegetation species
Energy Technology Data Exchange (ETDEWEB)
Irving, P.M.; Ballou, S.W.
1980-09-01
Over the past several years studies have been made on the interaction of sulfur dioxide (SO/sub 2/) and vegetation by performing field research and by developing analytical procedures for applying field observation data to energy impact assessments. As a result of this work, numerous reports have been prepared on crop-pollutant interactions, such as dose-response data; on the applications of such data to screening approaches for identifying crops at risk; and on models that predict crop yield reductions from point source emissions of SO/sub 2/. Data that were used for these studies, such as the crop-at-risk screening procedure, are presented in this report. Maps are also presented that show the national distribution of SO/sub 2/-sensitive crops and natural vegetation.
SynergyFinder: a web application for analyzing drug combination dose-response matrix data.
Ianevski, Aleksandr; He, Liye; Aittokallio, Tero; Tang, Jing
2017-08-01
Rational design of drug combinations has become a promising strategy to tackle the drug sensitivity and resistance problem in cancer treatment. To systematically evaluate the pre-clinical significance of pairwise drug combinations, functional screening assays that probe combination effects in a dose-response matrix assay are commonly used. To facilitate the analysis of such drug combination experiments, we implemented a web application that uses key functions of R-package SynergyFinder, and provides not only the flexibility of using multiple synergy scoring models, but also a user-friendly interface for visualizing the drug combination landscapes in an interactive manner. The SynergyFinder web application is freely accessible at https://synergyfinder.fimm.fi ; The R-package and its source-code are freely available at http://bioconductor.org/packages/release/bioc/html/synergyfinder.html . jing.tang@helsinki.fi. © The Author(s) 2017. Published by Oxford University Press.
International Nuclear Information System (INIS)
Israelsson, A.; Gustafsson, H.; Lund, E.
2013-01-01
The purpose of this investigation was to study the radiation-induced electron paramagnetic resonance signal in sweeteners xylitol and sorbitol for use in retrospective dosimetry. For both sweeteners and chewing gum, the signal changed at an interval of 1-84 d after irradiation with minimal changes after 4-8 d. A dependence on storage conditions was noticed and the exposure of the samples to light and humidity was therefore minimised. Both the xylitol and sorbitol signals showed linearity with dose in the measured dose interval, 0-20 Gy. The dose-response measurements for the chewing gum resulted in a decision threshold of 0.38 Gy and a detection limit of 0.78 Gy. A blind test illustrated the possibility of using chewing gums as a retrospective dosemeter with an uncertainty in the dose determination of 0.17 Gy (1 SD). (authors)
DEFF Research Database (Denmark)
Appelt, Ane L.; Bentzen, Søren M.; Jakobsen, Anders
2015-01-01
BACKGROUND: Long-course preoperative chemoradiotherapy (chemo-RT) improves outcomes for rectal cancer patients, but acute side effects during treatment may cause considerable patient discomfort and may compromise treatment compliance. We developed a dose-response model for acute urinary toxicity...... based on a large, single-institution series. MATERIAL AND METHODS: In total 345 patients were treated with (chemo-)RT for primary rectal cancer from January 2007 to May 2012. Urinary toxicity during RT was scored prospectively using the CTCAE v 3.0 cystitis score (grade 0-5). Clinical variables...... and radiation dose to the bladder were related to graded toxicity using multivariate ordinal logistic regression. Three models were optimized, each containing all available clinical variables and one of three dose metrics: Mean dose (Dmean), equivalent uniform dose (EUD), or relative volume given x Gy or above...
International Nuclear Information System (INIS)
Archambeau, J.O.
1987-01-01
This presentation lists gross and histologic changes produced by irradiation of the skin that have been quantified. It examines available cell kinetic radiobiological and morphological variables to identify interactions that occur between component populations. The dose response data of the hair and epidermal, fibrocytic, and endothelial cell populations are examined and a rank ordering is attempted. The contribution of the radiosensitivity of these populations to defining the dose tolerance of the skin is discussed. Future clinical needs are considered. The intent is to quantify or define tissue population changes in the irradiated skin so that the data may serve as guidelines to aid the radiation therapist to select therapy schedules that preserve skin function while improving cancer control
Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure.
Directory of Open Access Journals (Sweden)
Sara C Johnston
Full Text Available Marburg virus infection in humans causes a hemorrhagic disease with a high case fatality rate. Countermeasure development requires the use of well-characterized animal models that mimic human disease. To further characterize the cynomolgus macaque model of MARV/Angola, two independent dose response studies were performed using the intramuscular or aerosol routes of exposure. All animals succumbed at the lowest target dose; therefore, a dose effect could not be determined. For intramuscular-exposed animals, 100 PFU was the first target dose that was not significantly different than higher target doses in terms of time to disposition, clinical pathology, and histopathology. Although a significant difference was not observed between aerosol-exposed animals in the 10 PFU and 100 PFU target dose groups, 100 PFU was determined to be the lowest target dose that could be consistently obtained and accurately titrated in aerosol studies.
DEFF Research Database (Denmark)
Matthews, Charles E; Keadle, S. K.; Troiano, Richard P
2016-01-01
Background: Moderate-to-vigorous-intensity physical activity is recommended to maintain and improve health, but the mortality benefits of light activity and risk for sedentary time remain uncertain. Objectives: Using accelerometer-based measures, we 1) described the mortality dose-response...... for sedentary time and light-and moderateto-vigorous-intensity activity using restricted cubic splines, and 2) estimated the mortality benefits associated with replacing sedentary time with physical activity, accounting for total activity. Design: US adults (n = 4840) from NHANES (2003-2006) wore...... an accelerometer for #7 d and were followed prospectively for mortality. Proportional hazards models were used to estimate adjusted HRs and 95% CIs for mortality associations with time spent sedentary and in light-and moderate-to-vigorous-intensity physical activity. Splines were used to graphically present...
Iskandar, S M; Elias, S; Jumiah, H; Asri, M T M; Masrianis, A; Ab Rahman, M Z; Taiman, K; Abdul Rashid, M Y
2004-05-01
The radiation-response characteristics of polymetharylic acid gel dosimeter prepared with different concentrations of monomer and cross-linker is described in these studies. The dosimeters were prepared under the hypoxic condition in a glove box and were then irradiated with gamma-rays produced by Co-60 radionuclide that was generated at 1.25MeV energy. The irradiation took place at different doses ranged from 0Gy to 19Gy. Due to the radiation activities, chain-reaction polymerisation processes had taken place in the formation of polymethacrylic acid (PMAA) gel, which cause the dose response mechanism increased in the NMR relaxation rates of protons. It has been observed that for higher concentration of monomer and cross-linker, the polymerization rate was increased.
The influence of parameters of A-type carbonated apatites synthesis on radiation dose response
International Nuclear Information System (INIS)
Oliveira, Liana Macedo de; Lopes, Ricardo Tadeu
2000-01-01
The aim of this work is the investigation of dose response of A-type carbonated apatites prepared in different conditions. Irradiated samples prepared with carbonate content of 1.45 to 4.84% are studied by using electron paramagnetic resonance (EPR). The EPR spectra are mainly constituted of lines associated to axial CO 2 - species (g perp = 2.0028 and g // = 1.9973) and CO 3 - species (g 1 = 2,0170, g 2 = 2,0090 e g 3 = 2,0041). The production of CO 2 - species on gamma irradiation depends on the carbonate concentration and the hydroxyapatite stoichiometry. The lowest dose detection limit was achieved with stoichiometric samples and carbonate content around of 3.7%. (author)
Application of Dempster–Shafer theory in dose response outcome analysis
International Nuclear Information System (INIS)
Chen Wenzhou; Cui Yunfeng; Yu Yan; Galvin, James; Xiao Ying; He Yanyan; Hussaini, Yousuff M
2012-01-01
The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) reviews summarize the currently available three-dimensional dose/volume/outcome data from multi-institutions and numerous articles to update and refine the normal tissue dose/volume tolerance guidelines. As pointed out in the review, the data have limitations and even some inconsistency. However, with the help of new physical and statistical techniques, the information in the review could be updated so that patient care can be continually improved. The purpose of this work is to demonstrate the application of a mathematical theory, the Dempster–Shafer theory, in dose/volume/outcome data analysis. We applied this theory to the original data obtained from published clinical studies describing dose response for radiation pneumonitis. Belief and plausibility concepts were introduced for dose response evaluation. We were also able to consider the uncertainty and inconsistency of the data from these studies with Yager's combination rule, a special methodology of Dempster–Shafer theory, to fuse the data at several specific doses. The values of belief and plausibility functions were obtained at the corresponding doses. Then we applied the Lyman–Kutcher–Burman (LKB) model to fit these values and a belief–plausibility range was obtained. This range could be considered as a probability range to assist physicians and treatment planners in determining acceptable dose–volume constraints. Finally, the parameters obtained from the LKB model fitting were compared with those in Emami and Burman's papers and those from other frequentist statistics methods. We found that Emami and Burman's parameters are within the belief–plausibility range we calculated by the Dempster–Shafer theory. (paper)
International Nuclear Information System (INIS)
Skwarchuk, Mark W.; Jackson, Andrew; Zelefsky, Michael J.; Venkatraman, Ennapadam S.; Cowen, Didier M.; Levegruen, Sabine; Burman, Chandra M.; Fuks, Zvi; Leibel, Steven A.; Ling, C. Clifton
2000-01-01
Purpose: The purpose of this paper is to use the outcome of a dose escalation protocol for three-dimensional conformal radiation therapy (3D-CRT) of prostate cancer to study the dose-response for late rectal toxicity and to identify anatomic, dosimetric, and clinical factors that correlate with late rectal bleeding in multivariate analysis. Methods and Materials: Seven hundred forty-three patients with T1c-T3 prostate cancer were treated with 3D-CRT with prescribed doses of 64.8 to 81.0 Gy. The 5-year actuarial rate of late rectal toxicity was assessed using Kaplan-Meier statistics. A retrospective dosimetric analysis was performed for patients treated to 70.2 Gy (52 patients) or 75.6 Gy (119 patients) who either exhibited late rectal bleeding (RTOG Grade 2/3) within 30 months after treatment (i.e., 70.2 Gy--13 patients, 75.6 Gy--36 patients) or were nonbleeding for at least 30 months (i.e., 70.2 Gy--39 patients, 75.6 Gy--83 patients). Univariate and multivariate logistic regression was performed to correlate late rectal bleeding with several anatomic, dosimetric, and clinical variables. Results: A dose response for ≥ Grade 2 late rectal toxicity was observed. By multivariate analysis, the following factors were significantly correlated with ≥ Grade 2 late rectal bleeding for patients prescribed 70.2 Gy: 1) enclosure of the outer rectal contour by the 50% isodose on the isocenter slice (i.e., Iso50) (p max (p max
The dose-response relationship between in-ear occupational noise exposure and hearing loss.
Rabinowitz, Peter M; Galusha, Deron; Dixon-Ernst, Christine; Clougherty, Jane E; Neitzel, Richard L
2013-10-01
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. 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. 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. 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.
International Nuclear Information System (INIS)
Olson, J.J.; Friedman, R.; Orr, K.; Delaney, T.; Oldfield, E.H.
1990-01-01
Pentobarbital reduces cerebral radiation toxicity; however, the mechanism of this phenomenon remains unknown. As an anesthetic and depressant of cerebral metabolism, pentobarbital induces its effects on the central nervous system by stimulating the binding of gamma-aminobutyric acid (GABA) to its receptor and by inhibiting postsynaptic excitatory amino acid activity. The purpose of this study is to investigate the role of these actions as well as other aspects of the radioprotective activity of pentobarbital. Fischer 344 rats were separated into multiple groups and underwent two dose-response evaluations. In one set of experiments to examine the relationship of radioprotection to pentobarbital dose, a range of pentobarbital doses (0 to 75 mg/kg) were given intraperitoneally prior to a constant-level radiation dose (70 Gy). In a second series of experiments to determine the dose-response relationship of radiation protection to radiation dose, a range of radiation doses (10 to 90 Gy) were given with a single pentobarbital dose. Further groups of animals were used to evaluate the importance of the timing of pentobarbital administration, the function of the (+) and (-) isomers of pentobarbital, and the role of an alternative GABA agonist (diazepam). In addition, the potential protective effects of alternative methods of anesthesia (ketamine) and induction of cerebral hypometabolism (hypothermia) were examined. Enhancement of survival time from acute radiation injury due to high-dose single-fraction whole-brain irradiation was maximal with 60 mg/kg of pentobarbital, and occurred over the range of all doses examined between 30 to 90 Gy. Protection was seen only in animals that received the pentobarbital before irradiation. Administration of other compounds that enhance GABA binding (Saffan and diazepam) also significantly enhanced survival time
Directory of Open Access Journals (Sweden)
Jan B W J Cornelissen
Full Text Available High numbers of Toxoplasma gondii oocysts in the environment are a risk factor to humans. The environmental contamination might be reduced by vaccinating the definitive host, cats. An experimental challenge model is necessary to quantitatively assess the efficacy of a vaccine or drug treatment. Previous studies have indicated that bradyzoites are highly infectious for cats. To infect cats, tissue cysts were isolated from the brains of mice infected with oocysts of T. gondii M4 strain, and bradyzoites were released by pepsin digestion. Free bradyzoites were counted and graded doses (1000, 100, 50, 10, and 250 intact tissue cysts were inoculated orally into three cats each. Oocysts shed by these five groups of cats were collected from faeces by flotation techniques, counted microscopically and estimated by real time PCR. Additionally, the number of T. gondii in heart, tongue and brains were estimated, and serology for anti T. gondii antibodies was performed. A Beta-Poisson dose-response model was used to estimate the infectivity of single bradyzoites and linear regression was used to determine the relation between inoculated dose and numbers of oocyst shed. We found that real time PCR was more sensitive than microscopic detection of oocysts, and oocysts were detected by PCR in faeces of cats fed 10 bradyzoites but by microscopic examination. Real time PCR may only detect fragments of T. gondii DNA without the presence of oocysts in low doses. Prevalence of tissue cysts of T. gondii in tongue, heart and brains, and anti T. gondii antibody concentrations were all found to depend on the inoculated bradyzoite dose. The combination of the experimental challenge model and the dose response analysis provides a suitable reference for quantifying the potential reduction in human health risk due to a treatment of domestic cats by vaccination or by therapeutic drug application.
The Dose Response Relationship between In Ear Occupational Noise Exposure and Hearing Loss
Rabinowitz, Peter M.; Galusha, Deron; Dixon-Ernst, Christine; Clougherty, Jane E.; Neitzel, Richard L.
2014-01-01
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 hearing protection and with limited data regarding noise exposures below 85dBA. 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 program 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 six 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 85dBA (mean LAVG 76 dBA, interquartile range 74 to 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. Conclusion At-ear noise exposures below 85dBA 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 85dBA 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. PMID:23825197
Childhood adversity specificity and dose-response effect in non-affective first-episode psychosis.
Trauelsen, Anne Marie; Bendall, Sarah; Jansen, Jens Einar; Nielsen, Hanne-Grethe Lyse; Pedersen, Marlene Buch; Trier, Christopher Høier; Haahr, Ulrik H; Simonsen, Erik
2015-06-01
Reviews conclude that childhood and adolescence sexual, physical, emotional abuse and emotional and physical neglect are all risk factors for psychosis. However, studies suggest only some adversities are associated with psychosis. Dose-response effects of several adversities on risk of psychosis have not been consistently found. The current study aimed to explore adversity specificity and dose-response effects of adversities on risk of psychosis. Participants were 101 persons with first-episode psychosis (FEP) diagnosed with ICD-10 F20 - F29 (except F21) and 101 non-clinical control persons matched by gender, age and parents' socio-economic status. Assessment included the Childhood Trauma Questionnaire and parts of the Childhood Experience of Care and Abuse Questionnaire. Eighty-nine percent of the FEP group reported one or more adversities compared to 37% of the control group. Childhood and adolescent sexual, physical, emotional abuse, and physical and emotional neglect, separation and institutionalization were about four to 17 times higher for the FEP group (all p<0.01). The risk of psychosis increased two and a half times for each additional adversity. All associations between specific adversities and psychosis decreased when they were adjusted for other adversities. Our findings suggest that there is a large shared effect of adversities on the risk of psychosis. Contrary to the call for further research into specific adversities, we suggest a search for mechanisms in the shared effects of traumatization. Clinical implications are thorough assessment of adversities and their possible effects. Copyright © 2015 Elsevier B.V. All rights reserved.
[Occlusion treatment for amblyopia. Age dependence and dose-response relationship].
Fronius, M
2016-04-01
Based on clinical experience and studies on animal models the age of 6-7 years was regarded as the limit for treatment of amblyopia, although functional improvement was also occasionally reported in older patients. New technical developments as well as insights from clinical studies and the neurosciences have attracted considerable attention to this topic. Various aspects of the age dependence of amblyopia treatment are discussed in this article, e. g. prescription, electronic monitoring of occlusion dosage, calculation of indicators for age-dependent plasticity of the visual system, and novel, alternative treatment approaches. Besides a discussion of the recent literature, results of studies by our "Child Vision Research Unit" in Frankfurt are presented: results of a questionnaire about prescription habits concerning age limits of patching, electronic recording of occlusion in patients beyond the conventional treatment age, calculation of dose-response function and efficiency of patching and their age dependence. The results of the questionnaire illustrate the uncertainty about age limits of prescription with significant deviations from the guideline of the German Ophthalmological Society (DOG). Electronic recording of occlusion allowed the quantification of declining dose-response function and treatment efficiency between 5 and 16 years of age. Reports about successful treatment with conventional and novel methods in adults are at variance with the notion of a rigid adult visual system lacking plasticity. Electronic recording of patching allowed new insights into the age-dependent susceptibility of the visual system and contributes to a more evidence-based treatment of amblyopia. Alternative approaches for adults challenge established notions about age limits of amblyopia therapy. Further studies comparing different treatment options are urgently needed.
Dose-response relationship for breast cancer induction at radiotherapy dose
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Gruber Günther
2011-06-01
Full Text Available Abstract Purpose Cancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer. Materials and methods In this work a dose-response relationship for breast cancer is derived based on (i the analysis of breast cancer induction after Hodgkin's disease, (ii a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy, (iv the breast cancer induction of the A-bomb survivor data. Results The fitted model parameters for an α/β = 3 Gy were α = 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.
Application of Dempster-Shafer theory in dose response outcome analysis
Chen, Wenzhou; Cui, Yunfeng; He, Yanyan; Yu, Yan; Galvin, James; Hussaini, Yousuff M.; Xiao, Ying
2012-09-01
The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) reviews summarize the currently available three-dimensional dose/volume/outcome data from multi-institutions and numerous articles to update and refine the normal tissue dose/volume tolerance guidelines. As pointed out in the review, the data have limitations and even some inconsistency. However, with the help of new physical and statistical techniques, the information in the review could be updated so that patient care can be continually improved. The purpose of this work is to demonstrate the application of a mathematical theory, the Dempster-Shafer theory, in dose/volume/outcome data analysis. We applied this theory to the original data obtained from published clinical studies describing dose response for radiation pneumonitis. Belief and plausibility concepts were introduced for dose response evaluation. We were also able to consider the uncertainty and inconsistency of the data from these studies with Yager's combination rule, a special methodology of Dempster-Shafer theory, to fuse the data at several specific doses. The values of belief and plausibility functions were obtained at the corresponding doses. Then we applied the Lyman-Kutcher-Burman (LKB) model to fit these values and a belief-plausibility range was obtained. This range could be considered as a probability range to assist physicians and treatment planners in determining acceptable dose-volume constraints. Finally, the parameters obtained from the LKB model fitting were compared with those in Emami and Burman's papers and those from other frequentist statistics methods. We found that Emami and Burman's parameters are within the belief-plausibility range we calculated by the Dempster-Shafer theory.
On a correspondence between regular and non-regular operator monotone functions
DEFF Research Database (Denmark)
Gibilisco, P.; Hansen, Frank; Isola, T.
2009-01-01
We prove the existence of a bijection between the regular and the non-regular operator monotone functions satisfying a certain functional equation. As an application we give a new proof of the operator monotonicity of certain functions related to the Wigner-Yanase-Dyson skew information....
Tijs, S.H.; Moretti, S.; Brânzei, R.; Norde, H.W.
2005-01-01
A new way is presented to define for minimum cost spanning tree (mcst-) games the irreducible core, which is introduced by Bird in 1976.The Bird core correspondence turns out to have interesting monotonicity and additivity properties and each stable cost monotonic allocation rule for mcst-problems
An analysis of the stability and monotonicity of a kind of control models
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LU Yifa
2013-06-01
Full Text Available The stability and monotonicity of control systems with parameters are considered.By the iterative relationship of the coefficients of characteristic polynomials and the Mathematica software,some sufficient conditions for the monotonicity and stability of systems are given.
A simple algorithm for computing positively weighted straight skeletons of monotone polygons☆
Biedl, Therese; Held, Martin; Huber, Stefan; Kaaser, Dominik; Palfrader, Peter
2015-01-01
We study the characteristics of straight skeletons of monotone polygonal chains and use them to devise an algorithm for computing positively weighted straight skeletons of monotone polygons. Our algorithm runs in O(nlogn) time and O(n) space, where n denotes the number of vertices of the polygon. PMID:25648376
A simple algorithm for computing positively weighted straight skeletons of monotone polygons.
Biedl, Therese; Held, Martin; Huber, Stefan; Kaaser, Dominik; Palfrader, Peter
2015-02-01
We study the characteristics of straight skeletons of monotone polygonal chains and use them to devise an algorithm for computing positively weighted straight skeletons of monotone polygons. Our algorithm runs in [Formula: see text] time and [Formula: see text] space, where n denotes the number of vertices of the polygon.
Dose escalation with 3-D CRT in prostate cancer: five year dose responses and optimal treatment
International Nuclear Information System (INIS)
Hanks, Gerald; Hanlon, Alexandra; Pinover, Wayne; Hunt, Margie; Movsas, Benjamin; Schultheiss, Timothy
1997-01-01
Purpose: To report 5 yr dose responses in prostate cancer patients treated with 3D-CRT and describe optimal treatment based on dose response. Methods: Dose escalation was studied in 233 consecutive patients treated with 3D-CRT between 3/89 and 10/92. All surviving patients have >32 mo follow-up, the median follow-up is 55 mo. Estimated logistic cumulative distribution functions (logit response models) fit to 5 yr actuarial bNED outcome are reported for 3 dose groups in each of 3 pretreatment PSA groupings (10-19.9 ng/ml and 20+ ng/ml); no dose response is observed for patients with pretreatment PSA <10 ng/ml. Logit response models fit to 5 yr actuarial late morbidity rates (grade 2 GI, grade 2 GU, grade 3,4 GI) are also reported for 4 dose groups. Patients are treated with CT planned 4-field conformal technique where the PTV encompasses the CTV by 1.0 cm in all directions including the anterior rectal wall margin. Patients are followed at 6 mo intervals with PSA and DRE, and bNED failure is defined as PSA ≥1.5 ng/ml and rising on two consecutive measures. The Fox Chase modification of the LENT morbidity scale is used for GI morbidity including any blood transfusion and/or more than 2 coagulations as a grade 3 event. GU morbidity follows the RTOG scale. Results: The logit response models based on 5 yr bNED results have slopes of 27% and 18% for pretreatment PSA grouping 10-19.9 ng/ml and 20+ ng/ml, respectively. The 50% bNED response is observed at 71 Gy and 80 Gy respectively, while the 80% bNED response is observed at 76 Gy for the 10-19.9 ng/ml group and estimated at 88 Gy for the 20+ ng/ml group. Logit dose response models for grade 2 GI and grade 2 GU morbidity show markedly different slopes, 23% versus 4%, respectively. The slope for grade 3,4 GI is 12%. The dose response model indicates grade 3,4 GI complication rates at 5 yrs are 8% at 76 Gy and 12% at 80 Gy. Conclusion: Based on 5 yr results, we can draw some conclusions about appropriate dose from these
Generalized Yosida Approximations Based on Relatively A-Maximal m-Relaxed Monotonicity Frameworks
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Heng-you Lan
2013-01-01
Full Text Available We introduce and study a new notion of relatively A-maximal m-relaxed monotonicity framework and discuss some properties of a new class of generalized relatively resolvent operator associated with the relatively A-maximal m-relaxed monotone operator and the new generalized Yosida approximations based on relatively A-maximal m-relaxed monotonicity framework. Furthermore, we give some remarks to show that the theory of the new generalized relatively resolvent operator and Yosida approximations associated with relatively A-maximal m-relaxed monotone operators generalizes most of the existing notions on (relatively maximal monotone mappings in Hilbert as well as Banach space and can be applied to study variational inclusion problems and first-order evolution equations as well as evolution inclusions.
Mathematical Modeling of Column-Base Connections under Monotonic Loading
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Gholamreza Abdollahzadeh
2014-12-01
Full Text Available Some considerable damage to steel structures during the Hyogo-ken Nanbu Earthquake occurred. Among them, many exposed-type column bases failed in several consistent patterns, such as brittle base plate fracture, excessive bolt elongation, unexpected early bolt failure, and inferior construction work, etc. The lessons from these phenomena led to the need for improved understanding of column base behavior. Joint behavior must be modeled when analyzing semi-rigid frames, which is associated with a mathematical model of the moment–rotation curve. The most accurate model uses continuous nonlinear functions. This article presents three areas of steel joint research: (1 analysis methods of semi-rigid joints; (2 prediction methods for the mechanical behavior of joints; (3 mathematical representations of the moment–rotation curve. In the current study, a new exponential model to depict the moment–rotation relationship of column base connection is proposed. The proposed nonlinear model represents an approach to the prediction of M–θ curves, taking into account the possible failure modes and the deformation characteristics of the connection elements. The new model has three physical parameters, along with two curve-fitted factors. These physical parameters are generated from dimensional details of the connection, as well as the material properties. The M–θ curves obtained by the model are compared with published connection tests and 3D FEM research. The proposed mathematical model adequately comes close to characterizing M–θ behavior through the full range of loading/rotations. As a result, modeling of column base connections using the proposed mathematical model can give crucial beforehand information, and overcome the disadvantages of time consuming workmanship and cost of experimental studies.
Local Monotonicity and Isoperimetric Inequality on Hypersurfaces in Carnot groups
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Francesco Paolo Montefalcone
2010-12-01
Full Text Available Let G be a k-step Carnot group of homogeneous dimension Q. Later on we shall present some of the results recently obtained in [32] and, in particular, an intrinsic isoperimetric inequality for a C2-smooth compact hypersurface S with boundary @S. We stress that S and @S are endowed with the homogeneous measures n????1 H and n????2 H , respectively, which are actually equivalent to the intrinsic (Q - 1-dimensional and (Q - 2-dimensional Hausdor measures with respect to a given homogeneous metric % on G. This result generalizes a classical inequality, involving the mean curvature of the hypersurface, proven by Michael and Simon [29] and Allard [1], independently. One may also deduce some related Sobolev-type inequalities. The strategy of the proof is inspired by the classical one and will be discussed at the rst section. After reminding some preliminary notions about Carnot groups, we shall begin by proving a linear isoperimetric inequality. The second step is a local monotonicity formula. Then we may achieve the proof by a covering argument.We stress however that there are many dierences, due to our non-Euclidean setting.Some of the tools developed ad hoc are, in order, a \\blow-up" theorem, which holds true also for characteristic points, and a smooth Coarea Formula for the HS-gradient. Other tools are the horizontal integration by parts formula and the 1st variation formula for the H-perimeter n????1H already developed in [30, 31] and then generalized to hypersurfaces having non-empty characteristic set in [32]. These results can be useful in the study of minimal and constant horizontal mean curvature hypersurfaces in Carnot groups.
Chapman, Katherine E; Hoffmann, George R; Doak, Shareen H; Jenkins, Gareth J S
2017-07-01
Hormesis is defined as a biphasic dose-response where biological effects of low doses of a stressor demonstrate the opposite effect to high-dose effects of the same stressor. Hormetic, or J-shaped, dose-response relationships are relatively rarely observed in toxicology, resulting in a limited understanding and even some skepticism of the concept. Low dose-response studies for genotoxicity endpoints have been performed at Swansea University for over a decade. However, no statistically significant decreases below control genotoxicity levels have been detected until recently. A hormetic-style dose-response following a 24h exposure to the alkylating agent N-methyl-N-nitrosourea (MNU) was observed in a previous study for HPRT mutagenesis in the human lymphoblastoid cell line AHH-1. A second recent study demonstrated a J-shaped dose-response for the induction of micronuclei by MNU in a 24h treatment in a similar test system. Following mechanistic investigations, it was hypothesized that p53 may be responsible for the observed hormetic phenomenon. As genotoxic carcinogens are a major causative factor of many cancers, consideration of hormesis in carcinogenesis could be important in safety assessment. The data examined here offer possible insights into hormesis, including its estimated prevalence, underlying mechanisms and lack of generalizability. Copyright © 2017 Elsevier B.V. All rights reserved.
Calderón, M A; Larenas, D; Kleine-Tebbe, J; Jacobsen, L; Passalacqua, G; Eng, P A; Varga, E M; Valovirta, E; Moreno, C; Malling, H J; Alvarez-Cuesta, E; Durham, S; Demoly, P
2011-10-01
For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies. © 2011 John Wiley & Sons A/S.
International Nuclear Information System (INIS)
Evans, L.S.
1981-01-01
Experiments were performed with several plant species in natural environments as well in a greenhouse and/or tissue culture facilities to establish dose-response functions of plant responses to simulated acidic rain in order to determine environmental risk assessments to ambient levels of acidic rain. Response functions of foliar injury, biomass of leaves and seed of soybean and pinto beans, root yields of radishes and garden beets, and reproduction of bracken fern are considered. The dose-response function of soybean seed yields with the hydrogen ion concentration of simulated acidic rainfalls was expressed by the equation y = 21.06-1.01 log x where y = seed yield in grams per plant and x = the hydrogen concentration if μeq l -1 . The correlation coefficient of this relationship was -0.90. A similar dose-response function was generated for percent fertilization of ferns in a forest understory. When percent fertilization is plotted on logarithmic scale with hydrogen ion concentration of the simulated rain solution, the Y intercept is 51.18, slope -0.041 with a correlation coefficient of -0.98. Other dose-response functions were generated that assist in a general knowledge as to which plant species and which physiological processes are most impacted by acidic precipitation. Some responses did not produce convenient dose-response relationships. In such cases the responses may be altered by other environmental factors or there may be no differences among treatment means
DEFF Research Database (Denmark)
Christiansen, E; Goldney, R D; Beautrai, A L
2011-01-01
BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk for suic......BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk...... for suicide attempt.MethodWe designed a population-based two-generation nested case-control study and used Danish register data. A population of 403 431 individuals born between 1983 and 1989 was sampled. Among these, 3465 (0.8%) were registered as having had a suicide attempt. Twenty controls were matched...... to each case and a link to the offspring's biological parents was established. RESULTS: There was a dose-response relationship between the number of exposures and the risk of suicide attempts, with the increased risk seeming to be a multiplicative effect. Parental suicide, suicide attempt, psychiatric...
Lagrangian Curves on Spectral Curves of Monopoles
International Nuclear Information System (INIS)
Guilfoyle, Brendan; Khalid, Madeeha; Ramon Mari, Jose J.
2010-01-01
We study Lagrangian points on smooth holomorphic curves in TP 1 equipped with a natural neutral Kaehler structure, and prove that they must form real curves. By virtue of the identification of TP 1 with the space LE 3 of oriented affine lines in Euclidean 3-space, these Lagrangian curves give rise to ruled surfaces in E 3 , which we prove have zero Gauss curvature. Each ruled surface is shown to be the tangent lines to a curve in E 3 , called the edge of regression of the ruled surface. We give an alternative characterization of these curves as the points in E 3 where the number of oriented lines in the complex curve Σ that pass through the point is less than the degree of Σ. We then apply these results to the spectral curves of certain monopoles and construct the ruled surfaces and edges of regression generated by the Lagrangian curves.
Dose-response for X-ray induction of myeloid leukaemia in male CBA/H mice
Energy Technology Data Exchange (ETDEWEB)
Mole, R H; Papworth, D G; Corp, M J [Medical Research Council, Harwell (UK). Radiobiological Research Unit
1983-02-01
The form of the dose-response for induction of malignant diseases in vivo by ionizing radiation is not yet established in spite of its scientific interest and its practical importance. Considerably extended observations have confirmed that the dose-response for acute myeloid leukaemia induced in male CBA/H mice by X-ray exposure is highly curvilinear. The dose-response was well fitted by the expression aD/sup 2/esup(-..gamma..D) (D = dose) in agreement with induction at the cellular level in proportion to D/sup 2/ over the whole dose range 0.25-6.0 Gy. The factor esup(-..gamma..D) accounts for the inescapable concomitant inactivating action of the inducing irradiation. The quantitative aspects of induction of myeloid leukaemia by ionizing radiation are unlike the induction of genetic mutation or cell inactivation and suggest that interaction of two adjoining cells is an essential element in radiation leukaemogenesis.
International Nuclear Information System (INIS)
Calabrese, Edward J.
2004-01-01
The paper provides an account of how the hormetic dose response has emerged in recent years as a serious dose-response model in toxicology and risk assessment after decades of extreme marginalization. In addition to providing the toxicological basis of this dose-response revival, the paper reexamines the concept of a default dose model in toxicology and risk assessment and makes the argument that the hormetic model satisfies criteria (e.g., generalizability, frequency, application to risk assessment endpoints, false positive/negative potential, requirements for hazard assessment, reliability of estimating risks, capacity for validation of risk estimates, public health implications of risk estimates) for such a default model better than its chief competitors, the threshold and linear at low dose models. The selection of the hormetic model as the default model in risk assessment for noncarcinogens and specifically for carcinogens would have a profound impact on the practice of risk assessment and its societal implications
International Nuclear Information System (INIS)
Calabrese, Edward J.; Bachmann, Kenneth A.; Bailer, A. John; Bolger, P. Michael; Borak, Jonathan; Cai, Lu; Cedergreen, Nina; Cherian, M. George; Chiueh, Chuang C.; Clarkson, Thomas W.; Cook, Ralph R.; Diamond, David M.; Doolittle, David J.; Dorato, Michael A.; Duke, Stephen O.; Feinendegen, Ludwig; Gardner, Donald E.; Hart, Ronald W.; Hastings, Kenneth L.; Hayes, A. Wallace; Hoffmann, George R.; Ives, John A.; Jaworowski, Zbigniew; Johnson, Thomas E.; Jonas, Wayne B.; Kaminski, Norbert E.; Keller, John G.; Klaunig, James E.; Knudsen, Thomas B.; Kozumbo, Walter J.; Lettieri, Teresa; Liu, Shu-Zheng; Maisseu, Andre; Maynard, Kenneth I.; Masoro, Edward J.; McClellan, Roger O.; Mehendale, Harihara M.; Mothersill, Carmel; Newlin, David B.; Nigg, Herbert N.; Oehme, Frederick W.; Phalen, Robert F.; Philbert, Martin A.; Rattan, Suresh I.S.; Riviere, Jim E.; Rodricks, Joseph; Sapolsky, Robert M.; Scott, Bobby R.; Seymour, Colin; Sinclair, David A.; Smith-Sonneborn, Joan; Snow, Elizabeth T.; Spear, Linda; Stevenson, Donald E.; Thomas, Yolene; Tubiana, Maurice; Williams, Gary M.; Mattson, Mark P.
2007-01-01
Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines
Benford, Diane J
2016-05-01
Genotoxic substances are generally not permitted for deliberate use in food production. However, an appreciable number of known or suspected genotoxic substances occur unavoidably in food, e.g. from natural occurrence, environmental contamination and generation during cooking and processing. Over the past decade a margin of exposure (MOE) approach has increasingly been used in assessing the exposure to substances in food that are genotoxic and carcinogenic. The MOE is defined as a reference point on the dose-response curve (e.g. a benchmark dose lower confidences limit derived from a rodent carcinogenicity study) divided by the estimated human intake. A small MOE indicates a higher concern than a very large MOE. Whilst the MOE cannot be directly equated to risk, it supports prioritisation of substances for further research or for possible regulatory action, and provides a basis for communicating to the public. So far, the MOE approach has been confined to substances for which carcinogenicity data are available. In the absence of carcinogenicity data, evidence of genotoxicity is used only in hazard identification. The challenge to the genetic toxicology community is to develop approaches for characterising risk to human health based on data from genotoxicity studies. In order to achieve wide acceptance, it would be important to further address the issues that have been discussed in the context of dose-response modelling of carcinogenicity data in order to assign levels of concern to particular MOE values, and also whether it is possible to make generic conclusions on how potency in genotoxicity assays relates to carcinogenic potency. © Crown copyright 2015.
Li, Ting; Ye, Qiguang; Wu, Daozhu; Li, Jun; Yu, Jingui
2017-12-02
The sympathetic block of upper limb leading to increased blood flow has important clinical implication in microvascular surgery. However, little is known regarding the relationship between concentration of local anesthetic and blood flow of upper limb. The aim of this dose-response study was to determine the ED 50 and ED 95 of ropivacaine in blood flow after supraclavicular block (SB). Patients undergoing upper limb surgery and supraclavicular block were randomly assigned to receive 30ml ropivacaine in concentrations of 0.125%(A Group), 0.2%(B Group), 0.25%(C Group), 0.375%(D Group), 0.5%(E Group), or 0.75%(F Group) (n=13 per group). All patients received supraclavicular block (SB). Time average maximum velocity (TAMAX), cross-sectional area (CSA) of brachial artery and skin temperatures (T s ) were measured repeatedly at the same marked points, they were taken at baseline (before block, t 0 ) and at 30min after SB (t 1 ). Blood flow(BF) = TAMAX× CSA×60 sec.. Relative blood flow (ΔBF) = BF t1 / BF t0 . Success of SB was assessed simultaneously. Supplementary anesthesia and other adverse events (AE) were recorded. Significant increase in TAMAX, CSA, BF and T s were seen in all concentration groups at t 1 comparing with t 0 (Pblock were 0.18/0.33% (0.15-0.21/0.27-0.51), R 2 =0.904. The dose-response curve between SB ropivacaine and the changes of BF was determined. The ED 50 /ED 95 of ropivacaine of ΔBF are 0.35/1.94% (0.25-0.45/0.83-4.52). TAMAX, CSA and BF consistently increased with ropivacaine concentration. The maximal sympathetic block needs higher concentration than that complete sensation block needs which may benefit for microvascular surgery. Clinicaltrials.gov NCT02139982 . Retrospectively registered (Date of registration: May, 2014).
International Nuclear Information System (INIS)
Clewell, Harvey J.; Thomas, Russell S.; Gentry, P. Robinan; Crump, Kenny S.; Kenyon, Elaina M.; El-Masri, Hisham A.; Yager, Janice W.
2007-01-01
Cancer risk assessments for inorganic arsenic have been based on human epidemiological data, assuming a linear dose response below the range of observation of tumors. Part of the reason for the continued use of the linear approach in arsenic risk assessments is the lack of an adequate biologically based dose response (BBDR) model that could provide a quantitative basis for an alternative nonlinear approach. This paper describes elements of an ongoing collaborative research effort between the CIIT Centers for Health Research, the U.S. Environmental Protection Agency, ENVIRON International, and EPRI to develop BBDR modeling approaches that could be used to inform a nonlinear cancer dose response assessment for inorganic arsenic. These efforts are focused on: (1) the refinement of physiologically based pharmacokinetic (PBPK) models of the kinetics of inorganic arsenic and its metabolites in the mouse and human; (2) the investigation of mathematical solutions for multi-stage cancer models involving multiple pathways of cell transformation; (3) the review and evaluation of the literature on the dose response for the genomic effects of arsenic; and (4) the collection of data on the dose response for genomic changes in the urinary bladder (a human target tissue for arsenic carcinogenesis) associated with in vivo drinking water exposures in the mouse as well as in vitro exposures of both mouse and human cells. An approach is proposed for conducting a biologically based margin of exposure risk assessment for inorganic arsenic using the in vitro dose response for the expression of genes associated with the obligatory precursor events for arsenic tumorigenesis
Energy Technology Data Exchange (ETDEWEB)
Calabrese, Edward J. [Environmental Health Sciences, School of Public Health, Morrill I, N344, University of Massachusetts, Amherst, MA 01003 (United States)]. E-mail: edwardc@schoolph.umass.edu
2005-12-15
This paper provides an assessment of the toxicological basis of the hormetic dose-response relationship including issues relating to its reproducibility, frequency, and generalizability across biological models, endpoints measured and chemical class/physical stressors and implications for risk assessment. The quantitative features of the hormetic dose response are described and placed within toxicological context that considers study design, temporal assessment, mechanism, and experimental model/population heterogeneity. Particular emphasis is placed on an historical evaluation of why the field of toxicology rejected hormesis in favor of dose response models such as the threshold model for assessing non-carcinogens and linear no threshold (LNT) models for assessing carcinogens. The paper argues that such decisions were principally based on complex historical factors that emerged from the intense and protracted conflict between what is now called traditional medicine and homeopathy and the overly dominating influence of regulatory agencies on the toxicological intellectual agenda. Such regulatory agency influence emphasized hazard/risk assessment goals such as the derivation of no observed adverse effect levels (NOAELs) and the lowest observed adverse effect levels (LOAELs) which were derived principally from high dose studies using few doses, a feature which restricted perceptions and distorted judgments of several generations of toxicologists concerning the nature of the dose-response continuum. Such historical and technical blind spots lead the field of toxicology to not only reject an established dose-response model (hormesis), but also the model that was more common and fundamental than those that the field accepted. - The quantitative features of the hormetic dose/response are described and placed within the context of toxicology.
International Nuclear Information System (INIS)
Calabrese, Edward J.
2005-01-01
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
Habitual Chocolate Consumption May Increase Body Weight in a Dose-Response Manner
Greenberg, James A.; Buijsse, Brian
2013-01-01
Objective Habitual chocolate intake was recently found to be associated with lower body weight in three cross-sectional epidemiological studies. Our objective was to assess whether these cross-sectional results hold up in a more rigorous prospective analysis. Methods We used data from the Atherosclerosis Risk in Communities cohort. Usual dietary intake was assessed by questionnaire at baseline (1987–98), and after six years. Participants reported usual chocolate intake as the frequency of eating a 1-oz (∼28 g) serving. Body weight and height were measured at the two visits. Missing data were replaced by multiple imputation. Linear mixed-effects models were used to evaluate cross-sectional and prospective associations between chocolate intake and adiposity. Results Data were from 15,732 and 12,830 participants at the first and second visit, respectively. More frequent chocolate consumption was associated with a significantly greater prospective weight gain over time, in a dose-response manner. For instance, compared to participants who ate a chocolate serving less often than monthly, those who ate it 1–4 times a month and at least weekly experienced an increase in Body Mass Index (kg/m2) of 0.26 (95% CI 0.08, 0.44) and 0.39 (0.23, 0.55), respectively, during the six-year study period. In cross-sectional analyses the frequency of chocolate consumption was inversely associated with body weight. This inverse association was attenuated after excluding participants with preexisting obesity-related illness. Compared to participants without such illness, those with it had higher BMI and reported less frequent chocolate intake, lower caloric intake, and diets richer in fruits and vegetables. They tended to make these dietary changes after becoming ill. Conclusions Our prospective analysis found that a chocolate habit was associated with long-term weight gain, in a dose-response manner. Our cross-sectional finding that chocolate intake was associated with lower body
Dose response and factors related to interstitial pneumonitis after bone marrow transplant
International Nuclear Information System (INIS)
Sampath, Sagus; Schultheiss, Timothy E.; Wong, Jeffrey
2005-01-01
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 α/β 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
Olsson, C.; Thor, M.; Liu, M.; Moissenko, V.; Petersen, S. E.; Høyer, M.; Apte, A.; Deasy, J. O.
2014-07-01
When pooling retrospective data from different cohorts, slice thicknesses of acquired computed tomography (CT) images used for treatment planning may vary between cohorts. It is, however, not known if varying slice thickness influences derived dose-response relationships. We investigated this for rectal bleeding using dose-volume histograms (DVHs) of the rectum and rectal wall for dose distributions superimposed on images with varying CT slice thicknesses. We used dose and endpoint data from two prostate cancer cohorts treated with three-dimensional conformal radiotherapy to either 74 Gy (N = 159) or 78 Gy (N = 159) at 2 Gy per fraction. The rectum was defined as the whole organ with content, and the morbidity cut-off was Grade ≥2 late rectal bleeding. Rectal walls were defined as 3 mm inner margins added to the rectum. DVHs for simulated slice thicknesses from 3 to 13 mm were compared to DVHs for the originally acquired slice thicknesses at 3 and 5 mm. Volumes, mean, and maximum doses were assessed from the DVHs, and generalized equivalent uniform dose (gEUD) values were calculated. For each organ and each of the simulated slice thicknesses, we performed predictive modeling of late rectal bleeding using the Lyman-Kutcher-Burman (LKB) model. For the most coarse slice thickness, rectal volumes increased (≤18%), whereas maximum and mean doses decreased (≤0.8 and ≤4.2 Gy, respectively). For all a values, the gEUD for the simulated DVHs were ≤1.9 Gy different than the gEUD for the original DVHs. The best-fitting LKB model parameter values with 95% CIs were consistent between all DVHs. In conclusion, we found that the investigated slice thickness variations had minimal impact on rectal dose-response estimations. From the perspective of predictive modeling, our results suggest that variations within 10 mm in slice thickness between cohorts are unlikely to be a limiting factor when pooling multi-institutional rectal dose data that include slice thickness
Habitual chocolate consumption may increase body weight in a dose-response manner.
Greenberg, James A; Buijsse, Brian
2013-01-01
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. 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. 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. 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
Habitual chocolate consumption may increase body weight in a dose-response manner.
Directory of Open Access Journals (Sweden)
James A Greenberg
Full Text Available 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
The crooked shall be made straight: dose response relationships for carcinogenesis
International Nuclear Information System (INIS)
Hall, E.J.
2003-01-01
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
Directory of Open Access Journals (Sweden)
Mervan Pašić
2016-10-01
Full Text Available We study non-monotone positive solutions of the second-order linear differential equations: $(p(tx'' + q(t x = e(t$, with positive $p(t$ and $q(t$. For the first time, some criteria as well as the existence and nonexistence of non-monotone positive solutions are proved in the framework of some properties of solutions $\\theta (t$ of the corresponding integrable linear equation: $(p(t\\theta''=e(t$. The main results are illustrated by many examples dealing with equations which allow exact non-monotone positive solutions not necessarily periodic. Finally, we pose some open questions.
Energy Technology Data Exchange (ETDEWEB)
Reynoso V, M R; Vega C, J J; Fernandez A, J; Belmont M, E; Policroniades R, R; Moreno B, E [Instituto Nacional de Investigaciones Nucleares, Salazar, Edo. de Mexico. (Mexico)
1997-12-31
A ionization chamber was employed named Bragg curve spectroscopy. The Bragg peak amplitude is a monotone growing function of Z, which permits to identify elements through their measurement. A better technique for this measurement is to improve the use of neural networks with the purpose of the identification of the Bragg curve. (Author).
Dose Response for Monokaryon mycelium of Pleurotus pulmonarius After Acute Gamma Radiation
International Nuclear Information System (INIS)
Wan Safina Wan Abdul Razak; Azhar Mohamad; Nie, H.J.
2016-01-01
Pleurotus pulmonarius is locally known as Grey oyster. The species is popular and widely cultivated throughout the world mostly in Asia Europe as their simple and low cost production technology and higher biological efficiency. Mutation induction is an alternative ways for improving available commercial strain for better quality traits. Dose response is important in evaluating effects of mutagenesis via acute gamma radiation. Monokaryon mycelium of Pleurotus pulmonarius was exposed to acute gamma radiation ranged from 0 Gy, 0.1 kGy, 0.2 kGy, 0.3 kGy, 0.4 kGy, 0.5 kGy, 0.6 kGy, 0.7 kGy, 0.8 kGy, 0.9 kGy, 1.0 kGy, 1.5 Gy, 2.0 kGy, 3.0 kGy and 4.0 kGy at dose rate 0.013 kGy/ min. growth performance was measured at 2 days interval to get the LD_5_0. Increasing of the irradiation dose found to decrease the growth performance of the monokaryon mycelium. LD_5_0 was revealed at 1.56 kGy for mono karyon mycelium. Discoveries of the works are important for the improvement of Pleurotus species via acute gamma radiation and benefiting to growers and mushroom industries. (author)
Digitoxin medication and cancer; case control and internal dose-response studies
International Nuclear Information System (INIS)
Haux, Johan; Klepp, Olbjørn; Spigset, Olav; Tretli, Steinar
2001-01-01
Digitoxin induces apoptosis in different human malignant cell lines in vitro. In this paper we investigated if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population. Computer stored data on digitoxin concentrations in plasma from 9271 patients with cardiac disease were used to define a user population. Age and sex matched controls from the Norwegian Cancer Registry were used to calculate the number of expected cancer cases. The population on digitoxin showed a higher incidence of cancer compared to the control population. However, an additional analysis showed that the population on digitoxin had a general increased risk of cancer already, before the start on digitoxin. Leukemia/lymphoma were the cancer types which stood out with the highest risk in the digitoxin population before starting on digitoxin. This indicates that yet unknown risk factors exist for cardiovascular disease and lymphoproliferative cancer. An internal dose-response analysis revealed a relationship between high plasma concentration of digitoxin and a lower risk for leukemia/lymphoma and for cancer of the kidney/urinary tract. Morbidity and mortality are high in the population on digitoxin, due to high age and cardiac disease.These factors disturb efforts to isolate an eventual anticancer effect of digitoxin in this setting. Still, the results may indicate an anticancer effect of digitoxin for leukemia/lymphoma and kidney/urinary tract cancers. Prospective clinical cancer trials have to be done to find out if digitoxin and other cardiac glycosides are useful as anticancer agents
A dose-response analysis for classical Kaposi's sarcoma management by radiotherapy
International Nuclear Information System (INIS)
Oysul, K.; Beyzadeoglu, M.; Surenkok, S.; Ozyigit, G.; Dirican, B.
2008-01-01
Objective was to evaluate the dose-response relationship in classical Kaposi's sarcoma CKS patients treated with external beam radiotherapy. Between 1993 and 2004, patients with CKS treated at the Department of Radiation Oncology, Gulhane Military Medical School, Ankara, Turkey were evaluated in this retrospective study. The median age at initial presentation was 60 years. First we analyzed the overall response rates for normalized total dose2Gy NTD2Gy of 20Gy. Secondly we searched for whether better response rates could be obtained with the NTD2Gy of >/=20Gy compared to the NTD2Gy of /20Gy and 64% and 24%for NDT2Gyof 20< Gy and these were statistically different p=0.001. Late side effects of radiation therapy were acceptable in all but 4 patients with fibrosis and edema. This retrospective analysis showed that radiotherapy schedules with an NDT2Gy of 20 Gy and above by using local irradiation fields are effective in terms of complete response rates in the management of CKS compared to NDT2Gy of < 20 Gy. (author)
Dose - response relationship between noise exposure and the risk of occupational injury
Directory of Open Access Journals (Sweden)
Jin-Ha Yoon
2015-01-01
Full Text Available Many workers worldwide experience fatality and disability caused by occupational injuries. This study examined the relationship between noise exposure and occupational injuries at factories in Korea. A total of 1790 factories located in northern Gyeonggi Province, Korea was evaluated. The time-weighted average levels of dust and noise exposure were taken from Workplace Exposure Assessment data. Apart occupational injuries, sports events, traffic accidents, and other accidents occurring outside workplaces were excluded. The incidences of occupational injury in each factory were calculated by data from the Korea Workers′ Compensation and Welfare Services. Workplaces were classified according to the incidence of any occupational injuries (incident or nonincident workplaces, respectively. Workplace dust exposure was classified as 90 dB. Workplaces with high noise exposure were significantly associated with being incident workplaces, whereas workplaces with high dust exposure were not. The odds ratios (95% confidence intervals derived from a logistic regression model were 1.68 (1.27-2.24 and 3.42 (2.26-5.17 at 80-89 dB and ≥90 dB versus <80 dB. These associations remained significant when in a separate analysis according to high or low dust exposure level. Noise exposure increases the risk of occupational injury in the workplace. Furthermore, the risk of occupational injury increases with noise exposure level in a dose-response relationship. Therefore, strategies for reducing noise exposure level are required to decrease the risk of occupational injury.
Dose-response analysis of parotid gland function: what is the best measure of xerostomia?
Miah, Aisha B; Gulliford, Sarah L; Clark, Catharine H; Bhide, Shreerang A; Zaidi, Shane H; Newbold, Kate L; Harrington, Kevin J; Nutting, Christopher M
2013-03-01
To describe the dose-response relationships for the different measures of salivary gland recovery following radical radiotherapy for locally advanced head and neck squamous cell cancers (LA-HNSCC). Dosimetric analysis of data from the PARSPORT trial, a Phase III study of conventional RT (RT) and intensity modulated radiotherapy (IMRT) for LA-HNSCC was undertaken to determine the relationship between parotid gland mean dose and toxicity endpoints: high-grade subjective and objective xerostomia and xerostomia-related quality of life scores. LKB-NTCP parameters (TD50, m and n) were generated and tolerance doses (D50) reported using non-linear logistic regression analysis. Data were available on 63 patients from the PARSPORT trial. Parotid saliva flow rate provided the strongest association between mean dose and recovery, D50=23.4 Gy (20.6-26.2) and k=3.2 (1.9-4.5), R(2)=0.85. Corresponding LKB parameters were TD50=26.3 Gy (95% CI: 24.0-30.1), m=0.25 (0.18-1.0 and n=1). LENTSOMA subjective xerostomia also demonstrated a strong association D50=33.3 Gy (26.7-39.8), k=2.8 (91.4-4.4), R(2)=0.77). We recommend using the LENT SOMA subjective xerostomia score to predict recovery of salivation due to its strong association with dosimetry and ease of recording. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Three-dimensional dose-response models of risk for radiation injury carcinogenesis
International Nuclear Information System (INIS)
Raabe, O.G.
1988-01-01
The use of computer graphics in conjunction with three-dimensional models of dose-response relationships for chronic exposure to ionizing radiation dramaticly clarifies the separate and interactive roles of competing risks. The three dimensions are average dose rate, exposure time, and risk. As an example, the functionally injurious and carcinogenic responses after systemic uptake of Ra-226 by beagles, mice and people with consequent alpha particle irradiation of the bone are represented by three-dimensional dose-rate/time/response surfaces that demonstrate the contributions with the passage of time of the competing deleterious responses. These relationships are further evaluated by mathematical stripping with three-dimensional illustrations that graphically show the resultant separate contribution of each effect. Radiation bone injury predominates at high dose rates and bone cancer at intermediate dose rates. Low dose rates result in spontaneous deaths from natural aging, yielding a type of practical threshold for bone cancer induction. Risk assessment is benefited by the insights that become apparent with these three-dimensional models. The improved conceptualization afforded by them contributes to planning and evaluating epidemiological analyses and experimental studies
Dose-response relationships for female radium dial workers: A new look
International Nuclear Information System (INIS)
Rowland, R.E.
1994-01-01
The values of initial systemic intake and of skeletal dose for all of the U.S. radium cases have recently been revised. This revision was required following the demonstrations by Rundo and by Keane that humans who were exposed to radium as adults lost radium at a rate that depended on the quantity of radium originally deposited within their bodies. These new values have been used to define new dose-response relationships for both the bone sarcomas and the carcinomas arising in the paranasal sinuses and mastoid air cells induced by internally deposited radium. The population examined was employed in the U.S. dial painting industry prior to 1950 and consisted of 1530 female dial workers for whom radium body burden measurements were available. By the end of 1990, 46 cases of bone sarcomas and 19 cases of head carcinomas had been diagnosed in this cohort. The head carcinoma incidence can be adequately fitted by a simple linear function, as was found in previous analyses. The bone sarcoma cases were previously fitted by a dose-squared-exponential function. With the revised values of systemic intake, the sarcoma results could not be satisfactorily fitted with this expression. When the exponent on D was increased to larger values, excellent fits were obtained
Quantifying the dose-response of walking in reducing coronary heart disease risk: meta-analysis.
Zheng, Henry; Orsini, Nicola; Amin, Janaki; Wolk, Alicja; Nguyen, Van Thi Thuy; Ehrlich, Fred
2009-01-01
The evidence for the efficacy of walking in reducing the risk of and preventing coronary heart disease (CHD) is not completely understood. This meta-analysis aimed to quantify the dose-response relationship between walking and CHD risk reduction for both men and women in the general population. Studies on walking and CHD primary prevention between 1954 and 2007 were identified through Medline, SportDiscus and the Cochrane Database of Systematic Reviews. Random-effect meta-regression models were used to pool the relative risks from individual studies. A total of 11 prospective cohort studies and one randomized control trial study met the inclusion criteria, with 295,177 participants free of CHD at baseline and 7,094 cases at follow-up. The meta-analysis indicated that an increment of approximately 30 min of normal walking a day for 5 days a week was associated with 19% CHD risk reduction (95% CI = 14-23%; P-heterogeneity = 0.56; I (2) = 0%). We found no evidence of heterogeneity between subgroups of studies defined by gender (P = 0.67); age of the study population (P = 0.52); or follow-up duration (P = 0.77). The meta-analysis showed that the risk for developing CHD decreases as walking dose increases. Walking should be prescribed as an evidence-based effective exercise modality for CHD prevention in the general population.
The dose-response relationship of balance training in physically active older adults.
Maughan, Kristen K; Lowry, Kristin A; Franke, Warren D; Smiley-Oyen, Ann L
2012-10-01
A 6-wk group balance-training program was conducted with physically active older adults (based on American College of Sports Medicine requirements) to investigate the effect of dose-related static and dynamic balance-specific training. All participants, age 60-87 yr, continued their regular exercise program while adding balance training in 1 of 3 doses: three 20-min sessions/wk (n = 20), one 20-min session/wk (n = 21), or no balance training (n = 19). Static balance (single-leg-stance, tandem), dynamic balance (alternate stepping, limits of stability), and balance confidence (ABC) were assessed pre- and posttraining. Significant interactions were observed for time in single-leg stance, excursion in limits of stability, and balance confidence, with the greatest increase observed in the group that completed 3 training sessions/wk. The results demonstrate a dose-response relationship indicating that those who are already physically active can improve balance performance with the addition of balance-specific training.
Manzi, Vincenzo; Castagna, Carlo; Padua, Elvira; Lombardo, Mauro; D'Ottavio, Stefano; Massaro, Michele; Volterrani, Maurizio; Iellamo, Ferdinando
2009-06-01
In athletes, exercise training induces autonomic nervous system (ANS) adaptations that could be used to monitor training status. However, the relationship between training and ANS in athletes has been investigated without regard for individual training loads. We tested the hypothesis that in long-distance athletes, changes in ANS parameters are dose-response related to individual volume/intensity training load and could predict athletic performance. A spectral analysis of heart rate (HR), systolic arterial pressure variability, and baroreflex sensitivity by the sequences technique was investigated in eight recreational athletes during a 6-mo training period culminating with a marathon. Individualized training load responses were monitored by a modified training impulse (TRIMP(i)) method, which was determined in each athlete using the individual HR and lactate profiling determined during a treadmill test. Monthly TRIMP(i) steadily increased during the training period. All the ANS parameters were significantly and very highly correlated to the dose of exercise with a second-order regression model (r(2) ranged from 0.90 to 0.99; P marathon. These results suggest that in recreational athletes, ANS adaptations to exercise training are dose related on an individual basis, showing a progressive shift toward a sympathetic predominance, and that LF oscillations in HRV at peak training load could predict athletic achievement in this athlete population.
Dose-Response of High-Intensity Training (HIT) on Atheroprotective miRNA-126 Levels
Schmitz, Boris; Schelleckes, Katrin; Nedele, Johanna; Thorwesten, Lothar; Klose, Andreas; Lenders, Malte; Krüger, Michael; Brand, Eva; Brand, Stefan-Martin
2017-01-01
Aim: MicroRNA-126 (miR-126) exerts beneficial effects on vascular integrity, angiogenesis, and atherosclerotic plaque stability. The purpose of this investigation was to analyze the dose-response relationship of high-intensity interval training (HIIT) on miR-126-3p and -5p levels. Methods: Sixty-one moderately trained individuals (females = 31 [50.8%]; 22.0 ± 1.84 years) were consecutively recruited and allocated into three matched groups using exercise capacity. During a 4-week intervention a HIIT group performed three exercise sessions/week of 4 × 30 s at maximum speed (all-out), a progressive HIIT (proHIIT) group performed three exercise sessions/week of 4 × 30 s at maximum speed (all-out) with one extra session every week (up to 7 × 30 s) and a low-intensity training (LIT) control group performed three exercise sessions/week for 25 min HIIT groups (after 4 min of high-intensity running). After the intervention, the LIT group presented an increase in miR-126-3p, while in the HIIT group, miR-126-3p levels were still reduced (all p HIIT (−1.05 ± 2.6 units). Conclusions: LIT and proHIIT may be performed to increase individual miR-126 levels. HIIT without progression was less effective in increasing miR-126. PMID:28611681
Computational model of dose response for low-LET-induced complex chromosomal aberrations
International Nuclear Information System (INIS)
Eidelman, Y.A.; Andreev, S.G.
2015-01-01
Experiments with full-colour mFISH chromosome painting have revealed high yield of radiation-induced complex chromosomal aberrations (CAs). The ratio of complex to simple aberrations is dependent on cell type and linear energy transfer. Theoretical analysis has demonstrated that the mechanism of CA formation as a result of interaction between lesions at a surface of chromosome territories does not explain high complexes-to-simples ratio in human lymphocytes. The possible origin of high yields of γ-induced complex CAs was investigated in the present work by computer simulation. CAs were studied on the basis of chromosome structure and dynamics modelling and the hypothesis of CA formation on nuclear centres. The spatial organisation of all chromosomes in a human interphase nucleus was predicted by simulation of mitosis-to-interphase chromosome structure transition. Two scenarios of CA formation were analysed, 'static' (existing in a nucleus prior to irradiation) centres and 'dynamic' (formed in response to irradiation) centres. The modelling results reveal that under certain conditions, both scenarios explain quantitatively the dose-response relationships for both simple and complex γ-induced inter-chromosomal exchanges observed by mFISH chromosome painting in the first post-irradiation mitosis in human lymphocytes. (authors)
International Nuclear Information System (INIS)
Ulsh, B.A.; Miller, S.M.; Mallory, F.F.; Mitchel, R.E.J.; Morrison, D.P.; Boreham, D.R.
2004-01-01
In the studies reported here, the micronucleus assay, a common cytogenetic technique, was used to examine the dose-responses in fibroblasts from three ungulate species (white-tailed deer, woodland caribou, and Indian muntjac) exposed to high doses of ionizing radiation (1-4 Gy of 60 Co gamma radiation). This assay was also used to examine the effects of exposure to low doses (1-100 mGy) typical of what these species experience in a year from natural and anthropogenic environmental sources. An adaptive response, defined as the induction of resistance to a stressor by a prior exposure to a small 'adapting' stress, was observed after exposure to low doses. This work indicates that very small doses are protective for the endpoint examined. The same level of protection was seen at all adapting doses, including 1 radiation track per cell, the lowest possible cellular dose. These results are consistent with other studies in a wide variety of organisms that demonstrate a protective effect of low doses at both cellular and whole-organism levels. This implies that environmental regulations predicated on the idea that even the smallest dose of radiation carries a quantifiable risk of direct adverse consequences to the exposed organism require further examination. Cytogenetic assays provide affordable and feasible biological effects-based alternatives that are more biologically relevant than traditional contaminant concentration-based radioecological risk assessment
New flux based dose-response relationships for ozone for European forest tree species.
Büker, P; Feng, Z; Uddling, J; Briolat, A; Alonso, R; Braun, S; Elvira, S; Gerosa, G; Karlsson, P E; Le Thiec, D; Marzuoli, R; Mills, G; Oksanen, E; Wieser, G; Wilkinson, M; Emberson, L D
2015-11-01
To derive O3 dose-response relationships (DRR) for five European forest trees species and broadleaf deciduous and needleleaf tree plant functional types (PFTs), phytotoxic O3 doses (PODy) were related to biomass reductions. PODy was calculated using a stomatal flux model with a range of cut-off thresholds (y) indicative of varying detoxification capacities. Linear regression analysis showed that DRR for PFT and individual tree species differed in their robustness. A simplified parameterisation of the flux model was tested and showed that for most non-Mediterranean tree species, this simplified model led to similarly robust DRR as compared to a species- and climate region-specific parameterisation. Experimentally induced soil water stress was not found to substantially reduce PODy, mainly due to the short duration of soil water stress periods. This study validates the stomatal O3 flux concept and represents a step forward in predicting O3 damage to forests in a spatially and temporally varying climate. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.
High-LET dose-response characteristics by track structure theory of heavy charged particles
International Nuclear Information System (INIS)
Hansen, J.W.; Olsen, K.J.
1981-09-01
The track structure theory developed by Katz and co-workers ascribes the effect of high-LET radiation to the highly inhomogeneous dose distribution due to low energy Δ-rays ejected from the particle track. The theory predicts the effectiveness of high-LET radiation by using the ion parameters zsub(eff') effective charge of the ion, and β = v/c, the relative ion velocity, together with the characteristic dose D 37 derived from low-LET dose-response characteristic of the detector and the approximate size asub(0) of the sensitive element of the detector. 60 Co gamma-irradiation is used as a reference low-LET radiation, while high-LET radiation ranging from 16 MeV protons to 4 MeV/amu 16 0-ions covering an initial LET range of 30-5500 MeVcm 2 /g is obtained from a tandem Van de Graaff accelerator. A thin film (5mg/cm 2 ) radiochromic dye cyanide plastic dosemeter was used as detector with the characteristic dose of 16.8 Mrad and a sensitive element size of 10 -7 cm. Theoretical and experimental effectiveness, RBE, agreed within 10 to 25% depending on LET. (author)
Dose responses in a normoxic polymethacrylic acid gel dosimeter using optimal CT scanning parameters
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Cho, K.H. [Department of Radiation Oncology, College of Medicine, Soonchunhyang University, Bucheon 420-767 (Korea, Republic of); Department of Medical Physics, Kyonggi University, Suwon 443-760 (Korea, Republic of); Cho, S.J. [Department of Radiation Oncology, College of Medicine, Eulji University, Seongnam 461-713 (Korea, Republic of); Lee, S. [Department of Radiation Oncology, College of Medicine, Korea University, Seoul 130-701 (Korea, Republic of); Lee, S.H. [Cheil General Hospital and Women' s Healthcare Center, Kwandong University College of Medicine, Seoul 100-380 (Korea, Republic of); Min, C.K.; Kim, Y.H.; Moon, S.K.; Kim, E.S.; Chang, A.R. [Department of Radiation Oncology, College of Medicine, Soonchunhyang University, Bucheon 420-767 (Korea, Republic of); Kwon, S.I., E-mail: sikwon@kyonggi.ac.kr [Department of Medical Physics, Kyonggi University, Suwon 443-760 (Korea, Republic of)
2012-05-21
The dosimetric characteristics of normoxic polymethacrylic acid gels are investigated using optimal CT scanning parameters and the possibility of their clinical application is also considered. The effects of CT scanning parameters (tube voltage, tube current, scan time, slick thickness, field of view, and reconstruction algorithm) are experimentally investigated to determine the optimal parameters for minimizing the amount of noise in images obtained using normoxic polymethacrylic acid gel. In addition, the dose sensitivity, dose response, accuracy, and reproducibility of the normoxic polymethacrylic acid gel are evaluated. CT images are obtained using a head phantom that is fabricated for clinical applications. In addition, IMRT treatment planning is performed using a Tomotherapy radiation treatment planning system. A program for analyzing the results is produced using Visual C. A comparison between the treatment planning and the CT images of irradiated gels is performed. The dose sensitivity is found to be 2.41{+-}0.04 HGy{sup -1}. The accuracies of dose evaluation at doses of 2 Gy and 4 Gy are 3.0% and 2.6%, respectively, and their reproducibilities are 2.0% and 2.1%, respectively. In the comparison of gel and Tomotherpay planning, the pass rate of the {gamma}-index, based on the reference values of a dose error of 3% and a DTA of 3 mm, is 93.7%.
Dose responses in a normoxic polymethacrylic acid gel dosimeter using optimal CT scanning parameters
Cho, K. H.; Cho, S. J.; Lee, S.; Lee, S. H.; Min, C. K.; Kim, Y. H.; Moon, S. K.; Kim, E. S.; Chang, A. R.; Kwon, S. I.
2012-05-01
The dosimetric characteristics of normoxic polymethacrylic acid gels are investigated using optimal CT scanning parameters and the possibility of their clinical application is also considered. The effects of CT scanning parameters (tube voltage, tube current, scan time, slick thickness, field of view, and reconstruction algorithm) are experimentally investigated to determine the optimal parameters for minimizing the amount of noise in images obtained using normoxic polymethacrylic acid gel. In addition, the dose sensitivity, dose response, accuracy, and reproducibility of the normoxic polymethacrylic acid gel are evaluated. CT images are obtained using a head phantom that is fabricated for clinical applications. In addition, IMRT treatment planning is performed using a Tomotherapy radiation treatment planning system. A program for analyzing the results is produced using Visual C. A comparison between the treatment planning and the CT images of irradiated gels is performed. The dose sensitivity is found to be 2.41±0.04 HGy-1. The accuracies of dose evaluation at doses of 2 Gy and 4 Gy are 3.0% and 2.6%, respectively, and their reproducibilities are 2.0% and 2.1%, respectively. In the comparison of gel and Tomotherpay planning, the pass rate of the γ-index, based on the reference values of a dose error of 3% and a DTA of 3 mm, is 93.7%.
Gamma- and electron dose response of the electrical conductivity of polyaniline based polymer blends
International Nuclear Information System (INIS)
Sevil, U.A.; Gueven, O.; Slezsak, I.
2002-01-01
Complete text of publication follows. Conducting polymers, also known as 'synthetic metals' have been the subject of widespread investigations over the past decade due to their very promising characteristics. Polyaniline (PANI) holds a special position among conducting polymers in that its most highly conducting doped form can be reached by protonic acid doping or oxidative doping. It was published earlier, that the electrical conductivity of some polyaniline based polymer composites increases to a significant extent when irradiated to gamma, electron or UV radiation. The aim of the present study was to measure the high frequency conductivity of blended films of PANI with poly(vinylchloride), PVC, and chlorinated poly(propylene) irradiated in air to different doses. In order to find the most suitable composition od these composites the mass percentage of PANI within the PPCl and PVC matrix was changed between 5 - 30%. These samples were then gamma irradiated and the induced electrical conductivity was measured in the 1 kHz - 1 MHz frequency range to determine the most sensitive evaluation conditions. After selecting both the most suitable measuring conditions as well as the blend compositions the dose response of the chosen samples was determined in the dose range of 10 - 250 kGy. With respect to potential dosimetry application the effect of electron irradiation, the effect of irradiation temperature and the stability of the irradiated samples have also been investigated
Linking fluorescence induction curve and biomass in herbicide screening.
Christensen, Martin G; Teicher, Harald B; Streibig, Jens C
2003-12-01
A suite of dose-response bioassays with white mustard (Sinapis alba L) and sugar beet (Beta vulgaris L) in the greenhouse and with three herbicides was used to analyse how the fluorescence induction curves (Kautsky curves) were affected by the herbicides. Bentazone, a photosystem II (PSII) inhibitor, completely blocked the normal fluorescence decay after the P-step. In contrast, fluorescence decay was still obvious for flurochloridone, a PDS inhibitor, and glyphosate, an EPSP inhibitor, which indicated that PSII inhibition was incomplete. From the numerous parameters that can be derived from OJIP-steps of the Kautsky curve the relative changes at the J-step [Fvj = (Fm - Fj)/Fm] was selected to be a common response parameter for the herbicides and yielded consistent dose-response relationships. Four hours after treatment, the response Fvj on the doses of bentazone and flurochloridone could be measured. For glyphosate, the changes of the Kautsky curve could similarly be detected 4 h after treatment in sugar beet, but only after 24 hs in S alba. The best prediction of biomass in relation to Fvj was found for bentazone. The experiments were conducted between May and August 2002 and showed that the ambient temperature and solar radiation in the greenhouse could affect dose-response relationships. If the Kautsky curve parameters should be used to predict the outcome of herbicide screening experiments in the greenhouse, where ambient radiation and temperature can only partly be controlled, it is imperative that the chosen fluorescence parameters can be used to predict accurately the resulting biomass used in classical bioassays.
Low back pain in drivers exposed to whole body vibration: analysis of a dose-response pattern
Tiemessen, I. J. H.; Hulshof, C. T. J.; Frings-Dresen, M. H. W.
2008-01-01
Analysis of a dose-response pattern between exposure to whole body vibration (WBV) and low back pain (LBP) in a group of drivers. This study assessed individual factors, work-related risk factors, various LBP outcome measures and LBP disability in a group of drivers (n = 571) approached at baseline
Borde, Ron; Hortobagyi, Tibor; Granacher, Urs
2015-01-01
Background Resistance training (RT) is an intervention frequently used to improve muscle strength and morphology in old age. However, evidence-based, dose-response relationships regarding specific RT variables (e.g., training period, frequency, intensity, volume) are unclear in healthy old adults.
Demonty, I.; Ras, R.T.; Knaap, van der H.C.M.; Duchateau, G.S.M.J.E.; Meijer, L.; Zock, P.L.; Geleijnse, J.M.; Trautwein, E.A.
2009-01-01
Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)¿lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C¿lowering efficacy of different
Grabowski, Gregory A.; Kacena, Katherine; Cole, J. Alexander; Hollak, Carla E. M.; Zhang, Lin; Yee, John; Mistry, Pramod K.; Zimran, Ari; Charrow, Joel; vom Dahl, Stephan
2009-01-01
Purpose: To determine whether enzyme therapy with imiglucerase/ alglucerase demonstrates dose-response relationships with doses and disease parameters used in routine clinical practice for Gaucher disease type 1 patients. Methods: Analyses included all patients with Gaucher disease type 1 on enzyme
A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...
A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (BPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model p...
Zhang, Chao; Jia, Pengli; Yu, Liu; Xu, Chang
2018-05-01
Dose-response meta-analysis (DRMA) is widely applied to investigate the dose-specific relationship between independent and dependent variables. Such methods have been in use for over 30 years and are increasingly employed in healthcare and clinical decision-making. In this article, we give an overview of the methodology used in DRMA. We summarize the commonly used regression model and the pooled method in DRMA. We also use an example to illustrate how to employ a DRMA by these methods. Five regression models, linear regression, piecewise regression, natural polynomial regression, fractional polynomial regression, and restricted cubic spline regression, were illustrated in this article to fit the dose-response relationship. And two types of pooling approaches, that is, one-stage approach and two-stage approach are illustrated to pool the dose-response relationship across studies. The example showed similar results among these models. Several dose-response meta-analysis methods can be used for investigating the relationship between exposure level and the risk of an outcome. However the methodology of DRMA still needs to be improved. © 2018 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.
Kansanaho, M; Olkkola, KT; Wierda, JMKH
The dose-response and concentration-response relation of rocuronium infusion was studied in 20 adult surgical patients during proporfol-nitrous oxide and isoflurane (1 MAC) -nitrous oxide anaesthesia. Neuromuscular block was kept constant, initially at 90% and then at 50% with a closed-loop feedback
Gijsbers, L.; Geleijnse, J.M.; Soedamah-Muthu, S.S.
2011-01-01
Observational studies suggest an inverse association between dairy intake and incident type 2 diabetes, but the quantity of dairy is not known. Previous meta-analyses did not take into account the type of dairy product. Therefore, we examined dose-response associations between the intake of total
DEFF Research Database (Denmark)
Calderón, M A; Larenas, D; Kleine-Tebbe, J
2011-01-01
For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen prod...
DEFF Research Database (Denmark)
Malin, Steven K; Solomon, Thomas; Blaszczak, Alecia
2013-01-01
While some studies suggest that a linear dose-response relationship exists between exercise and insulin sensitivity, the exercise dose required to enhance pancreatic beta-cell function is unknown. Thirty-five older, obese adults with prediabetes underwent a progressive 12-week supervised exercise...
Lesinski, Melanie; Hortobagyi, Tibor; Muehlbauer, Thomas; Gollhofer, Albert; Granacher, Urs
Background Balance training (BT) has been used for the promotion of balance and sports-related skills as well as for prevention and rehabilitation of lower extremity sport injuries. However, evidence-based dose-response relationships in BT parameters have not yet been established. Objective The
International Nuclear Information System (INIS)
Upton, A.C.
2003-01-01
In recent decades, it has been customary, for radiation protection purposes, to assume that the overall risk of radiation-induced cancer increases as a linear-nonthreshold function of the dose. The existing data do not exclude the existence of a threshold, however, and the dose-response relationship is known to vary, depending on the type of cancer in queation, the dose, dose rate, and LET of the radiation, the age, sex, and physiological state of the exposed individuals, and other variables, including the potential influence of adaptive responses and bystander effects at low doses. In light of advncing knowledge, therefore, the dose-response relationship for carcinogenic effects of low-level radiation has been reevaluated periodically by the National Council on Radiation Protection and Measurements, the International Commission of Radiological Protection, the United Nations Scientific Committee on the Effects of Atomic Radiation, the U.S. National Academy of Sciences, and other organizations. The most recent such reviews have generally found the weight of evidence to suggest that lesions which are precursors to cancer (i.e., mutations and chromosome aberrations), and certain types of cancer as well, may increase in frequency linearly with the dose in the low-dose domain. On this basis, it is concluded that no alternative dose-response model for the carcinogenic effects of low-level radiation is more plausible than the linear-nonthreshold model, although other dose-response relationships cannot be excluded. (authors)
Use of archival resources has been limited to date by inconsistent methods for genomic profiling of degraded RNA from formalin-fixed paraffin-embedded (FFPE) samples. RNA-sequencing offers a promising way to address this problem. Here we evaluated transcriptomic dose responses us...
Logarithmically complete monotonicity of a function related to the Catalan-Qi function
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Qi Feng
2016-08-01
Full Text Available In the paper, the authors find necessary and sufficient conditions such that a function related to the Catalan-Qi function, which is an alternative generalization of the Catalan numbers, is logarithmically complete monotonic.
Monotone matrix transformations defined by the group inverse and simultaneous diagonalizability
International Nuclear Information System (INIS)
Bogdanov, I I; Guterman, A E
2007-01-01
Bijective linear transformations of the matrix algebra over an arbitrary field that preserve simultaneous diagonalizability are characterized. This result is used for the characterization of bijective linear monotone transformations . Bibliography: 28 titles.
Totally Optimal Decision Trees for Monotone Boolean Functions with at Most Five Variables
Chikalov, Igor; Hussain, Shahid; Moshkov, Mikhail
2013-01-01
In this paper, we present the empirical results for relationships between time (depth) and space (number of nodes) complexity of decision trees computing monotone Boolean functions, with at most five variables. We use Dagger (a tool for optimization
Calibration curve to establish the exposure dose at Co60 gamma radiation
International Nuclear Information System (INIS)
Guerrero C, C.; Brena V, M.
2000-01-01
The biological dosimetry is an adequate method for the dose determination in cases of overexposure to ionizing radiation or doubt of the dose obtained by physical methods. It is based in the aberrations analysis produced in the chromosomes. The behavior of leisure in chromosomes is of dose-response type and it has been generated curves in distinct laboratories. Next is presented the curve for gamma radiation produced in the National Institute of Nuclear Research (ININ) laboratory. (Author)
Monotone methods for solving a boundary value problem of second order discrete system
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Wang Yuan-Ming
1999-01-01
Full Text Available A new concept of a pair of upper and lower solutions is introduced for a boundary value problem of second order discrete system. A comparison result is given. An existence theorem for a solution is established in terms of upper and lower solutions. A monotone iterative scheme is proposed, and the monotone convergence rate of the iteration is compared and analyzed. The numerical results are given.
Global Attractivity Results for Mixed-Monotone Mappings in Partially Ordered Complete Metric Spaces
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Kalabušić S
2009-01-01
Full Text Available We prove fixed point theorems for mixed-monotone mappings in partially ordered complete metric spaces which satisfy a weaker contraction condition than the classical Banach contraction condition for all points that are related by given ordering. We also give a global attractivity result for all solutions of the difference equation , where satisfies mixed-monotone conditions with respect to the given ordering.
Reduction theorems for weighted integral inequalities on the cone of monotone functions
International Nuclear Information System (INIS)
Gogatishvili, A; Stepanov, V D
2013-01-01
This paper surveys results related to the reduction of integral inequalities involving positive operators in weighted Lebesgue spaces on the real semi-axis and valid on the cone of monotone functions, to certain more easily manageable inequalities valid on the cone of non-negative functions. The case of monotone operators is new. As an application, a complete characterization for all possible integrability parameters is obtained for a number of Volterra operators. Bibliography: 118 titles
Totally Optimal Decision Trees for Monotone Boolean Functions with at Most Five Variables
Chikalov, Igor
2013-01-01
In this paper, we present the empirical results for relationships between time (depth) and space (number of nodes) complexity of decision trees computing monotone Boolean functions, with at most five variables. We use Dagger (a tool for optimization of decision trees and decision rules) to conduct experiments. We show that, for each monotone Boolean function with at most five variables, there exists a totally optimal decision tree which is optimal with respect to both depth and number of nodes.
Directory of Open Access Journals (Sweden)
Heinz Werner Höppel
2012-02-01
Full Text Available The monotonic and cyclic deformation behavior of ultrafine-grained metastable austenitic steel AISI 304L, produced by severe plastic deformation, was investigated. Under monotonic loading, the martensitic phase transformation in the ultrafine-grained state is strongly favored. Under cyclic loading, the martensitic transformation behavior is similar to the coarse-grained condition, but the cyclic stress response is three times larger for the ultrafine-grained condition.
International Nuclear Information System (INIS)
Duan Shukai; Liao Xiaofeng
2007-01-01
A new chaotic delayed neuron model with non-monotonously increasing transfer function, called as chaotic Liao's delayed neuron model, was recently reported and analyzed. An electronic implementation of this model is described in detail. At the same time, some methods in circuit design, especially for circuit with time delayed unit and non-monotonously increasing activation unit, are also considered carefully. We find that the dynamical behaviors of the designed circuits are closely similar to the results predicted by numerical experiments
International Nuclear Information System (INIS)
Niedzielski, J; Martel, M; Tucker, S; Gomez, D; Court, L; Yang, J; Briere, T
2014-01-01
Purpose: Radiation induces an inflammatory response in the esophagus, discernible on CT studies. This work objectively quantifies the voxel esophageal radiation-response for patients with acute esophagitis. This knowledge is an important first-step towards predicting the effect of complex dose distributions on patient esophagitis symptoms. Methods: A previously validated voxel-based methodology of quantifying radiation esophagitis severity was used to identify the voxel dose-response for 18 NSCLC patients with severe esophagitis (CTCAE grading criteria, grade2 or higher). The response is quantified as percent voxel volume change for a given dose. During treatment (6–8 weeks), patients had weekly 4DCT studies and esophagitis scoring. Planning CT esophageal contours were deformed to each weekly CT using a demons DIR algorithm. An algorithm using the Jacobian Map from the DIR of the planning CT to all weekly CTs was used to quantify voxel-volume change, along with corresponding delivered voxel dose, to the planning voxel. Dose for each voxel for each time-point was calculated on each previous weekly CT image, and accumulated using DIR. Thus, for each voxel, the volume-change and delivered dose was calculated for each time-point. The data was binned according to when the volume-change first increased by a threshold volume (10%–100%, in 10% increments), and the average delivered dose calculated for each bin. Results: The average dose resulting in a voxel volume increase of 10–100% was 21.6 to 45.9Gy, respectively. The mean population dose to give a 50% volume increase was 36.3±4.4Gy, (range:29.8 to 43.5Gy). The average week of 50% response was 4.1 (range:4.9 to 2.8 weeks). All 18 patients showed similar dose to first response curves, showing a common trend in the initial inflammatoryresponse. Conclusion: We extracted the dose-response curve of the esophagus on a voxel-to-voxel level. This may be useful for estimating the esophagus response (and patient symptoms
Directory of Open Access Journals (Sweden)
Tamrakar Sushil B
2012-03-01
Full Text Available Abstract Background Rickettsia typhi (R. mooseri is the causative agent of murine typhus. It is one of the most widely distributed flea-borne diseases with a relatively mild febrile initial illness with six to 14 days of incubation period. The bacterium is gram negative and an obligate intracellular pathogen. The disease is transmitted to humans and vertebrate host through fleabites or via contact with infected feces. This paper develops dose-response models of different routes of exposure for typhus in rodents. Methods Data from published articles were analyzed using parametric dose-response relationship models. Dose-response relationships were fit to data using the method of maximum likelihood estimation (MLE. Results Dose-response models quantifying the effects of different ages of rats and time post inoculation in BALB/c mice were analyzed in the study. Both the adult rats (inoculated intradermally and newborn rats (inoculated subcutaneously were best fit by exponential models and both distributions could be described by a single dose-response relationship. The BALB/C mice inoculated subcutaneously were best fit by Beta-Poisson models. The time post inoculation analysis showed that there was a definite time and response relationship existed in this case. Conclusions Intradermally or subcutaneously inoculated rats (adult and newborn models suggest that less than 1 plaque-forming unit (PFU (1.33 to 0.38 in 95% confidence limits of the pathogen is enough to seroconvert 50% of the exposed population on average. For the BALB/c mouse time post inoculation model, an average dose of 0.28 plaque-forming units (PFU (0.75 to 0.11 in 95% confidence limits will seroconvert 50% of the exposed mice.
Yun, K L; Fann, J I; Sokoloff, M H; Fong, L G; Sarris, G E; Billingham, M E; Miller, D C
1991-01-01
With the advent of cyclosporin A, accelerated coronary arteriosclerosis has become the major impediment to the long-term survival of heart transplant recipients. Due to epidemiologic reports suggesting a salutary effect of fish oil, the dose response of fish oil on graft coronary arteriosclerosis in a rabbit heterotopic cardiac allograft model was assessed using safflower oil as a caloric control. Seven groups of New Zealand White rabbits (n = 10/group) received heterotropic heart transplants from Dutch-Belted donors and were immunosuppressed with low-dose cyclosporin A (7.5 mg/kg/day). Group 1 animals were fed a normal diet and served as control. Group 2, 3, and 4 animals received a daily supplement of low- (0.25 mL/kg/day), medium- (0.75 mL/kg/day), and high- (1.5 mL/kg/day) dose fish oil (116 mg n-3 polyunsaturated fatty acid/mL), respectively. Group 5, 6, and 7 animals were supplemented with equivalent dose of safflower oil (i.e., 0.25, 0.75, and 1.5 mL/kg/day). Oil-supplemented rabbits were pretreated for 3 weeks before transplantation and maintained on the same diet for 6 weeks after operation. The extent of graft coronary arteriosclerosis was quantified using computer-assisted, morphometric planimetry. When the animals were killed, cyclosporin A was associated with elevated plasma total cholesterol and triglyceride levels in the control group. While safflower oil prevented the increase in plasma lipids at all dosages, fish oil ameliorated the cyclosporin-induced increase in total cholesterol only with high doses. Compared to control animals, there was a trend for more graft vessel disease with increasing fish oil dose, as assessed by mean luminal occlusion and intimal thickness. A steeper trend was observed for increasing doses of safflower oil; compared to the high-dose safflower oil group, animals supplemented with low-dose safflower oil had less mean luminal occlusion (16.3% +/- 5.9% versus 41.4% +/- 7.6%, p less than 0.017) and intimal thickness (7
Dose response in prostate cancer with 8-12 years' follow-up
International Nuclear Information System (INIS)
Hanks, Gerald E.; Hanlon, Alexandra L.; Epstein, Barry; Horwitz, Eric M.
2002-01-01
ng/mL, although large numbers of patients are required to demonstrate a difference. The radiation dose, Gleason score, and palpation T stage were significant predictors for the entire patient set, as well as for those with pretreatment PSA levels between 10 and 20 ng/mL. The FDM rate for all patients included in this series was 89%, 83%, and 83% at 5, 10, and 12 years, respectively. For patients with pretreatment PSA levels 9 years of median follow-up confirm the existence of a dose response for both bNED control and FDM. The dose response in prostate cancer is real, and the absence of biochemical recurrence after 8 years demonstrates the lack of late failure and suggests cure
Arem, Hannah; Moore, Steven C; Patel, Alpa; Hartge, Patricia; Berrington de Gonzalez, Amy; Visvanathan, Kala; Campbell, Peter T; Freedman, Michal; Weiderpass, Elisabete; Adami, Hans Olov; Linet, Martha S; Lee, I-Min; Matthews, Charles E
2015-06-01
The 2008 Physical Activity Guidelines for Americans recommended a minimum of 75 vigorous-intensity or 150 moderate-intensity minutes per week (7.5 metabolic-equivalent hours per week) of aerobic activity for substantial health benefit and suggested additional benefits by doing more than double this amount. However, the upper limit of longevity benefit or possible harm with more physical activity is unclear. To quantify the dose-response association between leisure time physical activity and mortality and define the upper limit of benefit or harm associated with increased levels of physical activity. We pooled data from 6 studies in the National Cancer Institute Cohort Consortium (baseline 1992-2003). Population-based prospective cohorts in the United States and Europe with self-reported physical activity were analyzed in 2014. A total of 661,137 men and women (median age, 62 years; range, 21-98 years) and 116,686 deaths were included. We used Cox proportional hazards regression with cohort stratification to generate multivariable-adjusted hazard ratios (HRs) and 95% CIs. Median follow-up time was 14.2 years. Leisure time moderate- to vigorous-intensity physical activity. The upper limit of mortality benefit from high levels of leisure time physical activity. Compared with individuals reporting no leisure time physical activity, we observed a 20% lower mortality risk among those performing less than the recommended minimum of 7.5 metabolic-equivalent hours per week (HR, 0.80 [95% CI, 0.78-0.82]), a 31% lower risk at 1 to 2 times the recommended minimum (HR, 0.69 [95% CI, 0.67-0.70]), and a 37% lower risk at 2 to 3 times the minimum (HR, 0.63 [95% CI, 0.62-0.65]). An upper threshold for mortality benefit occurred at 3 to 5 times the physical activity recommendation (HR, 0.61 [95% CI, 0.59-0.62]); however, compared with the recommended minimum, the additional benefit was modest (31% vs 39%). There was no evidence of harm at 10 or more times the recommended minimum (HR
A discrete wavelet spectrum approach for identifying non-monotonic trends in hydroclimate data
Sang, Yan-Fang; Sun, Fubao; Singh, Vijay P.; Xie, Ping; Sun, Jian
2018-01-01
The hydroclimatic process is changing non-monotonically and identifying its trends is a great challenge. Building on the discrete wavelet transform theory, we developed a discrete wavelet spectrum (DWS) approach for identifying non-monotonic trends in hydroclimate time series and evaluating their statistical significance. After validating the DWS approach using two typical synthetic time series, we examined annual temperature and potential evaporation over China from 1961-2013 and found that the DWS approach detected both the warming and the warming hiatus in temperature, and the reversed changes in potential evaporation. Further, the identified non-monotonic trends showed stable significance when the time series was longer than 30 years or so (i.e. the widely defined climate timescale). The significance of trends in potential evaporation measured at 150 stations in China, with an obvious non-monotonic trend, was underestimated and was not detected by the Mann-Kendall test. Comparatively, the DWS approach overcame the problem and detected those significant non-monotonic trends at 380 stations, which helped understand and interpret the spatiotemporal variability in the hydroclimatic process. Our results suggest that non-monotonic trends of hydroclimate time series and their significance should be carefully identified, and the DWS approach proposed has the potential for wide use in the hydrological and climate sciences.
A discrete wavelet spectrum approach for identifying non-monotonic trends in hydroclimate data
Directory of Open Access Journals (Sweden)
Y.-F. Sang
2018-01-01
Full Text Available The hydroclimatic process is changing non-monotonically and identifying its trends is a great challenge. Building on the discrete wavelet transform theory, we developed a discrete wavelet spectrum (DWS approach for identifying non-monotonic trends in hydroclimate time series and evaluating their statistical significance. After validating the DWS approach using two typical synthetic time series, we examined annual temperature and potential evaporation over China from 1961–2013 and found that the DWS approach detected both the warming and the warming hiatus in temperature, and the reversed changes in potential evaporation. Further, the identified non-monotonic trends showed stable significance when the time series was longer than 30 years or so (i.e. the widely defined climate timescale. The significance of trends in potential evaporation measured at 150 stations in China, with an obvious non-monotonic trend, was underestimated and was not detected by the Mann–Kendall test. Comparatively, the DWS approach overcame the problem and detected those significant non-monotonic trends at 380 stations, which helped understand and interpret the spatiotemporal variability in the hydroclimatic process. Our results suggest that non-monotonic trends of hydroclimate time series and their significance should be carefully identified, and the DWS approach proposed has the potential for wide use in the hydrological and climate sciences.
Nabel, Moritz; Bueno Piaz Barbosa, Daniela; Horsch, David; Jablonowski, Nicolai David
2014-05-01
The global demand for energy security and the mitigation of climate change are the main drivers pushing energy-plant production in Germany. However, the cultivation of these plants can cause land use conflicts since agricultural soil is mostly used for plant production. A sustainable alternative to the conventional cultivation of food-based energy-crops is the cultivation of special adopted energy-plants on marginal lands. To further increase the sustainability of energy-plant cultivation systems the dependency on synthetic fertilizers needs to be reduced via closed nutrient loops. In the presented study the energy-plant Sida hermaphrodita (Malvaceae) will be used to evaluate the potential to grow this high potential energy-crop on a marginal sandy soil in combination with fertilization via digestate from biogas production. With this dose-response experiment we will further identify an optimum dose, which will be compared to equivalent doses of NPK-fertilizer. Further, lethal doses and deficiency doses will be observed. Two weeks old Sida seedlings were transplanted to 1L pots and fertilized with six doses of digestate (equivalent to a field application of 5, 10, 20, 40, 80, 160t/ha) and three equivalent doses of NPK-fertilizer. Control plants were left untreated. Sida plants will grow for 45 days under greenhouse conditions. We hypothesize that the nutrient status of the marginal soil can be increased and maintained by defined digestate applications, compared to control plants suffering of nutrient deficiency due to the low nutrient status in the marginal substrate. The dose of 40t/ha is expected to give a maximum biomass yield without causing toxicity symptoms. Results shall be used as basis for further experiments on the field scale in a field trial that was set up to investigate sustainable production systems for energy crop production under marginal soil conditions.
Digitoxin medication and cancer; case control and internal dose-response studies
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Spigset Olav
2001-08-01
Full Text Available Abstract Background Digitoxin induces apoptosis in different human malignant cell lines in vitro. In this paper we investigated if patients taking digitoxin for cardiac disease have a different cancer incidence compared to the general population. Methods Computer stored data on digitoxin concentrations in plasma from 9271 patients with cardiac disease were used to define a user population. Age and sex matched controls from the Norwegian Cancer Registry were used to calculate the number of expected cancer cases. Results The population on digitoxin showed a higher incidence of cancer compared to the control population. However, an additional analysis showed that the population on digitoxin had a general increased risk of cancer already, before the start on digitoxin. Leukemia/lymphoma were the cancer types which stood out with the highest risk in the digitoxin population before starting on digitoxin. This indicates that yet unknown risk factors exist for cardiovascular disease and lymphoproliferative cancer. An internal dose-response analysis revealed a relationship between high plasma concentration of digitoxin and a lower risk for leukemia/lymphoma and for cancer of the kidney/urinary tract. Conclusion Morbidity and mortality are high in the population on digitoxin, due to high age and cardiac disease.These factors disturb efforts to isolate an eventual anticancer effect of digitoxin in this setting. Still, the results may indicate an anticancer effect of digitoxin for leukemia/lymphoma and kidney/urinary tract cancers. Prospective clinical cancer trials have to be done to find out if digitoxin and other cardiac glycosides are useful as anticancer agents.
Intracoronary irradiation: dose response for the prevention of restenosis in swine
International Nuclear Information System (INIS)
Weinberger, Judah; Amols, Howard; Ennis, Ronald D.; Schwartz, Allan; Wiedermann, Joseph G.; Marboe, Charles
1996-01-01
Purpose: Restenosis after percutaneous transluminal coronary angioplasty represents, in part, a proliferative response of vascular smooth muscle at the site of injury. We have previously shown that high-dose radiation (20 Gy), delivered via an intracoronary 192 Ir source, causes focal medial fibrosis and markedly impairs the restenosis process after balloon angioplasty in swine. This study sought to delineate the dose-response characteristics of this effect. Methods and Materials: Forty juvenile swine underwent coronary angiography; a segment of the left coronary artery was chosen as a target for balloon injury. In 30 swine, a 2 cm ribbon of 192 Ir was positioned at the target segment and 20, 15, or 10 Gy were delivered to the vessel wall (10 animals/dose). Subsequently, overdilatation balloon angioplasty was performed at the irradiated segment. In 10 control swine, overdilatation balloon angioplasty was performed without previous irradiation. Thirty-eight animals survived until sacrifice at 30 ± 3 days. Histopathological analysis was performed by a pathologist in a blinded manner. The area of maximal luminal compromise within the target segment was analyzed via computer-assisted planimetry. Results: Neointimal area was decreased by 71.4% at 20 Gy and by 58.3% at 15 Gy compared with control animals (p < 0.05 for both). A stimulatory effect on smooth muscle cell proliferation was noted at 10 Gy, with a 123% increase in neointimal area compared with controls (p < 0.05). Mean percent area stenosis was also reduced by 63% at 20 Gy and by 74.8% at 15 Gy compared with controls (p < 0.05 for both). Conclusions: Intracoronary irradiation prior to overstretch balloon angioplasty markedly reduces neointima formation; this effect is dose dependent, with evidence of a significant stimulatory effect at 10 Gy. The effective therapeutic dose range for the prevention of restenosis in this model begins at approximately 15 Gy delivered to the vessel wall
Albumin treatment regimen for type 1 hepatorenal syndrome: a dose-response meta-analysis.
Salerno, Francesco; Navickis, Roberta J; Wilkes, Mahlon M
2015-11-25
Recommended treatment for type 1 hepatorenal syndrome consists of albumin and vasoconstrictor. The optimal albumin dose remains poorly characterized. This meta-analysis aimed to determine the impact of albumin dose on treatment outcomes. Clinical studies of type 1 hepatorenal syndrome treatment with albumin and vasoconstrictor were sought. Search terms included: hepatorenal syndrome; albumin; vasoconstrictor; terlipressin; midodrine; octreotide; noradrenaline; and norepinephrine. A meta-analysis was performed of hepatorenal syndrome reversal and survival in relation to albumin dose. Nineteen clinical studies with 574 total patients were included, comprising 8 randomized controlled trials, 8 prospective studies and 3 retrospective studies. The pooled percentage of patients achieving hepatorenal syndrome reversal was 49.5% (95% confidence interval, 40.0-59.1%). Increments of 100 g in cumulative albumin dose were accompanied by significantly increased survival (hazard ratio, 1.15; 95% confidence interval, 1.02-1.31; p = 0.023). A non-significant increase of similar magnitude in hepatorenal syndrome reversal was also observed (odds ratio, 1.15; 95% confidence interval, 0.97-1.37; p = 0.10). Expected survival rates at 30 days among patients receiving cumulative albumin doses of 200, 400 and 600 g were 43.2% (95% confidence interval, 36.4-51.3%), 51.4% (95% confidence interval, 46.3-57.1%) and 59.0% (95% confidence interval, 51.9-67.2), respectively. Neither survival nor hepatorenal syndrome reversal was significantly affected by vasoconstrictor dose or type, treatment duration, age, baseline serum creatinine, bilirubin or albumin, baseline mean arterial pressure, or study design, size or time period. This meta-analysis suggests a dose-response relationship between infused albumin and survival in patients with type 1 hepatorenal syndrome. The meta-analysis provides the best current evidence on the potential role of albumin dose selection in improving outcomes of
Effect of Photon Hormesis on Dose Responses to Alpha Particles in Zebrafish Embryos
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Candy Yuen Ping Ng
2017-02-01
Full Text Available Photon hormesis refers to the phenomenon where the biological effect of ionizing radiation with a high linear energy transfer (LET value is diminished by photons with a low LET value. The present paper studied the effect of photon hormesis from X-rays on dose responses to alpha particles using embryos of the zebrafish (Danio rerio as the in vivo vertebrate model. The toxicity of these ionizing radiations in the zebrafish embryos was assessed using the apoptotic counts at 20, 24, or 30 h post fertilization (hpf revealed through acridine orange (AO staining. For alpha-particle doses ≥ 4.4 mGy, the additional X-ray dose of 10 mGy significantly reduced the number of apoptotic cells at 24 hpf, which proved the presence of photon hormesis. Smaller alpha-particle doses might not have inflicted sufficient aggregate damages to trigger photon hormesis. The time gap T between the X-ray (10 mGy and alpha-particle (4.4 mGy exposures was also studied. Photon hormesis was present when T ≤ 30 min, but was absent when T = 60 min, at which time repair of damage induced by alpha particles would have completed to prevent their interactions with those induced by X-rays. Finally, the drop in the apoptotic counts at 24 hpf due to photon hormesis was explained by bringing the apoptotic events earlier to 20 hpf, which strongly supported the removal of aberrant cells through apoptosis as an underlying mechanism for photon hormesis.
Sludge reduction by ozone: Insights and modeling of the dose-response effects.
Fall, C; Silva-Hernández, B C; Hooijmans, C M; Lopez-Vazquez, C M; Esparza-Soto, M; Lucero-Chávez, M; van Loosdrecht, M C M
2018-01-15
Applying ozone to the return flow in an activated sludge (AS) process is a way for reducing the residual solids production. To be able to extend the activated sludge models to the ozone-AS process, adequate prediction of the tri-atoms effects on the particulate COD fractions is needed. In this study, the biomass inactivation, COD mineralization, and solids dissolution were quantified in batch tests and dose-response models were developed as a function of the reacted ozone doses (ROD). Three kinds of model-sludge were used. S1 was a lab-cultivated synthetic sludge with two components (heterotrophs X H and X P ). S2 was a digestate of S1 almost made by the endogenous residues, X P . S3 was from a municipal activated sludge plant. The specific ozone uptake rate (SO 3 UR, mgO 3 /gCOD.h) was determined as a tool for characterizing the reactivity of the sludges. SO 3 UR increased with the X H fraction and decreased with more X P . Biomass inactivation was exponential (e -β.ROD ) as a function of the ROD doses. The percentage of solids reduction was predictable through a linear model (C Miner + Y sol ROD), with a fixed part due to mineralization (C Miner ) and a variable part from the solubilization process. The parameters of the models, i.e. the inactivation and the dissolution yields (β, 0.008-0.029 (mgO 3 /mgCOD ini ) -1 vs Y sol , 0.5-2.8 mg COD sol /mgO 3 ) varied in magnitude, depending on the intensity of the scavenging reactions and potentially the compactness of the flocs for each sludge. Copyright © 2017 Elsevier Ltd. All rights reserved.
Liposomal bupivacaine as a single-injection peripheral nerve block: a dose-response study.
Ilfeld, Brian M; Malhotra, Nisha; Furnish, Timothy J; Donohue, Michael C; Madison, Sarah J
2013-11-01
Currently available local anesthetics approved for single-injection peripheral nerve blocks have a maximum duration of fashion. The end points included the maximum voluntary isometric contraction (MVIC) of the quadriceps femoris muscle and tolerance to cutaneous electrical current in the femoral nerve distribution. Measurements were performed from baseline until quadriceps MVIC returned to 80% of baseline bilaterally. There were statistically significant dose responses in MVIC (0.09%/mg, SE = 0.03, 95% confidence interval [CI], 0.04-0.14, P = 0.002) and tolerance to cutaneous current (-0.03 mA/mg, SE = 0.01, 95% CI, -0.04 to -0.02, P 40 mg, tolerance to cutaneous current did not return to within 20% above baseline until after 24 hours in 100% of subjects (95% CI, 56%-100%). MVIC did not consistently return to within 20% of baseline until after 24 hours in 90% of subjects (95% CI, 54%-100%). Motor block duration was not correlated with bupivacaine dose (0.06 hour/mg, SE = 0.14, 95% CI, -0.27 to 0.39, P = 0.707). The results of this investigation suggest that deposition of a liposomal bupivacaine formulation adjacent to the femoral nerve results in a partial sensory and motor block of >24 hours for the highest doses examined. However, the high variability of block magnitude among subjects and inverse relationship of dose and response magnitude attests to the need for a phase 3 study with a far larger sample size, and that these results should be viewed as suggestive, requiring confirmation in a future trial.
Dose-response relationship of octylphenol and radiation evaluated by tradescantia-micronucleus assay
International Nuclear Information System (INIS)
Kim, J. K.; Cheon, K. J.; Lee, B. H.; Shin, H. S.; Lee, J. H.
2002-01-01
Many kinds of synthetic chemicals have been being used for various purposes. Some of them are called 'Endocrine Disruptor's because they can disturb the endocrine system of organisms. Presently no technique is established for the quantitative assessment of biological risk of the environmental hormones. The pollen mother cells (PMC) of Tradescantia are very sensitive to chemical toxicants or ionizing radiation, and thus can be used as a biological end-point assessing their effect. Micronucleus frequencies in PMC showed a good dose- and concentration-response relationship for radiation, bisphenol A and octylphenol. A parallel series of experiment using five increasing doses of gamma-ray at 10, 20, 30, 40 and 50 cGy was conducted. The MCN frequencies of 12.0, 25.2, 41.7, 76 and 83 MCN/100 tetrads were observed from each of the increasing gamma-ray dosage groups, respectively. Lenear regression analysis of the gamma-ray data MCN frequencies yielded a correlation coefficient of 0.95. the MCN frequencies in pollen mother cells treated with bisphenol a and octylphenol showed dose-response relationship in a concentration of 0, 1, 2, 4 μM and 0, 4, 10, 20 μM. the MCN frequency for the bisphenol a and octylphenol group yields 2.33, 8.06, 12.7 and 19.6 MCN/100 tetrads for the bisphenol a and 2.33, 2.33, 11.47, 17.6 MCN/100 tetrads for the octylphenol. The MCN frequency of the control was 2.33 MCN/100 tetrads. It is known from the result that Trad-MCN assay can be an excellent tool for detection of biological risk due to environmental toxicants or synthetic chemicals
Dose response and efficacy of a live, attenuated human rotavirus vaccine in Mexican infants.
Ruiz-Palacios, Guillermo M; Guerrero, M Lourdes; Bautista-Márquez, Aurora; Ortega-Gallegos, Hilda; Tuz-Dzib, Fernando; Reyes-González, Leticia; Rosales-Pedraza, Gustavo; Martínez-López, Julia; Castañón-Acosta, Erika; Cervantes, Yolanda; Costa-Clemens, SueAnn; DeVos, Beatrice
2007-08-01
Immunization against rotavirus has been proposed as the most cost-effective intervention to reduce the disease burden associated with this infection worldwide. The objective of this study was to determine the dose response, immunogenicity, and efficacy of 2 doses of an oral, attenuated monovalent G1[P8] human rotavirus vaccine in children from the same setting in Mexico, where the natural protection against rotavirus infection was studied. From June 2001 through May 2003, 405 healthy infants were randomly assigned to 1 of 3 vaccine groups (virus concentrations 10(4.7), 10(5.2), and 10(5.8) infectious units) and to a placebo group and were monitored to the age of 2 years. The vaccine/placebo was administered concurrently with diphtheria-tetanus toxoid-pertussis/hepatitis B/Haemophilus influenzae type b vaccine at 2 and 4 months of age. After the administration of the first vaccine/placebo dose, weekly home visits to collect information regarding infant health were conducted. Stool samples were collected during each gastroenteritis episode and tested for rotavirus antigen and serotype. The vaccine was well tolerated and induced a greater rate of seroconversion than observed in infants who received placebo. For the pooled vaccine groups, efficacy after 2 oral doses was 80% and 95% against any and severe rotavirus gastroenteritis, respectively. Efficacy was 100% against severe rotavirus gastroenteritis and 70% against severe gastroenteritis of any cause with the vaccine at the highest virus concentration (10(5.8) infectious units). The predominant infecting rotavirus serotype in this cohort was wild-type G1 (85%). Adverse events, including fever, irritability, loss of appetite, cough, diarrhea, and vomiting, were similar among vaccinees and placebo recipients. This new oral, live, attenuated human rotavirus vaccine was safe, immunogenic, and highly efficacious in preventing any and, more importantly, severe rotavirus gastroenteritis in healthy infants. This vaccine
Defining a dose-response relationship with radiotherapy for prostate cancer: is more really better?
International Nuclear Information System (INIS)
Vicini, Frank A.; Abner, Anthony; Baglan, Kathy L.; Kestin, Larry L.; Martinez, Alvaro A.
2001-01-01
Purpose: Data were reviewed addressing the association between radiation therapy (RT) dose and treatment outcome for localized prostate cancer to help clarify the existence of a potential dose-response relationship. Methods and Materials: Articles were identified through the MEDLINE database, CancerLit database, and reference lists of relevant articles. Studies were categorized into four groups based upon the endpoint analyzed, including biochemical control (BC), local control (LC), pathologic control (PC), and cause-specific survival (CSS). The impact of increasing RT dose with each endpoint was recorded. Results: Twenty-two trials involving a total of 11,297 patients were identified. Of the 11 trials addressing the association of RT dose with LC, 9 showed statistically significant improvements. Of the 12 trials that reported BC with RT dose, all showed statistically significant improvements. Two out of 4 studies analyzing PC with increasing dose showed a positive correlation. Finally, 3 out of 9 studies addressing RT dose with CSS showed statistically significant improvements. Despite inconclusive results, patients with poor risk features (e.g., prostate-specific antigen [PSA] ≥10, Gleason score [GS] ≥7, or tumor stage ≥T2b) were most likely to benefit from increasing dose with respect to each endpoint. However, the optimal RT dose and the magnitude of benefit of dose escalation could not be identified. Conclusions: Although RT dose appears to correlate with various measures of treatment outcome, objective, high-quality data addressing this critical issue are still lacking. At the present time, the absolute improvement in outcome due to dose escalation, the subset of patients benefiting most, and the optimal dose remain to be defined
Dose-response relationships of propranolol in Chinese subjects with different CYP2D6 genotypes.
Huang, Chin-Wei; Lai, Ming-Liang; Lin, Min-Shung; Lee, Hwei-Ling; Huang, Jin-Ding
2003-01-01
For clinical treatment, a smaller dosage of propranolol is often used among Chinese people. Propranolol is metabolized by polymorphic CYP2D6. We postulate that the lower propranolol dosage in Chinese is due to a slower CYP2D6 metabolism. A majority of the Chinese population has the nucleotide T188 in the CYP2D6 gene (CYP2D6*10) instead of C188 (CYP2D6*1), which most white subjects have. Chinese subjects of different CYP2D6*1/CYP2D6*10 genotypes have been shown to have different propranolol pharmacokinetic characteristics. In this study, we compared the beta-blockade effects of propranolol in Chinese subjects of the two different CYP2D6 genotypes. Based on the nucleotide 188 genotypes, two groups of 10 healthy subjects each were selected. Each subject was given a 10-, 20-, or 40-mg rac-propranolol tablet three times a day for 3 days in 3 different phases. Heart rate and blood pressure were measured in both supine and upright positions. The heart rate was also determined during treadmill exercise test. Plasma concentration of S-propranolol at 2 hrs after the last-dose administration was measured. Despite therebeing higher S-propranolol plasma concentration in CYP2D6*10 subjects than in CYP2D6*1 subjects at 10- and 20-mg dosage, the dose-response relationship was not significantly different in these subjects. Our results do not support the hypothesis that CYP2D6*1/CYP2D6*10 polymorphism may affect the beta-blockade effect of propranolol in Chinese subjects.
Influence of Exercise Intensity for Improving Depressed Mood in Depression: A Dose-Response Study.
Meyer, Jacob D; Koltyn, Kelli F; Stegner, Aaron J; Kim, Jee-Seon; Cook, Dane B
2016-07-01
Exercise effectively improves mood in major depressive disorder (MDD), but the optimal exercise stimulus to improve depressed mood is unknown. To determine the dose-response relationship of acute exercise intensity with depressed mood responses to exercise in MDD. We hypothesized that the acute response to exercise would differ between light, moderate, and hard intensity exercise with higher intensities yielding more beneficial responses. Once weekly, 24 women (age: 38.6±14.0) diagnosed with MDD underwent a 30-minute session at one of three steady-state exercise intensities (light, moderate, hard; rating of perceived exertion 11, 13 or 15) or quiet rest on a stationary bicycle. Depressed mood was evaluated with the Profile of Mood States before, 10 and 30 minutes post-exercise. Exercise reduced depressed mood 10 and 30 minutes following exercise, but this effect was not influenced by exercise intensity. Participants not currently taking antidepressants (n=10) had higher baseline depression scores, but did not demonstrate a different antidepressant response to exercise compared to those taking antidepressants. To acutely improve depressed mood, exercise of any intensity significantly improved feelings of depression with no differential effect following light, moderate, or hard exercise. Pharmacological antidepressant usage did not limit the mood-enhancing effect of acute exercise. Acute exercise should be used as a symptom management tool to improve mood in depression, with even light exercise an effective recommendation. These results need to be replicated and extended to other components of exercise prescription (e.g., duration, frequency, mode) to optimize exercise guidelines for improving depression. Copyright © 2016. Published by Elsevier Ltd.
Exercise volume and intensity: a dose-response relationship with health benefits.
Foulds, Heather J A; Bredin, Shannon S D; Charlesworth, Sarah A; Ivey, Adam C; Warburton, Darren E R
2014-08-01
The health benefits of exercise are well established. However, the relationship between exercise volume and intensity and health benefits remains unclear, particularly the benefits of low-volume and intensity exercise. The primary purpose of this investigation was, therefore, to examine the dose-response relationship between exercise volume and intensity with derived health benefits including volumes and intensity of activity well below international recommendations. Generally healthy, active participants (n = 72; age = 44 ± 13 years) were assigned randomly to control (n = 10) or one of five 13-week exercise programs: (1) 10-min brisk walking 1×/week (n = 10), (2) 10-min brisk walking 3×/week (n = 10), (3) 30-min brisk walking 3×/week (n = 18), (4) 60-min brisk walking 3×/week (n = 10), and (5) 30-min running 3×/week (n = 14), in addition to their regular physical activity. Health measures evaluated pre- and post-training including blood pressure, body composition, fasting lipids and glucose, and maximal aerobic power (VO2max). Health improvements were observed among programs at least 30 min in duration, including body composition and VO2max: 30-min walking 28.8-34.5 mL kg(-1) min(-1), 60-min walking 25.1-28.9 mL kg(-1) min(-1), and 30-min running 32.4-36.4 mL kg(-1) min(-1). The greater intensity running program also demonstrated improvements in triglycerides. In healthy active individuals, a physical activity program of at least 30 min in duration for three sessions/per week is associated with consistent improvements in health status.
Parity and pancreatic cancer risk: a dose-response meta-analysis of epidemiologic studies.
Directory of Open Access Journals (Sweden)
Hong-Bo Guan
Full Text Available BACKGROUND: Previous epidemiologic studies have reported inconsistent results between parity and pancreatic cancer (PC risk. To our knowledge, a comprehensive and quantitative assessment of this association has not been conducted. METHODS: Relevant published studies of parity and PC were identified using MEDLINE (PubMed and Web of Science databases until November 2013. Two authors (H-BG and LW independently assessed eligibility and extracted data. Eleven prospective and 11 case-control studies reported relative risk (RR estimates and 95% confidence intervals (CIs of PC associated with parity. Fixed- and random-effects models were used to estimate the summary RR depending on the heterogeneity of effects. RESULTS: The summary RR for PC comparing the highest versus lowest parity was 0.86 (95% CI: 0.73-1.02; Q = 50.49, P<0.001, I2 = 58.4%. Significant inverse associations were also observed in the studies that adjusted for cigarette smoking (RR = 0.81; 95% CI: 0.68-0.98, Type 2 diabetes mellitus (RR = 0.83; 95% CI: 0.75-0.93, and those that included all confounders or important risk factors (RR = 0.85; 95% CI: 0.76-0.96. Additionally, in the dose-response analysis, the summary RR for per one live birth was 0.97 (95% CI: 0.94-1.01; Q = 62.83, P<0.001, I2 = 69.8%, which also indicated a borderline statistically significant inverse effect of parity on PC risk. No evidence of publication bias and significant heterogeneity between subgroups were detected by meta-regression analyses. CONCLUSION: In summary, these findings suggest that higher parity is associated with a decreased risk of PC. Future large consortia or pooled studies are warranted to fully adjust for potential confounders to confirm this association.
Demonstration of brachytherapy boost dose-response relationships in glioblastoma multiforme
International Nuclear Information System (INIS)
Sneed, Penny K.; Lamborn, Kathleen R.; Larson, David A.; Prados, Michael D.; Malec, Mary K.; McDermott, Michael W.; Weaver, Keith A.; Phillips, Theodore L.; Wara, William M.; Gutin, Philip H.
1996-01-01
Purpose: To evaluate brachytherapy dose-response relationships in adults with glioblastoma undergoing temporary 125 I implant boost after external beam radiotherapy. Methods and Materials: Since June 1987, orthogonal radiographs using a fiducial marker box have been used to verify brain implant source positions and generate dose-volume histograms at the University of California, San Francisco. For adults who underwent brachytherapy boost for glioblastoma from June 1987 through December 1992, tumor volumes were reoutlined to ensure consistency and dose-volume histograms were recalculated. Univariate and multivariate analyses of various patient and treatment parameters were performed evaluating for influence of dose on freedom from local failure (FFLF) and actuarial survival. Results: Of 102 implant boosts, 5 were excluded because computer plans were unavailable. For the remaining 97 patients, analyses with adjustment for known prognostic factors (age, KPS, extent of initial surgical resection) and prognostic factors identified on univariate testing (adjuvant chemotherapy) showed that higher minimum brachytherapy tumor dose was strongly associated with improved FFLF (p = 0.001). A quadratic relationship was found between total biological effective dose and survival, with a trend toward optimal survival probability at 47 Gy minimum brachytherapy tumor dose (corresponding to about 65 Gy to 95% of the tumor volume); survival decreased with lower or higher doses. Two patients expired and one requires hospice care because of brain necrosis after brachytherapy doses > 63 Gy to 95% of the tumor volume with 60 Gy to > 18 cm 3 of normal brain. Conclusion: Although higher minimum brachytherapy tumor dose was strongly associated with better local control, a brachytherapy boost dose > 50-60 Gy may result in life-threatening necrosis. We recommend careful conformation of the prescription isodose line to the contrast enhancing tumor volume, delivery of a minimum brachytherapy
DEFF Research Database (Denmark)
Bernstein, Daniel J.; Birkner, Peter; Lange, Tanja
2013-01-01
-arithmetic level are as follows: (1) use Edwards curves instead of Montgomery curves; (2) use extended Edwards coordinates; (3) use signed-sliding-window addition-subtraction chains; (4) batch primes to increase the window size; (5) choose curves with small parameters and base points; (6) choose curves with large...
Theoretical Current-Voltage Curve in Low-Pressure Cesium Diode for Electron-Rich Emission
Coldstein, C. M.
1964-01-01
Although considerable interest has been shown in the space-charge analysis of low-pressure (collisionless case) thermionic diodes, there is a conspicuous lack in the presentation of results in a way that allows direct comparison with experiment. The current-voltage curve of this report was, therefore, computed for a typical case within the realm of experimental interest. The model employed in this computation is shown in Fig. 1 and is defined by the limiting potential distributions [curves (a) and (b)]. Curve (a) represents the potential V as a monotonic function of position with a slope of zero at the anode; curve (b) is similarly monotonic with a slope of zero at the cathode. It is assumed that by a continuous variation of the anode voltage, the potential distributions vary continuously from one limiting form to the other. Although solutions for infinitely spaced electrodes show that spatically oscillatory potential distributions may exist, they have been neglected in this computation.
Dose-response study of thimerosal-induced murine systemic autoimmunity
International Nuclear Information System (INIS)
Havarinasab, S.; Lambertsson, L.; Qvarnstroem, J.; Hultman, P.
2004-01-01
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 μg Hg/kg bw and a concentration of 21 and 1.9 μg 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
Zhang, Qiang; Bhattacharya, Sudin; Andersen, Melvin E; Conolly, Rory B
2010-02-01
The new paradigm envisioned for toxicity testing in the 21st century advocates shifting from the current animal-based testing process to a combination of in vitro cell-based studies, high-throughput techniques, and in silico modeling. A strategic component of the vision is the adoption of the systems biology approach to acquire, analyze, and interpret toxicity pathway data. As key toxicity pathways are identified and their wiring details elucidated using traditional and high-throughput techniques, there is a pressing need to understand their qualitative and quantitative behaviors in response to perturbation by both physiological signals and exogenous stressors. The complexity of these molecular networks makes the task of understanding cellular responses merely by human intuition challenging, if not impossible. This process can be aided by mathematical modeling and computer simulation of the networks and their dynamic behaviors. A number of theoretical frameworks were developed in the last century for understanding dynamical systems in science and engineering disciplines. These frameworks, which include metabolic control analysis, biochemical systems theory, nonlinear dynamics, and control theory, can greatly facilitate the process of organizing, analyzing, and understanding toxicity pathways. Such analysis will require a comprehensive examination of the dynamic properties of "network motifs"--the basic building blocks of molecular circuits. Network motifs like feedback and feedforward loops appear repeatedly in various molecular circuits across cell types and enable vital cellular functions like homeostasis, all-or-none response, memory, and biological rhythm. These functional motifs and associated qualitative and quantitative properties are the predominant source of nonlinearities observed in cellular dose response data. Complex response behaviors can arise from toxicity pathways built upon combinations of network motifs. While the field of computational cell
Lipid metabolic dose response to dietary alpha-linolenic acid in monk parrot (Myiopsitta monachus).
Petzinger, Christina; Heatley, J J; Bailey, Christopher A; Bauer, John E
2014-03-01
Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA.
International Nuclear Information System (INIS)
Rousseau-Poivet, J.; Sas, N.; Nguyen, F.; Abadie, J.; Chouin, N.; Barbet, J.
2015-01-01
studied progenitor and blood cells. As compared to 0.8 Gy, one more week was necessary at 1.4 Gy. A mild anemia (21% erythrocyte depletion) was noticed only at this higher absorbed dose between D3 and D10. Conclusion: absorbed doses to the BM between 0.8 and 1.4 Gy induced hematological toxicity expressed by transient BM aplasia, neutropenia, thrombocytopenia and inconsistent anemia. These depletions and time to recovery were both dose-dependent. Higher absorbed doses will be achieved to better investigate the dose-response relationship and to further develop our compartmental model for platelets. Neutrophils and erythrocytes kinetics are also under investigation to generate satisfying simulations with the model. (authors)
Dose-Response of High-Intensity Training (HIT on Atheroprotective miRNA-126 Levels
Directory of Open Access Journals (Sweden)
Boris Schmitz
2017-05-01
Full Text Available Aim: MicroRNA-126 (miR-126 exerts beneficial effects on vascular integrity, angiogenesis, and atherosclerotic plaque stability. The purpose of this investigation was to analyze the dose-response relationship of high-intensity interval training (HIIT on miR-126-3p and -5p levels.Methods: Sixty-one moderately trained individuals (females = 31 [50.8%]; 22.0 ± 1.84 years were consecutively recruited and allocated into three matched groups using exercise capacity. During a 4-week intervention a HIIT group performed three exercise sessions/week of 4 × 30 s at maximum speed (all-out, a progressive HIIT (proHIIT group performed three exercise sessions/week of 4 × 30 s at maximum speed (all-out with one extra session every week (up to 7 × 30 s and a low-intensity training (LIT control group performed three exercise sessions/week for 25 min <75% of maximum heart rate. Exercise miR-126-3p/-5p plasma levels were determined using capillary blood from earlobes.Results: No exercise-induced increase in miR-126 levels was detected at baseline, neither in the LIT (after 25 min low-intensity running nor the HIIT groups (after 4 min of high-intensity running. After the intervention, the LIT group presented an increase in miR-126-3p, while in the HIIT group, miR-126-3p levels were still reduced (all p < 0.05. An increase for both, miR-126-3p and -5p levels (all p < 0.05, pre- vs. during and post-exercise was detected in the proHIIT group. Between group analysis revealed that miR-126-3p levels after LIT and proHIIT increased by 2.12 ± 2.55 and 1.24 ± 2.46 units (all p < 0.01, respectively, compared to HIIT (−1.05 ± 2.6 units.Conclusions: LIT and proHIIT may be performed to increase individual miR-126 levels. HIIT without progression was less effective in increasing miR-126.
[Dose-response relationship of ropivacaine for epidural block in early herpes zoster guided by CT].
Xie, K Y; Ma, J B; Xu, Q; Huang, B; Yao, M; Ni, H D; Deng, J J; Chen, G D
2017-12-26
Objective: To determine the dose-response relationship of ropivacaine for epidural block in early herpes zoster by CT guided. Methods: From January 2015 to February 2017, according to the principle of completely random digital table, 80 patients with early herpes zoster who were prepared for epidural block were divided into 4 groups(each group 20 patients): in group A the concentration of ropivacaine was 0.08%, in group B was 0.10%, in group C was 0.12% and in group D was 0.14%.Under CT guidance, epidural puncture was performed in the relevant section, mixing liquid 5.0 ml (with 10% iodohydrin)were injected into epidural gap.CT scan showed that the mixing liquid covered the relevant spinal nerve segmental.The numeric rating scale(NRS) values before treatment and at 30 minutes, the incidence of adverse reactions were recorded, and the treatment were evaluated. The response to ropivacaine for epidural block in early herpes zoster was defined as positive when the NRS values was less than or equal to one.The ED(50), ED(95) and 95% confidence interval ( CI ) of ropivacaine for epidural block in early herpes zoster guided by CT were calculated by probit analysis. Results: The NRS values before treatment were 5.00(4.00, 6.00), 5.00(4.25, 6.00), 5.50(5.00, 6.00) and 5.00(4.00, 6.00), the difference was no significant( Z =2.576, P =0.462). The NRS values at 30 minutes decreased and the effective rate of the treatment increased(χ(2)=8.371, P =0.004), following ropivacaine dose gradient increasing, they were 1.50(1.00, 2.00), 1.00(1.00, 2.00), 0.50(0.00, 1.00) and 0.00(0.00, 1.00), the difference was statistically significant ( Z =17.421, P =0.001). There was one case in group C and four cases in group D were hypoesthesia, others were no significant adverse reactions occurred. The ED(50) and ED(95) (95% CI ) of ropivacaine for epidural block in early herpes zoster guided by CT were 0.078%(0.015%-0.095%)and 0.157%(0.133%-0.271%), respectively. Conclusion: Ropivacaine for
Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?
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Chung, Eugene [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Corbett, James R. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Moran, Jean M. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Griffith, Kent A. [Department of Biostatistics, University of Michigan, Ann Arbor, Michigan (United States); Marsh, Robin B.; Feng, Mary; Jagsi, Reshma; Kessler, Marc L. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Ficaro, Edward C. [Division of Nuclear Medicine, Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Pierce, Lori J., E-mail: ljpierce@umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States)
2013-03-15
Purpose: To quantify cardiac radiation therapy (RT) exposure using sensitive measures of cardiac dysfunction; and to correlate dysfunction with heart doses, in the setting of adjuvant RT for left-sided breast cancer. Methods and Materials: On a randomized trial, 32 women with node-positive left-sided breast cancer underwent pre-RT stress single photon emission computed tomography (SPECT-CT) myocardial perfusion scans. Patients received RT to the breast/chest wall and regional lymph nodes to doses of 50 to 52.2 Gy. Repeat SPECT-CT scans were performed 1 year after RT. Perfusion defects (PD), summed stress defects scores (SSS), and ejection fractions (EF) were evaluated. Doses to the heart and coronary arteries were quantified. Results: The mean difference in pre- and post-RT PD was −0.38% ± 3.20% (P=.68), with no clinically significant defects. To assess for subclinical effects, PD were also examined using a 1.5-SD below the normal mean threshold, with a mean difference of 2.53% ± 12.57% (P=.38). The mean differences in SSS and EF before and after RT were 0.78% ± 2.50% (P=.08) and 1.75% ± 7.29% (P=.39), respectively. The average heart Dmean and D95 were 2.82 Gy (range, 1.11-6.06 Gy) and 0.90 Gy (range, 0.13-2.17 Gy), respectively. The average Dmean and D95 to the left anterior descending artery were 7.22 Gy (range, 2.58-18.05 Gy) and 3.22 Gy (range, 1.23-6.86 Gy), respectively. No correlations were found between cardiac doses and changes in PD, SSS, and EF. Conclusions: Using sensitive measures of cardiac function, no clinically significant defects were found after RT, with the average heart Dmean <5 Gy. Although a dose response may exist for measures of cardiac dysfunction at higher doses, no correlation was found in the present study for low doses delivered to cardiac structures and perfusion, SSS, or EF.
Jones, Rebecca Louise; Stellingwerff, Trent; Artioli, Guilherme Giannini; Saunders, Bryan; Cooper, Simon; Sale, Craig
2016-10-01
To defend against hydrogen cation accumulation and muscle fatigue during exercise, sodium bicarbonate (NaHCO 3 ) ingestion is commonplace. The individualized dose-response relationship between NaHCO 3 ingestion and blood biochemistry is unclear. The present study investigated the bicarbonate, pH, base excess and sodium responses to NaHCO 3 ingestion. Sixteen healthy males (23 ± 2 years; 78.6 ± 15.1 kg) attended three randomized order-balanced, nonblinded sessions, ingesting a single dose of either 0.1, 0.2 or 0.3 g·kg -1 BM of NaHCO 3 (Intralabs, UK). Fingertip capillary blood was obtained at baseline and every 10 min for 1 hr, then every 15 min for a further 2 hr. There was a significant main effect of both time and condition for all assessed blood analytes (p ≤ .001). Blood analyte responses were significantly lower following 0.1 g·kg -1 BM compared with 0.2 g·kg -1 BM; bicarbonate concentrations and base excess were highest following ingestion of 0.3 g·kg -1 BM (p ≤ .01). Bicarbonate concentrations and pH significantly increased from baseline following all doses; the higher the dose the greater the increase. Large interindividual variability was shown in the magnitude of the increase in bicarbonate concentrations following each dose (+2.0-5; +5.1-8.1; and +6.0-12.3 mmol·L -1 for 0.1, 0.2 and 0.3 g·kg -1 BM) and in the range of time to peak concentrations (30-150; 40-165; and 75-180 min for 0.1, 0.2 and 0.3 g·kg -1 BM). The variability in bicarbonate responses was not affected by normalization to body mass. These results challenge current practices relating to NaHCO 3 supplementation and clearly show the need for athletes to individualize their ingestion protocol and trial varying dosages before competition.
A NURBS approximation of experimental stress-strain curves
International Nuclear Information System (INIS)
Fedorov, Timofey V.; Morrev, Pavel G.
2016-01-01
A compact universal representation of monotonic experimental stress-strain curves of metals and alloys is proposed. It is based on the nonuniform rational Bezier splines (NURBS) of second order and may be used in a computer library of materials. Only six parameters per curve are needed; this is equivalent to a specification of only three points in a stress-strain plane. NURBS-functions of higher order prove to be surplus. Explicit expressions for both yield stress and hardening modulus are given. Two types of curves are considered: at a finite interval of strain and at infinite one. A broad class of metals and alloys of various chemical compositions subjected to various types of preliminary thermo-mechanical working is selected from a comprehensive data base in order to test the methodology proposed. The results demonstrate excellent correspondence to the experimental data. Keywords: work hardening, stress-strain curve, spline approximation, nonuniform rational B-spline, NURBS.
International Nuclear Information System (INIS)
Downs, T.
1992-01-01
The demonstration of hormetic effects is rendered difficult for a number of reasons: The spontaneous rate must be large enough for a difference to be detectable. In contrast with detrimental effects, there is a limited range of doses over which beneficial effects are likely to be found. Publication bias hampers publication of low-dose beneficial effects and discourages research in the area. Some scientists actually believe that hormetic effects are contary to reason. All these factors contribute to lessen the chances of detecting hormetic effects through synthesis of the scientific literature. The extra statistical power obtained from mathematical modeling is not available for hormetic studies when appropriate models are not available. Even a simple statistical device such as a test for linear trend does not work well for U-shaped data. The first part of this two-part chapter deals with the probabilities of determining qualitatively what kinds of health effects may result from exposures to substances, and the second part with characterizing quantitative relationships between such health effects and exposures. The health effects may be beneficial in some situations, and detrimental in others
Energy Technology Data Exchange (ETDEWEB)
Yoshikawa, I.; Ayaki, T.; Ohshima, K.
1984-01-01
Induction of recessive lethal mutation by N-ethyl-N-nitrosourea (ENU) was studied for the second chromosome of spermatogonia and spermatozoa in Drosophila melanogaster. ENU (0.03, 0.3, and 1.0 mM) was given to flies by dissolving it in feeding sucrose solution. When plotted against absorbed doses of ENU, the observed frequencies to recessive lethals showed a linear relationship for induction in spermatozoa but a sigmoidal relationship for induction in spermatogonia. These results suggest that in spermatogonia ENU-induced mutational damage is more repairable in a lower dose range of ENU. Mosaic lethal mutations were induced by ENU but not in spermatogonia.
Kong, Xirui; Fu, Zhilong; Que, Huiying; Fan, Yanwei; Chen, Zhaoyang; He, Chengfa
2018-05-01
The LiMgPO4: Tb, B ceramic disc is successfully synthesized via improved sintering method which enables the disc sample to have two flat and smooth surfaces. It is worth mentioning that the OSL signal intensity of LiMgPO4: Tb, B disc attenuates much faster than that of commercial Al2O3: C. It costs only 1 s to reduce the intensity to 10%, but the Al2O3:C needs more than 40 s to finish it. Some essential OSL properties related to the dose detection method of this sample also have been systematically investigated. Although the dose-response cure would have better linearity with longer recording time, extended recording time (≥6 s) will not make any contribution to the linearity of the curve. If the bleaching time is more than 35 s, the residue created by previous detection (high dose of 10 Gy) would do almost no influence (with a positive deviation lower than 5.59%) on next lower-dose detection (0.1 Gy). The material would reach its service life when the total-ionizing dose runs up to 30 k Gy. Therefore, the LiMgPO4: Tb, B ceramic material is a potential candidate for real-time dose monitoring with optical fiber telemetering technology.
International Nuclear Information System (INIS)
Drubay, Damien
2015-01-01
The relation between lung cancer risk and radon exposure has been clearly established, especially from the studies on uranium miner cohorts. But the association between radon exposure and extrapulmonary cancers and non-cancer diseases remains not well known. Moreover, the health risks associated with the other mining-related ionizing radiation exposures are still under consideration. The aim of this thesis is to contribute to the estimation of the radio-induced health risks at low-doses through the analysis of the kidney cancer and Circulatory System Disease (CSD) mortality risks among uranium miners. Kidney cancer mortality risk analyses were performed from the French cohort of uranium miners (n=5086; follow-up period: 1946-2007), the post-55 cohort (n=3,377; follow-up period: 1957-2007) and the German cohort of the Wismut (n=58,986; follow-up period: 1946-2003) which included 24, 11 and 174 deaths from kidney cancer, respectively. The exposures to radon and its short-lived progeny (expressed in Working Level Month WLM), to uranium ore dust (kBqh.m -3 ) and to external gamma rays (mSv) were estimated for each miners and the equivalent kidney dose was calculated. The dose-response relation was refined considering two responses: the instantaneous risk of kidney cancer mortality (corresponding to the classical analysis, Cause specific Hazard Ratio (CSHR) estimated with the Cox model) and its occurrence probability during the followup (Sub-distribution Hazard Ratio (SHR) estimated with the Fine and Gray model). An excess of kidney cancer mortality was observed only in the French cohort (SMR = 1.62 CI95%[1.04; 2.41]). In the Wismut cohort, a decrease of the kidney cancer mortality was observed (0.89 [0.78; 0.99]). For these three cohorts, the occupational radiological exposures (or the equivalent kidney dose) were significantly associated neither with the risk of kidney cancer mortality (e.g. CSHRWismut-radon/100 WLM=1.023 [0.993; 1.053]), nor with its occurrence
Kim, Dong Wook; Chung, Weon Kuu; Shin, Dong Oh; Yoon, Myonggeun; Hwang, Ui-Jung; Rah, Jeong-Eun; Jeong, Hojin; Lee, Sang Yeob; Shin, Dongho; Lee, Se Byeong; Park, Sung Yong
2012-04-01
This study examined the dose response of an optically stimulated luminescence dosemeter (OSLD) to megavoltage photon and electron beams. A nanoDot™ dosemeter was used to measure the dose response of the OSLD. Photons of 6-15 MV and electrons of 9-20 MeV were delivered by a Varian 21iX machine (Varian Medical System, Inc. Milpitas, CA, USA). The energy dependency was dose was linear until 200 cGy. The superficial dose measurements revealed photon irradiation to have an angular dependency. The nanoDot™ dosemeter has potential use as an in vivo dosimetric tool that is independent of the energy, has dose linearity and a rapid response compared with normal in vivo dosimetric tools, such as thermoluminescence detectors. However, the OSLD must be treated very carefully due to the high angular dependency of the photon beam.
International Nuclear Information System (INIS)
Datz, H.; Horowitz, Y.S.; Oster, L.; Margaliot, M.
2011-01-01
It is demonstrated that the method of data analysis, i.e., the method of the phenomenological/theoretical interpretation of dose response data, can greatly influence the estimation of the onset of deviation from dose response linearity of the high temperature thermoluminescence in LiF:Mg,Ti (TLD-100).
Energy Technology Data Exchange (ETDEWEB)
NONE
2005-07-01
This Part II of the report contains full versions of the case studies for air, water and land (Chapters 2-4), which were only summarised in Part I. In addition, during the work the research team has collected a large amount of literature and information on dose response relationships for air and water pollution relevant to China. This information is included as Chapters 5 and 6.
International Nuclear Information System (INIS)
2005-01-01
This Part II of the report contains full versions of the case studies for air, water and land (Chapters 2-4), which were only summarised in Part I. In addition, during the work the research team has collected a large amount of literature and information on dose response relationships for air and water pollution relevant to China. This information is included as Chapters 5 and 6
Brunner, Eric J; Shipley, Martin J; Britton, Annie R; Stansfeld, Stephen A; Heuschmann, Peter U; Rudd, Anthony G; Wolfe, Charles D A; Singh-Manoux, Archana; Kivimaki, Mika
2014-03-01
Systematic reviews examining associations of depressive disorder with coronary heart disease and stroke produce mixed results. Failure to consider reverse causation and dose-response patterns may have caused inconsistencies in evidence. This prospective cohort study on depressive disorder, coronary heart disease, and stroke analysed reverse causation and dose-response effects using four 5-year and three 10-year observation cycles (total follow up 24 years) based on multiple repeat measures of exposure. Participants in the Whitehall II study (n = 10,036, 31,395 person-observations, age at start 44.4 years) provided up to six repeat measures of depressive symptoms via the 30-item General Health Questionnaire (GHQ-30) and one measure via Center for Epidemiologic Studies Depression Scale (CES-D). The cohort was followed up for major coronary events (coronary death/nonfatal myocardial infarction) and stroke (stroke death/morbidity) through the national mortality register Hospital Episode Statistics, ECG-screening, medical records, and self-report questionnaires. GHQ-30 caseness predicted stroke over 0-5 years (age-, sex- and ethnicity-adjusted HR 1.60, 95% CI 1.1-2.3) but not over 5-10 years (HR 0.94, 95% CI 0.6-1.4). Using the last 5-year observation cycle, cumulative GHQ-30 caseness was associated with incident coronary heart disease in a dose-response manner (1-2 times a case: HR 1.12, 95% CI 0.7-1.7; 3-4 times: HR 2.06, 95% CI 1.2-3.7), and CES-D caseness predicted coronary heart disease (HR 1.81, 95% CI 1.1-3.1). There was evidence of a dose-response effect of depressive symptoms on risk of coronary heart disease. In contrast, prospective associations of depressive symptoms with stroke appeared to arise wholly or partly through reverse causation.
Zoladz, Phillip R.; Diamond, David M.
2008-01-01
Over a century of behavioral research has shown that stress can enhance or impair learning and memory. In the present review, we have explored the complex effects of stress on cognition and propose that they are characterized by linear and non-linear dose-response functions, which together reveal a hormetic relationship between stress and learning. We suggest that stress initially enhances hippocampal function, resulting from amygdala-induced excitation of hippocampal synaptic plasticity, as ...