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Sample records for dose response behavior

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

    Science.gov (United States)

    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...

  2. A review: Development of a microdose model for analysis of adaptive response and bystander dose response behavior.

    Science.gov (United States)

    Leonard, Bobby E

    2008-02-27

    Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type (125)I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite

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

    Science.gov (United States)

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

    2004-01-01

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

  4. Homeopathic Doses of Gelsemium sempervirens Improve the Behavior of Mice in Response to Novel Environments

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    Paolo Bellavite

    2011-01-01

    Full Text Available Gelsemium sempervirens is used in homeopathy for treating patients with anxiety related symptoms, however there have been few experimental studies evaluating its pharmacological activity. We have investigated the effects of homeopathic doses of G. sempervirens on mice, using validated behavioral models. Centesimal (CH dilutions/dynamizations of G. sempervirens, the reference drug diazepam (1 mg/kg body weight or a placebo (solvent vehicle were intraperitoneally delivered to groups of mice of CD1 strain during 8 days, then the effects were assessed by the Light-Dark (LD choice test and by the Open-Field (OF exploration test, in a fully blind manner. In the LD test, the mean time spent in the illuminated area by control and placebo-treated animals was 15.98%, for mice treated with diazepam it increased to 19.91% (P = .047, while with G. sempervirens 5 CH it was 18.11% (P = .341, non-significant. The number of transitions between the two compartments increased with diazepam from 6.19 to 9.64 (P < .001 but not with G. Sempervirens. In the OF test, G. sempervirens 5 CH significantly increased the time spent and the distance traveled in the central zone (P = .009 and P = .003, resp., while diazepam had no effect on these OF test parameters. In a subsequent series of experiments, G. sempervirens 7 and 30 CH also significantly improved the behavioral responses of mice in the OF test (P < .01 for all tested variables. Neither dilutions of G. sempervirens affected the total distance traveled, indicating that the behavioral effect was not due to unspecific changes in locomotor activity. In conclusion, homeopathic doses of G. sempervirens influence the emotional responses of mice to novel environments, suggesting an improvement in exploratory behavior and a diminution of thigmotaxis or neophobia.

  5. Unexpected Effects of Low Doses of a Neonicotinoid Insecticide on Behavioral Responses to Sex Pheromone in a Pest Insect

    Science.gov (United States)

    Rabhi, Kaouther K.; Esancy, Kali; Voisin, Anouk; Crespin, Lucille; Le Corre, Julie; Tricoire-Leignel, Hélène; Anton, Sylvia; Gadenne, Christophe

    2014-01-01

    In moths, which include many agricultural pest species, males are attracted by female-emitted sex pheromones. Although integrated pest management strategies are increasingly developed, most insect pest treatments rely on widespread use of neurotoxic chemicals, including neonicotinoid insecticides. Residual accumulation of low concentrations of these insecticides in the environment is known to be harmful to beneficial insects such as honey bees. This environmental stress probably acts as an “info-disruptor” by modifying the chemical communication system, and therefore decreases chances of reproduction in target insects that largely rely on olfactory communication. However, low doses of pollutants could on the contrary induce adaptive processes in the olfactory pathway, thus enhancing reproduction. Here we tested the effects of acute oral treatments with different low doses of the neonicotinoid clothianidin on the behavioral responses to sex pheromone in the moth Agrotis ipsilon using wind tunnel experiments. We show that low doses of clothianidin induce a biphasic effect on pheromone-guided behavior. Surprisingly, we found a hormetic-like effect, improving orientation behavior at the LD20 dose corresponding to 10 ng clothianidin. On the contrary, a negative effect, disturbing orientation behavior, was elicited by a treatment with a dose below the LD0 dose corresponding to 0.25 ng clothianidin. No clothianidin effect was observed on behavioral responses to plant odor. Our results indicate that risk assessment has to include unexpected effects of residues on the life history traits of pest insects, which could then lead to their adaptation to environmental stress. PMID:25517118

  6. Unexpected effects of low doses of a neonicotinoid insecticide on behavioral responses to sex pheromone in a pest insect.

    Directory of Open Access Journals (Sweden)

    Kaouther K Rabhi

    Full Text Available In moths, which include many agricultural pest species, males are attracted by female-emitted sex pheromones. Although integrated pest management strategies are increasingly developed, most insect pest treatments rely on widespread use of neurotoxic chemicals, including neonicotinoid insecticides. Residual accumulation of low concentrations of these insecticides in the environment is known to be harmful to beneficial insects such as honey bees. This environmental stress probably acts as an "info-disruptor" by modifying the chemical communication system, and therefore decreases chances of reproduction in target insects that largely rely on olfactory communication. However, low doses of pollutants could on the contrary induce adaptive processes in the olfactory pathway, thus enhancing reproduction. Here we tested the effects of acute oral treatments with different low doses of the neonicotinoid clothianidin on the behavioral responses to sex pheromone in the moth Agrotis ipsilon using wind tunnel experiments. We show that low doses of clothianidin induce a biphasic effect on pheromone-guided behavior. Surprisingly, we found a hormetic-like effect, improving orientation behavior at the LD20 dose corresponding to 10 ng clothianidin. On the contrary, a negative effect, disturbing orientation behavior, was elicited by a treatment with a dose below the LD0 dose corresponding to 0.25 ng clothianidin. No clothianidin effect was observed on behavioral responses to plant odor. Our results indicate that risk assessment has to include unexpected effects of residues on the life history traits of pest insects, which could then lead to their adaptation to environmental stress.

  7. Effects of acute sublethal gamma radiation exposure on aggressive behavior in male mice: A dose-response study

    International Nuclear Information System (INIS)

    Maier, D.M.; Landauer, M.R.

    1989-01-01

    The resident-intruder paradigm was used to assess the effects of gamma radiation (0, 3, 5, 7 Gray [Gy] cobalt-60) on aggressive offensive behavior in resident male mice over a 3-month period. The defensive behavior of nonirradiated intruder mice was also monitored. A dose of 3 Gy had no effect on either the residents' offensive behavior or the defensive behavior of the intruders paired with them. Doses of 5 and 7 Gy produced decreases in offensive behavior of irradiated residents during the second week postirradiation. The nonirradiated intruders paired with these animals displayed decreases in defensive behavior during this time period, indicating a sensitivity to changes in the residents' behavior. After the third week postirradiation, offensive and defensive behavior did not differ significantly between irradiated mice and sham-irradiated controls. This study suggests that sublethal doses of radiation can temporarily suppress aggressive behavior but have no apparent permanent effect on that behavior

  8. Synthetic food coloring and behavior: a dose response effect in a double-blind, placebo-controlled, repeated-measures study.

    Science.gov (United States)

    Rowe, K S; Rowe, K J

    1994-11-01

    To establish whether there is an association between the ingestion of synthetic food colorings and behavioral change in children referred for assessment of "hyperactivity." From approximately 800 children referred to the Royal Children's Hospital (Melbourne) for assessment of suspected hyperactivity, 200 were included in a 6-week open trial of a diet free of synthetic food coloring. The parents of 150 children reported behavioral improvement with the diet, and deterioration on the introduction of foods noted to contain synthetic coloring. A 30-item behavioral rating inventory was devised from an examination of the clinical histories of 50 suspected reactors. Thirty-four other children (23 suspected reactors, 11 uncertain reactors) and 20 control subjects, aged 2 to 14 years, were studied. A 21-day, double-blind, placebo-controlled, repeated-measures study used each child as his or her own control. Placebo, or one of six dose levels of tartrazine (1, 2, 5, 10, 20, 50 mg), was administered randomly each morning, and behavioral ratings were recorded by parents at the end of each 24 hours. The study identified 24 children as clear reactors (19 of 23 "suspected reactors," 3 of 11 "uncertain reactors," and 2 of 20 "control subjects"). They were irritable and restless and had sleep disturbance. Significant reactions were observed at all six dose levels. A dose response effect was obtained. With a dose increase greater than 10 mg, the duration of effect was prolonged. Behavioral changes in irritability, restlessness, and sleep disturbance are associated with the ingestion of tartrazine in some children. A dose response effect was observed.

  9. Dose-response characteristics of methylphenidate on locomotor behavior and on sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats

    Directory of Open Access Journals (Sweden)

    Swann Alan C

    2006-01-01

    Full Text Available Abstract Background Methylphenidate (MPD is a psychostimulant commonly prescribed for attention deficit/hyperactivity disorder. The mode of action of the brain circuitry responsible for initiating the animals' behavior in response to psychostimulants is not well understood. There is some evidence that psychostimulants activate the ventral tegmental area (VTA, nucleus accumbens (NAc, and prefrontal cortex (PFC. Methods The present study was designed to investigate the acute dose-response of MPD (0.6, 2.5, and 10.0 mg/kg on locomotor behavior and sensory evoked potentials recorded from the VTA, NAc, and PFC in freely behaving rats previously implanted with permanent electrodes. For locomotor behavior, adult male Wistar-Kyoto (WKY; n = 39 rats were given saline on experimental day 1 and either saline or an acute injection of MPD (0.6, 2.5, or 10.0 mg/kg, i.p. on experimental day 2. Locomotor activity was recorded for 2-h post injection on both days using an automated, computerized activity monitoring system. Electrophysiological recordings were also performed in the adult male WKY rats (n = 10. Five to seven days after the rats had recovered from the implantation of electrodes, each rat was placed in a sound-insulated, electrophysiological test chamber where its sensory evoked field potentials were recorded before and after saline and 0.6, 2.5, and 10.0 mg/kg MPD injection. Time interval between injections was 90 min. Results Results showed an increase in locomotion with dose-response characteristics, while a dose-response decrease in amplitude of the components of sensory evoked field responses of the VTA, NAc, and PFC neurons. For example, the P3 component of the sensory evoked field response of the VTA decreased by 19.8% ± 7.4% from baseline after treatment of 0.6 mg/kg MPD, 37.8% ± 5.9% after 2.5 mg/kg MPD, and 56.5% ± 3.9% after 10 mg/kg MPD. Greater attenuation from baseline was observed in the NAc and PFC. Differences in the intensity of

  10. 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

  11. 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

  12. Effects of sawdust bedding dry matter on lying behavior of dairy cows: a dose-dependent response.

    Science.gov (United States)

    Reich, L J; Weary, D M; Veira, D M; von Keyserlingk, M A G

    2010-04-01

    The objective was to determine the effect of sawdust bedding dry matter on the lying behavior of Holstein cows. Dry matter (DM) was varied systematically over 5 treatment levels to test how cows respond to damp bedding. This experiment was repeated during summer and winter to test if the effects of damp bedding varied with season. The 5 bedding treatments averaged (+/-SD) 89.8+/-3.7, 74.2+/-6.4, 62.2+/-6.3, 43.9+/-4.0, and 34.7+/-3.8% DM. Over the course of the trial, minimum and maximum temperatures in the barn were 2.6+/-2.0 and 6.8+/-2.2 degrees C in the winter and 13.3+/-2.5 and 22.6+/-4.1 degrees C in the summer. In both seasons, 5 groups of 3 nonlactating cows were housed in free stalls bedded with sawdust. Following a 5-d acclimation period on dry bedding, groups were exposed to the 5 bedding treatments in a 5 x 5 Latin square. Each treatment lasted 4 d, followed by 1 d when the cows were provided with dry bedding. Stall usage was assessed by 24-h video scanned at 5-min intervals. Responses were analyzed within group (n=5) as the observational unit. Bedding DM affected lying time, averaging 10.4+/-0.4 h/d on the wettest treatment and increasing to 11.5+/-0.4 h/d on the driest bedding. Lying time varied with season, averaging 12.1+/-0.4 h/d across treatments during the winter and 9.9+/-0.6 h/d during the summer, but season and bedding DM did not interact. These results indicate that access to dry bedding is important for dairy cows. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  13. Dose response relationship at low doses

    International Nuclear Information System (INIS)

    Schull, W.J.

    1992-01-01

    The data that have accrued in Hiroshima and Nagasaki on the effects of ionizing radiation on the developing human brain are reviewed. Effects considered are severe mental retardation, lowered IQ scores, decline in school performance, seizures, other neuropsychological effects, and small head size. All these factors may be related to radiation doses received by the mother during pregnancy. (L.L.) 3 figs., tab., 7 refs

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. Equivalent intraperitoneal doses of ibuprofen supplemented in drinking water or in diet: a behavioral and biochemical assay using antinociceptive and thromboxane inhibitory dose–response curves in mice

    Directory of Open Access Journals (Sweden)

    Raghda A.M. Salama

    2016-07-01

    Full Text Available Background. Ibuprofen is used chronically in different animal models of inflammation by administration in drinking water or in diet due to its short half-life. Though this practice has been used for years, ibuprofen doses were never assayed against parenteral dose–response curves. This study aims at identifying the equivalent intraperitoneal (i.p. doses of ibuprofen, when it is administered in drinking water or in diet. Methods. Bioassays were performed using formalin test and incisional pain model for antinociceptive efficacy and serum TXB2 for eicosanoid inhibitory activity. The dose–response curve of i.p. administered ibuprofen was constructed for each test using 50, 75, 100 and 200 mg/kg body weight (b.w.. The dose–response curves were constructed of phase 2a of the formalin test (the most sensitive phase to COX inhibitory agents, the area under the ‘change in mechanical threshold’-time curve in the incisional pain model and serum TXB2 levels. The assayed ibuprofen concentrations administered in drinking water were 0.2, 0.35, 0.6 mg/ml and those administered in diet were 82, 263, 375 mg/kg diet. Results. The 3 concentrations applied in drinking water lay between 73.6 and 85.5 mg/kg b.w., i.p., in case of the formalin test; between 58.9 and 77.8 mg/kg b.w., i.p., in case of the incisional pain model; and between 71.8 and 125.8 mg/kg b.w., i.p., in case of serum TXB2 levels. The 3 concentrations administered in diet lay between 67.6 and 83.8 mg/kg b.w., i.p., in case of the formalin test; between 52.7 and 68.6 mg/kg b.w., i.p., in case of the incisional pain model; and between 63.6 and 92.5 mg/kg b.w., i.p., in case of serum TXB2 levels. Discussion. The increment in pharmacological effects of different doses of continuously administered ibuprofen in drinking water or diet do not parallel those of i.p. administered ibuprofen. It is therefore difficult to assume the equivalent parenteral daily doses based on mathematical calculations.

  20. Dose-response-a challenge for allelopathy?

    Science.gov (United States)

    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.

  1. 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

  2. The Dose Response Relationship for Radiation Carcinogenesis

    Science.gov (United States)

    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

  3. Towards accurate emergency response behavior

    International Nuclear Information System (INIS)

    Sargent, T.O.

    1981-01-01

    Nuclear reactor operator emergency response behavior has persisted as a training problem through lack of information. The industry needs an accurate definition of operator behavior in adverse stress conditions, and training methods which will produce the desired behavior. Newly assembled information from fifty years of research into human behavior in both high and low stress provides a more accurate definition of appropriate operator response, and supports training methods which will produce the needed control room behavior. The research indicates that operator response in emergencies is divided into two modes, conditioned behavior and knowledge based behavior. Methods which assure accurate conditioned behavior, and provide for the recovery of knowledge based behavior, are described in detail

  4. 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

  5. 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...

  6. Single toxin dose-response models revisited

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Design of radiation dose tumor response assays

    International Nuclear Information System (INIS)

    Suit, H.D.; Hwang, T.; Hsieh, C.; Thames, H.

    1985-01-01

    The efficient utilization of animals in a radiation dose response assay for tumor control requires a definition of the goal, e.g., TCD50 or slope. A series of computer modelled ''experiments'' have been performed for each of a number of allocations of dose levels (DL) and number of animals/DL. The authors stipulated that the assumed TCD50 was .85 of true value; assumed slope was correct. They stipulated a binominal distribution of observed tumor control results at each dose level. A pilot assay used 6 tumors at 7 DL (from TCD1-TCD97). The second assay used 30 tumors assigned to 2,3,5 or 9 DL and to selected tumor control probabilities (TCP derived from the pilot run. Results from 100 test runs were combined with the pilot run for each of the combination of DL and TCP values. Logit regression lines were fitted through these ''data'' and the 95% CL around the TCD50 and the TCD37 values and the variances of the slopes were computed. These experiments were repeated using the method suggested by Porter (1980). Results show that a different strategy is needed depending upon the goal, viz. TCD50 or TCD37 vs slope. The differences between the two approaches are discussed

  8. MONTEC, an interactive fortran program to simulate radiation dose and dose-rate responses of populations

    International Nuclear Information System (INIS)

    Perry, K.A.; Szekely, J.G.

    1983-09-01

    The computer program MONTEC was written to simulate the distribution of responses in a population whose members are exposed to multiple radiation doses at variable dose rates. These doses and dose rates are randomly selected from lognormal distributions. The individual radiation responses are calculated from three equations, which include dose and dose-rate terms. Other response-dose/rate relationships or distributions can be incorporated by the user as the need arises. The purpose of this documentation is to provide a complete operating manual for the program. This version is written in FORTRAN-10 for the DEC system PDP-10

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

    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

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

    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

  11. Biological responses to low dose rate gamma radiation

    International Nuclear Information System (INIS)

    Magae, Junji; Ogata, Hiromitsu

    2003-01-01

    Linear non-threshold (LNT) theory is a basic theory for radioprotection. While LNT dose not consider irradiation time or dose-rate, biological responses to radiation are complex processes dependent on irradiation time as well as total dose. Moreover, experimental and epidemiological studies that can evaluate LNT at low dose/low dose-rate are not sufficiently accumulated. Here we analyzed quantitative relationship among dose, dose-rate and irradiation time using chromosomal breakage and proliferation inhibition of human cells as indicators of biological responses. We also acquired quantitative data at low doses that can evaluate adaptability of LNT with statistically sufficient accuracy. Our results demonstrate that biological responses at low dose-rate are remarkably affected by exposure time, and they are dependent on dose-rate rather than total dose in long-term irradiation. We also found that change of biological responses at low dose was not linearly correlated to dose. These results suggest that it is necessary for us to create a new model which sufficiently includes dose-rate effect and correctly fits of actual experimental and epidemiological results to evaluate risk of radiation at low dose/low dose-rate. (author)

  12. Theoretic simulation for CMOS device on total dose radiation response

    International Nuclear Information System (INIS)

    He Baoping; Zhou Heqin; Guo Hongxia; He Chaohui; Zhou Hui; Luo Yinhong; Zhang Fengqi

    2006-01-01

    Total dose effect is simulated for C4007B, CC4007RH and CC4011 devices at different absorbed dose rate by using linear system theory. When irradiation response and dose are linear, total dose radiation and post-irradiation annealing at room temperature are determined for one random by choosing absorbed dose rate, and total dose effect at other absorbed dose rate can be predicted by using linear system theory. The simulating results agree with the experimental results at different absorbed dose rate. (authors)

  13. Dose-rate dependence of thermoluminescence response

    International Nuclear Information System (INIS)

    McKeever, S.W.S.; Chen, R.; Groom, P.J.; Durrani, S.A.

    1980-01-01

    The previously observed dose-rate effect of thermoluminescence in quartz at high dose-rates is given at theoretical formulation. Computer calculations simulating the experimental conditions yield similar results to the experimental ones. (orig.)

  14. 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

  15. Dose/dose-rate responses of shrimp larvae to UV-B radiation

    International Nuclear Information System (INIS)

    Damkaer, D.M.

    1981-01-01

    Previous work indicated dose-rate thresholds in the effects of UV-B on the near-surface larvae of three shrimp species. Additional observations suggest that the total dose response varies with dose-rate. Below 0.002 Wm -2 sub([DNA]) irradiance no significant effect is noted in activity, development, or survival. Beyond that dose-rate threshold, shrimp larvae are significantly affected if the total dose exceeds about 85 Jm -2 sub([DNA]). Predictions cannot be made without both the dose-rate and the dose. These dose/dose-rate thresholds are compared to four-year mean dose/dose-rate solar UV-B irradiances at the experimental site, measured at the surface and calculated for 1 m depth. The probability that the shrimp larvae would receive lethal irradiance is low for the first half of the season of surface occurrence, even with a 44% increase in damaging UV radiation. (orig.)

  16. Alterations in offspring behavior induced by chronic prenatal cocaine dosing.

    Science.gov (United States)

    Smith, R F; Mattran, K M; Kurkjian, M F; Kurtz, S L

    1989-01-01

    Sperm-positive female Long-Evans hooded rats were dosed subcutaneously with 10 mg/kg/day cocaine or an equal volume of vehicle (0.9% sterile saline) from gestation day 4 (GD4) through GD18. Offspring were assessed for development of negative geotaxis, righting reflex, spontaneous alternation, and open field activity, and for adult behaviors including DRL-20 acquisition, water maze, visual discrimination, barbiturate sleep time, shuttlebox avoidance, footshock sensitivity, and tail flick latency. Cocaine dosing produced no significant effects on dam weight gain, any measure of litter size and weight, or early postnatal behavioral tests, but there were significant drug effects on development of spontaneous alternation, development of open field activity, DRL-20 acquisition, water maze performance, tail flick, and footshock sensitivity. These data suggest that chronic administration of a modest dose of cocaine during gestation in the rat alters a number of behaviors in the offspring.

  17. 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

  18. Statistical behavior of high doses in medical radiodiagnosis

    International Nuclear Information System (INIS)

    Barboza, Adriana Elisa

    2014-01-01

    This work has as main purpose statistically estimating occupational exposure in medical diagnostic radiology in cases of high doses recorded in 2011 at national level. For statistical survey of this study, doses of 372 IOE's diagnostic radiology in different Brazilian states were evaluated. Data were extracted from the work of monograph (Research Methodology Of High Doses In Medical Radiodiagnostic) that contains the database's information Sector Management doses of IRD/CNEN-RJ, Brazil. The identification of these states allows the Sanitary Surveillance (VISA) responsible, becomes aware of events and work with programs to reduce these events. (author)

  19. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    International Nuclear Information System (INIS)

    Levy, R.P.

    1991-01-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examining the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute γ-radiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. It was concluded that oligodendrocytes in irradiated cultures had significantly lower functional capacity than did unirradiated controls. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. At DIC 14, the group irradiated in a single fraction had significantly lower oligodendrocyte counts than any group given split doses; all irradiated cultures had marked depression of MBP synthesis, but to significant differences referable to time interval between doses. At DIC 21, cultures irradiated at intervals of 0 h to 2 h had similar oligodendrocyte counts to one another, but these counts were significantly lower than in cultures irradiated at intervals of 4 h to 6 h; MBP levels remained depressed at DIC 21 for all irradiated cultures. The oligodendrocyte response to dose rate (0.03 to 1.97 Gy/min) was evaluated at DIC 14 and DIC 21. Exposure at 0.03 Gy/min suppressed oligodendrocyte counts at DIC 21 less than did higher dose rates in 5-Gy irradiated cultures

  20. Statistical behavior of high doses in medical radiodiagnosis; Comportamento estatistico das altas doses em radiodiagnostico medico

    Energy Technology Data Exchange (ETDEWEB)

    Barboza, Adriana Elisa, E-mail: adrianaebarboza@gmail.com, E-mail: elisa@bolsista.ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    This work has as main purpose statistically estimating occupational exposure in medical diagnostic radiology in cases of high doses recorded in 2011 at national level. For statistical survey of this study, doses of 372 IOE's diagnostic radiology in different Brazilian states were evaluated. Data were extracted from the work of monograph (Research Methodology Of High Doses In Medical Radiodiagnostic) that contains the database's information Sector Management doses of IRD/CNEN-RJ, Brazil. The identification of these states allows the Sanitary Surveillance (VISA) responsible, becomes aware of events and work with programs to reduce these events. (author)

  1. Dose-Response Calculator for ArcGIS

    Science.gov (United States)

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

    2011-01-01

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

  2. Dose-dependent pheromone responses of mountain pine beetle in stands of lodgepole pine

    Science.gov (United States)

    Daniel R. Miller; B. Staffan Lindgren; John H. Borden

    2005-01-01

    We conducted seven behavioral choice tests with Lindgren multiple-funnel traps in stands of mature lodgepole pine in British Columbia, from 1988 to 1994, to determine the dosedependent responses of the mountain pine beetle, Dendroctonus ponderosae Hopkins, to its pheromones. Amultifunctional dose-dependent response was exhibited by D. ...

  3. Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within- subjects randomized dose-response fMRI trial

    OpenAIRE

    Quintana, Daniel; Westlye, Lars Tjelta; Alnæs, Dag; Rustan, Øyvind; Kaufmann, Tobias; Smerud, Knut Terje; Mahmoud, Ramy; Djupesland, Per G.; Andreassen, Ole Andreas

    2016-01-01

    It is unclear if and how exogenous oxytocin (OT) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response. To better understand the delivery routes of intranasal OT administration to the brain and the dose-response, we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging (fMRI) in four treatment conditions, including two different doses of intranasal OT using a novel Breath Powered device, intravenous (IV...

  4. 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)

  5. 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

  6. 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

  7. 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

  8. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    International Nuclear Information System (INIS)

    Levy, R.P.

    1991-12-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute γ-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain

  9. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    Energy Technology Data Exchange (ETDEWEB)

    Levy, Richard P. [Univ. of California, Berkeley, CA (United States)

    1991-12-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute γ-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.

  10. Oligodendroglial response to ionizing radiation: Dose and dose-rate response

    Energy Technology Data Exchange (ETDEWEB)

    Levy, R.P.

    1991-12-01

    An in vitro system using neuroglia from neonatal rat brain was developed to examine the morphologic, immunocytochemical and biochemical response of oligodendroglia to ionizing radiation. Following acute {gamma}-irradiation at day-in-culture (DIC) 8, oligodendrocyte counts at DIC 14 were 55% to 65% of control values after 2 Gy, and 29% to 36% after 5 Gy. Counts increased to near-normal levels at DIC 21 in the 2 Gy group and to 75% of normal in the 5 Gy group. Myelin basic protein levels (MBP) at DIC 14 were 60% of control values after 2 Gy, and 40% after 5 Gy. At DIC 21, MBP after 2 Gy was 45% greater than that observed at DIC 14, but MBP, as a fraction of age-matched control values, dropped from 60% to 50%. Following 5 Gy, absolute MBP changed little between DIC 14 and DIC 21, but decreased from 40% to 25% of control cultures. The response to split-dose irradiation indicated that nearly all sublethal damage in the oligodendrocyte population (and its precursors) was repaired within 3 h to 4 h. A new compartmental cell model for radiation response in vitro of the oligodendrocyte population is proposed and examined in relation to the potential reaction to radiation injury in the brain.

  11. 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

  12. 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)

  13. Dose/dose-rate responses of shrimp larvae to UV-B radiation

    Energy Technology Data Exchange (ETDEWEB)

    Damkaer, D.M.; Dey, D.B.; Heron, G.A.

    1981-01-01

    Previous work indicated dose-rate thresholds in the effects of UV-B on the near-surface larvae of three shrimp species. Additional observations suggest that the total dose response varies with dose-rate. Below 0.002 Wm/sup -2/sub((DNA)) irradiance no significant effect is noted in activity, development, or survival. Beyond that dose-rate threshold, shrimp larvae are significantly affected if the total dose exceeds about 85 Jm/sup -2/sub((DNA)). Predictions cannot be made without both the dose-rate and the dose. These dose/dose-rate thresholds are compared to four-year mean dose/dose-rate solar UV-B irradiances at the experimental site, measured at the surface and calculated for 1 m depth. The probability that the shrimp larvae would receive lethal irradiance is low for the first half of the season of surface occurrence, even with a 44% increase in damaging UV radiation.

  14. Assembled cross-species perchlorate dose-response data

    Data.gov (United States)

    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...

  15. 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.)

  16. The influence of dose fractionation and dose rate on normal tissue responses

    International Nuclear Information System (INIS)

    Barendsen, G.W.

    1982-01-01

    An analysis of responses of a variety of normal tissues in animals to fractionated irradiations has been made with the aim of developing a formalism for the prediction of tolerance doses as a function of the dose per fraction and the overall treatment time. An important feature of the formalism is that it is directly based on radiological insights and therefore provides a logical concept to account for the diversity of tissue responses. (Auth.)

  17. Updating Dosimetry for Emergency Response Dose Projections.

    Science.gov (United States)

    DeCair, Sara

    2016-02-01

    In 2013, the U.S. Environmental Protection Agency (EPA) proposed an update to the 1992 Protective Action Guides (PAG) Manual. The PAG Manual provides guidance to state and local officials planning for radiological emergencies. EPA requested public comment on the proposed revisions, while making them available for interim use by officials faced with an emergency situation. Developed with interagency partners, EPA's proposal incorporates newer dosimetric methods, identifies tools and guidelines developed since the current document was issued, and extends the scope of the PAGs to all significant radiological incidents, including radiological dispersal devices or improvised nuclear devices. In order to best serve the emergency management community, scientific policy direction had to be set on how to use International Commission on Radiological Protection Publication 60 age groups in dose assessment when implementing emergency guidelines. Certain guidelines that lend themselves to different PAGs for different subpopulations are the PAGs for potassium iodide (KI), food, and water. These guidelines provide age-specific recommendations because of the radiosensitivity of the thyroid and young children with respect to ingestion and inhalation doses in particular. Taking protective actions like using KI, avoiding certain foods or using alternative sources of drinking water can be relatively simple to implement by the parents of young children. Clear public messages can convey which age groups should take which action, unlike how an evacuation or relocation order should apply to entire households or neighborhoods. New in the PAG Manual is planning guidance for the late phase of an incident, after the situation is stabilized and efforts turn toward recovery. Because the late phase can take years to complete, decision makers are faced with managing public exposures in areas not fully remediated. The proposal includes quick-reference operational guidelines to inform re-entry to

  18. Place Attachment and Environmentally Responsible Behavior.

    Science.gov (United States)

    Vaske, Jerry J.; Kobrin, Katherine C.

    2001-01-01

    Illustrates how an attachment to a local natural resource can influence environmentally responsible behavior (ERB) in an individual's everyday life. Reports four general and three specific behavioral indicators reflecting a single environmentally responsible latent construct. Investigates the place dependence and place identity's role on ERB using…

  19. RADIOIODINE TREATMENT OF GRAVES’ DISEASE – DOSE/RESPONSE ANALYSIS

    Directory of Open Access Journals (Sweden)

    Jitka Čepková

    2014-01-01

    Full Text Available The clinical outcome of 153 Graves’ disease patients treated with a wide dose range of radioactive iodine-131 (RAI was analyzed retrospectively. Six to nine months after the first dose of RAI 60 patients (39% were hypothyroid (or rather thyroxine-substituted and 26 (17% were euthyroid, while 67 patients (44% did not respond properly: in 32 (21% their antithyroid drug (ATD dose could be reduced but not withdrawn (partial response and 35 (23% remained hyperthyroid or the same dose of ATD was necessary (no response. The outcome did not correspond significantly to the administered activity of RAI (medians 259, 259, 222, and 259 MBq for hypothyroid, euthyroid, partial, and no response subgroups, respectively, or the activity retained in the gland at 24 h (medians 127, 105, 143, and 152 MBq. The effect was, however, clearly, and in a stepwise pattern, dependent on initial thyroid volume (17, 26, 33 and 35 ml, P  6 MBq/g, cure rate 80% and lower (≤ 6 MBq/g, cure rate 46% doses gave highly significant difference (P < 0.001. With our dosing range we found a dose-dependent clinical outcome that suggests an optimum delivered dose near 6.5 MBq/g, resulting in successful treatment of ca 80% patients.

  20. 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

  1. 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...

  2. 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...

  3. Effects of dose fractionation on the response of alanine dosimetry

    International Nuclear Information System (INIS)

    Lundahl, Brad; Logar, John; Desrosiers, Marc; Puhl, James

    2014-01-01

    Alanine dosimetry is well established as a transfer standard and is becoming more prevalently used in routine dosimetry systems for radiation processing. Many routine measurement applications in radiation processing involve absorbed dose measurements resulting from fractioned exposures to ionizing radiation. Fractioning of absorbed dose is identified as an influence quantity (ISO/ASTM, 2013). This paper reports on study results of absorbed dose fractioning characteristics of alanine for gamma and high energy electron beam radiation sources. The results of this study indicate a radiation response difference due to absorbed dose fractioning in response can be observed after four fractionations for high-energy electron beams and no difference up to seven fractions for gamma rays using an ANOVA evaluation method. - Highlights: • Fractioning effects signaled in electron beam using an ANOVA at 6 equal increments. • Fractioning effects not signaled in gamma using an ANOVA up to 7 equal increments. • Insensitivity of alanine to dose fractioning indicates nominal impact on calibration

  4. Thymocyte apoptosis in response to low-dose radiation

    International Nuclear Information System (INIS)

    Shu-Zheng, Liu; Ying-Chun, Zhang; Ying, Mu; Xu, Su; Jian-Xiang, Liu

    1996-01-01

    Thymocyte apoptosis was assessed by counting apoptotic bodies with flow cytometry (FCM) and measuring DNA fragmentation with fluorescence spectrophotometry (FSP). J-shaped dose-response curves were obtained after both whole-body irradiation (WBI) of mice and in vitro irradiation of EL4 cells with doses ranging from 0.025 to 4 Gy X-rays. There was a significant reduction of apoptosis rate to below control level with doses within 0.2 Gy, and a dose-dependent increase in apoptosis with doses above 0.5 Gy. When thymocytes were cultured 24 h after WBI with 75 mGy X-rays in complete RPMI 1640 medium, a reduction in apoptosis was observed in the course of incubation for 72 h, and the presence of Con A in the medium accentuated this reduction in a dose- and time-dependent manner. The implications of these observations and the possible molecular mechanisms for future studies are proposed

  5. Responsible leader behavior in health sectors.

    Science.gov (United States)

    Longest, Beaufort

    2017-02-06

    Purpose The purpose of this paper is to expand attention to responsible leader behavior in the world's health sectors by explaining how this concept applies to health sectors, considering why health sector leaders should behave responsibly, reviewing how they can do so, and asserting potential impact through an applied example. Design/methodology/approach This paper is a viewpoint, reflecting conceptualizations rooted in leadership literature which are then specifically applied to health sectors. A definition of responsible leader behavior is affirmed and applied specifically in health sectors. Conceptualizations and viewpoints about practice of responsible leader behavior in health sectors and potential consequences are then discussed and asserted. Findings Leadership failures and debacles found in health, but more so in other sectors, have led leadership researchers to offer insights, many of them empirical, into the challenges of leadership especially by more clearly delineating responsible leader behavior. Practical implications Much of what has been learned in the research about responsible leader behavior offers pathways for health sector leaders to more fully practice responsible leadership. Social implications This paper asserts and provides a supporting example that greater levels of responsible leader behavior in health sectors hold potentially important societal benefits. Originality/value This paper is the first to apply emerging conceptualizations and early empirical findings about responsible leader behavior specifically to leaders in health sectors.

  6. 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

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

    Science.gov (United States)

    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.

  8. 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...

  9. Dose-response meta-analysis of differences in means

    Directory of Open Access Journals (Sweden)

    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

  10. A Generalized QMRA Beta-Poisson Dose-Response Model.

    Science.gov (United States)

    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.

  11. 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

  12. Determination of tolerance dose uncertainties and optimal design of dose response experiments with small animal numbers

    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

  13. 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)

  14. Response of cellulose nitrate track detectors to electron doses

    CERN Document Server

    Segovia, N; Moreno, A; Vazquez-Polo, G; Santamaría, T; Aranda, P; Hernández, A

    1999-01-01

    In order to study alternative dose determination methods, the bulk etching velocity and the latent track annealing of LR 115 track detectors was studied during electron irradiation runs from a Pelletron accelerator. For this purpose alpha irradiated and blank detectors were exposed to increasing electron doses from 10.5 to 317.5 kGy. After the irradiation with electrons the detectors were etched under routine conditions, except for the etching time, that was varied for each electron dose in order to reach a fixed residual thickness. The variation of the bulk etching velocity as a function of each one of the electron doses supplied, was interpolated in order to obtain dosimetric response curves. The observed annealing effect on the latent tracks is discussed as a function of the total electron doses supplied and the temperature.

  15. 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

  16. 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

  17. Methodology for Estimating Ingestion Dose for Emergency Response at SRS

    CERN Document Server

    Simpkins, A A

    2002-01-01

    At the Savannah River Site (SRS), emergency response models estimate dose for inhalation and ground shine pathways. A methodology has been developed to incorporate ingestion doses into the emergency response models. The methodology follows a two-phase approach. The first phase estimates site-specific derived response levels (DRLs) which can be compared with predicted ground-level concentrations to determine if intervention is needed to protect the public. This phase uses accepted methods with little deviation from recommended guidance. The second phase uses site-specific data to estimate a 'best estimate' dose to offsite individuals from ingestion of foodstuffs. While this method deviates from recommended guidance, it is technically defensibly and more realistic. As guidance is updated, these methods also will need to be updated.

  18. 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

  19. 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

  20. Dose-response relationship in the treatment of gastrointestinal disorders.

    Science.gov (United States)

    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.

  1. 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

  2. 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)

  3. 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.

  4. Mathematical model for evaluation of dose-rate effect on biological responses to low dose γ-radiation

    International Nuclear Information System (INIS)

    Ogata, H.; Kawakami, Y.; Magae, J.

    2003-01-01

    Full text: To evaluate quantitative dose-response relationship on the biological response to radiation, it is necessary to consider a model including cumulative dose, dose-rate and irradiation time. In this study, we measured micronucleus formation and [ 3 H] thymidine uptake in human cells as indices of biological response to gamma radiation, and analyzed mathematically and statistically the data for quantitative evaluation of radiation risk at low dose/low dose-rate. Effective dose (ED x ) was mathematically estimated by fitting a general function of logistic model to the dose-response relationship. Assuming that biological response depends on not only cumulative dose but also dose-rate and irradiation time, a multiple logistic function was applied to express the relationship of the three variables. Moreover, to estimate the effect of radiation at very low dose, we proposed a modified exponential model. From the results of fitting curves to the inhibition of [ 3 H] thymidine uptake and micronucleus formation, it was obvious that ED 50 in proportion of inhibition of [ 3 H] thymidine uptake increased with longer irradiation time. As for the micronuclei, ED 30 also increased with longer irradiation times. These results suggest that the biological response depends on not only total dose but also irradiation time. The estimated response surface using the three variables showed that the biological response declined sharply when the dose-rate was less than 0.01 Gy/h. These results suggest that the response does not depend on total cumulative dose at very low dose-rates. Further, to investigate the effect of dose-rate within a wider range, we analyzed the relationship between ED x and dose-rate. Fitted curves indicated that ED x increased sharply when dose-rate was less than 10 -2 Gy/h. The increase of ED x signifies the decline of the response or the risk and suggests that the risk approaches to 0 at infinitely low dose-rate

  5. Harderian Gland Tumorigenesis: Low-Dose and LET Response

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Polly Y. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cucinotta, Francis A. [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Bjornstad, Kathleen A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Bakke, James [SRI International, Menlo Park, CA (United States). Biosciences Div.; Rosen, Chris J. [SRI International, Menlo Park, CA (United States). Biosciences Div.; Du, Nicholas [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Fairchild, David G. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.; Cacao, Eliedonna [Univ. of Nevada, Las Vegas, NV (United States). Dept. of Health Physics and Diagnostic Sciences; Blakely, Eleanor A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Div.

    2016-04-19

    Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis. The historical data from the studies of Fry et al. and Alpen et al. for Harderian gland (HG) tumors in the female CB6F1 strain of mouse represent the most complete set of experimental observations, including dose dependence, available on a specific radiation-induced tumor in an experimental animal using heavy ion beams that are found in the cosmic radiation spectrum. However, these data lack complete information on low-dose responses below 0.1 Gy, and for chronic low-dose-rate exposures, and there are gaps in the LET region between 25 and 190 keV/μm. In this study, we used the historical HG tumorigenesis data as reference, and obtained HG tumor data for 260 MeV/u silicon (LET ~70 keV/μm) and 1,000 MeV/u titanium (LET ~100 keV/μm) to fill existing gaps of data in this LET range to improve our understanding of the dose-response curve at low doses, to test for deviations from linearity and to provide RBE estimates. Animals were also exposed to five daily fractions of 0.026 or 0.052 Gy of 1,000 MeV/u titanium ions to simulate chronic exposure, and HG tumorigenesis from this fractionated study were compared to the

  6. Optimal dose-response relationships in voice therapy.

    Science.gov (United States)

    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".

  7. Response of human fibroblasts to low dose rate gamma irradiation

    International Nuclear Information System (INIS)

    Dritschilo, A.; Brennan, T.; Weichselbaum, R.R.; Mossman, K.L.

    1984-01-01

    Cells from 11 human strains, including fibroblasts from patients with the genetic diseases of ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Fanconi's anemia (FA), were exposed to γ radiation at high (1.6-2.2 Gy/min) and at low (0.03-0.07 Gy/min) dose rates. Survival curves reveal an increase inthe terminal slope (D 0 ) when cells are irradiated at low dose rates compared to high dose rates. This was true for all cell lines tested, although the AT, FA, and XP cells are reported or postulated to have radiation repair deficiencies. From the response of these cells, it is apparent that radiation sensitivities differ; however, at low dose rate, all tested human cells are able to repair injury

  8. Prenatal exposure to a low fipronil dose disturbs maternal behavior and reflex development in rats.

    Science.gov (United States)

    Udo, Mariana S B; Sandini, Thaísa M; Reis, Thiago M; Bernardi, Maria Martha; Spinosa, Helenice S

    2014-01-01

    Fipronil (FPN) is a phenylpyrazole insecticide used in veterinary services and agriculture, and it is of considerable concern to public health. It inhibits the chloride channels associated with gamma-amino butyric acid (GABA) receptors in mammals and also inhibits the chloride channels associated with GABA and glutamate (Glu) receptors in insects. In this study, a commercial product containing fipronil was orally administered to pregnant Wistar rats at dose levels of 0.1, 1.0, or 10.0mg/kg/day from the sixth to twentieth day of gestation (n=10 pregnant rats/group). Its toxicity was evaluated based on maternal toxicity, reproductive quality, maternal behavior, and offspring physical as well as reflex development. All parameters observed in the observed offspring were assigned to one ink-marked couple in each litter (n=20 animals/group - 10 males and 10 females). The offspring couple represented the litter. Slight maternal toxicity presented during the second week of gestation for each fipronil dose and during the third gestational week at the highest dose due to lower chow intake. However, no effects were observed for gestational weight gain or gestation time, and the reproductive quality was not impaired, which suggests no adverse maternal effects from the doses during pregnancy. Moreover, the lowest fipronil dose compromised the active and reflexive maternal responses, but the highest dose induced a stereotyped active response without interfering in the reflexive reaction. For offspring development, no differences in physical growth parameters were observed between the groups. However, considering reflex development, our results showed that negative geotaxis reflex development was delayed in the offspring at the lowest fipronil dose, and palmar grasp was lost earlier at the lowest and intermediate fipronil doses. These results suggest that the alterations observed herein may be due to either the GABAergic system or endocrine disruption, considering that fipronil

  9. The alanine detector in BNCT dosimetry: dose response in thermal and epithermal neutron fields.

    Science.gov (United States)

    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

  10. Dose-response relation between physical activity and sick leave

    NARCIS (Netherlands)

    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

  11. Global DNA methylation responses to low dose radiation exposure

    International Nuclear Information System (INIS)

    Newman, M.R.; Ormsby, R.J.; Blyth, B.J.; Sykes, P.J.; Bezak, E.

    2011-01-01

    Full text: High radiation doses cause breaks in the DNA which are considered the critical lesions in initiation of radiation-induced cancer. However, at very low radiation doses relevant for the general public, the induction of such breaks will be rare, and other changes to the DNA such as DNA methylation which affects gene expression may playa role in radiation responses. We are studying global DNA methylation after low dose radiation exposure to determine if low dose radiation has short- and/or long-term effects on chromatin structure. We developed a sensitive high resolution melt assay to measure the levels of DNA methylation across the mouse genome by analysing a stretch of DNA sequence within Long Interspersed Nuclear Elements-I (LINE I) that comprise a very large proportion of the mouse and human genomes. Our initial results suggest no significant short-term or longterm) changes in global NA methylation after low dose whole-body X-radiation of 10 J1Gyor 10 mGy, with a significant transient increase in NA methylation observed I day after a high dose of I Gy. If the low radiation doses tested are inducing changes in bal DNA methylation, these would appear to be smaller than the variation observed between the sexes and following the general stress of the sham-irradiation procedure itself. This research was funded by the Low Dose Radiation Research Program, Biological and Environmental Research, US DOE, Grant DE-FG02-05ER64104 and MN is the recipient of the FMCF/BHP Dose Radiation Research Scholarship.

  12. 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

  13. 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

  14. TL response of citrine samples for high-dose dosimetry

    International Nuclear Information System (INIS)

    Teixeira, Maria Ines; Caldas, Linda V.E.

    2011-01-01

    The possibility of using samples of Brazilian stones as quartz, amethyst, topaz, etc. for high-dose dosimetry has been studied in recent years at IPEN, using the thermoluminescence technique (TL). In this work, the TL properties of citrine samples were studied. They were exposed to different doses of gamma radiation ( 60 Co). The natural citrine stone was extracted from a mine in Minas Gerais state, Brazil; it is a tectosilicate ranked as one of three-dimensional structure, showing clear yellow to golden brown color. The natural citrine stone is classified as quartz (SiO 2 ), and it has a lower symmetry and more compact reticulum. The citrine stone samples were powdered, and the selected grains were mixed with Teflon in the proportion 2 (Teflon):1 (Citrine). The mixture was pressed and sintered for production of Citrine -Teflon pellets of 50 mg. The TL emission curve showed two peaks at 160 deg C and 220 deg C. To remove the TL peak (160 deg C) of the sintered citrine pellet glow curves, different thermal treatments were tested during several time intervals. The TL dose-response curve between 50 Gy and 100 kGy, the reproducibility of TL response and the lower detection dose were obtained. The preliminary results show that citrine may be useful for high-dose dosimetry. (author)

  15. Diabetogenic action of streptozotocin: relationship of dose to metabolic response

    Science.gov (United States)

    Junod, Alain; Lambert, André E.; Stauffacher, Werner; Renold, Albert E.

    1969-01-01

    The relationship between the dose of intravenously administered streptozotocin (a N-nitroso derivative of glucosamine) and the diabetogenic response has been explored by use of the following indices of diabetogenic action: serum glucose, urine volume, and glycosuria, ketonuria, serum immunoreactive insulin (IRI), and pancreatic IRI content. Diabetogenic activity could be demonstrated between the doses of 25 and 100 mg/kg, all indices used showing some degree of correlation with the dose administered. Ketonuria was only seen with the largest dose, 100 mg/kg. The most striking and precise correlation was that between the dose and the pancreatic IRI content 24 hr after administration of the drug, and it is suggested that this represents a convenient test system either for both related and unrelated beta cytotoxic compounds or for screening for modifying agents or antidiabetic substances of a novel type. Ability to produce graded depletion of pancreatic IRI storage capacity led to an analysis of the relationship between pancreatic IRI content and deranged carbohydrate metabolism. Abnormal glucose tolerance and insulin response were seen when pancreatic IRI was depleted by about one-third, while fasting hyperglycemia and gross glycosuria occurred when the depletion had reached two-thirds and three-quarters, respectively. The mild yet persistent anomaly produced by the lowest effective streptozotocin dose, 25 mg/kg, exhibits characteristics resembling the state of chemical diabetes in humans and might thus warrant further study as a possible model. Finally, the loss of the diabetogenic action of streptozotocin by pretreatment with nicotinamide was confirmed and was shown to be a function of the relative doses of nicotinamide and streptozotocin and of the interval between injections. PMID:4241908

  16. 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

  17. Cellular response to low Gamma-ray doses

    Energy Technology Data Exchange (ETDEWEB)

    Manzanares A, E; Vega C, H R; Leon, L.C. de . [Unidades Academicas de Estudios Nucleares, Universidad Autonoma de Zacatecas, A.P. 336, 98000 Zacatecas (Mexico); Rebolledo D, O; Radillo J, F [Facultad de Ciencias Biologicas y Agropecuarias de la Universidad de Colima, Colima (Mexico)

    2002-07-01

    Lymphocytes, obtained from healthy donors, were exposed to a low strength gamma-ray field to determine heat shock protein expression in function of radiation dose. Protein identification was carried out using mAb raised against Hsp70 and Hsc70.Hsp70 protein was detected after lymphocyte irradiation. In all cases, an increasing trend of relative amounts of Hsp70 in function to irradiation time was observed. After 1.25 c Gy gamma-ray dose, lymphocytes expressed Hsp70 protein, indicating a threshold response to gamma rays. (Author)

  18. Cellular response to low Gamma-ray doses

    International Nuclear Information System (INIS)

    Manzanares A, E.; Vega C, H.R.; Leon, L.C. de; Rebolledo D, O.; Radillo J, F.

    2002-01-01

    Lymphocytes, obtained from healthy donors, were exposed to a low strength gamma-ray field to determine heat shock protein expression in function of radiation dose. Protein identification was carried out using mAb raised against Hsp70 and Hsc70.Hsp70 protein was detected after lymphocyte irradiation. In all cases, an increasing trend of relative amounts of Hsp70 in function to irradiation time was observed. After 1.25 c Gy gamma-ray dose, lymphocytes expressed Hsp70 protein, indicating a threshold response to gamma rays. (Author)

  19. Dose response of rat retinal microvessels to proton dose schedules used clinically: a pilot study

    International Nuclear Information System (INIS)

    Archambeau, John O.; Mao, Xiao W.; McMillan, Paul J.; Gouloumet, Vanessa L.; Oeinck, Steven C.; Grove, Roger; Yonemoto, Leslie T.; Slater, Jerry D.; Slater, James M.

    2000-01-01

    Purpose: This preclinical rat pilot study quantifies retinal microvessel, endothelial, and pericyte population changes produced by proton irradiation Methods and Materials: The left eyes of rats were irradiated with single doses of 8, 14, 20, and 28 Gy protons; right eyes, with two fractions. Animals were euthanized, and eyes were removed; elastase digests were prepared, and cell populations were counted in sample fields. Results were compared with unirradiated controls. Results: Progressive time- and dose-dependent endothelial cell loss occurred following all schedules. Cell loss was significantly different from control values (p 0 phase of the mitotic cycle. 28 Gy produced photoreceptor cell loss. Conclusion: The retinal digest is an elegant bioassay to quantify the microvessel population response. Single- and split-dose schedules appear to yield similar outcomes, in terms of endothelial cell density

  20. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby, R., Ph.D.

    2003-06-27

    OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on

  1. Speech Versus Action in Environmentally Responsible Behavior

    Directory of Open Access Journals (Sweden)

    Amanna Ferreira Peixoto

    2013-12-01

    Full Text Available The need of rethinking the consumption culture in contemporary society brings up the interest in researching how consumption habits are related to environmental preservation. Even though sustainable practices are valuable, the comparison amid how people act as consumers and their assumed ethical stance raises questions. Consumers advocate a concern for environmental issues but research shows that their consumption habits are still old fashioned. This study target the convergence and divergence between environmentally responsible speech and consumption behavior under the perspective of theories of action (Argyris, Putnam & Smith, 1985. Research utilized in-depth interviews and self-reports, using a logbook, to collect information about environmentally responsible discourse and consumption behavior of 11 participants. Data collection and analysis explore dimensions of environmentally responsible behavior (Stern, 1999, 2000: personal domain; behavioral domain; contextual domain; personal capabilities; and habits & routines. Results suggest that environmentally responsible behavior is not always consistent with the discourse due to influence of motivational issues (impotence, lack of interest, sacrifice, and convenience and contextual issues (financial situation, lack of public policies, time constraints, and culture.

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

    Directory of Open Access Journals (Sweden)

    Gruber Günther

    2011-06-01

    Full Text Available Abstract Purpose Cancer induction after radiation therapy is known as a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the patient to be treated including breast cancer. Materials and methods In this work a dose-response relationship for breast cancer is derived based on (i the analysis of breast cancer induction after Hodgkin's disease, (ii a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii the reconstruction of treatment plans for Hodgkin's patients treated with radiotherapy, (iv the breast cancer induction of the A-bomb survivor data. Results The fitted model parameters for an 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.

  3. Kinetics of the early adaptive response and adaptation threshold dose

    International Nuclear Information System (INIS)

    Mendiola C, M.T.; Morales R, P.

    2003-01-01

    The expression kinetics of the adaptive response (RA) in mouse leukocytes in vivo and the minimum dose of gamma radiation that induces it was determined. The mice were exposed 0.005 or 0.02 Gy of 137 Cs like adaptation and 1h later to the challenge dose (1.0 Gy), another group was only exposed at 1.0 Gy and the damage is evaluated in the DNA with the rehearsal it makes. The treatment with 0. 005 Gy didn't induce RA and 0. 02 Gy causes a similar effect to the one obtained with 0.01 Gy. The RA was show from an interval of 0.5 h being obtained the maximum expression with 5.0 h. The threshold dose to induce the RA is 0.01 Gy and in 5.0 h the biggest quantity in molecules is presented presumably that are related with the protection of the DNA. (Author)

  4. 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)

  5. 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.)

  6. Analysis of thermal-dose response to heat

    International Nuclear Information System (INIS)

    Storm, F.; Roe, D.; Drury, B.

    1987-01-01

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

  7. 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

  8. Bayesian Dose-Response Modeling in Sparse Data

    Science.gov (United States)

    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

  9. Cytogenetic dose-response and adaptive response in cells of ungulate species exposed to ionizing radiation

    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

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

    Science.gov (United States)

    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

  11. 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

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

    International Nuclear Information System (INIS)

    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

  13. Response of pig skin to fractionated radiation doses

    International Nuclear Information System (INIS)

    Wiernik, G.; Hopewell, J.W.; Patterson, T.J.S.; Young, C.M.A.; Foster, J.L.

    1977-01-01

    The individual components of a fractionated course of irradiation treatment have been considered separately. Methods of accurate measurement of individual parameters has brought to light different interpretations of the observations. Reasons are given for the necessity of having a radiobiological model which has a direct relevance to the clinical situation. Results are reported for fractionated regimes of irradiation in which the dose has been varied above and below normal tissue tolerance which has been equated with clinical skin necrosis. The components of the acute skin reaction, erythema, pigmentation and desquamation have been analysed separately and their contribution as a method of measurement assessed. Initially, the range of numerical scores attributed to erythema did not reach the scores attributed to necrosis but we now believe that radiation damage expressed as erythema can move directly into necrosis without passing through desquamation. Desquamation, on the other hand, only became a useful parameter at higher dose levels; it has also been shown to be a component associated with skin breakdown. Pigmentation showed no dose response at the dose levels employed in our experiments and it is our belief that this is due to this system being fully saturated under these circumstances. Measurement of the late radiation reaction in the skin has been considered in detail and our results have been expressed by comparing the relative lengths of irradiated and control fields in the same pig. From these findings iso-effect graphs have been constructed and time and fractionation factors have been derived. (author)

  14. Low dose effects and non-monotonic dose responses for endocrine active chemicals: Science to practice workshop: Workshop summary

    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...

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

    International Nuclear Information System (INIS)

    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

  16. Is There a Dose-Response Relationship for Heart Disease With Low-Dose Radiation Therapy?

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Effect of heterogeneity of human population in cell radiosensitivity on the extrapolation of dose-response relationships to low doses

    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

  18. Studies on adaptive response of lymphocyte transformation induced by low-dose irradiation

    International Nuclear Information System (INIS)

    Du Zeji; Su Liaoyuan; Tian Hailin; Zou Huawei

    1995-10-01

    Human peripheral blood lymphocytes stimulated by mitogen in vitro for 24 h were exposed to low-dose γ-ray irradiation (0.5∼4.0 cGy, adaptive dose). They showed an adaptive response to the inhibition of 3 H-TdR incorporation by subsequent higher acute doses of γ-ray (challenge dose). At the interval of 24 h between adaptive dose and challenge dose, the strongest adaptive response induced by low-dose irradiation was found. It is also found that the response induced by 1.0 cGy of adaptive dose was more obvious than that by other doses and that 3.0 Gy of challenge dose produced the strongest adaptive response. As the challenge doses increased, the adaptive response reduced. (2 figs., 2 tabs.)

  19. 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

  20. Establishment and verification of dose-response curve of chromosomal aberrations after exposure to very high dose γ-ray

    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)

  1. Response of radiation monitors for ambient dose equivalent, H*(10)

    International Nuclear Information System (INIS)

    Grecco, Claudio Henrique dos Santos

    2001-01-01

    Radiation monitors are used all over the world to evaluate if places with presence of ionising radiation present safe conditions for people. Radiation monitors should be tested according to international or national standards in order to be qualified for use. This work describes a methodology and procedures to evaluate the energy and angular responses of any radiation monitor for ambient dose equivalent, H*(10), according to the recommendations of ISO and IEC standards. The methodology and the procedures were applied to the Monitor Inteligente de Radiacao MIR 7026, developed by the Instituto em Engenharia Nuclear (IEN), to evaluate and to adjust its response for H*(10), characterizing it as an ambient dose equivalent meter. The tests were performed at the Laboratorio Nacional de Metrologia das Radiacoes Ionizantes (LNMRI), at Instituto de Radioprotecao e Dosimetria (IRD), and results showed that the Monitor Inteligente de Radiacao MIR 7026 can be used as an EI*(10) meter, in accordance to the IEC 60846 standard requirements. The overall estimated uncertainty for the determination of the MIR 7026 response, in all radiation qualities used in this work, was 4,5 % to a 95 % confidence limit. (author)

  2. Corporate Responsible Behavior in Multinational Enterprise

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    2017-01-01

    Purpose: This study aims to analyze how leadership influenced corporate responsible behavior in a complex multinational organization with ethical principles imposed by concrete actions on regulatory, environmental and international labor issues. Increasing functional specialization, multinational...... diversification and global expansion also diluted those values. Originality/value: Corporate responsible behavior is a significant challenge in large organizations with many and diverse multinational stakeholders. Ethical conduct derives from executive morality, but the role of leaders as instigators...... diversity and business acquisitions challenged the core values and called for more formal enforcement. Core values executed through investment in positive economic externalities enhanced the reputation and facilitated sustainable collaborative solutions. Design/methodology/approach: This single-case study...

  3. Safe and Responsible Online Behaviors for Children

    Directory of Open Access Journals (Sweden)

    Shu-Hsien L. Chen

    2003-06-01

    Full Text Available The Internet makes new learning opportunities possible for children by offering vast amount of resources and powerful communication means Oftentimes, the Internet is the first resource children choose for information seeking. Other than schoolwork related resources,the Internet. contains unlimited interesting and entertaining information for children. As going online becomes a favorite pastime for millions of children,teachers and parents need to caution children about the negative side of the Internet. They need to teach children online safety and responsibility, and further,monitor their online behaviors. The article, first, discusses the possible threats to childrens online safety, including potential sex offenders, pornographic materials,and unethical marketing tactics aimed at children. Then, it addresses unethical and irresponsible behaviors, such as plagiarism, spamming, and hacking, which are committed or may be committed by children. Finally, the article explains how teachers and parents can help children become responsible and ethical Internet users.

  4. A motivational model for environmentally responsible behavior.

    Science.gov (United States)

    Tabernero, Carmen; Hernández, Bernardo

    2012-07-01

    This paper presents a study examining whether self-efficacy and intrinsic motivation are related to environmentally responsible behavior (ERB). The study analysed past environmental behavior, self-regulatory mechanisms (self-efficacy, satisfaction, goals), and intrinsic and extrinsic motivation in relation to ERBs in a sample of 156 university students. Results show that all the motivational variables studied are linked to ERB. The effects of self-efficacy on ERB are mediated by the intrinsic motivation responses of the participants. A theoretical model was created by means of path analysis, revealing the power of motivational variables to predict ERB. Structural equation modeling was used to test and fit the research model. The role of motivational variables is discussed with a view to creating adequate learning contexts and experiences to generate interest and new sensations in which self-efficacy and affective reactions play an important role.

  5. Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner.

    Science.gov (United States)

    Tsutsui-Kimura, Iku; Ohmura, Yu; Yoshida, Takayuki; Yoshioka, Mitsuhiro

    2017-07-01

    Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, resident-intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively. A milnacipran dose of 10 mg/kg suppressed all behaviors, which was accompanied by increased dopamine and serotonin levels in the medial prefrontal cortex (mPFC) but not in the nucleus accumbens (NAc). Although the most effective dose for depressive-like behavior was 30 mg/kg, the highest dose increased aggressive behavior and unaffected impulsive behavior. Increased dopamine levels in the NAc could be responsible for the effects. In addition, the mice basal impulsivity was negatively correlated with the latency to the first agonistic behavior. Thus, the optimal dose range of milnacipran is narrower than previously thought. Finding drugs that increase serotonin and dopamine levels in the mPFC without affecting dopamine levels in the NAc is a potential strategy for developing novel antidepressants. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  6. Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner

    Directory of Open Access Journals (Sweden)

    Iku Tsutsui-Kimura

    2017-07-01

    Full Text Available Serotonin/noradrenaline reuptake inhibitors (SNRIs are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg, an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, resident–intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively. A milnacipran dose of 10 mg/kg suppressed all behaviors, which was accompanied by increased dopamine and serotonin levels in the medial prefrontal cortex (mPFC but not in the nucleus accumbens (NAc. Although the most effective dose for depressive-like behavior was 30 mg/kg, the highest dose increased aggressive behavior and unaffected impulsive behavior. Increased dopamine levels in the NAc could be responsible for the effects. In addition, the mice basal impulsivity was negatively correlated with the latency to the first agonistic behavior. Thus, the optimal dose range of milnacipran is narrower than previously thought. Finding drugs that increase serotonin and dopamine levels in the mPFC without affecting dopamine levels in the NAc is a potential strategy for developing novel antidepressants.

  7. Estimating adolescent sleep need using dose-response modeling.

    Science.gov (United States)

    Short, Michelle A; Weber, Nathan; Reynolds, Chelsea; Coussens, Scott; Carskadon, Mary A

    2018-04-01

    This study will (1) estimate the nightly sleep need of human adolescents, (2) determine the time course and severity of sleep-related deficits when sleep is reduced below this optimal quantity, and (3) determine whether sleep restriction perturbs the circadian system as well as the sleep homeostat. Thirty-four adolescents aged 15 to 17 years spent 10 days and nine nights in the sleep laboratory. Between two baseline nights and two recovery nights with 10 hours' time in bed (TIB) per night, participants experienced either severe sleep restriction (5-hour TIB), moderate sleep restriction (7.5-hour TIB), or no sleep restriction (10-hour TIB) for five nights. A 10-minute psychomotor vigilance task (PVT; lapse = response after 500 ms) and the Karolinska Sleepiness Scale were administered every 3 hours during wake. Salivary dim-light melatonin onset was calculated at baseline and after four nights of each sleep dose to estimate circadian phase. Dose-dependent deficits to sleep duration, circadian phase timing, lapses of attention, and subjective sleepiness occurred. Less TIB resulted in less sleep, more lapses of attention, greater subjective sleepiness, and larger circadian phase delays. Sleep need estimated from 10-hour TIB sleep opportunities was approximately 9 hours, while modeling PVT lapse data suggested that 9.35 hours of sleep is needed to maintain optimal sustained attention performance. Sleep restriction perturbs homeostatic and circadian systems, leading to dose-dependent deficits to sustained attention and sleepiness. Adolescents require more sleep for optimal functioning than typically obtained.

  8. Environmentally responsible behavior of nature-based tourists: A review

    Directory of Open Access Journals (Sweden)

    Lee, T.H.

    2013-03-01

    Full Text Available This study assesses the conceptualization of environmentally responsible behavior and methods for measuring such behavior based on a review of previous studies. Four major scales for the extent to which an individual’s behavior is responsible behavior are discussed. Various theoretical backgrounds and cultures provide diverse conceptualizations of environmentally responsible behavior. Both general and site-specific environmentally responsible behavior has been identified in the past studies. This study also discusses the precedents of environmentally responsible behavior and with a general overview; it provides insight into improving future research on this subject.

  9. Neuromuscular dose-response studies: determining sample size.

    Science.gov (United States)

    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.

  10. Emotional responses to behavioral economic incentives for health behavior change.

    Science.gov (United States)

    van der Swaluw, Koen; Lambooij, Mattijs S; Mathijssen, Jolanda J P; Zeelenberg, Marcel; Polder, Johan J; Prast, Henriëtte M

    2018-03-05

    Many people aim to change their lifestyle, but have trouble acting on their intentions. Behavioral economic incentives and related emotions can support commitment to personal health goals, but the related emotions remain unexplored. In a regret lottery, winners who do not attain their health goals do not get their prize but receive feedback on what their forgone earnings would have been. This counterfactual feedback should provoke anticipated regret and increase commitment to health goals. We explored which emotions were actually expected upon missing out on a prize due to unsuccessful weight loss and which incentive-characteristics influence their likelihood and intensity. Participants reported their expected emotional response after missing out on a prize in one of 12 randomly presented incentive-scenarios, which varied in incentive type, incentive size and deadline distance. Participants primarily reported feeling disappointment, followed by regret. Regret was expected most when losing a lottery prize (vs. a fixed incentive) and intensified with prize size. Multiple features of the participant and the lottery incentive increase the occurrence and intensity of regret. As such, our findings can be helpful in designing behavioral economic incentives that leverage emotions to support health behavior change.

  11. PROFOUND AND SEXUALLY DIMORPHIC EFFECTS OF CLINICALLY-RELEVANT LOW DOSE SCATTER IRRADIATION ON THE BRAIN AND BEHAVIOR

    Directory of Open Access Journals (Sweden)

    Anna eKovalchuk

    2016-06-01

    Full Text Available Irradiated cells can signal damage and distress to both close and distant neighbors that have not been directly exposed to the radiation (naïve bystanders. While studies have shown that such bystander effects occur in the shielded brain of animals upon body irradiation, their mechanism remains unexplored. Observed effects may be caused by some blood-borne factors; however they may also be explained, at least in part, by very small direct doses received by the brain that result from scatter or leakage. In order to establish the roles of low doses of scatter irradiation in the brain response, we developed a new model for scatter irradiation analysis whereby one rat was irradiated directly at the liver and the second rat was placed adjacent to the first and received a scatter dose to its body and brain. This work focuses specifically on the response of the latter rat brain to the low scatter irradiation dose. Here, we provide the first experimental evidence that very low, clinically relevant doses of scatter irradiation alter gene expression, induce changes in dendritic morphology, and lead to behavioral deficits in exposed animals. The results showed that exposure to radiation doses as low as 0.115 cGy caused changes in gene expression and reduced spine density, dendritic complexity, and dendritic length in the prefrontal cortex tissues of females, but not males. In the hippocampus, radiation altered neuroanatomical organization in males, but not in females. Moreover, low dose radiation caused behavioral deficits in the exposed animals. This is the first study to show that low dose scatter irradiation influences the brain and behavior in a sex-specific way.

  12. High-dose alcohol intoxication differentially modulates cognitive subprocesses involved in response inhibition.

    Science.gov (United States)

    Stock, Ann-Kathrin; Schulz, Tom; Lenhardt, Martin; Blaszkewicz, Meinolf; Beste, Christian

    2016-01-01

    Aside from well-known physiological effects, high-dose alcohol intoxication (a.k.a. binge drinking) can lead to aversive social and legal consequences because response inhibition is usually compromised under the influence of alcohol. Although the behavioral aspects of this phenomenon were reported on extensively, the underlying neurophysiological mechanisms mediating this disinhibition are unclear. To close this gap, we used both behavioral and neurophysiological measures (event-related potentials, ERPs) to investigate which subprocesses of response inhibition are altered under the influence of high-dose alcohol intoxication. Using a within-subject design, we asked young healthy participants (n = 27) to complete a GO/NOGO task once sober and once intoxicated (approximately 1.2‰). During intoxication, high-dose alcohol effects were highest in a condition where the participants could not rely on automated stimulus-response mapping processes during response inhibition. In this context, the NOGO-P3 (ERP), that likely depends on dopaminergic signaling within mesocorticolimbic pathways and is thought to reflect motor inhibition and/or the evaluation of inhibitory processes, was altered in the intoxicated state. In contrast to this, the N2 component, which largely depends on nigrostriatal dopamine pathways and is thought to reflect inhibition on a pre-motor level, was not altered. Based on these results, we demonstrate that alcohol-induced changes of dopaminergic neurotransmission do not exert a global effect on response inhibition. Instead, changes are highly subprocess-specific and seem to mainly target mesocorticolimbic pathways that contribute to motor inhibition and the evaluation of such. © 2014 Society for the Study of Addiction.

  13. Effect of des-Tyr1-[gamma]-endorphin and des-enkephalin-[gamma]-endorphin on active and passive avoidance behavior of rats; A dose-response relationship study

    NARCIS (Netherlands)

    Gaffori, O.; Wied, D. de

    1982-01-01

    The potency of two β-endorphin fragments, des-Tyr1-γ-endorphin (DTγE, βE-(2–17)) and des-enkephalin-γ-endorphin (DEγE, βE-(6–17)) was compared on extinction of pole-jumping avoidance behavior and on retention of a one-trial step-through passive avoidance procedure. Both peptides facilitated the

  14. Relationship of dose rate and total dose to responses of continuously irradiated beagles

    International Nuclear Information System (INIS)

    Fritz, T.E.; Norris, W.P.; Tolle, D.V.; Seed, T.M.; Poole, C.M.; Lombard, L.S.; Doyle, D.E.

    1978-01-01

    Young-adult beagles were exposed continuously (22 hours/day) to 60 Co γ rays in a specially constructed facility. The exposure rates were either 5, 10, 17, or 35 R/day, and the exposures were terminated at either 600, 1400, 2000, or 4000 R. A total of 354 dogs were irradiated; 221 are still alive as long-term survivors, some after more than 2000 days. The data on survival of these dogs, coupled with data from similar preliminary experiments, allow an estimate of the LD 50 for γ-ray exposures given at a number of exposure rates. They also allow comparison of the relative importance of dose rate and total dose, and the interaction of these two variables, in the early and late effects after protracted irradiation. The LD 50 for the beagle increases from 258 rad delivered at 15 R/minute to approximately 3000 rad at 10 R/day. Over this entire range, the LD 50 is dependent upon hematopoietic damage. At 5 R/day and less, no meaningful LD 50 can be determined; there is nearly normal continued hematopoietic function, survival is prolonged, and the dogs manifest varied individual responses in other organ systems. Although the experiment is not complete, interim data allow several important conclusions. Terminated exposures, while not as effective as radiation continued until death, can produce myelogenous leukemia at the same exposure rate, 10 R/day. More importantly, at the same total accumulated dose, lower exposure rates are more damaging than higher rates on the basis of the rate and degree of hematological recovery that occurs after termination of irradiation. Thus, the rate of hematologic depression, the nadir of the depression, and the rate of recovery are dependent upon exposure rate; the latter is inversely related and the former two are directly related to exposure rate

  15. Relationship of dose rate and total dose to responses of continuously irradiated beagles

    International Nuclear Information System (INIS)

    Fritz, T.E.; Norris, W.P.; Tolle, D.V.; Seed, T.M.; Poole, C.M.; Lombard, L.S.; Doyle, D.E.

    1978-01-01

    Young-adult beagles were exposed continuously (22 hours/day) to 60 Co gamma rays in a specially constructed facility. The exposure rates were 5, 19, 17 or 35 R/day, and the exposures were terminated at 600, 1400, 2000 or 4000 R. A total of 354 dogs were irradiated; 221 are still alive as long-term survivors, some after more than 2000 days. The data on survival of these dogs, coupled with data from similar preliminary experiments, allow an estimate of the LD 50 for gamma-ray exposures given at a number of exposure rates. They also allow comparison of the relativeimportance of dose rate and total dose, and the interaction of these two variables, in the early and late effects after protracted irradiation. The LD 50 for the beagle increases from 344 R (258 rads) delivered at 15 R/minute to approximately 4000 R (approximately 3000 rads) at 10 R/day. Over this entire range, the LD 50 is dependent upon haematopoietic damage. At 5 R/day and less, no definitive LD 50 can be determined; there is nearly normal continued haematopoietic function, survival is prolonged, and the dogs manifest varied individual responses in the organ systems. Although the experiment is not complete, interim data allow serveral important conclusions. Terminated exposures, while not as effective as irradiation continued until death, can produce myelogenous leukaemia at the same exposure rate, 10 R/day. More importantly, at the same total accumulated dose, lower exposure rates appear more damaging than higher rates on the basis of the rate and degree of haematological recovery that occurs after termination of irradiation. Thus, the rate of haematologic depression, the nadir of the depression and the rate of recovery are dependent upon exposure rate; the latter is inversely related and the first two are directly related to exposure rate. ( author)

  16. Regulation of operant oral ethanol self-administration: a dose-response curve study in rats.

    Science.gov (United States)

    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.

  17. 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

  18. Biological profiling and dose-response modeling tools ...

    Science.gov (United States)

    Through its ToxCast project, the U.S. EPA has developed a battery of in vitro high throughput screening (HTS) assays designed to assess the potential toxicity of environmental chemicals. At present, over 1800 chemicals have been tested in up to 600 assays, yielding a large number of concentration-response data sets. Standard processing of these data sets involves finding a best fitting mathematical model and set of model parameters that specify this model. The model parameters include quantities such as the half-maximal activity concentration (or “AC50”) that have biological significance and can be used to inform the efficacy or potency of a given chemical with respect to a given assay. All of this data is processed and stored in an online-accessible database and website: http://actor.epa.gov/dashboard2. Results from these in vitro assays are used in a multitude of ways. New pathways and targets can be identified and incorporated into new or existing adverse outcome pathways (AOPs). Pharmacokinetic models such as those implemented EPA’s HTTK R package can be used to translate an in vitro concentration into an in vivo dose; i.e., one can predict the oral equivalent dose that might be expected to activate a specific biological pathway. Such predicted values can then be compared with estimated actual human exposures prioritize chemicals for further testing.Any quantitative examination should be accompanied by estimation of uncertainty. We are developing met

  19. Patch test dose-response study of p-phenylenediamine

    DEFF Research Database (Denmark)

    Sosted, Heidi; Menné, Torkil; Johansen, Jeanne Duus

    2006-01-01

    The elicitation response in allergic contact dermatitis for the hair dye substance p-phenylenediamine (PPD) is dose dependent, but threshold concentrations have not previously been investigated. 15 PPD-sensitive patients participated in a serial dilution 48-hr patch test with PPD using 8...... concentrations of PPD ranging from 1 to 10 000 on the upper back. Petrolatum was applied as control. Three concentrations (50, 100 and 500 p.p.m. PPD) were also applied to the retroauricular area and on the lateral aspects of the upper arms. 14 of the 15 participants reacted to one or more of the test samples....... The threshold value for 10% of the tested persons (ED10) based on+or stronger reactions for PPD on the back was 38 p.p.m. (CI: 4.3-100). There were no statistically significant differences in the sensitivity of the three anatomical regions. The upper back is a suitable region for patch testing patients...

  20. 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...

  1. Dose-response curve estimation: a semiparametric mixture approach.

    Science.gov (United States)

    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.

  2. 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

  3. Low-dose radiation-induced adaptive response in bone marrow cells of mice

    International Nuclear Information System (INIS)

    Farooqi, Zeba; Kesavan, P.C.

    1993-01-01

    Using bone marrow cells of whole body irradiated mice, the cytogenetic adaptive response induced by low conditioning doses of gamma-rays was investigated. The conditioning doses (0.025 and 0.05 Gy) were given at a dose-rate of 1.67 Gy/min. The challenging dose of 1 Gy was given at a dose-rate of 0.045 Gy/s. The challenging dose was given at different time intervals after the conditioning dose. The time intervals between the conditioning dose and challenging dose were 2, 7.5, 13, 18.5 and 24 h. When the time interval between the conditioning dose and the challenging dose was 2 h, both conditioning doses (0.025 and 0.05 Gy) reduced the frequency of MNPCEs and chromosomal aberrations in the bone marrow cells. The data collected at different time intervals (7.5, 13, 18.5 h) reveal that the radioadaptive response persisted for a longer time when the lower conditioning dose (0.025 Gy) was given. With the higher conditioning dose (0.05 Gy), the radioadaptive response disappeared after a time interval of 13 h. When the time interval between the conditioning dose and the challenging doses was 18.5 or 24 h, only the lower conditioning dose appeared effective in inducing the radioadaptive response

  4. Quantitative analysis of biological responses to low dose-rate γ-radiation, including dose, irradiation time, and dose-rate

    International Nuclear Information System (INIS)

    Magae, J.; Furukawa, C.; Kawakami, Y.; Hoshi, Y.; Ogata, H.

    2003-01-01

    Full text: Because biological responses to radiation are complex processes dependent on irradiation time as well as total dose, it is necessary to include dose, dose-rate and irradiation time simultaneously to predict the risk of low dose-rate irradiation. In this study, we analyzed quantitative relationship among dose, irradiation time and dose-rate, using chromosomal breakage and proliferation inhibition of human cells. For evaluation of chromosome breakage we assessed micronuclei induced by radiation. U2OS cells, a human osteosarcoma cell line, were exposed to gamma-ray in irradiation room bearing 50,000 Ci 60 Co. After the irradiation, they were cultured for 24 h in the presence of cytochalasin B to block cytokinesis, cytoplasm and nucleus were stained with DAPI and propidium iodide, and the number of binuclear cells bearing micronuclei was determined by fluorescent microscopy. For proliferation inhibition, cells were cultured for 48 h after the irradiation and [3H] thymidine was pulsed for 4 h before harvesting. Dose-rate in the irradiation room was measured with photoluminescence dosimeter. While irradiation time less than 24 h did not affect dose-response curves for both biological responses, they were remarkably attenuated as exposure time increased to more than 7 days. These biological responses were dependent on dose-rate rather than dose when cells were irradiated for 30 days. Moreover, percentage of micronucleus-forming cells cultured continuously for more than 60 days at the constant dose-rate, was gradually decreased in spite of the total dose accumulation. These results suggest that biological responses at low dose-rate, are remarkably affected by exposure time, that they are dependent on dose-rate rather than total dose in the case of long-term irradiation, and that cells are getting resistant to radiation after the continuous irradiation for 2 months. It is necessary to include effect of irradiation time and dose-rate sufficiently to evaluate risk

  5. Dependence of total dose response of bipolar linear microcircuits on applied dose rate

    International Nuclear Information System (INIS)

    McClure, S.; Will, W.; Perry, G.; Pease, R.L.

    1994-01-01

    The effect of dose rate on the total dose radiation hardness of three commercial bipolar linear microcircuits is investigated. Total dose tests of linear bipolar microcircuits show larger degradation at 0.167 rad/s than at 90 rad/s even after the high dose rate test is followed by a room temperature plus a 100 C anneal. No systematic correlation could be found for degradation at low dose rate versus high dose rate and anneal. Comparison of the low dose rate with the high dose rate anneal data indicates that MIL-STD-883, method 1019.4 is not a worst-case test method when applied to bipolar microcircuits for low dose rate space applications

  6. gross behavioral effects of acute doses of artesunate in wistar rats

    African Journals Online (AJOL)

    sniffing, climbing and scratching activities and these later effects were also seen at the lower ... It was concluded that artesunate may have some clearly definable central nervous .... behavioral parameters at higher doses of the artesunate.

  7. Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate-Dependent Manner.

    Science.gov (United States)

    Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

    2018-01-01

    A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR.

  8. Gamma Low-Dose-Rate Ionizing Radiation Stimulates Adaptive Functional and Molecular Response in Human Aortic Endothelial Cells in a Threshold-, Dose-, and Dose Rate–Dependent Manner

    Science.gov (United States)

    Vieira Dias, Juliana; Gloaguen, Celine; Kereselidze, Dimitri; Manens, Line; Tack, Karine; Ebrahimian, Teni G

    2018-01-01

    A central question in radiation protection research is whether low-dose and low-dose-rate (LDR) exposures to ionizing radiation play a role in progression of cardiovascular disease. The response of endothelial cells to different LDR exposures may help estimate risk of cardiovascular disease by providing the biological mechanism involved. We investigated the effect of chronic LDR radiation on functional and molecular responses of human aorta endothelial cells (HAoECs). Human aorta endothelial cells were continuously irradiated at LDR (6 mGy/h) for 15 days and analyzed at time points when the cumulative dose reached 0.05, 0.5, 1.0, and 2.0 Gy. The same doses were administered acutely at high-dose rate (HDR; 1 Gy/min). The threshold for the loss of angiogenic capacity for both LDR and HDR radiations was between 0.5 and 1.0 Gy. At 2.0 Gy, angiogenic capacity returned to normal only for HAoEC exposed to LDR radiation, associated with increased expression of antioxidant and anti-inflammatory genes. Pre-LDR, but not pre-HDR, radiation, followed by a single acute 2.0 Gy challenge dose sustained the expression of antioxidant and anti-inflammatory genes and stimulated angiogenesis. Our results suggest that dose rate is important in cellular response and that a radioadaptive response is involved for a 2.0 Gy dose at LDR. PMID:29531508

  9. Dose-Response Associations Between Number and Frequency of Substance Use and High-Risk Sexual Behaviors Among HIV-Negative Substance-Using Men Who Have Sex With Men (SUMSM) in San Francisco

    Science.gov (United States)

    Santos, Glenn-Milo; Coffin, Phillip O.; Das, Moupali; Matheson, Tim; DeMicco, Erin; Raiford, Jerris L.; Vittinghoff, Eric; Dilley, James W.; Colfax, Grant; Herbst, Jeffrey H.

    2015-01-01

    We evaluated the relationship between frequency and number of substances used and HIV risk [ie, serodiscordant unprotected anal intercourse (SDUAI)] among 3173 HIV-negative substance-using MSM. Compared with nonusers, the adjusted odds ratio (AOR) for SDUAI among episodic and at least weekly users, respectively, was 3.31 [95% confidence interval (CI), 2.55 to 4.28] and 5.46 (95% CI, 3.80 to 7.84) for methamphetamine, 1.86 (95% CI, 1.51 to 2.29) and 3.13 (95% CI, 2.12 to 4.63) for cocaine, and 2.08 (95% CI, 1.68 to 2.56) and 2.54 (95% CI, 1.85 to 3.48) for poppers. Heavy alcohol drinkers reported more SDUAI than moderate drinkers [AOR, 1.90 (95% CI, 1.43 to 2.51)]. Compared with nonusers, AORs for using 1, 2, and ≥3 substances were 16.81 (95% CI, 12.25 to 23.08), 27.31 (95% CI, 18.93 to 39.39), and 46.38 (95% CI, 30.65 to 70.19), respectively. High-risk sexual behaviors were strongly associated with frequency and number of substances used. PMID:23572012

  10. Critical target and dose and dose-rate responses for the induction of chromosomal instability by ionizing radiation

    Science.gov (United States)

    Limoli, C. L.; Corcoran, J. J.; Milligan, J. R.; Ward, J. F.; Morgan, W. F.

    1999-01-01

    To investigate the critical target, dose response and dose-rate response for the induction of chromosomal instability by ionizing radiation, bromodeoxyuridine (BrdU)-substituted and unsubstituted GM10115 cells were exposed to a range of doses (0.1-10 Gy) and different dose rates (0.092-17.45 Gy min(-1)). The status of chromosomal stability was determined by fluorescence in situ hybridization approximately 20 generations after irradiation in clonal populations derived from single progenitor cells surviving acute exposure. Overall, nearly 700 individual clones representing over 140,000 metaphases were analyzed. In cells unsubstituted with BrdU, a dose response was found, where the probability of observing delayed chromosomal instability in any given clone was 3% per gray of X rays. For cells substituted with 25-66% BrdU, however, a dose response was observed only at low doses (1.0 Gy), the incidence of chromosomal instability leveled off. There was an increase in the frequency and complexity of chromosomal instability per unit dose compared to cells unsubstituted with BrdU. The frequency of chromosomal instability appeared to saturate around approximately 30%, an effect which occurred at much lower doses in the presence of BrdU. Changing the gamma-ray dose rate by a factor of 190 (0.092 to 17.45 Gy min(-1)) produced no significant differences in the frequency of chromosomal instability. The enhancement of chromosomal instability promoted by the presence of the BrdU argues that DNA comprises at least one of the critical targets important for the induction of this end point of genomic instability.

  11. Immune response and anamnestic immune response in children after a 3-dose primary hepatitis b vaccination

    International Nuclear Information System (INIS)

    Afzal, M.F.; Sultan, M.A.; Saleemi, A.I.

    2017-01-01

    Diseases caused by Hepatitis B virus (HBV) have a worldwide distribution. Pakistan adopted the recommendations of World Health Organization (WHO) for routine universal infant vaccination against hepatitis B in 2002, currently being administered at 6, 10, and 14 weeks of age in a combination vaccine. This study was conducted to determine the immune response and anamnestic immune response in children, 9 months-10 years of age, after a 3-dose primary Hepatitis B vaccination. Methods: This cross sectional study was conducted in the Department of Paediatrics, King Edward Medical University/Mayo Hospital, Lahore, Pakistan, from January to June, 2014. A total of 200 children of either sex between the ages of 9 months to 10 years, docu mented to have received 3 doses of hepatitis B vaccines according to Expanded Program of Immunization (6,10,14 weeks) schedule in infancy, were recruited by consecutive sampling. The level of serum anti-HBsAb by ELIZA was measured. Children with anti-HBs titers =10 mIU/mL were considered to be immune. Those with anti-HBsAb levels <10 mIU/mL were offered a booster dose of infant recombinant hepatitis B vaccine. The second serum sample was obtained 21-28 days following the administration of the booster dose and the anamnestic immune response was measured. Data was analysed using SPSS 17 to determine the relation between time interval since last vaccination and antibody titer. Chi square test was applied. Results: Of the 200 children, protective antibody response was found in 58 percent. Median serological response was 18.60 (range 2.82-65.15). Antibody levels were found to have a statistically significant (p-value 0.019) negative correlation with the time since last administration of vaccine. A booster dose of Hepatitis B vaccine was administered to all non-responders, with each registering a statistically significant (p-value 0.00) anamnestic response. Conclusion: The vaccination schedule with short dosage interval was unable to provide

  12. Phencyclidine retards autoshaping at a dose which does not suppress the required response.

    Science.gov (United States)

    Coveney, J R; Sparber, S B

    1982-06-01

    Four groups of five food-deprived hooded Long-Evans rats were injected subcutaneously with saline (vehicle) or 2, 4 or 8 mg phencyclidine (PCP) hydrochloride/kg fifteen minutes before being placed for the first time into operant chambers modified to detect exploratory behaviors. Rearing was found to be more sensitive to disruption by phencyclidine than was unconditioned level touching (a measure of floor-level exploratory activities). In an autoshaping session immediately following, the group of animals given the low dose of PCP made as many lever-touch responses as the group given saline, but consumed fewer of the food pellets delivered. In addition, none of the animals in the low-dose group showed within-session shortening of the latency to respond which was observed in four of five control animals. The two other groups given higher doses of PCP demonstrated dose-related decrements in responding as well as a reduction in food pellet consumption during the first session of autoshaping. Over the next two daily autoshaping sessions, performance improved in those groups initially suppressed. Performance converged in all group by the third autoshaping session.

  13. Early exposure to a low dose of bisphenol A affects socio-sexual behavior of juvenile female rats.

    Science.gov (United States)

    Porrini, Stefania; Belloni, Virginia; Della Seta, Daniele; Farabollini, Francesca; Giannelli, Giuletta; Dessì-Fulgheri, Francesco

    2005-04-15

    Play behavior is affected by alteration of the hormonal environment during development. In fact, congenital adrenal hyperplasia or early administration of diethylstilbestrol are able to modify female play behavior in mammals. In this research, play behavior of female rats was used to explore the effects of perinatal exposure to low, environmentally relevant dose of bisphenol A (BPA), a xenoestrogen widely diffused in the environment. We used 18 females born to mothers exposed to 40 microg/kg/day BPA during pregnancy and lactation, and 18 control females. The subjects were observed in a heterosexual social situation from 35 to 55 days of age. Six main behaviors were identified by principal component analysis (PCA): exploration, defensive behavior to males, play behavior with males, play behavior with females, low-intensity mating behavior, social grooming. Early administration of BPA was responsible for a significant increase of exploration (including social investigation) (pbehavior, but is able however to defeminize some aspects of female behavior. This result is compatible with the estrogenic properties of BPA, and suggests caution in the use of a chemical that, in the range of human exposure, is able to influence the development of the brain during a critical period, resulting in long-term effects on behavior.

  14. Ovarian and endocrine responses in tropical sheep treated with reduced doses of cloprostenol.

    Science.gov (United States)

    Contreras-Solis, Ignacio; Vasquez, B; Diaz, T; Letelier, C; Lopez-Sebastian, A; Gonzalez-Bulnes, A

    2009-09-01

    The present study aimed to assess the efficacy of reduced doses of cloprostenol for synchronizing estrus and ovulation in hair sheep. With the aim to evaluate the luteolytic activity of reduced cloprostenol doses, a first experiment was performed using a relatively large (group H: 126 microg; n=8), medium (group M: 68.25 microg; n=6) and small (group L: 38.5 microg; n=6) cloprostenol dose. Luteolysis was assessed at Days 3 and 6 after injection (Day 0) by progesterone concentrations (P(4)) and transrectal ultrasonography (US). In Experiment 2, sheep were randomly assigned to the same three doses to evaluate a protocol for estrous synchronization using two injections administered 9 days apart. A third trial was performed with ewes treated (9 days apart) with the large dose (H=126 microg; n=12) and with a small dose adjusted for facilitating volume management (LA=43.75 microg; n=12). Presence of estrous cycling was determined in all the ewes by US and P(4) assay, at Days -9, -6, -2, 0 (Day of second cloprostenol injection), 8 and 11. Bleeding and US were done every 4h from 16 h of the beginning of the estrus during the third trial to assess the preovulatory LH surge and timing of ovulation. Additionally, blood samples were drawn at Days 0, 1, 2 and 3 to assess estradiol (Experiments 2 and 3) and P(4) (Experiment 2) concentrations during the ovarian follicular phase. In all experiments, percentage of animals showing luteolysis, preovulatory follicular dynamics and function and percentage of ewes showing behavioral estrus in response to treatment was similar among groups. Timing of estrus for group H was earlier than group L (28.6+/-1.8h compared with 37.1+/-2.4h; Psheep, with the additional advantage of reducing treatment costs.

  15. Goal inferences about robot behavior : goal inferences and human response behaviors

    NARCIS (Netherlands)

    Broers, H.A.T.; Ham, J.R.C.; Broeders, R.; De Silva, P.; Okada, M.

    2014-01-01

    This explorative research focused on the goal inferences human observers draw based on a robot's behavior, and the extent to which those inferences predict people's behavior in response to that robot. Results show that different robot behaviors cause different response behavior from people.

  16. Radiobiological responses for two cell lines following continuous low dose-rate (CLDR) and pulsed dose rate (PDR) brachytherapy

    International Nuclear Information System (INIS)

    Hanisch, Per Henrik; Furre, Torbjoern; Olsen, Dag Rune; Pettersen, Erik O.

    2007-01-01

    The iso-effective irradiation of continuous low-dose-rate (CLDR) irradiation was compared with that of various schedules of pulsed dose rate (PDR) irradiation for cells of two established human lines, T-47D and NHIK 3025. Complete single-dose response curves were obtained for determination of parameters α and β by fitting of the linear quadratic formula. Sublethal damage repair constants μ and T 1/2 were determined by split-dose recovery experiments. On basis of the acquired parameters of each cell type the relative effectiveness of the two regimens of irradiation (CLDR and PDR) was calculated by use of Fowler's radiobiological model for iso-effect irradiation for repeated fractions of dose delivered at medium dose rates. For both cell types the predicted and observed relative effectiveness was compared at low and high iso-effect levels. The results indicate that the effect of PDR irradiation predicted by Fowler's model is equal to that of CLDR irradiation for both small and large doses with T-47D cells. With NHIK 3025 cells PDR irradiation induces a larger effect than predicted by the model for small doses, while it induces the predicted effect for high doses. The underlying cause of this difference is unclear, but cell-cycle parameters, like G2-accumulation is tested and found to be the same for the two cell lines

  17. Effect of radiation doses rate on SOS response induction in irradiated Escherichia coli Cells

    International Nuclear Information System (INIS)

    Cuetara Lugo, Elizabeth B.; Fuentes Lorenzo, Jorge L.; Almeida Varela, Eliseo; Prieto Miranda, Enrique F.; Sanchez Lamar, Angel; Llagostera Casal, Montserrat

    2005-01-01

    The present work is aimed to study the effect of radiation dose rate on the induction of SOS response in Escherichia coli cells. We measured the induction of sul A reporter gene in PQ-37 (SOS Chromotest) cells. Lead devises were built with different diameter and these were used for diminishing the dose rate of PX- -30M irradiator. Our results show that radiation doses rate significantly modifies the induction of SOS response. Induction factor increases proportionally to doses rate in Escherichia coli cells defective to nucleotide excision repair (uvrA), but not in wild type cells. We conclude that the dose rate affects the level of induction of SOS response

  18. Fertility of Tall Girls Treated with High-Dose Estrogen, a Dose-Response Relationship

    NARCIS (Netherlands)

    Hendriks, A. E. J.; Drop, S. L. S.; Laven, J. S. E.; Boot, A. M.

    Context: High-dose estrogen treatment to reduce final height of tall girls increases their risk for infertility in later life. Objective: The aim was to study the effect of estrogen dose on fertility outcome of these women. Design/Setting: We conducted a retrospective cohort study of university

  19. High-Dose Atomoxetine Treatment of ADHD in Youths with Limited Response to Standard Doses

    Science.gov (United States)

    Kratochvil, Christopher J.; Michelson, David; Newcorn, Jeffrey H.; Weiss, Margaret D.; Busner, Joan; Moore, Rodney J.; Ruff, Dustin D.; Ramsey, Janet; Dickson, Ruth; Turgay, Atilla; Saylor, Keith E.; Luber, Stephen; Vaughan, Brigette; Allen, Albert J.

    2007-01-01

    Objective: To assess the utility and tolerability of higher than standard atomoxetine doses to treat attention-deficit/hyperactivity disorder (ADHD). Method: Two randomized, double-blind trials of atomoxetine nonresponders ages 6 to 16 years were conducted comparing continued treatment with same-dose atomoxetine to treatment using greater than…

  20. Study on cellular survival adaptive response induced by low dose irradiation of 153Sm

    International Nuclear Information System (INIS)

    Zhu Shoupeng; Xiao Dong

    1999-01-01

    The present study engages in determining whether low dose irradiation of 153 Sm could cut down the responsiveness of cellular survival to subsequent high dose exposure of 153 Sm so as to make an inquiry into approach the protective action of adaptive response by second irradiation of 153 Sm. Experimental results indicate that for inductive low dose of radionuclide 153 Sm 3.7 kBq/ml irradiated beforehand to cells has obvious resistant effect in succession after high dose irradiation of 153 Sm 3.7 x 10 2 kBq/ml was observed. Cells exposed to low dose irradiation of 153 Sm become adapted and therefore the subsequent cellular survival rate induced by high dose of 153 Sm is sufficiently higher than high dose of 153 Sm merely. It is evident that cellular survival adaptive response could be induced by pure low dose irradiation of 153 Sm only

  1. Pivotal behavior as the mediator of the relationship between parental responsiveness and children's symbolic behavior.

    Science.gov (United States)

    Chiu, Chun-Hao; Lin, Chu-Sui; Mahoney, Gerald; Cheng, Shu-Fen; Chang, Shu-Hui

    2017-08-01

    Previous research with parents and children with developmental disabilities indicated that the relationship between mothers' responsive style of interaction and children's rate of development was mediated by the simultaneous relationship between mothers' responsiveness and children's social engagement, or pivotal behavior. In this study, we attempted to determine whether children's pivotal behavior might also mediate the relationship between responsiveness and child development in a sample of 165 typically developing toddlers and their Taiwanese parents. Child development was assessed with a parent report measure of children's symbolic behavior. Parental responsiveness and children's pivotal behavior were assessed from observations of parent-child play. Results indicated that parental responsiveness was correlated with children's pivotal behavior, and that both of these variables were correlated with children's symbolic behavior. Structural equation models indicated that the relationship between responsiveness and children's symbolic behavior was fully mediated by children's pivotal behavior. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. The effect of radiosensitizers on the survival response of hypoxic mammalian cells: The low X-ray dose region, hypersensitivity and induced radioresistance

    International Nuclear Information System (INIS)

    Skov, K.A.; MacPhail, H.S.; Marples, B.

    1994-01-01

    It has been shown previously that the extent of chemical modification of the hypoxic radiation response is dependent on dose. Some types of sensitizer are more effective at low doses (to 4 Gy) than at higher doses. Since such drugs are possible adjuvants to radiotherapy, the mechanisms responsible for the variable response at clinical doses are summarized, and the effects of cisplatin and buthionine sulfoximine on the purported induced response to radiation in hypoxic cells are presented. Cisplatin at a low, nontoxic concentration (1 μM) appears to abolish the increased radioresistant portion of the survival response. A role for high-mobility-group protein binding by platinum drugs is hypothesized to explain their interaction with radiation, and conversely, it is suggested that the heretofore unexplained different behavior of certain hypoxic sensitizers at low doses could be, at least in part, an effect on the induction of resistance. 36 refs., 2 figs

  3. Chronic periodontitis and smoking. Prevalence and dose-response relationship.

    Science.gov (United States)

    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.

  4. Dose-response relationship of autonomic nervous system responses to individualized training impulse in marathon runners.

    Science.gov (United States)

    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.

  5. Low dose intranasal oxytocin delivered with Breath Powered device dampens amygdala response to emotional stimuli: A peripheral effect-controlled within-subjects randomized dose-response fMRI trial.

    Science.gov (United States)

    Quintana, Daniel S; Westlye, Lars T; Alnæs, Dag; Rustan, Øyvind G; Kaufmann, Tobias; Smerud, Knut T; Mahmoud, Ramy A; Djupesland, Per G; Andreassen, Ole A

    2016-07-01

    It is unclear if and how exogenous oxytocin (OT) reaches the brain to improve social behavior and cognition and what is the optimal dose for OT response. To better understand the delivery routes of intranasal OT administration to the brain and the dose-response, we compared amygdala response to facial stimuli by means of functional magnetic resonance imaging (fMRI) in four treatment conditions, including two different doses of intranasal OT using a novel Breath Powered device, intravenous (IV) OT, which provided similar concentrations of blood plasma OT, and placebo. We adopted a randomized, double-blind, double-dummy, crossover design, with 16 healthy male adults administering a single-dose of these four treatments. We observed a treatment effect on right amygdala activation during the processing of angry and happy face stimuli, with pairwise comparisons revealing reduced activation after the 8IU low dose intranasal treatment compared to placebo. These data suggest the dampening of amygdala activity in response to emotional stimuli occurs via direct intranasal delivery pathways rather than across the blood-brain barrier via systemically circulating OT. This trial is registered at the U.S. National Institutes of Health clinical trial registry (www.clinicaltrials.gov; NCT01983514) and as EudraCT no. 2013-001608-12. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Dose-Response of Sodium Bicarbonate Ingestion Highlights Individuality in Time Course of Blood Analyte Responses.

    Science.gov (United States)

    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.

  7. Biochemical and immunological responses to low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Shabon, M.H.; Sayed, Z.S.; Mahdy, E.M.; El-Gawish, M.A.; Shosha, W.

    2006-01-01

    Malondialdehyde, lactate dehydrogenase, iron concentration, IL-6 and IL-1b concentration, hemoglobin content, red cells, white cells and platelet counts were determined in seventy-two male albino rats divided into two main groups. The first one was subdivided into 7 subgroups; control and 6 irradiated subgroups with 0.1, 0.2, 0.3, 0.5, 0.7 and 1 Gy single dose of gamma radiation. The other was subdivided into 4 subgroups irradiated with fractionated doses of gamma radiation; three groups were irradiated with 0.3, 0.7 and 1 Gy (0.1 Gy/day) and the last subgroup with 1 Gy (0.2 Gy/day). All animals were sacrificed after three days of the last irradiation dose. The results revealed that all biochemical parameters were increased in rats exposed to fractionated doses more than the single doses. Hematological parameters were decreased in rats exposed to single doses more than the fractionated ones. In conclusion, the data of this study highlights the stimulatory effect of low ionizing radiation doses (= 1 Gy), whether single or fractionated, on some biochemical and immunological parameters

  8. Dose-response effects in an outbreak of Salmonella enteritidis.

    OpenAIRE

    Mintz, E. D.; Cartter, M. L.; Hadler, J. L.; Wassell, J. T.; Zingeser, J. A.; Tauxe, R. V.

    1994-01-01

    The effects of ingested Salmonella enteritidis (SE) dose on incubation period and on the severity and duration of illness were estimated in a cohort of 169 persons who developed gastroenteritis after eating hollandaise sauce made from grade-A shell eggs. The cohort was divided into three groups based on self-reported dose of sauce ingested. As dose increased, median incubation period decreased (37 h in the low exposure group v. 21 h in the medium exposure group v. 17.5 h in the high exposure ...

  9. A Single Sub-anesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats

    Science.gov (United States)

    Wang, Jing; Goffer, Yossef; Xu, Duo; Tukey, David S.; Shamir, D. B.; Eberle, Sarah E.; Zou, Anthony H.; Blanck, Thomas J.J.; Ziff, Edward B.

    2011-01-01

    Background Chronic pain is associated with depression. In rodents, pain is often assessed by sensory hypersensitivity, which does not sufficiently measure affective responses. Low-dose ketamine has been used to treat both pain and depression, but it is not clear whether ketamine can relieve depression associated with chronic pain and whether this antidepressant effect depends on its anti-nociceptive properties. Methods We examined whether the spared nerve injury (SNI) model of neuropathic pain induces depressive behavior in rats, using sucrose preference test and forced swim test, and tested whether a subanesthetic dose of ketamine treats SNI-induced depression. Results SNI-treated rats, compared with control, showed decreased sucrose preference (0.719 ± 0.068 (mean ± SEM) vs. 0.946 ± 0.010) and enhanced immobility in the forced swim test (107.3 ± 14.6s vs. 56.2 ± 12.5s). Further, sham-operated rats demonstrated depressive behaviors in the acute postoperative period (0.790 ± 0.062 on postoperative day 2). A single subanesthetic dose of ketamine (10mg/kg) did not alter SNI-induced hypersensitivity; however, it treated SNI-associated depression-like behaviors (0.896 ± 0.020 for ketamine vs. 0.663 ± 0.080 for control 1 day after administration; 0.858 ± 0.017 for ketamine vs. 0.683 ± 0.077 for control 5 days after administration). Conclusions Chronic neuropathic pain leads to depression-like behaviors. The postoperative period also confers vulnerability to depression, possibly due to acute pain. Sucrose preference test and forced swim test may be used to compliment sensory tests for assessment of pain in animal studies. Low-dose ketamine can treat depression-like behaviors induced by chronic neuropathic pain. PMID:21934410

  10. Tumor and normal tissue responses to fractioned non-uniform dose delivery

    Energy Technology Data Exchange (ETDEWEB)

    Kaellman, P; Aegren, A; Brahme, A [Karolinska Inst., Stockholm (Sweden). Dept. of Radiation Physics

    1996-08-01

    The volume dependence of the radiation response of a tumor is straight forward to quantify because it depends primarily on the eradication of all its clonogenic cells. A tumor therefore has a parallel organization as any surviving clonogen in principle can repopulate the tumor. The difficulty with the response of the tumor is instead to know the density and sensitivity distribution of the most resistant clonogenic cells. The increase in the 50% tumor control dose and the decrease in the maximum normalized slope of the dose response relation, {gamma}, in presence of small compartments of resistant tumor cells have therefore been quantified to describe their influence on the dose response relation. Injury to normal tissue is a much more complex and gradual process. It depends on earlier effects induced long before depletion of the differentiated and clonogenic cells that in addition may have a complex structural and functional organization. The volume dependence of the dose response relation of normal tissues is therefore described here by the relative seriality, s, of the infrastructure of the organ. The model can also be generalized to describe the response of heterogeneous tissues to non uniform dose distributions. The new model is compared with clinical and experimental data on normal tissue response, and shows good agreement both with regard to the shape of dose response relation and the volume dependence of the isoeffect dose. The response of tumors and normal tissues are quantified for arbitrary dose fractionations using the linear quadratic cell survival parameters {alpha} and {beta}. The parameters of the dose response relation are derived both for a constant dose per fraction and a constant number of dose fractions, thus in the latter case accounting also for non uniform dose delivery. (author). 26 refs, 4 figs.

  11. 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

  12. The dependence of radiation response on the dose per fraction

    International Nuclear Information System (INIS)

    Joiner, M.C.

    1989-01-01

    The linear-quadratic (LQ) model explains the dependence of total dose in a fractionated course on the dose per fraction, in a very wide range of tumour and normal tissue studies, providing the dose per fraction remains above 2 Gy. In the range 2-1 Gy per fraction, some experimental studies show less increase in total dose than predicted by LQ; a probable explanation is incomplete repair between fractions given 2 seen between 1 and 0.1 Gy per fraction. This cannot be explained by incomplete repair; a modified LQ model where α decreases sharply with increasing dose per fraction in the range 0-1 Gy fits these data. The basic LQ model describes data from neutron fractionation studies, so the relationship between relative biological effectiveness (RBE) and X-ray dose per fraction can be expressed in terms of LQ parameters and fitted directly to RBE data. Results from different experiments, different assays and both top-up and full-course fractionation techniques, can all be included in one analysis. (author)

  13. The evolutionary reserve cell concept and model of cellular response induced by low doses of radiation

    International Nuclear Information System (INIS)

    Spitkovsky, D.M.; Talyzina, T.A.

    1995-01-01

    The model is based on the concept of programmed initiation of genetic damage in sub-populations of specific evolutionary reserve cells (ERC). The model quantitatively predicts a dose response of genetic lesions at low dose range and furnishes an explanation of the minimum observed in the dose-response curve at doses corresponding to one (on the average) event of energy deposition per ERC. The complex shape of the dose-response curve is demonstrated to result from superposition of processes in different sub-populations within the exposed cell population (at low doses mainly in ERC). Programmed initiation of genetic lesions in ERC requires two hits to cell membrane and probably, at the same time, to the cell nucleus. The equation for dicentric yield in human lymphocytes as a function of dose describes the experimental observations rather well. (Author)

  14. Linear and Non-Linear Dose-Response Functions Reveal a Hormetic Relationship Between Stress and Learning

    OpenAIRE

    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 ...

  15. Dose-dependent hepatic transcriptional responses in Atlantic salmon (Salmo salar) exposed to sublethal doses of gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Song, You, E-mail: you.song@niva.no [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway); Salbu, Brit; Teien, Hans-Christian; Heier, Lene Sørlie [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Rosseland, Bjørn Olav [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian University of Life Sciences (NMBU), Department of Ecology and Natural Resource Management, P.O. Box 5003, N-1432 Ås (Norway); Tollefsen, Knut Erik [Norwegian University of Life Sciences (NMBU), Faculty of Environmental Science and Technology, Department of Environmental Sciences (IMV), Centre for Environmental Radioactivity - CERAD, P.O. Box 5003, N-1432 Ås (Norway); Norwegian Institute for Water Research (NIVA), Gaustadalléen 21, N-0349 Oslo (Norway)

    2014-11-15

    Highlights: • First study on early stress responses in salmon exposed to low-dose gamma radiation. • Dramatic dose-dependent transcriptional responses characterized. • Multiple modes of action proposed for gamma radiation. - Abstract: Due to the production of free radicals, gamma radiation may pose a hazard to living organisms. The high-dose radiation effects have been extensively studied, whereas the ecotoxicity data on low-dose gamma radiation is still limited. The present study was therefore performed using Atlantic salmon (Salmo salar) to characterize effects of low-dose (15, 70 and 280 mGy) gamma radiation after short-term (48 h) exposure. Global transcriptional changes were studied using a combination of high-density oligonucleotide microarrays and quantitative real-time reverse transcription polymerase chain reaction (qPCR). Differentially expressed genes (DEGs; in this article the phrase gene expression is taken as a synonym of gene transcription, although it is acknowledged that gene expression can also be regulated, e.g., at protein stability and translational level) were determined and linked to their biological meanings predicted using both Gene Ontology (GO) and mammalian ortholog-based functional analyses. The plasma glucose level was also measured as a general stress biomarker at the organism level. Results from the microarray analysis revealed a dose-dependent pattern of global transcriptional responses, with 222, 495 and 909 DEGs regulated by 15, 70 and 280 mGy gamma radiation, respectively. Among these DEGs, only 34 were commonly regulated by all radiation doses, whereas the majority of differences were dose-specific. No GO functions were identified at low or medium doses, but repression of DEGs associated with GO functions such as DNA replication, cell cycle regulation and response to reactive oxygen species (ROS) were observed after 280 mGy gamma exposure. Ortholog-based toxicity pathway analysis further showed that 15 mGy radiation

  16. Development and Examination of Personal and Social Responsibility Behaviors Scale

    OpenAIRE

    Bijen FİLİZ; Gıyasettin DEMİRHAN

    2018-01-01

    In this study, “Personal and Social Responsibility Behaviors Scale (PSRB-S)” was developed in order to determine students’ responsibility behaviors in accordance with “Personal and Social Responsibility” model developed by Don Hellison and students’ personal and social responsibility levels were examined in terms of gender, age and years of sport practice through this scale. Pertaining to personal and social dimension of responsibility, four-category Likert type trial scale consisting of 52 i...

  17. Dose-response effects in an outbreak of Salmonella enteritidis.

    Science.gov (United States)

    Mintz, E D; Cartter, M L; Hadler, J L; Wassell, J T; Zingeser, J A; Tauxe, R V

    1994-02-01

    The effects of ingested Salmonella enteritidis (SE) dose on incubation period and on the severity and duration of illness were estimated in a cohort of 169 persons who developed gastroenteritis after eating hollandaise sauce made from grade-A shell eggs. The cohort was divided into three groups based on self-reported dose of sauce ingested. As dose increased, median incubation period decreased (37 h in the low exposure group v. 21 h in the medium exposure group v. 17.5 h in the high exposure group, P = 0.006) and greater proportions reported body aches (71 v. 85 v. 94%, P = 0.0009) and vomiting (21 v. 56 v. 57%, P = 0.002). Among 118 case-persons who completed a follow-up questionnaire, increased dose was associated with increases in median weight loss in kilograms (3.2 v. 4.5 v. 5.0, P = 0.0001), maximum daily number of stools (12.5 v. 15.0 v. 20.0, P = 0.02), subjective rating of illness severity (P = 0.0007), and the number of days of confinement to bed (3.0 v. 6.5 v. 6.5, P = 0.04). In this outbreak, ingested dose was an important determinant of the incubation period, symptoms and severity of acute salmonellosis.

  18. Quantitative radiation dose-response relationships for normal tissues in man. II. Response of the salivary glands during radiotherapy

    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

  19. 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

  20. 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...

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

    NARCIS (Netherlands)

    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

  2. An effective dose of ketamine for eliminating pain during injection of propofol: a dose response study.

    Science.gov (United States)

    Wang, M; Wang, Q; Yu, Y Y; Wang, W S

    2013-09-01

    Ketamine can completely eliminate pain associated with propofol injection. However, the effective dose of ketamine to eliminate propofol injection pain has not been determined. The purpose of this study was to determine the effective dose of ketamine needed to eliminate pain in 50% and 95% of patients (ED50 and ED95, respectively) during propofol injections. This study was conducted in a double-blinded fashion and included 50 patients scheduled for elective gynecological laparoscopy under general anesthesia. The initial dose of ketamine used in the first patient was 0.25mg/kg. The dosing modifications were in increments or decrements of 0.025 mg/kg. Ketamine was administered 15 seconds before injecting propofol (2.5mg/kg), which was injected at a rate of 1mL/s. Patients were asked to rate their pain during propofol injection every 5s econds using a 0-3 pain scale. The highest pain score was recorded. The ED50, ED95 and 95% confidence intervals (CI) were determined by probit analyses. The dose of ketamine ranged from 0.175 to 0.275 mg/kg. The ED50 and ED95 of ketamine for eliminating pain during propofol injection were 0.227 mg/kg and 0.283 mg/kg, respectively (95%CI: 0.211-0.243 mg/kg and 0.26-0.364 mg/kg, respectively). Ketamine at an approximate dose of 0.3mg/kg was effective in eliminating pain during propofol injection. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

  3. Dose response study of PVA-Fx gel for three dimensional dose distribution

    International Nuclear Information System (INIS)

    Brindha, S.; Ayyangar, Komanduri M.; Shen, Bin; Saw, Cheng B.

    2001-01-01

    Modern radiotherapy techniques involve complex field arrangements using conformal and intensity modulated radiation that requires three dimensional treatment planning. The verification of these plans poses even more challenge. In 1984, Gore et al., proposed that ferrous gel dosimeters combined with magnetic resonance imaging (MRI) could be used to measure three dimensional radiation dose distributions. Since then, there has been much interest in the development of gel dosimetry to aid the determination of three dimensional dose distributions during field arrangements. In this work, preparation and study of the MR characteristics of a PVA-Fx gel reported in the literature is presented

  4. An Introduction to Item Response Theory for Health Behavior Researchers

    Science.gov (United States)

    Warne, Russell T.; McKyer, E. J. Lisako; Smith, Matthew L.

    2012-01-01

    Objective: To introduce item response theory (IRT) to health behavior researchers by contrasting it with classical test theory and providing an example of IRT in health behavior. Method: Demonstrate IRT by fitting the 2PL model to substance-use survey data from the Adolescent Health Risk Behavior questionnaire (n = 1343 adolescents). Results: An…

  5. Play Initiating Behaviors and Responses in Red Colobus Monkeys

    Science.gov (United States)

    Worch, Eric A.

    2012-01-01

    Red colobus monkeys are playful primates, making them an important species in which to study animal play. The author examines play behaviors and responses in the species for its play initiation events, age differences in initiating frequency and initiating behavior, and the types of social play that result from specific initiating behaviors. Out…

  6. Emotional responses to behavioral economic incentives for health behavior change

    NARCIS (Netherlands)

    van der Swaluw, Koen; Lambooij, Mattijs S.; Mathijssen, Jolanda J.P.; Zeelenberg, Marcel; Polder, Johan J.; Prast, Henriëtte M.

    2018-01-01

    Many people aim to change their lifestyle, but have trouble acting on their intentions. Behavioral economic incentives and related emotions can support commitment to personal health goals, but the related emotions remain unexplored. In a regret lottery, winners who do not attain their health goals

  7. Emotional Responses to Behavioral Economic Incentives for Health Behavior Change

    NARCIS (Netherlands)

    van der Swaluw, Koen; Lambooij, Mattijs S; Mathijssen, Jolanda; Zeelenberg, Marcel; Polder, Johan; Prast, Henriette

    2018-01-01

    Many people aim to change their lifestyle, but have trouble acting on their intentions. Behavioral economic incentives and related emotions can support commitment to personal health goals, but the related emotions remain unexplored. In a regret lottery, winners who do not attain their health goals

  8. Development and Validation of Children's Responsible Environmental Behavior Scale

    Science.gov (United States)

    Erdogan, Mehmet; Ok, Ahmet; Marcinkowski, Thomas Joseph

    2012-01-01

    Though environmentally responsible behavior (ERB) has been a focus of many studies in the field of environmental education, very few scales have been developed to assess children's ERB. In this regard, this article focuses on the development and validation of Children's Responsible Environmental Behavior Scale (CREBS) and also reports the…

  9. Non-linear dose-response of aluminium hydroxide adjuvant particles: Selective low dose neurotoxicity

    International Nuclear Information System (INIS)

    Crépeaux, Guillemette; Eidi, Housam; David, Marie-Odile; Baba-Amer, Yasmine; Tzavara, Eleni; Giros, Bruno; Authier, François-Jérôme; Exley, Christopher; Shaw, Christopher A.; Cadusseau, Josette

    2017-01-01

    Aluminium (Al) oxyhydroxide (Alhydrogel ® ), the main adjuvant licensed for human and animal vaccines, consists of primary nanoparticles that spontaneously agglomerate. Concerns about its safety emerged following recognition of its unexpectedly long-lasting biopersistence within immune cells in some individuals, and reports of chronic fatigue syndrome, cognitive dysfunction, myalgia, dysautonomia and autoimmune/inflammatory features temporally linked to multiple Al-containing vaccine administrations. Mouse experiments have documented its capture and slow transportation by monocyte-lineage cells from the injected muscle to lymphoid organs and eventually the brain. The present study aimed at evaluating mouse brain function and Al concentration 180 days after injection of various doses of Alhydrogel ® (200, 400 and 800 μg Al/kg of body weight) in the tibialis anterior muscle in adult female CD1 mice. Cognitive and motor performances were assessed by 8 validated tests, microglial activation by Iba-1 immunohistochemistry, and Al level by graphite furnace atomic absorption spectroscopy. An unusual neuro-toxicological pattern limited to a low dose of Alhydrogel ® was observed. Neurobehavioural changes, including decreased activity levels and altered anxiety-like behaviour, were observed compared to controls in animals exposed to 200 μg Al/kg but not at 400 and 800 μg Al/kg. Consistently, microglial number appeared increased in the ventral forebrain of the 200 μg Al/kg group. Cerebral Al levels were selectively increased in animals exposed to the lowest dose, while muscle granulomas had almost Completely disappeared at 6 months in these animals. We conclude that Alhydrogel ® injected at low dose in mouse muscle may selectively induce long-term Al cerebral accumulation and neurotoxic effects. To explain this unexpected result, an avenue that could be explored in the future relates to the adjuvant size since the injected suspensions corresponding to the lowest dose

  10. Blocking Avoidance and Escape Responses: Relations With Clinically Relevant Behaviors

    Directory of Open Access Journals (Sweden)

    Juliana Maria Bubna Popovitz

    Full Text Available Abstract: The current study aims to evaluate the possible effects of interrupting problematic clinically relevant behaviors on the percentage of these responses and of clinical improvement-related responses. Two clients were treated with Functional Analytic Psychotherapy (FAP, alternating two conditions (ABAB. On condition A, procedures to the therapist consisted of responding to the clinical improvement responses, and to description of outside of therapeutic setting behaviors, but therapists were advised to ignore problem behaviors emitted in session. During condition B, therapists followed the same procedures, but they were oriented to block (interrupt problematic responses emitted in session. Results suggest increase in the percentage of problem behaviors during condition B. Results are discussed, highlighting the viability of planning the contingent response the therapist emits to clinically relevant behaviors.

  11. Dose-response relationships and risk estimates for the induction of cancer due to low doses of low-LET radiation

    International Nuclear Information System (INIS)

    Elaguppillai, V.

    1981-01-01

    Risk estimates for radiation-induced cancer at low doses can be obtained only by extrapolation from the known effects at high doses and high dose rates, using a suitable dose-response model. The applicability of three different models, linear, sublinear and supralinear, are discussed in this paper. Several experimental studies tend to favour a sublinear dose-response model (linear-quadratic model) for low-LET radiation. However, human epidemiological studies do not exclude any of the dose-response relationships. The risk estimates based on linear and linear quadratic dose-response models are compared and it is concluded that, for low-LET radiation, the linear dose-response model would probably over-estimate the actual risk of cancer by a factor of two or more. (author)

  12. 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)

  13. Everyday stress response targets in the science of behavior change.

    Science.gov (United States)

    Smyth, Joshua M; Sliwinski, Martin J; Zawadzki, Matthew J; Scott, Stacey B; Conroy, David E; Lanza, Stephanie T; Marcusson-Clavertz, David; Kim, Jinhyuk; Stawski, Robert S; Stoney, Catherine M; Buxton, Orfeu M; Sciamanna, Christopher N; Green, Paige M; Almeida, David M

    2018-02-01

    Stress is an established risk factor for negative health outcomes, and responses to everyday stress can interfere with health behaviors such as exercise and sleep. In accordance with the Science of Behavior Change (SOBC) program, we apply an experimental medicine approach to identifying stress response targets, developing stress response assays, intervening upon these targets, and testing intervention effectiveness. We evaluate an ecologically valid, within-person approach to measuring the deleterious effects of everyday stress on physical activity and sleep patterns, examining multiple stress response components (i.e., stress reactivity, stress recovery, and stress pile-up) as indexed by two key response indicators (negative affect and perseverative cognition). Our everyday stress response assay thus measures multiple malleable stress response targets that putatively shape daily health behaviors (physical activity and sleep). We hypothesize that larger reactivity, incomplete recovery, and more frequent stress responses (pile-up) will negatively impact health behavior enactment in daily life. We will identify stress-related reactivity, recovery, and response in the indicators using coordinated analyses across multiple naturalistic studies. These results are the basis for developing a new stress assay and replicating the initial findings in a new sample. This approach will advance our understanding of how specific aspects of everyday stress responses influence health behaviors, and can be used to develop and test an innovative ambulatory intervention for stress reduction in daily life to enhance health behaviors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. COMPARING BEHAVIORAL DOSE-EFFECT CURVES FOR HUMANS AND LABORATORY ANIMALS ACUTELY EXPOSED TO TOLUENE.

    Science.gov (United States)

    The utility of laboratory animal data in toxicology depends upon the ability to generalize the results quantitatively to humans. To compare the acute behavioral effects of inhaled toluene in humans to those in animals, dose-effect curves were fitted by meta-analysis of published...

  15. Responses of epithelial cells to low and very low doses of low let radiation

    International Nuclear Information System (INIS)

    Mothersill, Carmel; Seymour, Colin

    2003-01-01

    Recent advances in our knowledge of the biological effects of low doses of ionizing radiation have shown unexpected phenomena. These vary in the endpoint used to detect them and in the dose range examined but all occur as high-frequency events in cell populations. They include: 1. a 'bystander effect' which can be demonstrated at low doses as a transferable.factor(s) causing radiobiological effects in unexposed cells, 2. an assortment of delayed effects' occurring in progeny of cells exposed to low doses, 3. Low-dose Hypersensitivity (HRS) and Increased radioresistance (IRR) which can collectively be demonstrated as a change in the dose-effect relationship, occurring around 0.5-1 Gy of low LET radiation and 4. adaptive responses where cells exposed to very low doses followed by higher doses, exhibit an induced relatively resistant response to the second dose. In all cases, the effect of very low doses is greater than would be predicted by extrapolation of high dose data and is inconsistent with conventional DNA break/repair-based radiobiology. In practical risk assessment terms, the relative importance of the effects are high at low doses where they dominate the response, and small at high doses. This paper reviews these assorted phenomena and in particular seeks to explore whether related or distinct mechanisms underlie these various effects Understanding the mechanistic basis of these phenomena may suggest new approaches to controlling death or survival sectoring at low radiation doses. The key question is whether these low dose phenomena necessitate a new approach to risk assessment. (author)

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

    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

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

    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...

  18. The role of dose inhomogeneity in biological models of dose response

    International Nuclear Information System (INIS)

    Crawford-Brown, D.J.

    1989-01-01

    The paper focuses on the semi-empirical functions proposed by NAS (1980), ICRP (1977), in which terms for initiation and cell killing appear. The extent is not to produce a new model of carcinogenesis, or to reanalyse existing epidemiological data, but to explore whether an existing extrapolation function (proposed by the NAS) can be shown to have coherent theoretical support, while at the same time reproducing (however reasonably) the features of epidemiological data. Attention is restricted to irradiation by high LET radiations such as alpha particles, which may produce large inhomogeneities in both emission density and dose in cellular populations. Particular interest is directed towards epidemiological studies of uranium miners (Hornung and Meinhardt, 1987) and persons injected with 224 Ra (Spiess and Mays, 1970), although the results of the radium dial studies are included since they are discussed in the NAS report. Both populations are characterized by large uncertainties in dose estimation (mean organ dose) and by highly inhomogeneous patterns of irradiation within a single organ (Arnold and Jee, 1959; Diel, 1978; Singh, Bennettee and Wrenn, 1987; Rowland and Marshall, 1959). (author)

  19. Dose equivalent response of personal neutron dosemeters as a function of angle

    International Nuclear Information System (INIS)

    Tanner, J.E.; McDonald, J.C.; Stewart, R.D.; Wernli, C.

    1997-01-01

    The measured and calculated dose equivalent response as a function of angle has been examined for an albedo-type thermoluminescence dosemeter (TLD) that was exposed to unmoderated and D 2 O-moderated 252 Cf neutron sources while mounted on a 40 x 40 15 cm 3 polymethylmethacrylate phantom. The dosemeter used in this study is similar to many neutron personal dosemeters currently in use. The detailed construction of the dosemeter was modelled, and the dose equivalent response was calculated, using the MCNP code. Good agreement was found between the measured and calculated values of the relative dose equivalent angular response for the TLD albedo dosemeter. The relative dose equivalent angular response was also compared with the values of directional and personal dose equivalent as a function of angle published by Siebert and Schuhmacher. (author)

  20. Cytogenetic adaptive response of cultured fish cells to low doses of X-rays

    International Nuclear Information System (INIS)

    Kurihara, Yasuyuki; Etoh, Hisami; Rienkjkarn, M.

    1992-01-01

    The adaptive response was examining chromosomal aberrations and micronucleus in cultured fish cells, ULF-23 (mudminnow) and CAF-31 (gold fish). When cultured fish cells were first irradiated with small doses of X-rays, they became less sensitive to subsequent exposures to high doses. The effective adaptive dose was 4.8 cGy-9.5 cGy. Adaptive doses given cells in the G1 phase were more effective than when given in the S phase. The adaptive response was maximal at 5 hours and disappeared at 10 hours after the adaptive dose. The expression of the response was inhibited by treatment with 3-aminobenzamide, as reported for mammalian cells, and with arabinofuranoside cytosine, an inhibitor of DNA polymerase alpha. Caffeine, an inhibitor of post-replicational repair, had no effect on the response. (author)

  1. Cytogenetic adaptive response of cultured fish cells to low doses of X-rays

    Energy Technology Data Exchange (ETDEWEB)

    Kurihara, Yasuyuki; Etoh, Hisami (National Inst. of Radiological Sciences, Chiba (Japan)); Rienkjkarn, M.

    1992-12-01

    The adaptive response was examining chromosomal aberrations and micronucleus in cultured fish cells, ULF-23 (mudminnow) and CAF-31 (gold fish). When cultured fish cells were first irradiated with small doses of X-rays, they became less sensitive to subsequent exposures to high doses. The effective adaptive dose was 4.8 cGy-9.5 cGy. Adaptive doses given cells in the G1 phase were more effective than when given in the S phase. The adaptive response was maximal at 5 hours and disappeared at 10 hours after the adaptive dose. The expression of the response was inhibited by treatment with 3-aminobenzamide, as reported for mammalian cells, and with arabinofuranoside cytosine, an inhibitor of DNA polymerase alpha. Caffeine, an inhibitor of post-replicational repair, had no effect on the response. (author).

  2. Response of human lymphocytes to low gamma ray doses

    International Nuclear Information System (INIS)

    Vega Carrillo, HR; Banuelos Valenzuela, R; Manzanares Acuna, E; Sanchez-Rodriguez, S.H

    2001-01-01

    Radiation and non-radiation workers lymphocytes were exposed to a low strength gamma-ray field to determine heat shock protein expression in function of radiation dose. Protein identification was carried out using mAb raised against Hsp25, Hsp60, Hsp70 and Hsp90; from these, only Hsp70 protein was detected before and after lymphocyte irradiation. In all cases, an increasing trend of relative amounts of Hsp70 in function to irradiation time was observed. After 70.5 mGy gamma-ray dose, radiation worker's lymphocytes expressed more Hsp70 protein, than non-radiation workers' lymphocytes, indicating a larger tolerance to gamma rays (gamma tolerance), due to an adaptation process developed by their labor condition (Au)

  3. The response of mouse skin to multiple small doses of radiation

    International Nuclear Information System (INIS)

    Denekamp, J.; Harris, S.R.

    1975-01-01

    The response of mouse skin has been tested by irradiating the foot of albino mice and scoring erythema and desquamation during the following month. Multiple small doses of 150, 250 and 350 rad have been given 'daily', and the test dose necessary to achieve a given reaction has been determined one day after the last small fraction. This test dose has been compared with the single dose necessary to produce the same reaction level in previously untreated mice, in order to determine the ratio of the slopes of the dose-response curve at low and high doses: Slope ratio = (single dose - test dose)/total fractionated priming dose. In three separate experiments the slope ratio decreased as the dose per fraction was reduced from 350 to 150 rad. This conflicts with the data of Dutreix et al, who found a constant slope ratio over this dose range. The present data are compared with those obtained by Denekamp using 4, 9 and 14 fractions of 300 rad and by Douglas et al, using the same experimental technique, over the dose range 45 to 200 rad/fraction. In addition, the results from multifraction experiments in which equal dose increments were administered until the requisite skin reaction was achieved are also analysed in terms of their slope ratio (Fowler et al. Douglas et al). When all these results are plotted it is impossible to be sure whether the slope ratio is decreasing over the range 300 to 45 rad per fraction, although it seems likely. Most of the values at low doses lie in the range 0.15 to 0.25, indicating that at low doses the radiation is only 15 to 25% as effective per rad in causing cell death as at higher doses. (author)

  4. Response of human and rabbit lymphocytes to low doses of X-rays

    International Nuclear Information System (INIS)

    Fabry, L.

    1982-01-01

    The response of human and rabbit lymphocytes to low doses of X-rays was studied by the yields of dicentrics in first division metaphases. For both species, the dose-response curve was best fitted to the linear-quadratic model with a linear component predominating up to 67 and 42 rad respectively for man and rabbit. A calibration curve (5-400 rad) was obtained by combining the present results on man with previous data at higher doses. On the other hand, it appears that, at low doses, the radiosentivity of human lymphocytes is significantly higher than that of rabbit lymphocytes [fr

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

    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.

  6. Adaptive response of DNA strand breaks in lymphocytes to low dose and γ-rays

    International Nuclear Information System (INIS)

    Du Zeji; Su Liaoyuan; Kong Xiangrong; Tian Hailin

    1996-01-01

    Fluorometric analysis of DNA unwinding was used to study the adaptive response of DNA strand breaks induced by low dose γ-rays and the effect of pADPRT inhibitor-3-AB on the adaptive response. The results indicated that 0.5-4 cGy γ-rays could induce adaptive response of DNA strand breaks in lymphocytes, especially at the doses of 2.0 and 4.0 cGy. This response was not obvious after 8.0 cGy γ-rays irradiation. A challenge dose of 5-20 Gy could make the response expressed, 15 Gy was the best one and 30 Gy was too high to give an adaptive response . 0.5 mM 3-AB could inhibit the response vigorously. As the concentration increased, the adaptive response could be inhibited completely

  7. Quantitative radiation dose-response relationships for normal tissues in man - I. Gustatory tissues response during photon and neutron radiotherapy

    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

  8. Children's Behavior Responses to TV Food Advertisements

    Science.gov (United States)

    Clancy-Hepburn, Katherine; And Others

    1974-01-01

    Two preliminary studies of children's responses to TV advertisements demonstrate the complexity of responses and indicate the need for research conducted within a multidisciplinary framework. The use of the entire family as the unit of analysis is suggested. (Author/RH)

  9. Relationships among Sensory Responsiveness, Anxiety, and Ritual Behaviors in Children with and without Atypical Sensory Responsiveness.

    Science.gov (United States)

    Bart, Orit; Bar-Shalita, Tami; Mansour, Hanin; Dar, Reuven

    2017-08-01

    To explore relationships between sensory responsiveness, anxiety, and ritual behaviors in boys with typical and atypical sensory responsiveness. Forty-eight boys, ages 5-9 participated in the study (28 boys with atypical sensory responsiveness and 20 controls). Atypical sensory responsiveness was defined as a score of ≤154 on the Short Sensory Profile. Parents completed the Sensory Profile, the Screen for Child Anxiety Related Emotional Disorders, and the Childhood Routines Inventory. Children with atypical sensory responsiveness had significantly higher levels of anxiety and a higher frequency of ritual behaviors than controls. Atypical sensory responsiveness was significantly related to both anxiety and ritual behaviors, with anxiety mediating the relationship between sensory modulation and ritual behaviors. The findings elucidate the potential consequences of atypical sensory responsiveness and could support the notion that ritual behaviors develop as a coping mechanism in response to anxiety stemming from primary difficulty in modulating sensory input.

  10. Adaptive Feeding behavior and functional responses in pelagic copepods

    DEFF Research Database (Denmark)

    Kiørboe, Thomas; Saiz, Enrico; Tiselius, Peter

    2018-01-01

    Zooplankton may modify their feeding behavior in response to prey availability and presence of predators with implications to populations of both predators and prey. Optimal foraging theory predicts that such responses result in a type II functional response for passive foragers and a type III re...

  11. Response of rat spinal cord to single and fractionated doses of accelerated heavy ions

    International Nuclear Information System (INIS)

    Leith, J.L.; McDonald, M.; Powers-Risius, P.; Bliven, S.F.; Walton, R.E.; Woodruff, K.H.; Howard, J.

    1980-01-01

    The response of rat spinal cord to irradiation with accelerated heavy ions, in particular carbon and neon ions has been studied. Two different ionization regions in the modified Bragg curve for each ion have been studied for both single and fractionated exposures. We have defined the paralytic response as a function of dose and dose per fraction, and we have determined RBE and repair values. The response of rat spinal cord is both dose and LET dependent, which allows the derivation of RBE and repair values

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

    Science.gov (United States)

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

    2010-02-01

    The new paradigm envisioned for toxicity testing in the 21st century advocates shifting from the current animal-based testing process to a combination of in vitro cell-based studies, high-throughput techniques, and in silico modeling. A strategic component of the vision is the adoption of the systems biology approach to acquire, analyze, and interpret toxicity pathway data. As key toxicity pathways are identified and their wiring details elucidated using traditional and high-throughput techniques, there is a pressing need to understand their qualitative and quantitative behaviors in response to perturbation by both physiological signals and exogenous stressors. The complexity of these molecular networks makes the task of understanding cellular responses merely by human intuition challenging, if not impossible. This process can be aided by mathematical modeling and computer simulation of the networks and their dynamic behaviors. A number of theoretical frameworks were developed in the last century for understanding dynamical systems in science and engineering disciplines. These frameworks, which include metabolic control analysis, biochemical systems theory, nonlinear dynamics, and control theory, can greatly facilitate the process of organizing, analyzing, and understanding toxicity pathways. Such analysis will require a comprehensive examination of the dynamic properties of "network motifs"--the basic building blocks of molecular circuits. Network motifs like feedback and feedforward loops appear repeatedly in various molecular circuits across cell types and enable vital cellular functions like homeostasis, all-or-none response, memory, and biological rhythm. These functional motifs and associated qualitative and quantitative properties are the predominant source of nonlinearities observed in cellular dose response data. Complex response behaviors can arise from toxicity pathways built upon combinations of network motifs. While the field of computational cell

  13. Effect of Variable Doses of Zinc Oxide Nanoparticles on Male Albino Mice Behavior.

    Science.gov (United States)

    Zahra, Javeria; Iqbal, Shahid; Zahra, Kiran; Javed, Zulha; Shad, Muhammad Aslam; Akbar, Atif; Ashiq, Muhammad Naeem; Iqbal, Furhan

    2017-02-01

    Zinc oxide nanoparticles (ZnO NPs) have diverse utility these days ranging from being part of nanosensors to be ingredient of cosmetics. Present study was designed to report the effect of variable doses of ZnO NPs on selected aspects of male albino mice behavior. Nano particles were synthesized by sol-gel auto-combustion method (Data not shown here). 10 week old male albino mice were divided into four experimental groups; group A, B and C were orally supplemented with 50 (low dose), 300 (medium dose) and 600 mg/ml solvent/kg body weight (high dose) of ZnO NPs for 4 days. Group D (control) orally received 0.2 M sodium phosphate buffer (solvent for ZnO NPs) for the same duration. A series of neurological tests (Rota rod, open field, novel object and light-dark box test) were conducted in all groups and performance was compared between ZnO NPs treated and control group. Muscular functioning during rota rod test was significantly improved in all ZnO NPs treated mice as compared to control group. While no significant differences in open field, novel object and light-dark box test performance were observed when data from studied parameters of specific ZnO NPs treatment were compared with the control group indicating that applied doses of ZnO NPs did not affect the exploratory, anxiolytic behavior and object recognition capability of adult male albino mice.

  14. Urochloa ruziziensis responses to sources and doses of urea

    Directory of Open Access Journals (Sweden)

    João E. S. Lima

    2016-05-01

    Full Text Available ABSTRACT The use of products that promote reduction of nitrogen (N losses from the urea fertilizer can contribute to increasing its use efficiency in forage grasses. This study aimed to evaluate the effects of N sources and doses on the growth of Urochloa ruziziensis. The experiment was carried out in the growing season of 2007/2008 in Santo Antônio de Goiás-GO, in a Brazilian Oxisol. A completely randomized block was used, with four replicates in a factorial scheme, corresponding to two N sources (conventional urea and urea with urease inhibitor and five N doses (0, 50, 100, 200 and 300 kg ha-1, divided into equal applications in five periods (Nov 14 to Dec 13, Dec 14 to Jan 12, Jan 13 to Feb 11 - rainy season, Mar 24 to Apr 22 and Jul 10 to Aug 08 - dry season. The effects of the treatments were evaluated for: shoot dry matter, tiller density, total N content in the leaves and relative chlorophyll content. N fertilizer sources did not affect the evaluated variables; however, N fertilization allowed linear increases in all variables with higher values during the rainy period. The relative chlorophyll content in U. ruziziensis had positive correlation with its dry matter productivity.

  15. Radiation effect and response of DNA synthesis in lymphocytes induced by low dose irradiation

    International Nuclear Information System (INIS)

    Zhao Yujie; Su Liaoyuan; Zou Huawei; Kong Xiangrong

    1999-01-01

    The ability of DNA synthesis in lymphocytes were measured by using 3 H-TdR incorporation method. This method was used to observe the damage of lymphocytes irradiated by several challenge doses (0.5-0.8 Gy) and adaptive response induced by previous low dose irradiation. The results show that DNA synthesis was inhibited by challenge dose of radiation and was adapted by previous 0.048 Gy irradiation

  16. I-131 Dose Response for Incident Thyroid Cancers in Ukraine Related to the Chornobyl Accident

    OpenAIRE

    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 ...

  17. Responses of some normal tissues to low doses of γ-radiation

    International Nuclear Information System (INIS)

    Withers, H.R.

    1975-01-01

    The response of four normal tissues to low doses of γ-radiation was measured in mice using three indirect methods. The survival curves for cells of the tissues studied (colon, jejunum, testis and haemoleucopoietic system) may be exponential over an uncertain dose range (from zero to between 100 to 230 rad), the slope being about one third of that in the high-dose region. Some of the uncertainties in the data probably reflect variations in age-density distribution. (author)

  18. A unified dose response relationship to predict high dose fractionation response in the lung cancer stereotactic body radiation therapy

    Directory of Open Access Journals (Sweden)

    Than S Kehwar

    2017-01-01

    Full Text Available Aim: This study is designed to investigate the superiority and applicability of the model among the linear-quadratic (LQ, linear-quadratic-linear (LQ-L and universal-survival-curve (USC models by fitting published radiation cell survival data of lung cancer cell lines. Materials and Method: The radiation cell survival data for small cell (SC and non-small cell (NSC lung cancer cell lines were obtained from published reports, and were used to determine the LQ and cell survival curve parameters, which ultimately were used in the curve fitting of the LQ, LQ-L and USC models. Results: The results of this study demonstrate that the LQ-L(Dt-mt model, compared with the LQ and USC models, provides best fit with smooth and gradual transition to the linear portion of the curve at transition dose Dt-mt, where the LQ model loses its validity, and the LQ-L(Dt-2α/β and USC(Dt-mt models do not transition smoothly to the linear portion of the survival curve. Conclusion: The LQ-L(Dt-mt model is able to fit wide variety of cell survival data over a very wide dose range, and retains the strength of the LQ model in the low-dose range.

  19. No-threshold dose-response curves for nongenotoxic chemicals: Findings and applications for risk assessment

    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

  20. Radiation dose-response relationship of micronucleus occurrence in pollen mother cells of tradescantia

    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

  1. PSOD: an interactive Fortran program to simulate the radiation dose response of membrane populations

    International Nuclear Information System (INIS)

    Perry, K.A.; Szekely, J.G.

    1982-04-01

    Program PSOD was written to simulate the distribution in responses of membrane populations subjected to random radiation doses and dose rates. It computes the response (damage) according to one of three formulas selected by the user, and outputs statistical results to the terminal. It will plot simulated dose- and response-frequency distributions in two or three dimensions. Doses and dose rates are selected from the log normal distribution; other distributions can be incorporated as the need arises. A true log normal curve with defined mean and standard deviation can also be generated. The purpose of this documentation is to provide a complete operating manual for the program. A user guide is available on-line after initiating a session of PSOD. Detailed examinations of the statistical validity of various steps have been included to aid future modifications and updating

  2. Dose Response of MARV/Angola Infection in Cynomolgus Macaques following IM or Aerosol Exposure

    Science.gov (United States)

    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

  3. Dramatic response to high-dose icotinib in a lung adenocarcinoma patient after erlotinib failure.

    Science.gov (United States)

    Guan, Yin; Zhao, Hong; Meng, Jing; Yan, Xiang; Jiao, ShunChang

    2014-02-01

    Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) retreatment is rarely administered for non-small cell lung cancer (NSCLC) patients who did not respond to previous TKI treatment. A high dose of TKI may overcome resistance to the standard dose of TKI and have different effectiveness toward cancer compared with the standard dose of TKI. This manuscript describes a dramatic and durable response to high-dose icotinib in a NSCLC patient who did not respond to a previous standard dose of erlotinib. The treatment extended the life of the patient for one additional year. A higher dose of icotinib deserves further study not only for patients whose therapy failed with the standard dose of TKI but also for newly diagnosed NSCLC patients with a sensitive mutation. Serial mutation testing during disease development is necessary for analysis and evaluation of EGFR TKI treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  4. 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.

  5. Combination of behaviorally sub-effective doses of glutamate NMDA and dopamine D1 receptor antagonists impairs executive function.

    Science.gov (United States)

    Desai, Sagar J; Allman, Brian L; Rajakumar, Nagalingam

    2017-04-14

    Impairment of executive function is a core feature of schizophrenia. Preclinical studies indicate that injections of either N-methyl d-aspartate (NMDA) or dopamine D 1 receptor blockers impair executive function. Despite the prevailing notion based on postmortem findings in schizophrenia that cortical areas have marked suppression of glutamate and dopamine, recent in vivo imaging studies suggest that abnormalities of these neurotransmitters in living patients may be quite subtle. Thus, we hypothesized that modest impairments in both glutamate and dopamine function can act synergistically to cause executive dysfunction. In the present study, we investigated the effect of combined administration of "behaviorally sub-effective" doses of NMDA and dopamine D 1 receptor antagonists on executive function. An operant conditioning-based set-shifting task was used to assess behavioral flexibility in rats that were systemically injected with NMDA and dopamine D 1 receptor antagonists individually or in combination prior to task performance. Separate injections of the NMDA receptor antagonist, MK-801, and the dopamine D 1 receptor antagonist, SCH 23390, at low doses did not impair set-shifting; however, the combined administration of these same behaviorally sub-effective doses of the antagonists significantly impaired the performance during set-shifting without affecting learning, retrieval of the memory of the initial rule, latency of responses or the number of omissions. The combined treatment also produced an increased number of perseverative errors. Our results indicate that NMDA and D 1 receptor blockade act synergistically to cause behavioral inflexibility, and as such, subtle abnormalities in glutamatergic and dopaminergic systems may act cooperatively to cause deficits in executive function. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Linear and non-linear dose-response functions reveal a hormetic relationship between stress and learning.

    Science.gov (United States)

    Zoladz, Phillip R; Diamond, David M

    2008-10-16

    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 well as the excitatory effects of several neuromodulators, including corticosteroids, norepinephrine, corticotropin-releasing hormone, acetylcholine and dopamine. We propose that this rapid activation of the amygdala-hippocampus brain memory system results in a linear dose-response relation between emotional strength and memory formation. More prolonged stress, however, leads to an inhibition of hippocampal function, which can be attributed to compensatory cellular responses that protect hippocampal neurons from excitotoxicity. This inhibition of hippocampal functioning in response to prolonged stress is potentially relevant to the well-described curvilinear dose-response relationship between arousal and memory. Our emphasis on the temporal features of stress-brain interactions addresses how stress can activate, as well as impair, hippocampal functioning to produce a hormetic relationship between stress and learning.

  7. Proof of concept and dose estimation with binary responses under model uncertainty.

    Science.gov (United States)

    Klingenberg, B

    2009-01-30

    This article suggests a unified framework for testing Proof of Concept (PoC) and estimating a target dose for the benefit of a more comprehensive, robust and powerful analysis in phase II or similar clinical trials. From a pre-specified set of candidate models, we choose the ones that best describe the observed dose-response. To decide which models, if any, significantly pick up a dose effect, we construct the permutation distribution of the minimum P-value over the candidate set. This allows us to find critical values and multiplicity adjusted P-values that control the familywise error rate of declaring any spurious effect in the candidate set as significant. Model averaging is then used to estimate a target dose. Popular single or multiple contrast tests for PoC, such as the Cochran-Armitage, Dunnett or Williams tests, are only optimal for specific dose-response shapes and do not provide target dose estimates with confidence limits. A thorough evaluation and comparison of our approach to these tests reveal that its power is as good or better in detecting a dose-response under various shapes with many more additional benefits: It incorporates model uncertainty in PoC decisions and target dose estimation, yields confidence intervals for target dose estimates and extends to more complicated data structures. We illustrate our method with the analysis of a Phase II clinical trial. Copyright (c) 2008 John Wiley & Sons, Ltd.

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

    International Nuclear Information System (INIS)

    Metz-Flamant, Camille

    2011-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    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.

  11. 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)

  12. Toward a unified approach to dose-response modeling in ecotoxicology.

    Science.gov (United States)

    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.

  13. Behavioral Theory and Culture Special Issue: Authors' Response to Commentaries

    Science.gov (United States)

    Pasick, Rena J.; Burke, Nancy J.; Joseph, Galen

    2009-01-01

    This article presents the authors' response to commentaries that focus on the "Behavioral Constructs and Culture in Cancer Screening" (3Cs) study. The 3Cs study had an unremarkable beginning, with two colleagues discussing their frustration over the narrow range of behavioral theories and the limited guidance the theories offered for a study…

  14. Emotional Responses to Environmental Messages and Future Behavioral Intentions

    Science.gov (United States)

    Perrin, Jeffrey L.

    2011-01-01

    The present research investigated effects of message framing (losses-framed or gains-framed), message modality (video with text or text-only) and emotional arousal on environmentally responsible behavioral intentions. The sample consisted of 161 college students. The present research did not find a significant difference in behavioral intentions…

  15. Infant Communicative Behaviors and Maternal Responsiveness

    Science.gov (United States)

    DiCarlo, Cynthia F.; Onwujuba, Chinwe; Baumgartner, Jennifer I.

    2014-01-01

    Background: This study applies attachment and transactional theories in evaluating the dyadic interactions observed between a mother and her infant. Infant communication and maternal responsivity are highlighted as the medium for positive interaction. Objective: The impact of individualized maternal training on mother infant communicative…

  16. A Unified Probabilistic Framework for Dose-Response Assessment of Human Health Effects.

    Science.gov (United States)

    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.

  17. Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment

    OpenAIRE

    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...

  18. 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)

  19. Can prenatal low-dose irradiation affect behavior of adult rats?

    International Nuclear Information System (INIS)

    Smajda, B.; Tomasova, L.; Kokocova, N.

    2011-01-01

    The aim of our study was to determine whether exposure of very low dose gamma-rays during the critical phase of brain development affects some selected behavioral parameters in adult rats. Pregnant female Wistar rats were irradiated with 1 Gy gamma-rays from a cobalt source at 17 th day of pregnancy. The progeniture of irradiated as well as non-irradiated females have undergone behavioral tests at the age of 3 months. Irradiated animals exhibited lower locomotor and exploratory activity in the open field test. (authors)

  20. THE IMPACTS OF PHILANTHROPY RESPONSIBILITY AND ETHICAL RESPONSIBILITY TOWARD CUSTOMER PURCHASE BEHAVIOR AND CUSTOMER LOYALTY

    OpenAIRE

    Kurniawati Chrisjatmiko; Danthy Margareth

    2018-01-01

    The purpose of this research is to analyze the impact of philanthropy responsibility and ethical responsibility towards customer purchase behavior and customer loyalty on fast food restaurants. The research was conducted by using quantitative research design and hypothetical testing to explore philanthropic responsibility, ethical responsibility, customer purchase behavior, and customer loyalty variables. Samples were taken from 186 respondents of employee population in Jakarta. Structural eq...

  1. Cetacean Social Behavioral Response to Sonar Exposure

    Science.gov (United States)

    2015-09-30

    likely a social response which anticipates against potential loss of social cohesion, which may be induced by masking of their communication signals...Discrimination of fast click series produced by Risso’s dolphins for echolocation or communication . Wensveen P. et al (in review). The effectiveness of ramp...up of naval sonar to reduce sound levels received by marine mammals : experimental tests with humpback whales. Kvadsheim et al. (2015). The 3S2

  2. Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer's disease.

    Science.gov (United States)

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J

    2009-01-01

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues and pathways that were specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down-regulated in normal human aging and Alzheimer's disease.

  3. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    International Nuclear Information System (INIS)

    Lowe, Xiu R.; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-01-01

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p -53 ) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease

  4. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    Energy Technology Data Exchange (ETDEWEB)

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-06-06

    Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.

  5. Dose-response and concentration-response relation of rocuronium infusion during propofol nitrous oxide and isoflurane nitrous oxide anaesthesia

    NARCIS (Netherlands)

    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

  6. 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)

  7. 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)

  8. NRC source term assessment for incident response dose projections

    International Nuclear Information System (INIS)

    Easley, P.; Pasedag, W.

    1984-01-01

    The NRC provides advice and assistance to licensees and State and local authorities in responding to accidents. The TACT code supports this function by providing source term projections for two situations during early (15 to 60 minutes) accident response: (1) Core/containment damage is indicated, but there are no measured releases. Quantification of a predicted release permits emergency response before people are exposed. With TACT, response personnel can estimate releases based on fuel and cladding conditions, coolant boundary and containment integrity, and mitigative systems operability. For this type of estimate, TACT is intermediate between default assumptions and time-consuming mechanistic codes. (2) A combination of plant status and limited release data are available. For this situation, iterations between predictions based on known conditions which are compared to measured releases gives reasonable confidence in supplemental source term information otherwise unavailable: nuclide mix, releases not monitored, and trending or abrupt changes. The assumptions and models used in TACT, and examples of its use, are given in this paper

  9. Study of the dose response of the system ferrous ammonium sulfate–sucrose–xylenol orange in acid aqueous solution

    International Nuclear Information System (INIS)

    Juarez-Calderon, J.M.; Negron-Mendoza, A.; Ramos-Bernal, S.

    2014-01-01

    An aqueous solution of ammonium ferrous sulfate–sucrose–xylenol orange in sulfuric acid (FSX) is proposed as a dosimetric system for the processes of gamma irradiation in a range between 0.3 and 6 Gy. This system is based on the indirect oxidation of ferrous ion by an organic compound (sucrose) to ferric ion and on the formation of a color complex of Fe 3+ in an acidic medium with xylenol orange (a dye). After gamma radiation, an observable change occurs in the color of the system. Irradiation was executed at three different temperatures (13 °C, 22 °C, and 40 °C). A spectrometric readout method at 585 nm was employed to evaluate the system's dose response. In all of the cases analyzed, the responses had a linear behavior, and a slight effect of irradiation temperature was observed. Post-irradiation response was also evaluated and showed the stability of the solutions 24 h after the irradiation. The results obtained suggest that FSX might be used as a dosimeter for low doses of gamma irradiation because it provides a stable signal, good reproducibility, and an accessible technique for analysis. - Highlights: • The system ferrous-sucrose-xylenol is reproducibility with less than 5% error. • The dosimeter has low cost and easy readout using UV-vis spectrometry, and the response is stable for several days. • The system proposed is suitable for low irradiation doses

  10. Erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA

    International Nuclear Information System (INIS)

    Speight, E.L.; Farr, P.M.

    1994-01-01

    In PUVA treatment of psoriasis, clinical observation suggests that uninvolved skin is more susceptible to PUVA erythema than lesions of psoriasis. If this is the case, then the efficacy of PUVA treatment might be increased by using localized high-dose UVA restricted to lesional skin. We have therefore studied the erythemal and therapeutic response of psoriasis to PUVA using high-dose UVA and, for comparison, the erythemal response to UVB. This study demonstrates that psoriasis may clear rapidly, without burning, using high-dose UVA. Availability of a suitable irradiation apparatus would allow rapid and effective PUVA treatment to be used for localized, resistant disease. (author)

  11. 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

  12. The Key Events Dose-Response Framework: a cross-disciplinary mode-of-action based approach to examining dose-response and thresholds.

    Science.gov (United States)

    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.

  13. Comparison of dose response functions for EBT3 model GafChromic™ film dosimetry system.

    Science.gov (United States)

    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.

  14. 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

  15. 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.

  16. Effect and adaptive response of lymphocytes DNA induced by low dose irradiation

    International Nuclear Information System (INIS)

    Du Zeji; Su Liaoyuan; Tian Hailin

    1994-09-01

    Fluorometric analysis of DNA unwinding (FADU) was conducted and was proved to be an optimal method for studying DNA strand breaks induced by low dose irradiation. The linear dose response curve was obtained. The minimum detected dose was 0.3 Gy. There was no effect of low dose γ-rays (0.5∼8.0 cGy) on DNA strand breaks of quiescent and mitogen-induced lymphocytes. The 0.5∼4.0 cGy γ-rats could induce adaptive response of lymphocytes' DNA strand breaks, especially, at the doses of 2.0 and 4.0 cGy. The challenge doses of 5∼20 Gy could make the adaptive response appearance, and the 15 Gy was the best one. The 3-AB could powerfully inhibit the adaptive response. The repair of DNA strand breaks (37 degree C, 15∼60 min) caused by 15 Gy γ-rays could be promoted by the low dose γ-ray irradiation (2.0 cGy), but no difference was found at 37 degree C, 120 min

  17. Radiation dose response of N channel MOSFET submitted to filtered X-ray photon beam

    Science.gov (United States)

    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.

  18. Threshold dose for behavioral discrimination of cigarette nicotine content in menthol vs. non-menthol smokers.

    Science.gov (United States)

    Perkins, Kenneth A; Kunkle, Nicole; Karelitz, Joshua L

    2017-04-01

    The lowest threshold content (or "dose") of nicotine discriminated in cigarettes may differ due to menthol preference. Menthol and non-menthol Spectrum research cigarettes differing in nicotine content were used to determine discrimination thresholds. Dependent smokers preferring menthol (n = 40) or non-menthol (n = 21) brands were tested on ability to discriminate cigarettes (matched for their menthol preference) with nicotine contents of 16-17, 11-12, 5, 2, and 1 mg/g, one per session, from an "ultra-low" cigarette with 0.4 mg/g. Controlled exposure to each cigarette was four puffs/trial, and the number of sessions was determined by the lowest nicotine content they could discriminate on >80% of trials (i.e., ≥5 of 6). We also assessed subjective perceptions and behavioral choice between cigarettes to relate them to discrimination responses. Controlling for Fagerstrom Test of Nicotine Dependence score, discrimination thresholds were more likely to be at higher nicotine content cigarettes for menthol vs. non-menthol smokers (p vs. 11 mg/g, respectively. Compared to the ultra-low, threshold and subthreshold (next lowest) cigarettes differed on most perceptions and puff choice, but menthol preference did not alter these associations. Notably, threshold cigarettes did, but subthreshold did not, increase choice over the ultra-low. Threshold for discriminating nicotine via smoking may be generally higher for menthol vs. non-menthol smokers. More research is needed to identify why menthol smoking is related to higher nicotine thresholds and to verify that cigarettes unable to be discriminated do not support reinforcement.

  19. A study on measurement on artificial radiation dose rate using the response matrix method

    International Nuclear Information System (INIS)

    Kidachi, Hiroshi; Ishikawa, Yoichi; Konno, Tatsuya

    2004-01-01

    We examined accuracy and stability of estimated artificial dose contribution which is distinguished from natural background gamma-ray dose rate using Response Matrix method. Irradiation experiments using artificial gamma-ray sources indicated that there was a linear relationship between observed dose rate and estimated artificial dose contribution, when irradiated artificial gamma-ray dose rate was higher than about 2 nGy/h. Statistical and time-series analyses of long term data made it clear that estimated artificial contribution showed almost constant values under no artificial influence from the nuclear power plants. However, variations of estimated artificial dose contribution were infrequently observed due to of rainfall, detector maintenance operation and occurrence of calibration error. Some considerations on the factors to these variations were made. (author)

  20. Computational Modeling of Micrometastatic Breast Cancer Radiation Dose Response

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Daniel L.; Debeb, Bisrat G. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Thames, Howard D. [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Woodward, Wendy A., E-mail: wwoodward@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Morgan Welch Inflammatory Breast Cancer Research Program and Clinic, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

    2016-09-01

    Purpose: Prophylactic cranial irradiation (PCI) involves giving radiation to the entire brain with the goals of reducing the incidence of brain metastasis and improving overall survival. Experimentally, we have demonstrated that PCI prevents brain metastases in a breast cancer mouse model. We developed a computational model to expand on and aid in the interpretation of our experimental results. Methods and Materials: MATLAB was used to develop a computational model of brain metastasis and PCI in mice. Model input parameters were optimized such that the model output would match the experimental number of metastases per mouse from the unirradiated group. An independent in vivo–limiting dilution experiment was performed to validate the model. The effect of whole brain irradiation at different measurement points after tumor cells were injected was evaluated in terms of the incidence, number of metastases, and tumor burden and was then compared with the corresponding experimental data. Results: In the optimized model, the correlation between the number of metastases per mouse and the experimental fits was >95. Our attempt to validate the model with a limiting dilution assay produced 99.9% correlation with respect to the incidence of metastases. The model accurately predicted the effect of whole-brain irradiation given 3 weeks after cell injection but substantially underestimated its effect when delivered 5 days after cell injection. The model further demonstrated that delaying whole-brain irradiation until the development of gross disease introduces a dose threshold that must be reached before a reduction in incidence can be realized. Conclusions: Our computational model of mouse brain metastasis and PCI correlated strongly with our experiments with unirradiated mice. The results further suggest that early treatment of subclinical disease is more effective than irradiating established disease.

  1. Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake.

    Science.gov (United States)

    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.

  2. Exercise and Osteoporosis: A Dose-Response Meta-Analysis

    Science.gov (United States)

    2013-05-01

    ground reaction force topic (701) Petersen T. The booming boomer market . American Fitness 2008 May;26(3):48-50. Not a BMD and/or ground reaction...K, Grunfeld C, Daar ES, LaMarca A, Kotler DP, Wang J, Bozzette SA, Breitmeyer JB. Recombinant human growth hormone in patients with HIV-associated...Skerry, “e response of bone to mechanical load- ing and disuse� fundamental principles and in�uences on osteoblast/osteocyte homeostasis,”Archives of

  3. 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.

  4. Influence of environmental factors on some high dose dosimeter responses in Yazd Radiation Processing Center

    International Nuclear Information System (INIS)

    Ziaie, F.; Tahami, S.M.; Zareshahi, H.; Lanjanian, H.; Durrani, S.A.

    2008-01-01

    In this paper attempt has been made to study the influence of temperature and UV light (exist in laboratory due to the fluorescent light or diffused sunlight) on some high dose dosimetry responses that are being used in Yazd Radiation Processing Center (YRPC). The CTA, FWT and B3 film dosimeters were used for this investigation. The correction of the read response of the dosimeters to the real absorbed dose values is very important especially while we need to measure the precise dose values in the medical devices and in foodstuff materials. Yazd city is near to the desert, and so temperature and UV light due to the sun are very different in compare to other cities. Therefore, we tried to investigate the temperature and UV light effects on the dosimeter response in different doses and obtain its variation as a function of temperature (up to ∼60 0 C) and exposure time (up to ∼1 year), respectively

  5. Dose-response investigation into glucose facilitation of memory performance and mood in healthy young adults.

    Science.gov (United States)

    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.

  6. Hypertonic Saline in Conjunction with High-Dose Furosemide Improves Dose-Response Curves in Worsening Refractory Congestive Heart Failure.

    Science.gov (United States)

    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

    Diuretic responsiveness in patients with chronic heart failure (CHF) is better assessed by urine production per unit diuretic dose than by the absolute urine output or diuretic dose. Diuretic resistance arises over time when the plateau rate of sodium and water excretion is reached prior to optimal fluid elimination and may be overcome when hypertonic saline solution (HSS) is added to high doses of furosemide. Forty-two consecutively hospitalized patients with refractory CHF were randomized in a 1:1:1 ratio to furosemide doses (125 mg, 250 mg, 500 mg) so that all patients received intravenous furosemide diluted in 150 ml of normal saline (0.9%) in the first step (0-24 h) and the same furosemide dose diluted in 150 ml of HSS (1.4%) in the next step (24-48 h) as to obtain 3 groups as follows: Fourteen patients receiving 125 mg (group 1), fourteen patients receiving 250 mg (group 2), and fourteen patients receiving 500 mg (group 3) of furosemide. Urine samples of all patients were collected at 30, 60, and 90 min, and 3, 4, 5, 6, 8, and 24 h after infusion. Diuresis, sodium excretion, osmolality, and furosemide concentration were evaluated for each urine sample. After randomization, 40 patients completed the study. Two patients, one in group 2 and one in group 3 dropped out. Patients in group 1 (125 mg furosemide) had a mean age of 77 ± 17 years, 43% were male, 6 (43%) had heart failure with a preserved ejection fraction (HFpEF), and 64% were in New York Heart Association (NYHA) class IV; the mean age of patients in group 2 (250 mg furosemide) was 80 ± 8.1 years, 15% were male, 5 (38%) had HFpEF, and 84% were in NYHA class IV; and the mean age of patients in group 3 (500 mg furosemide) was 73 ± 12 years, 54% were male, 6 (46%) had HFpEF, and 69% were in NYHA class IV. HSS added to furosemide increased total urine output, sodium excretion, urinary osmolality, and furosemide urine delivery in all patients and at all time points. The percentage increase was 18,14, and

  7. 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

  8. Simulation of salt behavior using in situ response

    International Nuclear Information System (INIS)

    Li, W.T.

    1986-01-01

    The time-dependent nonlinear structural behavior in a salt formation around the openings can be obtained by either performing computational analysis of measuring in situ responses. However, analysis using laboratory test data may often deviate from the actual in situ conditions and geomechanical instruments can provide information only up to the time when the measurements were taken. A method has been suggested for simulating the salt behavior by utilizing the steady-state portion of in situ response history. Governing equations for computational analysis were normalized to the creep constant, the equations were solved, and the analytical response history was then computed in terms of normalized time. By synchronizing the response history obtained from the analysis to the one measured at the site, the creep constant was determined. Then the structural response of the salt was computed. This paper presents an improved method for simulating the salt behavior. In this method, the governing equations are normalized to the creep function, which represents the transient and the steady-state creep behavior. Both the transient and the steady-state portions of in situ response history are used in determining the creep function. Finally, a nonlinear mapping process relating the normalized and real time domains determines the behavior of the salt

  9. 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

  10. Dose - Response Curves for Dicentrics and PCC Rings: Preparedness for Radiological Emergency in Thailand

    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.

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

    International Nuclear Information System (INIS)

    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).

  12. Dose-dependent headache response and dilatation of limb and extracranial arteries after three doses of 5-isosorbide-mononitrate

    DEFF Research Database (Denmark)

    Iversen, Helle Klingenberg; Nielsen, T H; Garre, K

    1992-01-01

    of the temporal artery, but not for the radial artery. It is concluded that headache after 5-ISMN is caused by arterial dilatation or by mechanisms responsible for the arterial dilatation. Ultrasound monitoring of arterial diameters is an important and sensitive tool in the evaluation of nitrates and other...... and placebo on separate days. The diameters of the radial and superficial temporal arteries were repeatedly measured with high frequency ultrasound and pain was scored using a 10 point verbal scale. A clear dose-relationship was found for plasma concentrations and headache, and for changes in the diameter...

  13. Dose response of bone-targeted enzyme replacement for murine hypophosphatasia.

    Science.gov (United States)

    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.

  14. THE IMPACTS OF PHILANTHROPY RESPONSIBILITY AND ETHICAL RESPONSIBILITY TOWARD CUSTOMER PURCHASE BEHAVIOR AND CUSTOMER LOYALTY

    Directory of Open Access Journals (Sweden)

    Kurniawati Chrisjatmiko

    2018-02-01

    Full Text Available The purpose of this research is to analyze the impact of philanthropy responsibility and ethical responsibility towards customer purchase behavior and customer loyalty on fast food restaurants. The research was conducted by using quantitative research design and hypothetical testing to explore philanthropic responsibility, ethical responsibility, customer purchase behavior, and customer loyalty variables. Samples were taken from 186 respondents of employee population in Jakarta. Structural equation modeling was used in order to test the proposed hypotheses. Research result showed the positive and significant impact of philanthropic responsibility towards customer purchase behavior. On contrary, there was no positive ethical responsibility impact found towards customer purchase behavior. These findings are supported by the fact that the majority of consumers purchased fast food base on impulsive buying and not driven by the fast food restaurants ethically responsible behavior. However, the research does show a positive and significant impact of customer purchase behavior on customer loyalty. Further research recommendation should be taken from more respondents in a broader population area. Companies are suggested to approach a strategic and relevant caused-related marketing and caused promotions in relation to philanthropy responsibility to increase customer purchase behavior.

  15. Adaptive response and split-dose effect of radiation on the survival ...

    Indian Academy of Sciences (India)

    Unknown

    In the present work, we report radioadaptive response in terms of survival of ... Group 4: mice pre-treated with conditioning dose of 0⋅5 Gy ... week in mice exposed to 8 Gy. For mice .... The adaptive response is known to remain for a few hours.

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

    Science.gov (United States)

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

    2011-01-01

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

  17. Chronic low-dose γ-irradiation of Drosophila melanogaster larvae induces gene expression changes and enhances locomotive behavior

    International Nuclear Information System (INIS)

    Kim, Cha Soon; Lee, Byung Sub; Lee, In Kyung; Yang, Kwang Hee; Kim, Ji-Young; Nam, Seon Young; Seong, Ki Moon

    2015-01-01

    Although radiation effects have been extensively studied, the biological effects of low-dose radiation (LDR) are controversial. This study investigates LDR-induced alterations in locomotive behavior and gene expression profiles of Drosophila melanogaster. We measured locomotive behavior using larval pupation height and the rapid iterative negative geotaxis (RING) assay after exposure to 0.1 Gy γ-radiation (dose rate of 16.7 mGy/h). We also observed chronic LDR effects on development (pupation and eclosion rates) and longevity (life span). To identify chronic LDR effects on gene expression, we performed whole-genome expression analysis using gene-expression microarrays, and confirmed the results using quantitative real-time PCR. The pupation height of the LDR-treated group at the first larval instar was significantly higher (∼2-fold increase in PHI value, P < 0.05). The locomotive behavior of LDR-treated male flies (∼3 − 5 weeks of age) was significantly increased by 7.7%, 29% and 138%, respectively (P < 0.01), but pupation and eclosion rates and life spans were not significantly altered. Genome-wide expression analysis identified 344 genes that were differentially expressed in irradiated larvae compared with in control larvae. We identified several genes belonging to larval behavior functional groups such as locomotion (1.1%), oxidation reduction (8.0%), and genes involved in conventional functional groups modulated by irradiation such as defense response (4.9%), and sensory and perception (2.5%). Four candidate genes were confirmed as differentially expressed genes in irradiated larvae using qRT-PCR (>2-fold change). These data suggest that LDR stimulates locomotion-related genes, and these genes can be used as potential markers for LDR. (author)

  18. Transcriptional profiling of the dose response: a more powerful approach for characterizing drug activities.

    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.

  19. 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

  20. Dose dependent effect of progesterone on hypoxic ventilatory response in newborn rats.

    Science.gov (United States)

    Hichri, Oubeidallah; Laurin, Jean-C; Julien, Cécile A; Joseph, Vincent; Bairam, Aida

    2012-01-01

    The effect of progesterone as a respiratory stimulant in newborn subjects is less known than that in adults. This study investigated the dose-response curve (0, 2, 4, and 8 mg/kg, ip) of progesterone on ventilation in non-anesthetized newborn rats at 4- and 12-days old using plethysmography. Progesterone had no effects in the regulation of normoxic ventilation. However, it enhanced the response to moderate hypoxia (FiO(2) 12%, 20 min) in 4- but not in 12-days old pups. This response was similar between the dose of 4 and 8 mg/kg. These observations suggested that progesterone enhances in age- and dose-dependent manner the hypoxic ventilatory response in newborn rats.

  1. Relaxation behavior and dose dependence of radiation induced radicals in irradiated mango

    International Nuclear Information System (INIS)

    Kameya, Hiromi; Kakita, Daisuke; Kaimori, Yoshihiko; Ukai, Mitsuko; Kikuchi, Masahiro; Kobayashi, Yasuhiko; Shimoyama, Yuhei

    2010-01-01

    Mangoes are imported to Japan after treated with hot water. Recently, irradiated mangoes imported to U. S. are widely used. This paper reports on the ESR method for analyzing the radiation induced radicals of irradiated mangoes. Upon the γ ray irradiation, a strong single peak in the flesh and skin of mangoes was observed at g=2.004. This singlet peak may be attributed to organic free radicals. The ESR spectra of the flesh and skin of mangoes showed the radiation induced radicals due to cellulose by irradiation over 12 kGy. The relaxation times (T 1 and T 2 ) of the singlet signal were calculated. T 2 showed dose response according to increasing the irradiation dose levels, while T 1 was almost constant. The value of (T 1 T 2 ) 1/2 showed the dependence of irradiation dose level. (author)

  2. 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

  3. 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

  4. Effect of Low Amphetamine Doses on Cardiac Responses to Emotional Stress in Aged Rats

    NARCIS (Netherlands)

    Nyakas, Csaba; Buwalda, Bauke; Luiten, Paul G.M.; Bohus, Bela

    1992-01-01

    In young Wistar rats conditioned emotional stress can be characterized by a learned bradycardiac response to an inescapable footshock. In aged rats this bradycardiac response is attenuated and accompanied by suppressed behavioral arousal in response to novelty. In the present study, cardiac

  5. Dose-response of acute urinary toxicity of long-course preoperative chemoradiotherapy for rectal cancer

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-02-15

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

  7. Rationale for nonlinear dose response functions of power greater or less than one

    International Nuclear Information System (INIS)

    Baum, J.W.

    1977-08-01

    Risk estimates and radiation protection standards are generally made using a nonthreshold premise and linear extrapolations from existing data to estimate biological radiation effects at lower doses and at lower dose rates. This seems reasonable in light of the variety of shapes of dose-effect relations which have been observed both in animal studies and in human epidemiological studies. An unexplained observation in several studies was a response which followed a power function of dose with exponent less than one. One explanation offered for this type of response in humans was a postulated population of heterogeneous sensitivity. An alternate, though related, way of considering this question is in terms of multiple-stresses, and this postulate is discussed

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

    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%

  9. Study of the response reduction of LiF:Mg, Ti dosimeter for high dose dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Torkzadeh, Falamarz [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Applications Research School; AEOI, Tehran (Iran, Islamic Republic of); Faripour, Heidar [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Laser and Optics Research School; AEOI, Tehran (Iran, Islamic Republic of); Mardashti, Forough; Manouchehri, Farhad [Nuclear Sciences and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Applications Research School

    2017-07-15

    A single crystal and 5 polycrystalline samples of LiF:Mg, Ti and their pellets were prepared and investigated so as to apply thermoluminescence high gamma dose dosimetry. Three zones of single crystal with dopant concentrations of 200 ppm of Mg and 20 ppm of Ti were also used to prepare the single crystal samples. For polycrystalline samples, dopant concentrations of 0.062 mol% Mg and Ti concentrations in the range of 0.016 and 0.046 mol% were used. All the samples were exposed to gamma doses of 1 kGy to 700 kGy and their response changes were determined by a gamma dose test of about 60 mGy. According to the results obtained, the use of response reduction by curve-fitting up to about 300 kGy can be performed reliably for high dose gamma dosimetry.

  10. 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)

  11. Context and strain-dependent behavioral response to stress

    Directory of Open Access Journals (Sweden)

    Baum Amber E

    2008-06-01

    Full Text Available Abstract Background This study posed the question whether strain differences in stress-reactivity lead to differential behavioral responses in two different tests of anxiety. Strain differences in anxiety-measures are known, but strain differences in the behavioral responses to acute prior stress are not well characterized. Methods We studied male Fisher 344 (F344 and Wistar Kyoto (WKY rats basally and immediately after one hour restraint stress. To distinguish between the effects of novelty and prior stress, we also investigated behavior after repeated exposure to the test chamber. Two behavioral tests were explored; the elevated plus maze (EPM and the open field (OFT, both of which are thought to measure activity, exploration and anxiety-like behaviors. Additionally, rearing, a voluntary behavior, and grooming, a relatively automatic, stress-responsive stereotyped behavior were measured in both tests. Results Prior exposure to the test environment increased anxiety-related measures regardless of prior stress, reflecting context-dependent learning process in both tests and strains. Activity decreased in response to repeated testing in both tests and both strains, but prior stress decreased activity only in the OFT which was reversed by repeated testing. Prior stress decreased anxiety-related measures in the EPM, only in F344s, while in the OFT, stress led to increased freezing mainly in WKYs. Conclusion Data suggest that differences in stressfulness of these tests predict the behavior of the two strains of animals according to their stress-reactivity and coping style, but that repeated testing can overcome some of these differences.

  12. Naltrexone and human eating behavior: a dose-ranging inpatient trial in moderately obese men.

    Science.gov (United States)

    Maggio, C A; Presta, E; Bracco, E F; Vasselli, J R; Kissileff, H R; Pfohl, D N; Hashim, S A

    1985-06-01

    To investigate the effects of the long-acting opiate antagonist naltrexone on spontaneous human eating behavior, eight moderately obese male paid volunteers were housed in a hospital metabolic unit for 28 days and offered palatable foods ad lib by a platter service method. Under double-blind conditions, equally divided doses of 100, 200 and 300 mg naltrexone, or an acetaminophen placebo, were administered twice daily in tablet form for 3-day periods each, according to a Latin Square design. The doses of naltrexone resulted in decreases of daily caloric intake from placebo level, but these reductions were neither statistically significant nor dose-related. When the averaged effects of the doses were compared to placebo, five subjects showed intake reductions but the overall intake reduction of 301.5 +/- 198.1 kcal/day (mean +/- SEM) was not statistically significant. Naltrexone administration failed to selectively alter intakes of individual meals and snacks or macronutrient consumption patterns. During active drug periods, subjects lost 0.62 +/- 0.22 lb over 3 days, while during the placebo period, subjects gained 0.46 +/- 0.68 lb. However, there was no reliable change of basal metabolic rate as a function of naltrexone administration. The present results, which indicate that naltrexone administration is relatively ineffective in reducing food intake and inducing body weight loss in obese humans, are thus in contrast with reports that administration of opiate antagonist agents promote significant reductions of food intake and attenuations of body weight gain in experimental animals.

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

    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

  14. Response of mouse tongue epithelium to single doses of bleomycin and radiation

    International Nuclear Information System (INIS)

    Dorr, W.; Hirler, E.; Honig, M.

    1993-01-01

    Both bleomycin (BLM) and local X-irradiation (25 kV) induce denudation in the tongue epithelium of the C3H-Neuherberg mouse in a dose-dependent manner. In the present study the effect of BLM alone and of combined single doses of drug and radiation were studied using the incidence of epithelial denudation as the end-point. In 'time-line' experiments, 8 mg/kg BLM were given before or after graded doses of X-rays. BLM treatment required a reduction of the radiation dose (ED 50 ) from 15 Gy to 5-7 Gy, independent of sequence or time interval. In contrast, the time course of the response was clearly dependent on the treatment interval. Latency decreased when the drug was injected less than 2 h before irradiation with minimum latency observed at 30 min. Isobologram analysis of experiments with varying combinations of X-rays and BLM demonstrated that small drug doses were relatively more effective than larger doses, suggesting an upward concavity of the BLM dose-effective curve in vivo, i.e. a 'negative shoulder' of the curve in the low dose region. In contrast to the response to X-rays alone, which has a constant latent time to ulcer of 10 days, the latency in combined treatment was clearly shortened with increasing drug dose and at high doses eventually approximated the epithelial turnover time of 5 days. The data suggest that BLM both as a single agent and in combination with X-rays reduced the probability of abortive divisions and through this effect shortened the latent time to epithelial denudation. (author)

  15. 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.

  16. 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.

  17. 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.

  18. Influence of dose history on thermoluminescence response of Ge-doped silica optical fibre dosimeters

    International Nuclear Information System (INIS)

    Moradi, F.; Mahdiraji, G.A.; Dermosesian, E.; Khandaker, M.U.; Ung, N.M.; Mahamd Adikan, F.R.; Amin, Y.M.

    2017-01-01

    Nowadays, silica based optical fibres show enough potential to be used as TL dosimeters in different applications. Reuse of optical fibre as a practical dosimeter demands to complete removal of accumulated doses via previous irradiations. This work investigates the existence and/or effect of remnant doses in fibre dosimeter from the previous irradiations, and proposes a method to control this artifact. A single mode Ge-doped optical fibre is used as TL radiation sensor, while a well calibrated Gammacell with 60 Co source is used for irradiations. The effect of irradiation history on the TL response of optical fibres is surveyed extensively for doses ranged from 1 to 1000 Gy. The results show that the absorbed dose history in a fibre affects its response in the next irradiation cycles. It is shown that a dose history of around 100 Gy can increase the response of optical fibre by a factor of 1.72. The effect of annealing at higher temperatures on stabilizing the fibre response is also examined and results revealed that another alteration in the structure of trapping states occurs in glass medium which can change the sensitivity of fibres. Preservation of the sensitivity during successive irradiation cycles can be achieved by a proper annealing procedure accompanied by a pre-dose treatment. - Highlights: • Influence of dose history on TL characteristics of fibre dosimeter is explored. • The phenomenon behind the TL variation caused by dose history is discussed. • Effect of annealing temperature on performance of fibre dosimeter is studied. • Pre-treatment methods for mitigating variation in reproducibility are proposed.

  19. 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)

  20. Electrical resistance behavior with gamma radiation dose in bulk carbon nanostrutured samples

    International Nuclear Information System (INIS)

    Lage, J.; Leyva, A.; Pinnera, I.; Desdin, L. F.; Abreu, Y.; Cruz, C. M.; Leyva, D.; Toledo, C.

    2013-01-01

    The aim of this paper is to study the effects of 60 Co gamma radiation on the electrical resistance and V-I characteristic of bulk carbon nano structured samples obtained by electric arc discharge in water method. Images of pristine samples obtained with scanning electron, and the results in graphical form of the electrical characterization of irradiated samples are presented in the text. It was observed that the electrical resistance vs. dose behavior shows an initial increment reaching the maximum at approximately 135 kGy, followed by a drop of the resistance values. These behaviors are associated with the progressive generation of radiation induced defects in the sample, whose number increases to reach saturation at 135 kGy. From this dose, defects could lead to cross-links between different nano structures present in the sample conducting to a gradually drop in electrical resistance. The measured V-I curves show that, increasing exposure to the 60 Co gamma radiation, the electrical properties of the studied samples transit from a semiconductor towards a predominantly metallic behavior. These results were compared with those obtained for a sample of graphite powder irradiated under the same conditions. (Author)

  1. Low-dose neutron dose response of zebrafish embryos obtained from the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility

    International Nuclear Information System (INIS)

    Ng, C.Y.P.; Kong, E.Y.; Konishi, T.; Kobayashi, A.; Suya, N.; Cheng, S.H.; Yu, K.N.

    2015-01-01

    The dose response of embryos of the zebrafish, Danio rerio, irradiated at 5 h post fertilization (hpf) by 2-MeV neutrons with ≤100 mGy was determined. The neutron irradiations were made at the Neutron exposure Accelerator System for Biological Effect Experiments (NASBEE) facility in the National Institute of Radiological Sciences (NIRS), Chiba, Japan. A total of 10 neutron doses ranging from 0.6 to 100 mGy were employed (with a gamma-ray contribution of 14% to the total dose), and the biological effects were studied through quantification of apoptosis at 25 hpf. The responses for neutron doses of 10, 20, 25, and 50 mGy approximately fitted on a straight line, while those for neutron doses of 0.6, 1 and 2.5 mGy exhibited neutron hormetic effects. As such, hormetic responses were generically developed by different kinds of ionizing radiations with different linear energy transfer (LET) values. The responses for neutron doses of 70 and 100 mGy were significantly below the lower 95% confidence band of the best-fit line, which strongly suggested the presence of gamma-ray hormesis. - Highlights: • Neutron dose response was determined for embryos of the zebrafish, Danio rerio. • Neutron doses of 0.6, 1 and 2.5 mGy led to neutron hormetic effects. • Neutron doses of 70 and 100 mGy accompanied by gamma rays led to gamma-ray hormesis

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

  4. 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.)

  5. Reappraising social insect behavior through aversive responsiveness and learning.

    Science.gov (United States)

    Roussel, Edith; Carcaud, Julie; Sandoz, Jean-Christophe; Giurfa, Martin

    2009-01-01

    The success of social insects can be in part attributed to their division of labor, which has been explained by a response threshold model. This model posits that individuals differ in their response thresholds to task-associated stimuli, so that individuals with lower thresholds specialize in this task. This model is at odds with findings on honeybee behavior as nectar and pollen foragers exhibit different responsiveness to sucrose, with nectar foragers having higher response thresholds to sucrose concentration. Moreover, it has been suggested that sucrose responsiveness correlates with responsiveness to most if not all other stimuli. If this is the case, explaining task specialization and the origins of division of labor on the basis of differences in response thresholds is difficult. To compare responsiveness to stimuli presenting clear-cut differences in hedonic value and behavioral contexts, we measured appetitive and aversive responsiveness in the same bees in the laboratory. We quantified proboscis extension responses to increasing sucrose concentrations and sting extension responses to electric shocks of increasing voltage. We analyzed the relationship between aversive responsiveness and aversive olfactory conditioning of the sting extension reflex, and determined how this relationship relates to division of labor. Sucrose and shock responsiveness measured in the same bees did not correlate, thus suggesting that they correspond to independent behavioral syndromes, a foraging and a defensive one. Bees which were more responsive to shock learned and memorized better aversive associations. Finally, guards were less responsive than nectar foragers to electric shocks, exhibiting higher tolerance to low voltage shocks. Consequently, foragers, which are more sensitive, were the ones learning and memorizing better in aversive conditioning. Our results constitute the first integrative study on how aversive responsiveness affects learning, memory and social

  6. Reappraising social insect behavior through aversive responsiveness and learning.

    Directory of Open Access Journals (Sweden)

    Edith Roussel

    Full Text Available The success of social insects can be in part attributed to their division of labor, which has been explained by a response threshold model. This model posits that individuals differ in their response thresholds to task-associated stimuli, so that individuals with lower thresholds specialize in this task. This model is at odds with findings on honeybee behavior as nectar and pollen foragers exhibit different responsiveness to sucrose, with nectar foragers having higher response thresholds to sucrose concentration. Moreover, it has been suggested that sucrose responsiveness correlates with responsiveness to most if not all other stimuli. If this is the case, explaining task specialization and the origins of division of labor on the basis of differences in response thresholds is difficult.To compare responsiveness to stimuli presenting clear-cut differences in hedonic value and behavioral contexts, we measured appetitive and aversive responsiveness in the same bees in the laboratory. We quantified proboscis extension responses to increasing sucrose concentrations and sting extension responses to electric shocks of increasing voltage. We analyzed the relationship between aversive responsiveness and aversive olfactory conditioning of the sting extension reflex, and determined how this relationship relates to division of labor.Sucrose and shock responsiveness measured in the same bees did not correlate, thus suggesting that they correspond to independent behavioral syndromes, a foraging and a defensive one. Bees which were more responsive to shock learned and memorized better aversive associations. Finally, guards were less responsive than nectar foragers to electric shocks, exhibiting higher tolerance to low voltage shocks. Consequently, foragers, which are more sensitive, were the ones learning and memorizing better in aversive conditioning.Our results constitute the first integrative study on how aversive responsiveness affects learning, memory and

  7. Induction of IgG memory responses with polyvinylpyrrolidone (PVP) is antigen dose dependent

    International Nuclear Information System (INIS)

    Lite, H.S.; Braley-Mullen, H.

    1981-01-01

    Irradiated recipients of spleen cells from mice primed with a very low dose (0.0025 μ/g) of the thymus-independent (TI) antigen polyvinylpyrrolidone (PVP) produced PVP-specific IgG memory responses after secondary challenge with a T-dependent (TD) form of PVP, PVP-HRBC. The IgG memory responses induced by low doses of PVP were similar in magnitude to those induced by the TD antigen PVP-HRBC. The induction of IgG memory by the TI form of antigen was markedly dependent on the dose of PVP used to prime donor mice. Spleen cells from mice primed with an amount of PVP (0.25 μg) that induces an optimal primary IgM response did not produce significant IgG antibody after challenge with PVP-HRBC. The inability of higher doses of PVP to induce IgG memory may be due, at least in part, to the fact that such doses of PVP were found to induce tolerance in PVP-specific B cells and could suppress the induction of memory induced by PVP-HRBC. Low doses of PVP did not interfere with the induction of memory by PVP-HRBC. Expression of IgG memory responses in recipients of PVP-HRBC or low-dose PVP-primed cells was found to be T cell dependent. Moreover, only primed T cells could reconstitute the respnse of recipients of primed B cells, suggesting that the ability of PVP to induce IgG memory may be related to its ability to prime T helper cells. Expression of the IgG memory response in recipient mice also required the use of a TD antigen for secondary challenge, i.e., mice challenged with PVP did not develop IgG

  8. Implications of effects ''adaptive response'', ''low-dose hypersensitivity'' und ''bystander effect'' for cancer risk at low doses and low dose rates

    International Nuclear Information System (INIS)

    Jacob, P

    2006-01-01

    A model for carcinogenesis (the TSCE model) was applied in order to examine the effects of ''Low-dose hypersensitivity (LDH)'' and the ''Bystander effect (BE)'' on the derivation of radiation related cancer mortality risks. LDH has been discovered to occur in the inactivation of cells after acute exposure to low LET radiation. A corresponding version of the TSCE model was applied to the mortality data on the Abomb survivors from Hiroshima and Nagasaki. The BE has been mainly observed in cells after exposure to high LET radiation. A Version of the TSCE model which included the BE was applied to the data on lung cancer mortality from the workers at the Mayak nuclear facilities who were exposed to Plutonium. In general an equally good description of the A-bomb survivor mortality data (for all solid, stomach and lung tumours) was found for the TSCE model and the (conventional) empirical models but fewer parameters were necessary for the TSCE model. The TSCE model which included the effects of radiation induced cell killing resulted in non-linear dose response curves with excess relative risks after exposure at young ages that were generally lower than in the models without cell killing. The main results from TSCE models which included cell killing described by either conventional survival curves or LDH were very similar. A sub multiplicative effect from the interaction of smoking and exposure to plutonium was found to result from the analysis of the Mayak lung cancer mortality data. All models examined resulted in the predominant number of Mayak lung cancer deaths being ascribed to smoking. The interaction between smoking and plutonium exposures was found to be the second largest effect. The TSCE model resulted in lower estimates for the lung cancer excess relative risk per unit plutonium dose than the empirical risk model, but this difference was not found to be statistically significant. The excess relative risk dose responses were linear in the empirical model and

  9. Non-Linear Dose Response Relationships in Biology, Toxicology, and Medicine (June 8-10, 2004). Final Report

    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

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

    Science.gov (United States)

    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.

  11. Health effects of low-dose radiation: Molecular, cellular, and biosystem response

    International Nuclear Information System (INIS)

    Pollycove, M.; Paperiello, C.J.

    1997-01-01

    Since the fifties, the prime concern of radiation protection has been protecting DNA from damage. UNSCEAR initiated a focus on biosystem response to damage with its 1994 report, ''Adaptive Responses to Radiation of Cells and Organisms''. The DNA damage-control biosystem is physiologically operative on both metabolic and radiation induced damage, both effected predominantly by free radicals. These adaptive responses are suppressed by high-dose and stimulated by low dose radiation. Increased biosystem efficiently reduces the number of mutations that accumulate during a lifetime and decrease DNA damage-control with resultant aging and malignancy. Several statistically significant epidemiologic studies have shown risk decrements of cancer mortality and mortality from all causes in populations exposed to low-dose radiation. Further biologic and epidemiologic research is needed to establish a valid threshold below which risk decrements occur. (author)

  12. Direct and transgenerational effects of low doses of perinatal di-(2-ethylhexyl phthalate (DEHP on social behaviors in mice.

    Directory of Open Access Journals (Sweden)

    Kayla M Quinnies

    Full Text Available Di-(2-ethylhexyl phthalate (DEHP is an endocrine disrupting chemical commonly used as a plasticizer in medical equipment, food packaging, flooring, and children's toys. DEHP exposure during early development has been associated with adverse neurobehavioral outcomes in children. In animal models, early exposure to DEHP results in abnormal development of the reproductive system as well as altered behavior and neurodevelopment. Based on these data, we hypothesized that developmental exposure to DEHP would decrease social interactions and increase anxiety-like behaviors in mice in a dose-dependent manner, and that the effects would persist over generations. C57BL/6J mice consumed one of three DEHP doses (0, 5, 40, and 400 μg/kg body weight throughout pregnancy and during the first ten days of lactation. The two higher doses yielded detectable levels of DEHP metabolites in serum. Pairs of mice from control, low, and high DEHP doses were bred to create three dose lineages in the third generation (F3. Average anogenital index (AGI: anogenital distance/body weight was decreased in F1 males exposed to the low dose of DEHP and in F1 females exposed to the highest dose. In F1 mice, juvenile pairs from the two highest DEHP dose groups displayed fewer socially investigative behaviors and more exploratory behaviors as compared with control mice. The effect of DEHP on these behaviors was reversed in F3 mice as compared with F1 mice. F1 mice exposed to low and medium DEHP doses spent more time in the closed arms of the elevated plus maze than controls, indicating increased anxiety-like behavior. The generation-dependent effects on behavior and AGI suggest complex mechanisms by which DEHP directly impacts reproductive and neurobehavioral development and influences germline-inherited traits.

  13. Mechanisms underlying cellular responses of cells from haemopoietic tissue to low dose/low LET radiation

    Energy Technology Data Exchange (ETDEWEB)

    Munira A Kadhim

    2010-03-05

    To accurately define the risks associated with human exposure to relevant environmental doses of low LET ionizing radiation, it is necessary to completely understand the biological effects at very low doses (i.e., less than 0.1 Gy), including the lowest possible dose, that of a single electron track traversal. At such low doses, a range of studies have shown responses in biological systems which are not related to the direct interaction of radiation tracks with DNA. The role of these “non-targeted” responses in critical tissues is poorly understood and little is known regarding the underlying mechanisms. Although critical for dosimetry and risk assessment, the role of individual genetic susceptibility in radiation risk is not satisfactorily defined at present. The aim of the proposed grant is to critically evaluate radiation-induced genomic instability and bystander responses in key stem cell populations from haemopoietic tissue. Using stem cells from two mouse strains (CBA/H and C57BL/6J) known to differ in their susceptibility to radiation effects, we plan to carefully dissect the role of genetic predisposition on two non-targeted radiation responses in these models; the bystander effect and genomic instability, which we believe are closely related. We will specifically focus on the effects of low doses of low LET radiation, down to doses approaching a single electron traversal. Using conventional X-ray and γ-ray sources, novel dish separation and targeted irradiation approaches, we will be able to assess the role of genetic variation under various bystander conditions at doses down to a few electron tracks. Irradiations will be carried out using facilities in routine operation for bystander targeted studies. Mechanistic studies of instability and the bystander response in different cell lineages will focus initially on the role of cytokines which have been shown to be involved in bystander signaling and the initiation of instability. These studies also aim

  14. Guidelines for Use of the Approximate Beta-Poisson Dose-Response Model.

    Science.gov (United States)

    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.

  15. Continuous Dose-Response Response Relationship of the LDL-Cholesterol-Lowering Effect of Phytosterol Intake 1,2

    NARCIS (Netherlands)

    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

  16. EPR response of sucrose and microcrystalline cellulose to measure high doses of gamma radiation

    International Nuclear Information System (INIS)

    Torijano, E.; Cruz, L.; Gutierrez, G.; Azorin, J.; Aguirre, F.; Cruz Z, E.

    2015-10-01

    Solid dosimeters of sucrose and microcrystalline cellulose (Avicel Ph-102) were prepared, following the same process, in order to compare their EPR response against that of the l-alanine dosimeters considered as reference. All lots of dosimeters were irradiated with gamma radiation in Gamma beam irradiator with 8 kGy/h of the Nuclear Sciences Institute of UNAM. Doses ranged from 1 to 10 kGy respectively. We found that both the response of sucrose as microcrystalline cellulose were linear; however, the response intensity was, on average, twenty times more for sucrose. Comparing this against the EPR response of l-alanine in the range of doses, it was found that the response to sucrose is a third part; and microcrystalline cellulose is a sixtieth, approximately. The results agree with those found in the literature for sucrose, leaving open the possibility of investigating other dosage ranges for cellulose. (Author)

  17. 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

  18. Prediction analysis of dose equivalent responses of neutron dosemeters used at a MOX fuel facility

    International Nuclear Information System (INIS)

    Tsujimura, N.; Yoshida, T.; Takada, C.

    2011-01-01

    To predict how accurately neutron dosemeters can measure the neutron dose equivalent (rate) in MOX fuel fabrication facility work environments, the dose equivalent responses of neutron dosemeters were calculated by the spectral folding method. The dosemeters selected included two types of personal dosemeter, namely a thermoluminescent albedo neutron dosemeter and an electronic neutron dosemeter, three moderator-based neutron survey meters, and one special instrument called an H p (10) monitor. The calculations revealed the energy dependences of the responses expected within the entire range of neutron spectral variations observed in neutron fields at workplaces. (authors)

  19. 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)

  20. Prediction of response to continuous irradiation at low dose rate for repeated administrations in radiotherapy with beta emitters

    International Nuclear Information System (INIS)

    Calderon, Carlos; Gonzalez, Joaquin; Quesada, Waldo

    2009-01-01

    The absorbed dose to tumors after systemic administration of radiopharmaceuticals is not sufficient to achieve acceptable levels of probability of tumor control without compromising on critical tissue toxicity (kidney and / or bone marrow (BM)). There are reports of trials with multiple administrations, about tolerance level inter-administration intervals to allow recovery of the BM, with good results. The biokinetic behavior of some radiopharmaceuticals known makes possible the application of several administrations with short intervals of time.It is the present work combines two kinetic models of tumor growth and cell kinetics in the BM for predicting the response to continuous irradiation at low dose rate. The estimation of the effects of irradiation on tumor and kidneys was done using a formulation of the linear-quadratic model functions suitable for dose rate and multi-exponential repair. The estimation of the response in WB performed using a compartmental model previously reported. The absorbed dose to organs were calculated using the MIRD formulation taking into account the effect of irradiation cross. Biokinetic data were used for therapeutic radiopharmaceuticals 90Y, 131I and 177Lu, as well as radiobiological parameters reported for experimental animals. The effect on the response by the variation of inter-administration interval in slow-growing tumors and fast, so as the radiosensitive and radioresistant tumors. You can set conditions irradiation to an acceptable level of thrombocytopenia (onset and duration of the minimum in the curve) and renal irradiation below the limit of tolerance. It is possible to design experiments evaluation of therapeutic radiopharmaceuticals with a greater degree of refinement. (author)

  1. Behavioral response of manatees to variations in environmental sound levels

    Science.gov (United States)

    Miksis-Olds, Jennifer L.; Wagner, Tyler

    2011-01-01

    Florida manatees (Trichechus manatus latirostris) inhabit coastal regions because they feed on the aquatic vegetation that grows in shallow waters, which are the same areas where human activities are greatest. Noise produced from anthropogenic and natural sources has the potential to affect these animals by eliciting responses ranging from mild behavioral changes to extreme aversion. Sound levels were calculated from recordings made throughout behavioral observation periods. An information theoretic approach was used to investigate the relationship between behavior patterns and sound level. Results indicated that elevated sound levels affect manatee activity and are a function of behavioral state. The proportion of time manatees spent feeding and milling changed in response to sound level. When ambient sound levels were highest, more time was spent in the directed, goal-oriented behavior of feeding, whereas less time was spent engaged in undirected behavior such as milling. This work illustrates how shifts in activity of individual manatees may be useful parameters for identifying impacts of noise on manatees and might inform population level effects.

  2. Arsenite Effects on Mitochondrial Bioenergetics in Human and Mouse Primary Hepatocytes Follow a Nonlinear Dose Response

    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.

  3. Recent results on the linearity of the dose-response relationship for radiation-induced mutations in human cells by low dose levels

    International Nuclear Information System (INIS)

    Traut, H.

    1987-01-01

    Five studies made by various authors in the last years are discussed, which are significant in that the response of human cells to low-dose irradiation is determined directly and not by extrapolation, and which also provide information on the mutagenic effects of low radiation doses. The results of these studies do not indicate any other than a linear response for induction of mutations by low-dose irradiation, nor are there any reasons observable for assuming the existence of a threshold dose. It is very likely therefore that cancer initiation at the low dose level also is characterized by a linear relationship. Although threshold dose levels cannot generally be excluded, and maybe are only too low to be detected by experiment, there is no plausible biophysical argument for assuming the existence of such microdose threshold. (orig./MG) [de

  4. Modeling individuals’ cognitive and affective responses in spatial learning behavior

    NARCIS (Netherlands)

    Han, Q.; Arentze, T.A.; Timmermans, H.J.P.; Janssens, D.; Wets, G.; Lo, H.P.; Leung, Stephen C.H.; Tan, Susanna M.L.

    2008-01-01

    Activity-based analysis has slowly shifted gear from analysis of daily activity patterns to analysis and modeling of dynamic activity-travel patterns. In this paper, we describe a dynamic model that is concerned with simulating cognitive and affective responses in spatial learning behavior for a

  5. Physiological and behavioral responses of horses during police training

    NARCIS (Netherlands)

    Munsters, C.C.B.M.; Visser, E.K.; Broek, van den J.; Sloet van Oldruitenborgh-Oosterbaan, M.M.

    2013-01-01

    Mounted police horses have to cope with challenging, unpredictable situations when on duty and it is essential to gain insight into how these horses handle stress to warrant their welfare. The aim of the study was to evaluate physiological and behavioral responses of 12 (six experienced and six

  6. Behavioral responses of broilers to different gaseous atmospheres

    NARCIS (Netherlands)

    Gerritzen, M.A.; Lambooij, E.; Hillebrand, S.J.W.; Lankhaar, J.A.C.; Pieterse, C.

    2000-01-01

    This study was conducted to determine the differences in behavioral response of broilers when they come into contact for the first time with gas mixtures that can be used for stunning. The six test groups were divided into four experimental groups that were exposed to gas mixtures used for stunning

  7. Consistency in behavior of the CEO regarding corporate social responsibility

    NARCIS (Netherlands)

    Elving, W.J.L.; Kartal, D.

    2012-01-01

    Purpose - When corporations adopt a corporate social responsibility (CSR) program and use and name it in their external communications, their members should act in line with CSR. The purpose of this paper is to present an experiment in which the consistent or inconsistent behavior of a CEO was

  8. Workplace mobbing: How the victim's coping behavior influences bystander responses.

    Science.gov (United States)

    Mulder, Roelie; Bos, Arjan E R; Pouwelse, Mieneke; van Dam, Karen

    2017-01-01

    Victims of workplace mobbing show diverse coping behavior. We investigated the impact of this behavior on bystander cognitions, emotions, and helping toward the victim, integrating coping literature with attribution theory. Adult part-time university students (N = 161) working at various organizations participated in a study with a 3(Coping: approach/avoidance/neutral) × 2(Gender Victim: male/female) × 2(Gender Bystander: male/female) design. Victims showing approach (vs. avoidance) coping were considered to be more self-reliant and less responsible for the continuation of the mobbing, and they elicited less anger. Continuation responsibility and self-reliance mediated the relationship between the victim's coping behavior and bystanders' helping intentions. Female (vs. male) participants reported more sympathy for the victim and greater willingness to help, and female (vs. male) victims elicited less anger. Theoretical and practical implications of the findings are discussed.

  9. Bone cancer from radium: canine dose response explains data for mice and humans

    International Nuclear Information System (INIS)

    Raabe, O.G.; Book, S.A.; Parks, N.J.

    1980-01-01

    Analysis of lifetime studies of 243 beagles with skeletal burdens of radium-226 shows that the distribution of bone cancers clusters about a linear function of the logarithms of radiation dose rate to the skeleton and time from exposure until death. Similar relations displaced by species-dependent response ratios also provide satisfactory descriptions of the reported data on deaths from primary bone cancers in people and mice exposed to radium-226. The median cumulative doses (or times) leading to death from bone tumors are 2.9 times larger for dogs than for mice and 3.6 times larger for people than for dogs. These response ratios are well correlated with the normal life expectancies. The cumulative radiation dose required to give significant risk of bone cancer is found to be much less at lower dose rates than at higher rates, but the time required for the tumors to be manifested is longer. At low dose rates, this time exceeds the normal life-span and appears as a practical threshold, which for bone cancer is estimated to occur at an average cumulative radiation dose to the skeleton of about 50 to 110 rads for the three species

  10. 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

  11. Bayesian dose selection design for a binary outcome using restricted response adaptive randomization.

    Science.gov (United States)

    Meinzer, Caitlyn; Martin, Renee; Suarez, Jose I

    2017-09-08

    In phase II trials, the most efficacious dose is usually not known. Moreover, given limited resources, it is difficult to robustly identify a dose while also testing for a signal of efficacy that would support a phase III trial. Recent designs have sought to be more efficient by exploring multiple doses through the use of adaptive strategies. However, the added flexibility may potentially increase the risk of making incorrect assumptions and reduce the total amount of information available across the dose range as a function of imbalanced sample size. To balance these challenges, a novel placebo-controlled design is presented in which a restricted Bayesian response adaptive randomization (RAR) is used to allocate a majority of subjects to the optimal dose of active drug, defined as the dose with the lowest probability of poor outcome. However, the allocation between subjects who receive active drug or placebo is held constant to retain the maximum possible power for a hypothesis test of overall efficacy comparing the optimal dose to placebo. The design properties and optimization of the design are presented in the context of a phase II trial for subarachnoid hemorrhage. For a fixed total sample size, a trade-off exists between the ability to select the optimal dose and the probability of rejecting the null hypothesis. This relationship is modified by the allocation ratio between active and control subjects, the choice of RAR algorithm, and the number of subjects allocated to an initial fixed allocation period. While a responsive RAR algorithm improves the ability to select the correct dose, there is an increased risk of assigning more subjects to a worse arm as a function of ephemeral trends in the data. A subarachnoid treatment trial is used to illustrate how this design can be customized for specific objectives and available data. Bayesian adaptive designs are a flexible approach to addressing multiple questions surrounding the optimal dose for treatment efficacy

  12. Concord Grape Juice Polyphenols and Cardiovascular Risk Factors: Dose-Response Relationships

    Science.gov (United States)

    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

  13. Effect of increased CRM₁₉₇ carrier protein dose on meningococcal C bactericidal antibody response.

    Science.gov (United States)

    Lee, Lucia H; Blake, Milan S

    2012-04-01

    New multivalent CRM(197)-based conjugate vaccines are available for childhood immunization. Clinical studies were reviewed to assess meningococcal group C (MenC) antibody responses following MenC-CRM(197) coadministration with CRM(197)-based pneumococcal or Haemophilus influenzae type b conjugate vaccines. Infants receiving a total CRM(197) carrier protein dose of ∼50 μg and concomitant diphtheria-tetanus-acellular pertussis (DTaP)-containing vaccine tended to have lower MenC geometric mean antibody titers and continued to have low titers after the toddler dose. Nevertheless, at least 95% of children in the reported studies achieved a MenC serum bactericidal antibody (SBA) titer of ≥ 1:8 after the last infant or toddler dose. SBA was measured using an assay with a baby rabbit or human complement source. Additional studies are needed to assess long-term antibody persistence and MenC CRM(197) conjugate vaccine immunogenicity using alternative dosing schedules.

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

    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)

  15. Uncertainty of fast biological radiation dose assessment for emergency response scenarios.

    Science.gov (United States)

    Ainsbury, Elizabeth A; Higueras, Manuel; Puig, Pedro; Einbeck, Jochen; Samaga, Daniel; Barquinero, Joan Francesc; Barrios, Lleonard; Brzozowska, Beata; Fattibene, Paola; Gregoire, Eric; Jaworska, Alicja; Lloyd, David; Oestreicher, Ursula; Romm, Horst; Rothkamm, Kai; Roy, Laurence; Sommer, Sylwester; Terzoudi, Georgia; Thierens, Hubert; Trompier, Francois; Vral, Anne; Woda, Clemens

    2017-01-01

    Reliable dose estimation is an important factor in appropriate dosimetric triage categorization of exposed individuals to support radiation emergency response. Following work done under the EU FP7 MULTIBIODOSE and RENEB projects, formal methods for defining uncertainties on biological dose estimates are compared using simulated and real data from recent exercises. The results demonstrate that a Bayesian method of uncertainty assessment is the most appropriate, even in the absence of detailed prior information. The relative accuracy and relevance of techniques for calculating uncertainty and combining assay results to produce single dose and uncertainty estimates is further discussed. Finally, it is demonstrated that whatever uncertainty estimation method is employed, ignoring the uncertainty on fast dose assessments can have an important impact on rapid biodosimetric categorization.

  16. 'Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans

    Energy Technology Data Exchange (ETDEWEB)

    Jetten, Marlon J.A.; Gaj, Stan [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Ruiz-Aracama, Ainhoa [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Kok, Theo M. de [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Delft, Joost H.M. van, E-mail: j.vandelft@maastrichtuniversity.nl [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Lommen, Arjen [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Someren, Eugene P. van [Research Group Microbiology and Systems Biology, TNO, PO Box 360 3700 AJ Zeist (Netherlands); Jennen, Danyel G.J.; Claessen, Sandra M. [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands); Peijnenburg, Ad A.C.M. [RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen (Netherlands); Stierum, Rob H. [Research Group Microbiology and Systems Biology, TNO, PO Box 360 3700 AJ Zeist (Netherlands); Kleinjans, Jos C.S. [Department of Toxicogenomics, Maastricht University, Universitiessingel 50 6229 ER Maastricht (Netherlands)

    2012-03-15

    Acetaminophen is the primary cause of acute liver toxicity in Europe/USA, which led the FDA to reconsider recommendations concerning safe acetaminophen dosage/use. Unfortunately, the current tests for liver toxicity are no ideal predictive markers for liver injury, i.e. they only measure acetaminophen exposure after profound liver toxicity has already occurred. Furthermore, these tests do not provide mechanistic information. Here, 'omics techniques (global analysis of metabolomic/gene-expression responses) may provide additional insight. To better understand acetaminophen-induced responses at low doses, we evaluated the effects of (sub-)therapeutic acetaminophen doses on metabolite formation and global gene-expression changes (including, for the first time, full-genome human miRNA expression changes) in blood/urine samples from healthy human volunteers. Many known and several new acetaminophen-metabolites were detected, in particular in relation to hepatotoxicity-linked, oxidative metabolism of acetaminophen. Transcriptomic changes indicated immune-modulating effects (2 g dose) and oxidative stress responses (4 g dose). For the first time, effects of acetaminophen on full-genome human miRNA expression have been considered and confirmed the findings on mRNA level. 'Omics techniques outperformed clinical chemistry tests and revealed novel response pathways to acetaminophen in humans. Although no definitive conclusion about potential immunotoxic effects of acetaminophen can be drawn from this study, there are clear indications that the immune system is triggered even after intake of low doses of acetaminophen. Also, oxidative stress-related gene responses, similar to those seen after high dose acetaminophen exposure, suggest the occurrence of possible pre-toxic effects of therapeutic acetaminophen doses. Possibly, these effects are related to dose-dependent increases in levels of hepatotoxicity-related metabolites. -- Highlights: ► 'Omics techniques

  17. 'Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans

    International Nuclear Information System (INIS)

    Jetten, Marlon J.A.; Gaj, Stan; Ruiz-Aracama, Ainhoa; Kok, Theo M. de; Delft, Joost H.M. van; Lommen, Arjen; Someren, Eugene P. van; Jennen, Danyel G.J.; Claessen, Sandra M.; Peijnenburg, Ad A.C.M.; Stierum, Rob H.; Kleinjans, Jos C.S.

    2012-01-01

    Acetaminophen is the primary cause of acute liver toxicity in Europe/USA, which led the FDA to reconsider recommendations concerning safe acetaminophen dosage/use. Unfortunately, the current tests for liver toxicity are no ideal predictive markers for liver injury, i.e. they only measure acetaminophen exposure after profound liver toxicity has already occurred. Furthermore, these tests do not provide mechanistic information. Here, 'omics techniques (global analysis of metabolomic/gene-expression responses) may provide additional insight. To better understand acetaminophen-induced responses at low doses, we evaluated the effects of (sub-)therapeutic acetaminophen doses on metabolite formation and global gene-expression changes (including, for the first time, full-genome human miRNA expression changes) in blood/urine samples from healthy human volunteers. Many known and several new acetaminophen-metabolites were detected, in particular in relation to hepatotoxicity-linked, oxidative metabolism of acetaminophen. Transcriptomic changes indicated immune-modulating effects (2 g dose) and oxidative stress responses (4 g dose). For the first time, effects of acetaminophen on full-genome human miRNA expression have been considered and confirmed the findings on mRNA level. 'Omics techniques outperformed clinical chemistry tests and revealed novel response pathways to acetaminophen in humans. Although no definitive conclusion about potential immunotoxic effects of acetaminophen can be drawn from this study, there are clear indications that the immune system is triggered even after intake of low doses of acetaminophen. Also, oxidative stress-related gene responses, similar to those seen after high dose acetaminophen exposure, suggest the occurrence of possible pre-toxic effects of therapeutic acetaminophen doses. Possibly, these effects are related to dose-dependent increases in levels of hepatotoxicity-related metabolites. -- Highlights: ► 'Omics techniques outperformed

  18. Measurement of radioactive aerosol behavior during dismantling and reflection to the exposure dose evaluation - 16107

    International Nuclear Information System (INIS)

    Iguchi, Yukihiro; Kato, Masami

    2009-01-01

    Radioactive aerosol disperses slightly via contamination prevention systems such as control enclosures and filters when the nuclear installation is dismantled, and it might impact the environment. Therefore, when decommissioning is planned, it is necessary to assess the safety such as exposure dose evaluation to the public. For the radioactive aerosol, it is possible that the dispersion ratio is different according to the contamination condition, the dismantlement method of the material, nuclides (elements), etc. The radiation exposure evaluation for the decommissioning plan has been executed by operators in Japan based on a number of experiments (mostly cold tests) and overseas results. The decommissioning is now being carried out at the Tokai Power Station (GCR) and Fugen Decommissioning Engineering Center in Japan. In this study, the results data is acquired at the decommissioning sites, and the methodology and data for the exposure dose evaluation are verified and confirmed. These examination results will lead to the upgrading and improvement of the exposure evaluation methodology. In particular, the dismantlement work of connected piping of the heat exchanger (steam generator) was executed in the Tokai Power Station in 2008. In this study, we paid attention to the radionuclides of Co-60 and Cs-137 that adhered to piping, and the dispersion behavior of aerosol was measured and contamination prevention effect was assured. As a result, the data show that the cesium concentrates about four times higher than cobalt. Moreover, the effects of the prevention measures of contamination were confirmed and the behavior of the radioactive aerosol became clear and the effective findings about the dose evaluation of the dismantling were collected. (authors)

  19. Development and Examination of Personal and Social Responsibility Behaviors Scale

    Directory of Open Access Journals (Sweden)

    Bijen FİLİZ

    2018-03-01

    Full Text Available In this study, “Personal and Social Responsibility Behaviors Scale (PSRB-S” was developed in order to determine students’ responsibility behaviors in accordance with “Personal and Social Responsibility” model developed by Don Hellison and students’ personal and social responsibility levels were examined in terms of gender, age and years of sport practice through this scale. Pertaining to personal and social dimension of responsibility, four-category Likert type trial scale consisting of 52 items and Exploratory Factor Analysis (EFA were applied to 330 high-school students. Items that did not apply as a result of the analysis were omitted from 52-item trial scale and the scale was reduced to 14 items. A final scale consisting of two factors was created. Obtained scale was applied to different 250 high-school students for Confirmatory Factor Analysis (CFA. It has been determined that EFA and CFA results of two-factor PSRB-S and reliability and validity of internal consistency coefficients are at an acceptable level. It was not detected a significance difference in total scores of athlete students’ responsibility behaviors in terms of gender and age variables while there were significant difference in their total scores of years of sport practice.

  20. Application of Dempster-Shafer theory in dose response outcome analysis

    Science.gov (United States)

    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.

  1. The genomic response of Ishikawa cells to bisphenol A exposure is dose- and time-dependent

    International Nuclear Information System (INIS)

    Naciff, Jorge M.; Khambatta, Zubin S.; Reichling, Timothy D.; Carr, Gregory J.; Tiesman, Jay P.; Singleton, David W.; Khan, Sohaib A.; Daston, George P.

    2010-01-01

    A reliable in vitro model to determine the potential estrogenic activity of chemicals of interest is still unavailable. To further investigate the usefulness of a human-derived cell line, we determined the transcriptional changes induced by bisphenol A (BPA) in Ishikawa cells at various doses (1 nM, 100 nM, 10 μM, and 100 μM) and time points (8, 24 and 48 h) by comparing the response of approximately 38,500 human genes and ESTs between treatment groups and controls (vehicle-treated). By trend analysis, we determined that the expression of 2794 genes was modified by BPA in a dose- and time-dependent manner (p ≤ 0.0001). However, the majority of gene expression changes induced in Ishikawa cells were elicited by the highest doses of BPA evaluated (10-100 μM), while the genomic response of the cells exposed to low doses of BPA was essentially negligible. By comparing the Ishikawa cells' response to BPA vs.17α-ethynyl estradiol we determined that the change in the expression of 307 genes was identical in the direction of the change, although the magnitude of the change for some genes was different. Further, the response of Ishikawa cells to high doses of BPA shared similarities to the estrogenic response of the rat uterus, specifically, 362 genes were regulated in a similar manner in vivo as well as in vitro. Gene ontology analysis indicated that BPA results in changes to multiple molecular pathways affecting various biological processes particularly associated with cell organization and biogenesis, regulation of translation, cell proliferation, and intracellular transport; processes also affected by estrogen exposure in the uterus of the rat. These results indicate that Ishikawa cells are capable of generating a biologically relevant estrogenic response after exposure to chemicals with varied estrogenic activity, and offer an in vitro model to assess this mode of action.

  2. 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...

  3. Linear, no threshold response at low doses of ionizing radiation: ideology, prejudice and science

    International Nuclear Information System (INIS)

    Kesavan, P.C.

    2014-01-01

    The linear, no threshold (LNT) response model assumes that there is no threshold dose for the radiation-induced genetic effects (heritable mutations and cancer), and it forms the current basis for radiation protection standards for radiation workers and the general public. The LNT model is, however, based more on ideology than valid radiobiological data. Further, phenomena such as 'radiation hormesis', 'radioadaptive response', 'bystander effects' and 'genomic instability' are now demonstrated to be radioprotective and beneficial. More importantly, the 'differential gene expression' reveals that qualitatively different proteins are induced by low and high doses. This finding negates the LNT model which assumes that qualitatively similar proteins are formed at all doses. Thus, all available scientific data challenge the LNT hypothesis. (author)

  4. Salmonella fecal shedding and immune responses are dose- and serotype- dependent in pigs.

    Directory of Open Access Journals (Sweden)

    Renata Ivanek

    Full Text Available Despite the public health importance of Salmonella infection in pigs, little is known about the associated dynamics of fecal shedding and immunity. In this study, we investigated the transitions of pigs through the states of Salmonella fecal shedding and immune response post-Salmonella inoculation as affected by the challenge dose and serotype. Continuous-time multistate Markov models were developed using published experimental data. The model for shedding had four transient states, of which two were shedding (continuous and intermittent shedding and two non-shedding (latency and intermittent non-shedding, and one absorbing state representing permanent cessation of shedding. The immune response model had two transient states representing responses below and above the seroconversion level. The effects of two doses [low (0.65×10(6 CFU/pig and high (0.65×10(9 CFU/pig] and four serotypes (Salmonella Yoruba, Salmonella Cubana, Salmonella Typhimurium, and Salmonella Derby on the models' transition intensities were evaluated using a proportional intensities model. Results indicated statistically significant effects of the challenge dose and serotype on the dynamics of shedding and immune response. The time spent in the specific states was also estimated. Continuous shedding was on average 10-26 days longer, while intermittent non-shedding was 2-4 days shorter, in pigs challenged with the high compared to low dose. Interestingly, among pigs challenged with the high dose, the continuous and intermittent shedding states were on average up to 10-17 and 3-4 days longer, respectively, in pigs infected with S. Cubana compared to the other three serotypes. Pigs challenged with the high dose of S. Typhimurium or S. Derby seroconverted on average up to 8-11 days faster compared to the low dose. These findings highlight that Salmonella fecal shedding and immune response following Salmonella challenge are dose- and serotype-dependent and that the detection of

  5. Cytogenetics dosimetry: dose-response curve for low doses of X-ray; Dosimetria citogenetica: curva dosis-respuesta para bajas dosis de rayos-X

    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.

  6. Meteorological monitoring for dose assessment and emergency response modeling - how much is enough?

    International Nuclear Information System (INIS)

    Glantz, C.S.

    1990-01-01

    Individuals responsible for emergency response or environmental/dose assessment routinely ask if there are enough meteorological data to adequately support their objectives. The answer requires detailed consideration of the intended applications, capabilities of the atmospheric dispersion model data, pollutant release characteristics, terrain in the modeling region, and size and distribution of the human population in the modeling domain. The meteorologist's detailed knowledge of, and experience in, studying atmospheric transport and diffusion can assist in determining the appropriate level of meteorological monitoring

  7. Adaptive response of yeast cultures (Saccharomyces Cerevisiae) exposed to low dose of gamma radiation

    International Nuclear Information System (INIS)

    Kulcsar, Agnes; Savu, D.; Petcu, I.; Gherasim, Raluca

    2003-01-01

    The present study was planned as follows: (i) setting up of standard experimental conditions for investigation of radio-induced adaptive response in lower Eucaryotes; (ii) developing of procedures for synchronizing Saccharomyces cerevisiae X 310 D cell cultures and cell cycle stages monitoring; (iii) investigation of gamma (Co-60) and UV irradiation effects on the viability of synchronized and non-synchronized cell cultures of Saccharomyces cerevisiae; the effects were correlated with the cell density and cell cycle stage; (iv) study of the adaptive response induced by irradiation and setting up of the experimental conditions for which this response is optimized. The irradiations were performed by using a Co-60 with doses of 10 2 - 10 4 Gy and dose rates ranging from 2.2 x 10 2 Gy/h to 8.7 x 10 3 Gy/h. The study of radioinduced adaptive response was performed by applying a pre-irradiation treatment of 100-500 Gy, followed by challenge doses of 2-4 kGy delivered at different time intervals, ranging from 1 h to 4 h. The survival rate of synchronized and non-synchronized cultures as a function of exposure dose shows an exponential decay shape. No difference in viability of the cells occurred between synchronized and non-synchronized cultures. The pre-irradiation of cells with 100 and 200 Gy were most efficient to induce an adaptive response for the yeast cells. In this stage of work we proved the occurrence of the adaptive response in the case of synchronized yeast cultures exposed to gamma radiation. The results will be used in the future to investigate the dependence of this response on the cell cycle and the possibility to induce such a response by a low level electromagnetic field. (authors)

  8. Dosimetric behavior of thermoluminescent dosimeters at low doses in diagnostic radiology

    International Nuclear Information System (INIS)

    Del Sol F, S.; Garcia S, R.; Guzman M, J.; Sanchez G, D.; Rivera M, T.; Ramirez R, G.; Gaona, E.

    2015-10-01

    Thermoluminescent (Tl) characteristics of TLD-100, LiF:Mg,Cu,P, and CaSO 4 : Dy the under homogeneous field of X-ray beams of diagnostic irradiation and its verification using thermoluminescent dosimetry is presented. The irradiations were performed utilizing an X-ray beam generated by a Radiology Mexican Company: MRH-II E GMX 325-AF SBV-1 model, with Rotating Anode X-Ray Tube installed in the Hospital Juarez Norte de Mexico in Mexico City. Different thermoluminescent characteristics of dosimetric material were studied, such as, batch homogeneity, Tl glow curve, Tl response as a function of X-ray dose, reproducibility and fading. Materials were calibrated in terms of absorbed dose to the standard calibration distance and positioned in a generic Phantom was used. Dose verification and comparison with the measurements made with that obtained by TLD-100 were analyzed. Preliminary results indicate the dosimetric peak appears at 243, 236 and 277 ± 5 degrees C respectively, these peaks are in agreement with that reported in the literature. Tl glow curve as a function of X-ray dose showed a linearity in the range from 1.76 mGy up to 14.70 mGy for all materials. Fading for a period of one month at room temperature showed low fading LiF:Mg,Cu,P, medium and high for TLD-100 and CaSO 4 : Dy. The results suggest that the three materials are suitable for measurements at low doses in radiodiagnostic, however, for its dosimetric characteristics are most effective for individual applications: personal dosimetry and monitors limb (LiF:Mg,Cu,P), clinical dosimetry and environmental (TLD-100 and CaSO 4 : Dy). (Author)

  9. Treatment dose-response in amblyopia therapy: the Monitored Occlusion Treatment of Amblyopia Study (MOTAS).

    Science.gov (United States)

    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

  10. Dose response association of pregnancy cigarette smoke exposure, childhood stature, overweight and obesity

    NARCIS (Netherlands)

    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

  11. 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....

  12. Response of Nigerian local breed of dog to graded doses of ...

    African Journals Online (AJOL)

    The experiment investigated the response of Nigerian local breed of dog to different doses of Ancylostoma caninum infection. Sixteen dogs aged 6 to 7 months and assigned to 4 groups (A – D) of 4 dogs each were used. Groups A, B and C were infected with 100, 200 and 400 A. caninum infective larvae (L3) while group D ...

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

    Science.gov (United States)

    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.

  14. IsoGeneGUI : Multiple approaches for dose-response analysis of microarray data using R

    NARCIS (Netherlands)

    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

  15. QUANTITATION OF MOLECULAR ENDPOINTS FOR THE DOSE-RESPONSE COMPONENT OF CANCER RISK ASSESSMENT

    Science.gov (United States)

    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...

  16. 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...

  17. Radiation response of industrial materials: Dose-rate and morphology implications

    International Nuclear Information System (INIS)

    Berejka, Anthony J.

    2007-01-01

    Industrial uses of ionizing radiation mostly rely upon high current, high dose-rate (100 kGy/s) electron beam (EB) accelerators. To a lesser extent, industry uses low dose-rate (2.8 x 10 -3 kGy/s) radioactive Cobalt-60 as a gamma source, generally for some rather specific purposes, as medical device sterilization and the treatment of food and foodstuffs. There are nearly nine times as many (∼1400) high current EB units in commercial operation than gamma sources (∼160). However, gamma sources can be easily scaled-down so that much research on materials effects is conducted using gamma radiation. Likewise, laboratories are more likely to have very low beam current and consequently low dose-rate accelerators such as Van de Graaff generators and linear accelerators. With the advent of very high current EB accelerators, X-ray processing has become an industrially viable option. With X-rays from high power sources, dose-rates can be modulated based upon accelerator power and the attenuation of the X-ray by the distance of the material from the X-ray target. Dose and dose-rate dependence has been found to be of consequence in several commercial applications which can employ the use of ionizing radiation. The combination of dose and dose-rate dependence of the polymerization and crosslinking of wood impregnants and of fiber composite matrix materials can yield more economically viable results which have promising commercial potential. Monomer and oligomer structure also play an important role in attaining these desirable results. The influence of morphology is shown on the radiation response of olefin polymers, such as ethylene, propylene and isobutylene polymers and their copolymers. Both controlled morphology and controlled dose-rate have commercial consequences. These are also impacted both by the adroit selection of materials and through the possible use of X-ray processing

  18. Albumin treatment regimen for type 1 hepatorenal syndrome: a dose-response meta-analysis.

    Science.gov (United States)

    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

  19. West Nile virus infection in American Robins: new insights on dose response.

    Directory of Open Access Journals (Sweden)

    Kaci K VanDalen

    Full Text Available West Nile virus (WNV is a vector-borne pathogen that was first detected in the United States in 1999. The natural transmission cycle of WNV involves mosquito vectors and avian hosts, which vary in their competency to transmit the virus. American robins are an abundant backyard species in the United States and appear to have an important role in the amplification and dissemination of WNV. In this study we examine the response of American robins to infection with various WNV doses within the range of those administered by some natural mosquito vectors. Thirty American robins were assigned a WNV dosage treatment and needle inoculated with 10(0.95 PFU, 10(1.26 PFU, 10(2.15 PFU, or 10(3.15 PFU. Serum samples were tested for the presence of infectious WNV and/or antibodies, while oral swabs were tested for the presence of WNV RNA. Five of the 30 (17% robins had neutralizing antibodies to WNV prior to the experiment and none developed viremia or shed WNV RNA. The proportion of WNV-seronegative birds that became viremic after WNV inoculation increased in a dose dependent manner. At the lowest dose, only 40% (2/5 of the inoculated birds developed productive infections while at the highest dose, 100% (7/7 of the birds became viremic. Oral shedding of WNV RNA followed a similar trend where robins inoculated with the lower two doses were less likely to shed viral RNA (25% than robins inoculated with one of the higher doses (92%. Viremia titers and morbidity did not increase in a dose dependent manner; only two birds succumbed to infection and, interestingly, both were inoculated with the lowest dose of WNV. It is clear that the disease ecology of WNV is a complex interplay of hosts, vectors, and viral dose delivered.

  20. Evaluation of energy responses for neutron dose-equivalent meters made in Japan

    International Nuclear Information System (INIS)

    Saegusa, J.; Yoshizawa, M.; Tanimura, Y.; Yoshida, M.; Yamano, T.; Nakaoka, H.

    2004-01-01

    Energy responses of three types of Japanese neutron dose-equivalent (DE) meters were evaluated by Monte Carlo simulations and measurements. The energy responses were evaluated for thermal neutrons, monoenergetic neutrons with energies up to 15.2 MeV, and also for neutrons from such radionuclide sources as 252 Cf and 241 Am-Be. The calculated results were corroborated with the measured ones. The angular dependence of the response and the DE response were also evaluated. As a result, reliable energy responses were obtained by careful simulations of the proportional counter, moderator and absorber of the DE meters. Furthermore, the relationship between pressure of counting gas and response of the DE meter was discussed. By using the obtained responses, relations between predicted readings of the DE meters and true DE values were studied for various workplace spectra

  1. Angular dependence of dose equivalent response of an albedo neutron dosimeter

    International Nuclear Information System (INIS)

    Torres, B.A.; Boswell, E.; Schwartz, R.B.

    1994-01-01

    The ANSI provides procedures for testing the performance of dosimetry services. Although neutron dose equivalent angular response studies are not now mandated, future standards may well require that such studies be performed. Current studies with an albedo dosimeter will yield information regarding the angular dependence of dose equivalent response for this type of personnel dosimeter. Preliminary data for bare 252 Cf fluences show a marked decrease in dosimeter reading with increasing angle. The response decreased by an approximate factor of four. For the horizontal orientation, the same response was noted from both positive and negative angles. However, for the vertical orientation, the response was unexplainably assymetric. We are also examining the response of the personnel badge in moderated 252 Cf fluences. Responses from the moderated and unmoderated 252 Cf fields and theoretical calculations of the neutron angular response will be compared. This information will assist in building a data base for future comparisons of neutron angular responses with other neutron albedo dosimeters and phantoms

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

    Science.gov (United States)

    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

  3. 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

  4. Dose-specific transcriptional responses in thyroid tissue in mice after 131I administration

    International Nuclear Information System (INIS)

    Rudqvist, Nils; Schüler, Emil; Parris, Toshima Z.; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

    2015-01-01

    Introduction: In the present investigation, microarray analysis was used to monitor transcriptional activity in thyroids in mice 24 h after 131 I exposure. The aims of this study were to 1) assess the transcriptional patterns associated with 131 I exposure in normal mouse thyroid tissue and 2) propose biomarkers for 131 I exposure of the thyroid. Methods: Adult BALB/c nude mice were i.v. injected with 13, 130 or 260 kBq of 131 I and killed 24 h after injection (absorbed dose to thyroid: 0.85, 8.5, or 17 Gy). Mock-treated mice were used as controls. Total RNA was extracted from thyroids and processed using the Illumina platform. Results: In total, 497, 546, and 90 transcripts were regulated (fold change ≥ 1.5) in the thyroid after 0.85, 8.5, and 17 Gy, respectively. These were involved in several biological functions, e.g. oxygen access, inflammation and immune response, and apoptosis/anti-apoptosis. Approximately 50% of the involved transcripts at each absorbed dose level were dose-specific, and 18 transcripts were commonly detected at all absorbed dose levels. The Agpat9, Plau, Prf1, and S100a8 gene expression displayed a monotone decrease in regulation with absorbed dose, and further studies need to be performed to evaluate if they may be useful as dose-related biomarkers for 131I exposure. Conclusion: Distinct and substantial differences in gene expression and affected biological functions were detected at the different absorbed dose levels. The transcriptional profiles were specific for the different absorbed dose levels. We propose that the Agpat9, Plau, Prf1, and S100a8 genes might be novel potential absorbed dose-related biomarkers to 131 I exposure of thyroid. Advances in knowledge: During the recent years, genomic techniques have been developed; however, they have not been fully utilized in nuclear medicine and radiation biology. We have used RNA microarrays to investigate genome-wide transcriptional regulations in thyroid tissue in mice after low

  5. Pathological Imitative Behavior and Response Preparation in Schizophrenia.

    Science.gov (United States)

    Dankinas, Denisas; Melynyte, Sigita; Siurkute, Aldona; Dapsys, Kastytis

    2017-08-01

    Pathological imitative behavior (ehopraxia) is occasionally observed in schizophrenia patients. However, only a severe form of echopraxia can be detected with the help of a direct observation. Therefore, our goal was to study a latent form of pathological imitative behavior in this disorder, which is indicated by an increase of imitative tendencies. In our study, 14 schizophrenia patients and 15 healthy subjects were employed in two tasks: (a) in an imitative task they had to copy a hand action seen on a screen; (b) in a counter-imitative task they had to make a different movement (which involves an inhibition of prepotent imitative tendency that is impaired in case of pathological imitative behavior). Imitative tendencies were assessed by an interference score - a difference between counter-imitative and imitative response parameters. We also studied a response preparation in both groups by employing precueing probabilistic information. Our results revealed that schizophrenia patients were able to employ probabilistic information to prepare properly not only the imitative, but also the counter-imitative responses, the same as the healthy subjects did. Nevertheless, we detected increased prepotent imitative tendencies in schizophrenia patients, what indicates the latent pathological imitative behavior in case of this disorder. The obtained results suggest that in the case of schizophrenia problems with pathological imitative behavior more likely occurred in executive rather than in the preparatory stage of response. Our findings can help to detect a latent echopraxia in schizophrenia patients that cannot be revealed by direct observation. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  6. Low-dose dose-response for reduced cell viability after exposure of human keratinocyte (HEK001 cells to arsenite

    Directory of Open Access Journals (Sweden)

    Kenneth T. Bogen

    Full Text Available The in vitro arsenite (AsIII cytotoxicity dose-response (DR of human keratinocytes (HEK001 was examined at greater statistical resolution than ever previously reported using the MTT assay to determine cell viability. Fifty-four 96-well plates were treated with AsIII concentrations of 0.25, 0.5, 1, 2, 3, 4, 5, 7, 10, 15, 20, 25, or 30 μM. Because of unexpected variation in viability response patterns, a two-stage DR analysis was used in which data on plate-specific viability (%, estimated as 100% times the ratio of measured viability in exposed to unexposed cells, were fit initially to a generalized lognormal response function positing that HEK001 cells studied consisted of: a proportion P of relatively highly sensitive (HS cells, a proportion Po of relatively resistant cells, and a remaining (1–P–Po fraction of typical-sensitivity (TS cells exhibiting the intermediate level of AsIII sensitivity characteristic of most cells in each assay. The estimated fractions P and Po were used to adjust data from all 54 plates (and from the 28 plates yielding the best fits to reflect the condition that P = Po = 0 to provide detailed DR analysis specifically for TS cells. Four DR models fit to the combined adjusted data were each very predictive (R2 > 0.97 overall but were inconsistent with at least one of the data set examined (p  0.30 and exceeded 100% significance (p ≤ 10−6. A low-dose hormetic model provided the best fit to the combined adjusted data for TS cells (R2 = 0.995. Marked variability in estimates of P (the proportion of apparent HS cells was unexpected, not readily explained, and warrants further study using additional cell lines and assay methods, and in vivo. Keywords: Arsenic, Arsenate, Cell culture, Cell death, Cytotoxicity, HEK001 cells

  7. 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.

  8. Behavioral changes in rats prenatally irradiated with low dose of gamma-rays

    International Nuclear Information System (INIS)

    Kiskova, J.; Smajda, B.; Capicikova, M.; Lievajova, K.

    2006-01-01

    In this work, the effects of prenatal gamma-irradiation on behavior in adult Sprague-Dawley rats were studied. Four months old female rats were irradiated with a dose of 1 Gy of gamma-rays on day 15 of gestation. The offspring of irradiated mothers (n=26) and that of control, non-irradiated mothers (n=36) of both sexes at the age of 3 month were tested in Morris's water maze and in open field test. All experimental groups showed a tendency to shortening the time needed to reach the platform in each trial in Morris water maze. Statistically significant difference between irradiated and control rats was detected only in males on 3 rd experimental day. The ability to remember the position of the platform was not altered in irradiated animals after a 4 day pause. In open field test, statistically significant differences in comparison with controls were detected in number of squares entered and in crossings of the central square (P ≤ 0.05) in males. These findings suggest, when comparing with results of other authors, that irradiation effects on postnatal behavior in rats are extremely dependent on the time point of irradiation and that a correlation exist between the developmental stage of the individual brain structures at time of irradiation and the late behavioral effects. (authors)

  9. Correlation between dose and tumor response in the radiotherapy of lung cancer of various histological types

    International Nuclear Information System (INIS)

    Koga, Kenji; Kusuhara, Toshiyuki; Nishikawa, Kiyoshi; Asada, Keiko; Watanabe, Katsushi

    1984-01-01

    Correlation between dose and tumor response by cell types was determined in 50 patients with lung cancer in order to predict the possibility of further tumor regression. The TDF (time-dose-fractionation) concept was used as dose factor. The radiation source was a cobalt-60 γ-ray or linear accelerator 10 MV X-ray. As a routine regime a fraction dose of 2 Gy five times per week was given to 39 of the 50 patients, but a dose of 2 Gy three times per week or of 1.5 Gy five times per week was given to seven and four patients, respectively. Radiation response was the best in small cell carcinoma and better in adenocarcinoma than in squamous cell carcinoma, showing a tumor regression rate of 50% or more in 90%, 80% and 58% of the patients, respectively. The correlation between tumor regression rate and TDF values was good in squamous cell carcinoma (r = 0.73) and small cell carcinoma (r = - 0.72), but poor in adenocarcinoma (r = - 0.10). These results suggest that in squamous cell carcinoma improvement of tumor regression can be expected by increasing TDF values, and in adenocarcinoma and small cell carcinoma the optimal TDF values are about 100 and 60 to 80, respectively. (author)

  10. Response of mouse lung to irradiation at different dose-rates

    International Nuclear Information System (INIS)

    Hill, R.P.

    1983-01-01

    Groups of LAF1 mice were given thoracic irradiation using 60 Co γ-rays at dose-rates of 0.05 Gy/min (LDR) or 1.1 Gy/min (HDR) and the death of the animals was monitored as a function of time. It was found that the time pattern of animal deaths was similar for the two different dose-rates. Dose response curves for animals dying at various times up to 500 days after irradiation were calculated and the LD 50 values determined. The curves for the LD 50 values, plotted as a function of the time at analysis for treatment at HDR or LDR, were essentially parallel to each other but separated by a factor (LDR/HDR) of about 1.8. This indicates that the sparing effect of LDR treatment is the same for deaths occurring during the early pneumonitis phase or during the late fibrotic phase of lung damage. The available information on the response of patients to whole thoracic irradiation, given for either palliation or piror to bone marrow transplantation, suggests that for similar dose-rates to those studied here the ratio (LDR/HDR) is only 1.2 to 1.3. This difference between the animal and human data may reflect the modifying effect of the large doses of cytotoxic drugs used in combination with the irradiation of bone marrow transplant patients

  11. Dose-response study of the hematological toxicity induced by vectorized radionuclides in a mouse model

    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)

  12. Plastic packaging and burn-in effects on ionizing dose response in CMOS microcircuits

    International Nuclear Information System (INIS)

    Clark, S.D.; Bings, J.P.; Maher, M.C.; Williams, M.K.; Alexander, D.R.; Pease, R.L.

    1995-01-01

    Results are reported from an investigation of the effects of packaging and burn-in on the post-irradiation performance of National Semiconductor 54AC02 Quad 2-input NOR gates. The test population was drawn from a single wafer fabricated in the National process qualified under Mil-Prf-38535 to an ionizing radiation hardness of 100 krads(Si). The test sample was divided between plastic and ceramic packages. Additionally, half of the plastic samples and half of the two ceramic samples received a 168 hour/125 C burn-in. Two irradiation schemes were used. The first followed Mil-Std-883 Method 1019.4 (dose rate = 50 rads(Si)/s). The second used a low dose rate (0.1 rads(Si)/s). AC, DC, transfer function and functional behavior were monitored throughout the tests. Significant differences among the package types and burn-in variations were noted with the plastic, burned-in components demonstrating enhanced degradation. They show the worst post-irradiation parameter values as well as very broad post-irradiation parameter distributions. Degradation is highly dependent upon dose rate and anneal conditions. Two different radiation induced leakage paths have been identified, and their characteristics have been correlated to variations in high dose rate and low dose rate circuit performance. Caution is recommended for system developers to ensure that radiation hardness characterization is performed for the same package/burn-in configuration to be used in the system

  13. The Microbiome-Gut-Behavior Axis: Crosstalk Between the Gut Microbiome and Oligodendrocytes Modulates Behavioral Responses.

    Science.gov (United States)

    Ntranos, Achilles; Casaccia, Patrizia

    2018-01-01

    Environmental and dietary stimuli have always been implicated in brain development and behavioral responses. The gut, being the major portal of communication with the external environment, has recently been brought to the forefront of this interaction with the establishment of a gut-brain axis in health and disease. Moreover, recent breakthroughs in germ-free and antibiotic-treated mice have demonstrated the significant impact of the microbiome in modulating behavioral responses in mice and have established a more specific microbiome-gut-behavior axis. One of the mechanisms by which this axis affects social behavior is by regulating myelination at the prefrontal cortex, an important site for complex cognitive behavior planning and decision-making. The prefrontal cortex exhibits late myelination of its axonal projections that could extend into the third decade of life in humans, which make it susceptible to external influences, such as microbial metabolites. Changes in the gut microbiome were shown to alter the composition of the microbial metabolome affecting highly permeable bioactive compounds, such as p-cresol, which could impair oligodendrocyte differentiation. Dysregulated myelination in the prefrontal cortex is then able to affect behavioral responses in mice, shifting them towards social isolation. The reduced social interactions could then limit microbial exchange, which could otherwise pose a threat to the survival of the existing microbial community in the host and, thus, provide an evolutionary advantage to the specific microbial community. In this review, we will analyze the microbiome-gut-behavior axis, describe the interactions between the gut microbiome and oligodendrocytes and highlight their role in the modulation of social behavior.

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

    Energy Technology Data Exchange (ETDEWEB)

    Cho, K.H. [Department of Radiation Oncology, College of Medicine, Soonchunhyang University, Bucheon 420-767 (Korea, Republic of); Department of Medical Physics, Kyonggi University, Suwon 443-760 (Korea, Republic of); Cho, S.J. [Department of Radiation Oncology, College of Medicine, Eulji University, Seongnam 461-713 (Korea, Republic of); Lee, S. [Department of Radiation Oncology, College of Medicine, Korea University, Seoul 130-701 (Korea, Republic of); Lee, S.H. [Cheil General Hospital and Women' s Healthcare Center, Kwandong University College of Medicine, Seoul 100-380 (Korea, Republic of); Min, C.K.; Kim, Y.H.; Moon, S.K.; Kim, E.S.; Chang, A.R. [Department of Radiation Oncology, College of Medicine, Soonchunhyang University, Bucheon 420-767 (Korea, Republic of); Kwon, S.I., E-mail: sikwon@kyonggi.ac.kr [Department of Medical Physics, Kyonggi University, Suwon 443-760 (Korea, Republic of)

    2012-05-21

    The dosimetric characteristics of normoxic polymethacrylic acid gels are investigated using optimal CT scanning parameters and the possibility of their clinical application is also considered. The effects of CT scanning parameters (tube voltage, tube current, scan time, slick thickness, field of view, and reconstruction algorithm) are experimentally investigated to determine the optimal parameters for minimizing the amount of noise in images obtained using normoxic polymethacrylic acid gel. In addition, the dose sensitivity, dose response, accuracy, and reproducibility of the normoxic polymethacrylic acid gel are evaluated. CT images are obtained using a head phantom that is fabricated for clinical applications. In addition, IMRT treatment planning is performed using a Tomotherapy radiation treatment planning system. A program for analyzing the results is produced using Visual C. A comparison between the treatment planning and the CT images of irradiated gels is performed. The dose sensitivity is found to be 2.41{+-}0.04 HGy{sup -1}. The accuracies of dose evaluation at doses of 2 Gy and 4 Gy are 3.0% and 2.6%, respectively, and their reproducibilities are 2.0% and 2.1%, respectively. In the comparison of gel and Tomotherpay planning, the pass rate of the {gamma}-index, based on the reference values of a dose error of 3% and a DTA of 3 mm, is 93.7%.

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

    Science.gov (United States)

    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%.

  16. γ irradiation with different dose rates induces different DNA damage responses in Petunia x hybrida cells.

    Science.gov (United States)

    Donà, Mattia; Ventura, Lorenzo; Macovei, Anca; Confalonieri, Massimo; Savio, Monica; Giovannini, Annalisa; Carbonera, Daniela; Balestrazzi, Alma

    2013-05-15

    In plants, there is evidence that different dose rate exposures to gamma (γ) rays can cause different biological effects. The dynamics of DNA damage accumulation and molecular mechanisms that regulate recovery from radiation injury as a function of dose rate are poorly explored. To highlight dose-rate dependent differences in DNA damage, single cell gel electrophoresis was carried out on regenerating Petunia x hybrida leaf discs exposed to LDR (total dose 50 Gy, delivered at 0.33 Gy min(-1)) and HDR (total doses 50 and 100 Gy, delivered at 5.15 Gy min(-1)) γ-ray in the 0-24h time period after treatments. Significant fluctuations of double strand breaks and different repair capacities were observed between treatments in the 0-4h time period following irradiation. Dose-rate-dependent changes in the expression of the PhMT2 and PhAPX genes encoding a type 2 metallothionein and the cytosolic isoform of ascorbate peroxidase, respectively, were detected by Quantitative RealTime-Polymerase Chain Reaction. The PhMT2 and PhAPX genes were significantly up-regulated (3.0- and 0.7-fold) in response to HDR. The results are discussed in light of the potential practical applications of LDR-based treatments in mutation breeding. Copyright © 2013 Elsevier GmbH. All rights reserved.

  17. 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)

  18. A direct method for estimating the alpha/beta ratio from quantitative dose-response data

    International Nuclear Information System (INIS)

    Stuschke, M.

    1989-01-01

    A one-step optimization method based on a least squares fit of the linear quadratic model to quantitative tissue response data after fractionated irradiation is proposed. Suitable end-points that can be analysed by this method are growth delay, host survival and quantitative biochemical or clinical laboratory data. The functional dependence between the transformed dose and the measured response is approximated by a polynomial. The method allows for the estimation of the alpha/beta ratio and its confidence limits from all observed responses of the different fractionation schedules. Censored data can be included in the analysis. A method to test the appropriateness of the fit is presented. A computer simulation illustrates the method and its accuracy as examplified by the growth delay end point. A comparison with a fit of the linear quadratic model to interpolated isoeffect doses shows the advantages of the direct method. (orig./HP) [de

  19. 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

  20. 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

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

    Science.gov (United States)

    Nabel, Moritz; Bueno Piaz Barbosa, Daniela; Horsch, David; Jablonowski, Nicolai David

    2014-05-01

    The global demand for energy security and the mitigation of climate change are the main drivers pushing energy-plant production in Germany. However, the cultivation of these plants can cause land use conflicts since agricultural soil is mostly used for plant production. A sustainable alternative to the conventional cultivation of food-based energy-crops is the cultivation of special adopted energy-plants on marginal lands. To further increase the sustainability of energy-plant cultivation systems the dependency on synthetic fertilizers needs to be reduced via closed nutrient loops. In the presented study the energy-plant Sida hermaphrodita (Malvaceae) will be used to evaluate the potential to grow this high potential energy-crop on a marginal sandy soil in combination with fertilization via digestate from biogas production. With this dose-response experiment we will further identify an optimum dose, which will be compared to equivalent doses of NPK-fertilizer. Further, lethal doses and deficiency doses will be observed. Two weeks old Sida seedlings were transplanted to 1L pots and fertilized with six doses of digestate (equivalent to a field application of 5, 10, 20, 40, 80, 160t/ha) and three equivalent doses of NPK-fertilizer. Control plants were left untreated. Sida plants will grow for 45 days under greenhouse conditions. We hypothesize that the nutrient status of the marginal soil can be increased and maintained by defined digestate applications, compared to control plants suffering of nutrient deficiency due to the low nutrient status in the marginal substrate. The dose of 40t/ha is expected to give a maximum biomass yield without causing toxicity symptoms. Results shall be used as basis for further experiments on the field scale in a field trial that was set up to investigate sustainable production systems for energy crop production under marginal soil conditions.

  2. Model of avascular tumor growth and response to low dose exposure

    International Nuclear Information System (INIS)

    Rodriguez Aguirre, J M; Custidiano, E R

    2011-01-01

    A single level cellular automata model is described and used to simulate early tumor growth, and the response of the tumor cells under low dose radiation affects. In this model the cell cycle of the population of normal and cancer cells is followed. The invasion mechanism of the tumor is simulated by a local factor that takes into account the microenvironment hardness to cell development, in a picture similar to the AMTIH model. The response of normal and cancer cells to direct effects of radiation is tested for various models and a model of bystander response is implemented.

  3. Identification of low-dose responsive metabolites in X-irradiated human B lymphoblastoid cells and fibroblasts

    International Nuclear Information System (INIS)

    Tsuyama, Naohiro; Katafuchi, Atsushi; Abe, Yu; Kurosu, Yumiko; Yoshida, Mitsuaki; Kamiya, Kenji; Sakai, Akira; Mizuno, Hajime

    2015-01-01

    Ionizing radiation (IR) induces cellular stress responses, such as signal transduction, gene expression, protein modification, and metabolite change that affect cellular behavior. We analyzed X-irradiated human Epstein-Barr virus-transformed B lymphoblastoid cells and normal fibroblasts to search for metabolites that would be suitable IR-responsive markers by Liquid Chromotography–Mass spectrometry (LC–MS). Mass spectra, as analyzed with principal component analysis, showed that the proportion of peaks with IR-induced change was relatively small compared with the influence of culture time. Dozens of peaks that had either been upregulated or downregulated by IR were extracted as candidate IR markers. The IR-changed peaks were identified by comparing mock-treated groups to 100 mGy-irradiated groups that had recovered after 10 h, and the results indicated that the metabolites involved in nucleoside synthesis increased and that some acylcarnitine levels decreased in B lymphoblastoids. Some peaks changed by as much as 20 mGy, indicating the presence of an IR-sensitive signal transduction/metabolism control mechanism in these cells. On the other hand, we could not find common IR-changed peaks in fibroblasts of different origin. These data suggest that cell phenotype-specific pathways exist, even in low-dose responses, and could determine cell behavior. (author)

  4. Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Daila S. Gridley, PhD

    2012-03-30

    FINAL TECHNICAL REPORT Supported by the Low Dose Radiation Research Program, Office of Science U.S. Department of Energy Grant No. DE-FG02-07ER64345 Project ID: 0012965 Award Register#: ER64345 Project Manager: Noelle F. Metting, Sc.D. Phone: 301-903-8309 Division SC-23.2 noelle.metting@science.doe.gov Submitted March 2012 To: https://www.osti.gov/elink/241.3.jsp Title: Th Cell Gene Expression and Function in Response to Low Dose and Acute Radiation PI: Daila S. Gridley, Ph.D. Human low dose radiation data have been derived primarily from studies of space and airline flight personnel, nuclear plant workers and others exposed occupationally, as well as victims in the vicinity of atomic bomb explosions. The findings remain inconclusive due to population inconsistencies and complex interactions among total dose, dose rate, radiation quality and age at exposure. Thus, safe limits for low dose occupational irradiation are currently based on data obtained with doses far exceeding the levels expected for the general population and health risks have been largely extrapolated using the linear-nonthreshold dose-response model. The overall working hypothesis of the present study is that priming with low dose, low-linear energy transfer (LET) radiation can ameliorate the response to acute high-dose radiation exposure. We also propose that the efficacy of low-dose induced protection will be dependent upon the form and regimen of the high-dose exposure: photons versus protons versus simulated solar particle event protons (sSPE). The emphasis has been on gene expression and function of CD4+ T helper (Th) lymphocytes harvested from spleens of whole-body irradiated C57BL/6 mice, a strain that provides the genetic background for many genetically engineered strains. Evaluations of the responses of other selected cells, tissues such as skin, and organs such as lung, liver and brain were also initiated (partially funded by other sources). The long-term goal is to provide information

  5. Persistence of Meningococcal Antibodies and Response to a Third Dose After a Two-dose Vaccination Series with Investigational MenABCWY Vaccine Formulations in Adolescents.

    Science.gov (United States)

    Saez-Llorens, Xavier; Aguilera Vaca, Diana Catalina; Abarca, Katia; Maho, Emmanuelle; Han, Linda; Smolenov, Igor; Dull, Peter

    2015-10-01

    In a primary study, healthy adolescents received 2 doses (months 0/2) of 1 of the 4 investigational meningococcal ABCWY vaccine formulations, containing components of licensed quadrivalent glycoconjugate vaccine MenACWY-CRM, combined with different amounts of recombinant proteins (rMenB) and outer membrane vesicles (OMV) from a licensed serogroup B vaccine, or 2 doses of rMenB alone or 1 dose of MenACWY-CRM then a placebo. This phase 2 extension study evaluated antibody persistence up to 10 months after the 2-dose series and the immunogenicity and safety of a third dose (month 6). Immune responses against serogroups ACWY and serogroup B test strains were measured by serum bactericidal assay with human complement. At month 12, antibody persistence against serogroups ACWY in all 2-dose MenABCWY groups was at least comparable with the 1-dose MenACWY-CRM group. Bactericidal antibodies against most serogroup B test strains declined by month 6, then plateaued over the subsequent 6 months, with overall higher antibody persistence associated with OMV-containing formulations. A third MenABCWY vaccine dose induced robust immune responses against vaccine antigens, although antibody levels 6 months later were comparable with those observed 5 months after the 2-dose series. All investigational MenABCWY vaccines were well tolerated. Two or three doses of investigational MenABCWY vaccines elicited immune responses against serogroups ACWY that were at least comparable with those after 1 dose of MenACWY-CRM. After either vaccination series, investigational MenABCWY vaccine formulations containing OMV had the highest immunogenicity against most serogroup B test strains. No safety concerns were identified in this study.

  6. Are cyberbullies less empathic? Adolescents' cyberbullying behavior and empathic responsiveness.

    Science.gov (United States)

    Steffgen, Georges; König, Andreas; Pfetsch, Jan; Melzer, André

    2011-11-01

    Meta-analyses confirm a negative relationship between aggressive behavior and empathy, that is, the ability to understand and share the feelings of others. Based on theoretical considerations, it was, therefore, hypothesized that a lack of empathic responsiveness may be characteristic for cyberbullies in particular. In the present study, 2.070 students of Luxembourg secondary schools completed an online survey that included a cyberbullying questionnaire(4) and a novel empathy short scale. According to the main hypothesis, analyses of variances indicated that cyberbullies demonstrated less empathic responsiveness than non-cyberbullies. In addition, cyberbullies were also more afraid of becoming victims of cyberbullying. The findings confirm and substantially extend the research on the relationship between empathy and aggressive behavior. From an educational point of view, the present findings suggest that training of empathy skills might be an important tool to decrease cyberbullying.

  7. Doubling the infliximab dose versus halving the infusion intervals in Crohn's disease patients with loss of response

    DEFF Research Database (Denmark)

    Katz, Lior; Gisbert, Javier P; Manoogian, Beth

    2012-01-01

    Intensifying infliximab therapy is often practiced in Crohn's disease (CD) patients losing response to the drug but there are no data if halving the interval is superior to doubling the dose. We aimed to assess the efficacy of infliximab dose intensification by interval-halving compared with dose...

  8. The ethical and socially responsible behavior of the commercial companies

    Directory of Open Access Journals (Sweden)

    Mureşan, L.

    2010-11-01

    Full Text Available In the Romanian society and economy the need to distinguish certain behaviors based on the principles of ethics and social responsibility becomes obvious. The totality of the decisions made by the commercial companies must ensure the observance of the interests of all entities which interact with these. The situation of each commercial company whose decisions are inconsistent with the requirements of ethics and social responsibility will sooner or later be endangered because it affects the interests of others, it means in fact affecting one’s own interests.

  9. Acute topiramate differentially affects human aggressive responding at low vs. moderate doses in subjects with histories of substance abuse and antisocial behavior.

    Science.gov (United States)

    Lane, Scott D; Gowin, Joshua L; Green, Charles E; Steinberg, Joel L; Moeller, F Gerard; Cherek, Don R

    2009-04-01

    Anticonvulsant drugs have demonstrated efficacy in the management of irritability and aggression in a variety of psychiatric populations. We examined the acute effects of topiramate on aggression using a laboratory model of human aggression (PSAP) in individuals at high risk for aggressive and violent behavior.Twelve subjects, on parole/probation and with an Axis-II personality disorder and/or a substance use disorder, received 100, 200, 300, and 400 mg in an ascending sequence, with intervening placebo doses.Subjects participated 2-3 days per week over 4-6 weeks. Due to cognitive side effects at 300 mg, two subjects only completed through the 200 mg dose. Topiramate produced an inverted U-shaped dose response curve, with increases in aggression peaking at 200 mg and a modest decrease at 400 mg. Statistical analysis revealed a polynomial trend for dose (p=0.001). The observed inverted U-shaped function in aggressive responding is consistent with non-human aggression studies of GABA-A modulators. Acute topiramate doses >400 mg may have anti-aggressive effects, but dose levels in the 200-300 mg range may produce increases in aggression and side effects.

  10. Behavioral responses of silverback gorillas (Gorilla gorilla gorilla) to videos.

    Science.gov (United States)

    Maloney, Margaret A; Leighty, Katherine A; Kuhar, Christopher W; Bettinger, Tamara L

    2011-01-01

    This study examined the impact of video presentations on the behavior of 4 silverback, western lowland gorillas (Gorilla gorilla gorilla). On each of 5 occasions, gorillas viewed 6 types of videos (blue screen, humans, an all-male or mixed-sex group engaged in low activity, and an all-male or mixed-sex group engaged in agonistic behavior). The study recorded behavioral responses and watching rates. All gorillas preferred dynamic over static videos; 3 watched videos depicting gorillas significantly more than those depicting humans. Among the gorilla videos, the gorillas clearly preferred watching the mixed-sex group engaged in agonistic behavior; yet, this did not lead to an increase in aggression or behavior indicating agitation. Further, habituation to videos depicting gorillas did not occur. This supports the effectiveness of this form of enrichment, particularly for a nonhuman animal needing to be separated temporarily due to illness, shipment quarantine, social restructuring, or exhibit modification. Copyright © The Walt Disney Company®

  11. Summary of dosimetry, pathology, and dose response for bone sarcomas in beagles injected with radium-226

    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

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

    Science.gov (United States)

    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.

  13. A biological basis for the linear non-threshold dose-response relationship for low-level carcinogen exposure

    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

  14. Transient Genome-Wide Transcriptional Response to Low-Dose Ionizing Radiation In Vivo in Humans

    International Nuclear Information System (INIS)

    Berglund, Susanne R.; Rocke, David M.; Dai Jian; Schwietert, Chad W.; Santana, Alison; Stern, Robin L.; Lehmann, Joerg; Hartmann Siantar, Christine L.; Goldberg, Zelanna

    2008-01-01

    Purpose: The in vivo effects of low-dose low linear energy transfer ionizing radiation on healthy human skin are largely unknown. Using a patient-based tissue acquisition protocol, we have performed a series of genomic analyses on the temporal dynamics over a 24-hour period to determine the radiation response after a single exposure of 10 cGy. Methods and Materials: RNA from each patient tissue sample was hybridized to an Affymetrix Human Genome U133 Plus 2.0 array. Data analysis was performed on selected gene groups and pathways. Results: Nineteen gene groups and seven gene pathways that had been shown to be radiation responsive were analyzed. Of these, nine gene groups showed significant transient transcriptional changes in the human tissue samples, which returned to baseline by 24 hours postexposure. Conclusions: Low doses of ionizing radiation on full-thickness human skin produce a definable temporal response out to 24 hours postexposure. Genes involved in DNA and tissue remodeling, cell cycle transition, and inflammation show statistically significant changes in expression, despite variability between patients. These data serve as a reference for the temporal dynamics of ionizing radiation response following low-dose exposure in healthy full-thickness human skin

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

    Science.gov (United States)

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

    2014-07-01

    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

  16. Nonlinear response and avalanche behavior in metallic glasses

    Science.gov (United States)

    Riechers, B.; Samwer, K.

    2017-08-01

    The response to different stress amplitudes at temperatures below the glass transition temperature is analyzed by mechanical oscillatory excitation of Pd40Ni40P20 metallic glass samples in single cantilever bending geometry. While low amplitude oscillatory excitations are commonly used in mechanical spectroscopy to probe the relaxation spectrum, in this work the response to comparably high amplitudes is investigated. The strain response of the material is well below the critical yield stress even for highest stress amplitudes, implying the expectation of a linear relation between stress and strain according to Hooke's Law. However, a deviation from the linear behavior is evident, which is analyzed in terms of temperature dependence and influence of the applied stress amplitude by two different approaches of evaluation. The nonlinear approach is based on a nonlinear expansion of the stress-strain-relation, assuming an intrinsic nonlinear character of the shear or elastic modulus. The degree of nonlinearity is extracted by a period-by-period Fourier-analysis and connected to nonlinear coefficients, describing the intensity of nonlinearity at the fundamental and higher harmonic frequencies. The characteristic timescale to adapt to a significant change in stress amplitude in terms of a recovery timescale to a steady state value is connected to the structural relaxation time of the material, suggesting a connection between the observed nonlinearity and primary relaxation processes. The second approach of evaluation is termed the incremental analysis and relates the observed response behavior to avalanches, which occur due to the activation and correlation of local microstructural rearrangements. These rearrangements are connected with shear transformation zones and correspond to localized plastic events, which are superimposed on the linear response behavior of the material.

  17. Pre-irradiation at a low dose-rate blunted p53 response

    International Nuclear Information System (INIS)

    Takahashi, A.; Ohnishi, K.; Asakawa, I.; Tamamoto, T.; Yasumoto, J.; Yuki, K.; Ohnishi, T.; Tachibana, A.

    2003-01-01

    Full text: We have studied whether the p53-centered signal transduction pathway induced by acute radiation is interfered with chronic pre-irradiation at a low dose-rate in human cultured cells and whole body of mice. In squamous cell carcinoma cells, we found that a challenge irradiation with X-ray immediately after chronic irradiation resulted in lower levels of p53 than those observed after the challenge irradiation alone. In addition, the induction of p53-centered apoptosis and the accumulation of its related proteins after the challenge irradiation were strongly correlated with the above-mentioned phenomena. In mouse spleen, the induction of apoptosis and the accumulation of p53 and Bax were observed dose-dependently at 12 h after a challenge irradiation. In contrast, we found significant suppression of them induced by challenge irradiation at a high dose-rate when mice were pre-irradiated with chronic irradiation at a low dose-rate. These findings suggest that chronic pre-irradiation suppressed the p53 function through radiation-induced p53-dependent signal transduction processes. There are numerous papers about p53 functions in apoptosis, radiosensitivity, genomic instability and cancer incidence in cultured cells or animals. According to our data and other findings, since p53 can prevent carcinogenesis, pre-irradiation at a low dose-rate might enhance the predisposition to cancer. Therefore, it is possible that different maximal permissible dose equivalents for the public populations are appropriate. Furthermore, concerning health of human beings, studies of the adaptive responses to radiation are quite important, because the radiation response strongly depends on experience of prior exposure to radiation

  18. An experimental Toxoplasma gondii dose response challenge model to study therapeutic or vaccine efficacy in cats.

    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.

  19. The Pupillary Orienting Response Predicts Adaptive Behavioral Adjustment after Errors.

    Directory of Open Access Journals (Sweden)

    Peter R Murphy

    Full Text Available Reaction time (RT is commonly observed to slow down after an error. This post-error slowing (PES has been thought to arise from the strategic adoption of a more cautious response mode following deployment of cognitive control. Recently, an alternative account has suggested that PES results from interference due to an error-evoked orienting response. We investigated whether error-related orienting may in fact be a pre-cursor to adaptive post-error behavioral adjustment when the orienting response resolves before subsequent trial onset. We measured pupil dilation, a prototypical measure of autonomic orienting, during performance of a choice RT task with long inter-stimulus intervals, and found that the trial-by-trial magnitude of the error-evoked pupil response positively predicted both PES magnitude and the likelihood that the following response would be correct. These combined findings suggest that the magnitude of the error-related orienting response predicts an adaptive change of response strategy following errors, and thereby promote a reconciliation of the orienting and adaptive control accounts of PES.

  20. Synthesis of fast response crosslinked PVA-g-NIPAAm nanohydrogels by very low radiation dose in dilute aqueous solution

    International Nuclear Information System (INIS)

    Fathi, Marziyeh; Reza Farajollahi, Ali; Akbar Entezami, Ali

    2013-01-01

    Nanohydrogels of poly(vinyl alcohol)-g-N-isopropylacrylamide (PVA-g-NIPAAm) are synthesized by PVA and NIPAAm dilute aqueous solution using much less radiation dose of 1–20 Gy via intramolecular crosslinking at ambient temperature. The radiation synthesis of nanohydrogels is performed in the presence of tetrakis (hydroxymethyl) phosphonium chloride (THPC) due to its rapid oxygen scavenging abilities and hydrogen peroxide (H 2 O 2 ) as a source of hydroxyl radicals. The effect of radiation dose, feed composition ratio of PVA and H 2 O 2 is investigated on swelling properties such as temperature and pH dependence of equilibrium swelling ratio as well as deswelling kinetics. Experimental data exhibit high equilibrium swelling ratio and fast response time for the synthesized nanohydrogels. The average molecular weight between crosslinks (M c ) and crosslinking density (ρ x ) of the obtained nanohydrogels are calculated from swelling data as a function of radiation dose, H 2 O 2 and PVA amount. Fourier transform infrared spectroscopy (FT-IR), elemental analysis of nitrogen content and thermogravimetric analysis (TGA) are used to confirm the grafting reaction. Lower critical solution temperature (LCST) is measured around 33 °C by differential scanning calorimetry (DSC) for PVA-g-NIPAAm nanohydrogels. Dynamic light scattering (DLS) data demonstrate that the increase of radiation dose leads to the decreasing in dimension of nanohydrogels. Also, rheological studies are confirmed an improvement in the mechanical properties of the nanohydrogels with increasing the radiation dose. A cytotoxicity study exhibits a good biocompatibility for the obtained nanohydrogels. The prepared nanohydrogels show fast swelling/deswelling behavior, high swelling ratio, dual sensitivity and good cytocompatibility, which may find potential applications as biomaterial. - Highlights: ► A new radiation polymerization method is offered in dilute aqueous solution.► This method provides PVA

  1. A procedure for estimating the dose modifying effect of chemotherapy on radiation response

    International Nuclear Information System (INIS)

    Hao, Y.; Keane, T.

    1994-01-01

    A procedure based on a logistic regression model was used to estimate the dose-modifying effect of chemotherapy on the response of normal tissues to radiation. The DEF in the proposed procedure is expressed as a function of logistic regression coefficients, response levels and values of covariates in the model. The proposed procedure is advantageous as it allows consideration of both the response levels and the values of covariates in calculating the DEF. A plot of the DEF against the response or a covariate describes how the DEF varies with the response levels or the covariate values. Confidence intervals of the DEF were obtained based on the normal approximation of the distribution of the estimated DEF and on a non-parametric Bootstrap method. An example is given to illustrate the proposed procedure. (Author)

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

    Science.gov (United States)

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

    2014-10-01

    This study utilizes old and new Norovirus (NoV) human challenge data to model the dose-response relationship for human NoV infection. The combined data set is used to update estimates from a previously published beta-Poisson dose-response model that includes parameters for virus aggregation and for a beta-distribution that describes variable susceptibility among hosts. The quality of the beta-Poisson model is examined and a simpler model is proposed. The new model (fractional Poisson) characterizes hosts as either perfectly susceptible or perfectly immune, requiring a single parameter (the fraction of perfectly susceptible hosts) in place of the two-parameter beta-distribution. A second parameter is included to account for virus aggregation in the same fashion as it is added to the beta-Poisson model. Infection probability is simply the product of the probability of nonzero exposure (at least one virus or aggregate is ingested) and the fraction of susceptible hosts. The model is computationally simple and appears to be well suited to the data from the NoV human challenge studies. The model's deviance is similar to that of the beta-Poisson, but with one parameter, rather than two. As a result, the Akaike information criterion favors the fractional Poisson over the beta-Poisson model. At low, environmentally relevant exposure levels (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.

  3. Low-Active Male Adolescents: A Dose Response to High-Intensity Interval Training.

    Science.gov (United States)

    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.

  4. Three-dimensional dose-response models of competing risks and natural life span

    International Nuclear Information System (INIS)

    Raabe, O.G.

    1987-01-01

    Three-dimensional dose-rate/time/response surfaces for chronic exposure to carcinogens, toxicants, and ionizing radiation dramatically clarify the separate and interactive roles of competing risks. The three dimensions are average dose rate, exposure time, and risk. An illustration with computer graphics shows the contributions with the passage of time of the competing risks of death from radiation pneumonitis/fibrosis, lung cancer, and natural aging consequent to the inhalation of plutonium-239 dioxide by beagles. These relationships are further evaluated by mathematical stripping with three-dimensional illustrations that graphically show the resultant separate contribution of each fatal effect. Radiation pneumonitis predominates at high dose rates and lung cancer at intermediate dose rates. Low dose rates result in spontaneous deaths from natural aging, yielding a type of practical threshold for lung 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 the planning and evaluation of epidemiological analyses and experimental studies involving chronic exposure to toxicants

  5. I-131 dose response for incident thyroid cancers in Ukraine related to the Chornobyl accident.

    Science.gov (United States)

    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.

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

    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)

  7. Determining dose rate with a semiconductor detector - Monte Carlo calculations of the detector response

    Energy Technology Data Exchange (ETDEWEB)

    Nordenfors, C

    1999-02-01

    To determine dose rate in a gamma radiation field, based on measurements with a semiconductor detector, it is necessary to know how the detector effects the field. This work aims to describe this effect with Monte Carlo simulations and calculations, that is to identify the detector response function. This is done for a germanium gamma detector. The detector is normally used in the in-situ measurements that is carried out regularly at the department. After the response function is determined it is used to reconstruct a spectrum from an in-situ measurement, a so called unfolding. This is done to be able to calculate fluence rate and dose rate directly from a measured (and unfolded) spectrum. The Monte Carlo code used in this work is EGS4 developed mainly at Stanford Linear Accelerator Center. It is a widely used code package to simulate particle transport. The results of this work indicates that the method could be used as-is since the accuracy of this method compares to other methods already in use to measure dose rate. Bearing in mind that this method provides the nuclide specific dose it is useful, in radiation protection, since knowing what the relations between different nuclides are and how they change is very important when estimating the risks

  8. Response of booster dose of cuban recombinant hepatitis-B vaccine in nonresponder and hyporesponder children

    International Nuclear Information System (INIS)

    Dahifar, H.; Mousavi, F.; Ghorbani, A.

    2007-01-01

    Acute hepatitis B infection can debilitate a patient for weeks and occasionally has a fatal outcome, while chronic infection is a major threat to the individual. To assess response of nonresponder and hyporesponder children to booster dose of Cuban recombinant hepatitis B vaccine. An interventional, descriptive study has been conducted on children who had been immunized with Cuban recombinant Hepatitis B vaccine and their antibody titers were <10mIU/ml (nonresponder) and 10-100mIU/ml (hyporesponder) administered booster dose of the same vaccine in their Deltoid muscles. The response of 141 children with the mean age of 1.9 years to booster dose of vaccine were 94.3% and 100% vaccines with the first and second booster dose of vaccination respectively. The anti-HBs titer in nonresponders and hyporesponders were 468+-346 and 783+-346mIU/ml respectively with significant differences between two groups (P=0.001). This study demonstrate moderately increase antibody production in the majority of vaccines with single supplementary vaccine. (author)

  9. Copepod behavior response to Burgers' vortex treatments mimicking turbulent eddies

    Science.gov (United States)

    Elmi, D.; Webster, D. R.; Fields, D. M.

    2017-11-01

    Copepods detect hydrodynamic cues in the water by their mechanosensory setae. We expect that copepods sense the flow structure of turbulent eddies in order to evoke behavioral responses that lead to population-scale distribution patterns. In this study, the copepods' response to the Burgers' vortex is examined. The Burgers' vortex is a steady-state solution of three-dimensional Navier-Stokes equations that allows us to mimic turbulent vortices at the appropriate scale and eliminate the stochastic nature of turbulence. We generate vortices in the laboratory oriented in the horizontal and vertical directions each with four intensity levels. The objective of including vortex orientation as a parameter in the study is to quantify directional responses that lead to vertical population distribution patterns. The four intensity levels correspond to target vortex characteristics of eddies corresponding to the typical dissipative vortices in isotropic turbulence with mean turbulent dissipation rates in the range of 0.002 to 0.25 cm2/s3. These vortices mimic the characteristics of eddies that copepods most likely encounter in coastal zones. We hypothesize that the response of copepods to hydrodynamic features depends on their sensory architecture and relative orientation with respect to gravity. Tomo-PIV is used to quantify the vortex circulation and axial strain rate for each vortex treatment. Three-dimensional trajectories of the copepod species Calanus finmarchicus are analyzed to examine their swimming kinematics in and around the vortex to quantify the hydrodynamic cues that trigger their behavior.

  10. Responses of rat R-1 cells to low dose rate gamma radiation and multiple daily dose fractions

    International Nuclear Information System (INIS)

    Kal, H.B.; Bijman, J.Th.

    1981-01-01

    Multifraction irradiation may offer the same therapeutic gain as continuous irradiation. Therefore, a comparison of the efficacy of low dose rate irradiation and multifraction irradiation was the main objective of the experiments to be described. Both regimens were tested on rat rhabdomyosarcoma (R-1) cells in vitro and in vivo. Exponentially growing R-1 cells were treated in vitro by a multifraction irradiation procedure with dose fractions of 2 Gy gamma radiation and time intervals of 1 to 3 h. The dose rate was 1.3 Gy.min -1 . The results indicate that multifractionation of the total dose is more effective with respect to cell inactivation than continuous irradiation. (Auth.)

  11. European Academy of Allergy and Clinical Immunology task force report on 'dose-response relationship in allergen-specific immunotherapy'.

    Science.gov (United States)

    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.

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

    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)

  13. Dose-response relationship between periodontal inflamed surface area and HbA1c in type 2 Diabetics

    NARCIS (Netherlands)

    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

  14. A new method for synthesizing radiation dose-response data from multiple trials applied to prostate cancer

    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)....

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

    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...

  16. Dependence of alanine gel dosimeter response as a function of photon clinical beams dose rate

    International Nuclear Information System (INIS)

    Silva, Cleber Feijo; Campos, Leticia Lucente

    2013-01-01

    Gel dosimetry is a new area developed by Gore, it is ery useful for application in radiotherapy because using NMR imaging as evaluation technique is possible to evaluate three dimensional absorbed dose distribution. The measure technique is based on difference of ferrous (Fe 2+ ) and ferric (Fe 3+ ) ) ions concentration that can be measured also by spectrophotometry technique. The Alanine gel dosimeter was developed at IPEN. The alanine is an amino acid and tissue equivalent material that presents significant improvement on previous alanine dosimetry systems. The addition of Alanine increases the production of ferric ions in the solution. This work aims to study the dose rate dependence of photon clinical beams radiation on the alanine gel dosimeter optical response, as well as the response repeatability and gel production reproducibility, since this property is very important for characterization and standardization of any dosimeter. (author)

  17. 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...

  18. Dose-response functions for effects of acidic precipitation on vegetation

    Energy Technology Data Exchange (ETDEWEB)

    Jacobson, J S; Troiano, J J

    1983-01-01

    Research on the effect of sulfuric and nitric acids, as well as other substances, in rain on plant growth has focused on quantifying the relationship between doses of acids in precipitation and plant response. After eight years, there has been no direct demonstration of harmful effects to plants by ambient acidic rain in North America, and there remains considerable uncertainty about the potential risk to cultivated and native plants. Current efforts to describe the relationships between dose of acidity and effects on plants need better experimental approaches if the results are to be more relevant to actual field situations. Mechanistic models that describe the physiological and biochemical basis for effects of acidic rain on plants will be needed to provide confidence in the predictions of plant response. 34 references, 1 figure.

  19. Bayesian nonparametric estimation of continuous monotone functions with applications to dose-response analysis.

    Science.gov (United States)

    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.

  20. Dose response characteristics of polymethacrylic acid gel (PMAAG) for a polymerization-based dosimeter using NMR.

    Science.gov (United States)

    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.

  1. Bulgarian Emergency Response System (BERS) in case of nuclear accident with exposure doses estimation

    Energy Technology Data Exchange (ETDEWEB)

    Syrakov, D.; Prodanova, M.; Slavov, K.; Veleva, B.

    2015-07-01

    A PC-oriented Emergency Response System in case of nuclear accident (BERS) is developed and works operationally in the National Institute of Meteorology and Hydrology (NIMH). The creation and development of BERS was highly stimulated by the ETEX (European Tracer Experiment) project. BERS comprises two main parts - the operational and the accidental ones. The operational part, run automatically every 12 hours, prepares the input meteorological file used by both trajectory and dispersion models, runs the trajectory models, visualizes the results and uploads the maps of trajectories to a dedicated web-site. The accidental part is activated manually when a real radioactive releases occur or during emergency exercises. Its core is the Bulgarian dispersion models EMAP. Outputs are concentration, accumulated deposition and selected doses fields. In the paper, the BERS overall structure is described and examples of its products are presented. Key words: nuclear accident, emergency response, early warning system, air dispersion models, radioactive exposure dose. (Author)

  2. 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.)

  3. Dose-rate and the reciprocity law: TL response of Ge-doped SiO2 optical fibers at therapeutic radiation doses

    International Nuclear Information System (INIS)

    Abdul Rahman, A.T.; Nisbet, A.; Bradley, D.A.

    2011-01-01

    An investigation has been made on commercially available Ge-doped SiO 2 optical fibers as a novel thermoluminescence system for radiotherapy dosimetry. This dosimeter has previously been shown by the group to provide sensitive dosimetry over a wide range of electron and photon dose, suitable for the needs of radiotherapy. In addition the optical fiber offers small physical size (125 μm diameter) and hence high spatial resolution. The reciprocity between thermoluminescence (TL) yield of Ge-doped SiO 2 optical fibers and dose has been investigated for fixed radiation dose for a range of photon and electron dose rates. For electron beams of nominal energies in the range of 9-20 MeV, we have investigated the TL response of these fibers for dose rates between 100 and 1000 cGy min -1 . For photon beams of nominal energies in the range of 6-15 MV, we have used dose rates of 100-600 cGy min -1 . Reproducibility and fading at fixed absorbed dose (3 Gy) and dose rate for the optical fibers were also investigated. At fixed dose rates, the TL optical fibers were found to produce a flat TL yield within 4% (1σ) and 3% (1σ) for electron and photon beams, respectively. The optical fibers demonstrated good reproducibility (±1.5%), low residual signal for a readout temperature of 300 o C and negligible fading. A weak dependence on dose-rate has been observed in the range of 3.4-3.9% for electrons (with an associated uncertainty of 4%) and 2.4-2.9% for photons (with an associated uncertainty of <4%). For electron and photon energies we note a consistent trend towards lower response in the TL yield of between 3.4-3.9% and 2.4-2.7%, respectively, at the higher dose rates in comparison with the response at lower dose rates. In addition we note an appreciable systematic energy dependence for both electron and photon beams. It is important to take such factors into account for providing precise and accurate radiotherapy dosimetry. It is also apparent that the optical fibers can be re

  4. Dose-rate and the reciprocity law: TL response of Ge-doped SiO{sub 2} optical fibers at therapeutic radiation doses

    Energy Technology Data Exchange (ETDEWEB)

    Abdul Rahman, A.T., E-mail: a.t.abdulrahman@surrey.ac.uk [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH, Surrey (United Kingdom); School of Physics and Material Studies, Faculty of Applied Sciences, Universiti Teknologi MARA Malaysia (UiTM), Campus of Negeri Sembilan, 72000 Kuala Pilah (Malaysia); Nisbet, A. [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH, Surrey (United Kingdom); Departments of Medical Physics, the Royal Surrey County Hospital (RSCH) NHS Trust, Edgerton Road, Guildford GU2 7XX, Surrey (United Kingdom); Bradley, D.A. [Centre for Nuclear and Radiation Physics, Department of Physics, University of Surrey, Guildford GU2 7XH, Surrey (United Kingdom)

    2011-10-01

    An investigation has been made on commercially available Ge-doped SiO{sub 2} optical fibers as a novel thermoluminescence system for radiotherapy dosimetry. This dosimeter has previously been shown by the group to provide sensitive dosimetry over a wide range of electron and photon dose, suitable for the needs of radiotherapy. In addition the optical fiber offers small physical size (125 {mu}m diameter) and hence high spatial resolution. The reciprocity between thermoluminescence (TL) yield of Ge-doped SiO{sub 2} optical fibers and dose has been investigated for fixed radiation dose for a range of photon and electron dose rates. For electron beams of nominal energies in the range of 9-20 MeV, we have investigated the TL response of these fibers for dose rates between 100 and 1000 cGy min{sup -1}. For photon beams of nominal energies in the range of 6-15 MV, we have used dose rates of 100-600 cGy min{sup -1}. Reproducibility and fading at fixed absorbed dose (3 Gy) and dose rate for the optical fibers were also investigated. At fixed dose rates, the TL optical fibers were found to produce a flat TL yield within 4% (1{sigma}) and 3% (1{sigma}) for electron and photon beams, respectively. The optical fibers demonstrated good reproducibility ({+-}1.5%), low residual signal for a readout temperature of 300 {sup o}C and negligible fading. A weak dependence on dose-rate has been observed in the range of 3.4-3.9% for electrons (with an associated uncertainty of 4%) and 2.4-2.9% for photons (with an associated uncertainty of <4%). For electron and photon energies we note a consistent trend towards lower response in the TL yield of between 3.4-3.9% and 2.4-2.7%, respectively, at the higher dose rates in comparison with the response at lower dose rates. In addition we note an appreciable systematic energy dependence for both electron and photon beams. It is important to take such factors into account for providing precise and accurate radiotherapy dosimetry. It is also

  5. Impact of HSCT conditioning and glucocorticoid dose on exercise adherence and response

    OpenAIRE

    Wiskemann, Joachim; Herzog, Benedikt; Kuehl, Rea; Schmidt, Martina E.; Steindorf, Karen; Schwerdtfeger, Rainer; Dreger, Peter; Bohus, Martin

    2017-01-01

    Abstract: Purpose: Evidence from randomized controlled trials (RCT) that exercise interventions have beneficial effects in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) is growing. However, intensive chemotherapy conditioning and glucocorticoid (GC) treatment is always part of an allo-HSCT and possibly affect exercise adherence and training response. Therefore, we aimed to examine whether various conditioning protocols or different doses of GC treatment af...

  6. Dose response of thin-film dosimeters irradiated with 80-120 keV electrons

    DEFF Research Database (Denmark)

    Helt-Hansen, J.; Miller, A.; Sharpe, P.

    2005-01-01

    Thin-film dosimeters (Riso B3 and alanine films) were irradiated at 10 MeV and 80-120 keV electron accelerators, and it has been shown that the radiation response of the dosimeter materials (the radiation chemical yields) are constant at these irradiation energies. However, dose gradients within ...... are present within the dosimeter. (C) 2005 Elsevier Ltd. All rights reserved....

  7. A study of the responses of neutron dose equivalent survey meters with computer codes

    International Nuclear Information System (INIS)

    Sartori, D.E.; Beer, G.P. de

    1983-01-01

    The ANISN and DOT discrete-ordinates radiation transport codes for one and two dimensions have been proved as effective and simple techniques to study the response of dose equivalent neutron detectors. Comparisons between results of an experimental calibration of the Harwell 95/0075 survey meter and calculated results rendered satisfactory agreement, considering the different techniques and sources of error involved. Possible improvements in the methods and designs and causes of error are discussed. (author)

  8. 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.

  9. role of altruistic behavior, empathetic concern, and social responsibility motivation in blood donation behavior.

    Science.gov (United States)

    Steele, Whitney Randolph; Schreiber, George B; Guiltinan, Anne; Nass, Catharie; Glynn, Simone A; Wright, David J; Kessler, Debra; Schlumpf, Karen S; Tu, Yongling; Smith, James W; Garratty, George

    2008-01-01

    Blood donation can be described as a prosocial behavior, and donors often cite prosocial reasons such as altruism, empathy, or social responsibility for their willingness to donate. Previous studies have not quantitatively evaluated these characteristics in donors or examined how they relate to donation frequency. As part of a donor motivation study, 12,064 current and lapsed donors answered questions used to create an altruistic behavior, empathetic concern, and social responsibility motivation score for each donor. Analysis of variance was used to compare mean scores by demographics and donor status and to determine the influence of each variable on the mean number of donations in the past 5 years. The mean score for each prosocial characteristic appeared high, with lower scores in male and younger donors. Higher altruistic behavior and social responsibility motivation scores were associated with increased past donation frequency, but the effects were minor. Empathetic concern was not associated with prior donation. The largest differences in prior donations were by age and donor status, with older and current donors having given more frequently. Most blood donors appear to have high levels of the primary prosocial characteristics (altruism, empathy, and social responsibility) commonly thought to be the main motivators for donation, but these factors do not appear to be the ones most strongly related to donation frequency. Traditional donor appeals based on these characteristics may need to be supplemented by approaches that address practical concerns like convenience, community safety, or personal benefit.

  10. Humoral response to blastospores and mycelium in mice injected with different doses of Candida albicans.

    Science.gov (United States)

    Mesón, O E; Valdez, J C; de Alderete, N G; Sirena, A; Perdigón, G

    1992-01-01

    An indirect immunofluorescence assay was carry out to determine the IgM and IgG antibody responses to yeast and mycelial forms of Candida albicans in mice injected with a 5 x 5(5) and 5 x 10(7) live cells suspensions. Prior adsorption of the serum samples with heat-killed blastospores enabled us to follow the specific antimycelial response which were detected considerably later than expected. Slow level of antibodies were obtained within an infection of 5 x 10(5) cell for both antibody classes and for yeast and mycelial forms. When a 5 x 10(7) cell dose was used for inoculation, maximum titers of antibodies to blastospores and mycelium in non-adsorbed sera appeared almost simultaneously (days 15 and 13, respectively). When serum samples from mice infected with the same dose were previously adsorbed with blastospores, the antimycelium antibodies for both types of Igs, were detected delayed during the infection course. In this case the higher titer for IgG appeared on day 33 and on day 23 for IgM. We suggest that the high titer obtained with the blastospore forms for the 5 x 10(7) cell dose may be due to a major immunogenicity of this forms, for to induce an immune response in the host, or that the delay in the antimycelium antibodies detection could be due to that a blastospore form is the predominant in the infection early stages. Implications of this fact for pathogenesis are discussed.

  11. Effect of a single dose of levodopa on sexual response in men and women

    NARCIS (Netherlands)

    Both, Stephanie; Everaerd, Walter; Laan, Ellen; Gooren, Louis

    2005-01-01

    From animal research, there is ample evidence for a facilitating effect of dopamine on sexual behavior. In humans, little experimental research has been conducted on the inter-relation between dopamine and sexual response, even less so in women than in men. We investigated the effect of levodopa

  12. 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).

  13. Electiveness of photorepair, influence of dark-repair on shape of dose-response curves, and high-dose decline, in UV-induced colour mutations of Serratia

    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.)

  14. A model for inverse dose-rate effects - low dose-rate hyper-sensibility in response to targeted radionuclide therapy

    International Nuclear Information System (INIS)

    Murray, I.; Mather, S.J.

    2015-01-01

    Full text of publication follows. The aim of this work was to test the hypothesis that the Linear-Quadratic (LQ) model of cell survival, developed for external beam radiotherapy (EBRT), could be extended to targeted radionuclide therapy (TRT) in order to predict dose-response relationships in a cell line exhibiting low dose hypersensitivity (LDH). Methods: aliquots of the PC-3 cancer cell line were treated with either EBRT or an in-vitro model of TRT (Irradiation of cell culture with Y-90 EDTA over 24, 48, 72 or 96 hours). Dosimetry for the TRT was calculated using radiation transport simulations with the Monte Carlo PENELOPE code. Clonogenic as well as functional biological assays were used to assess cell response. An extension of the LQ model was developed which incorporated a dose-rate threshold for activation of repair mechanisms. Results: accurate dosimetry for in-vitro exposures of cell cultures to radioactivity was established. LQ parameters of cell survival were established for the PC-3 cell line in response to EBRT. The standard LQ model did not predict survival in PC-3 cells exposed to Y 90 irradiation over periods of up to 96 hours. In fact cells were more sensitive to the same dose when irradiation was carried out over 96 hours than 24 hours. I.e. at a lower dose-rate. Deviations from the LQ predictions were most pronounced below a threshold dose-rate of 0.5 Gy/hr. These results led to an extension of the LQ model based upon a dose-rate dependent sigmoid model of single strand DNA repair. This extension to the model resulted in predicted cell survival curves that closely matched the experimental data. Conclusion: the LQ model of cell survival to radiation has been shown to be largely predictive of response to low dose-rate irradiation. However, in cells displaying LDH, further adaptation of the model was required. (authors)

  15. 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

  16. Protective response to technological emergency: risk perception and behavioral intention

    International Nuclear Information System (INIS)

    Lindell, M.K.; Barnes, V.E.

    1986-01-01

    This article examines why, as suggested by the Three Mile Island Nuclear Station (TMI) event, the public is more inclined to evacuate in response to a radiation release than to a natural hazard. During the TMI incident, for example, did authorities present confusing or conflicting information or did the public have an exaggerated perception of radiation risk. Behavioral intention studies are combined with risk perception analyses to ascertain (1) the extent to which intentions to evacuate can be generalized from one sample to another and from one hazard to another, (2) the degree to which behavioral intentions are related to specific dimensions of risk perception, and (3) how public perceptions of risk compare with estimates of risk produced by reactor accident consequence analyses

  17. Dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro

    International Nuclear Information System (INIS)

    Liu Shuchun; Lu Zhe; Li Yanbo; Kang Shunai; Gong Shouliang; Zhao Wenju

    2008-01-01

    Objective: To observe the dose-rate effect of adaptive response of apoptosis and cell cycle progression induced by low-dose ionizing radiation in EL-4 lymphoma cells in vitro in order to reveal the possible mechanism of biological effect and adaptive response induced by low dose radiation. Methods: The experiment was divided into D2 (challenging dose), D1 (inductive dose) + D2 and sham-irradiation groups. EL-4 lymphoma cells were irradiated with D1 (75 mGy, 6.25-200.00 mGy·mm -1 ) and D2(1.5 Gy, 287 mGy·min -1 ), the time interval between D1 and D2 was 6 h. The percentage of apoptosis and each cell cycle phase were measured with flow cytometry. Results: When the dose rates of D1 were 6.25-50.00 mGy·min -1 , the percentages of apoptosis in the D1 + D2 group were significantly lower than those in the D2 group (P 0 /G 1 phase cells decreased significantly (P -1 , D2 is 1.5 Gy (287 mGy·min -1 ), and the time interval between D1 and D2 is 6 h, the adaptive response of apoptosis and cell cycle progression in EL-4 lymphoma cells in vitro could be induced. (authors)

  18. The effect of low dose rate on metabolomic response to radiation in mice

    International Nuclear Information System (INIS)

    Goudarzi, Maryam; Mak, Tytus D.; Chen, Congju; Smilenov, Lubomir B.; Brenner, David J.; Fornace, Albert J.

    2014-01-01

    Metabolomics has been shown to have utility in assessing responses to exposure by ionizing radiation (IR) in easily accessible biofluids such as urine. Most studies to date from our laboratory and others have employed γ-irradiation at relatively high dose rates (HDR), but many environmental exposure scenarios will probably be at relatively low dose rates (LDR). There are well-documented differences in the biologic responses to LDR compared to HDR, so an important question is to assess LDR effects at the metabolomics level. Our study took advantage of a modern mass spectrometry approach in exploring the effects of dose rate on the urinary excretion levels of metabolites 2 days after IR in mice. A wide variety of statistical tools were employed to further focus on metabolites, which showed responses to LDR IR exposure (0.00309 Gy/min) distinguishable from those of HDR. From a total of 709 detected spectral features, more than 100 were determined to be statistically significant when comparing urine from mice irradiated with 1.1 or 4.45 Gy to that of sham-irradiated mice 2 days post-exposure. The results of this study show that LDR and HDR exposures perturb many of the same pathways such as TCA cycle and fatty acid metabolism, which also have been implicated in our previous IR studies. However, it is important to note that dose rate did affect the levels of particular metabolites. Differences in urinary excretion levels of such metabolites could potentially be used to assess an individual's exposure in a radiobiological event and thus would have utility for both triage and injury assessment. (orig.)

  19. Neoplastic transformation in vitro by low doses of ionizing radiation: Role of adaptive response and bystander effects

    International Nuclear Information System (INIS)

    Ko, M.; Lao, X.-Y.; Kapadia, R.; Elmore, E.; Redpath, J.L.

    2006-01-01

    The shape of the dose-response curve for cancer induction by low doses of ionizing radiation is of critical importance to the assessment of cancer risk at such doses. Epidemiologic analyses are limited by sensitivity to doses typically greater than 50-100 mGy for low LET radiation. Laboratory studies allow for the examination of lower doses using cancer-relevant endpoints. One such endpoint is neoplastic transformation in vitro. It is known that this endpoint is responsive to both adaptive response and bystander effects. The relative balance of these processes is likely to play an important role in determining the shape of the dose-response curve at low doses. A factor that may influence this balance is cell density at time of irradiation. The findings reported in this paper indicate that the transformation suppressive effect of low doses previously seen following irradiation of sub-confluent cultures, and attributed to an adaptive response, is reduced for irradiated confluent cultures. However, even under these conditions designed to optimize the role of bystander effects the data do not fit a linear no-threshold model and are still consistent with the notion of a threshold dose for neoplastic transformation in vitro by low LET radiation

  20. Influence of dose and its distribution in time on dose-response relationships for low-LET radiation

    International Nuclear Information System (INIS)

    Anon.

    1980-01-01

    This book examines the influence of dose rate and magnitude on the genetic and carcinogenic effects of radiation exposure in animals and man. It systematically examines a broad range of biological effects in simple systems, plants, laboratory animals, and man with special attention given to the effects of prenatal irradiation, changes in life span, and tumorigenesis. An enormous volume of data is provided about human tumorigenesis and the data and shortcomings are summarized. There is an extended general discussion of the consideration in quantitative dose and dose rate relationships and of the limitations of the data and analyses which have led to a linear interpolation of risk at low doses and dose rates. An argument is made for dose rate dependence in tumorigenesis as being consistent with all other radiation effects and for the applicability of Dose Rate Effectiveness Factors (DREF) in providing a more realistic assessment of the risk of radiation carcinogenesis. The report is documented with 24 pages of references. There are numerous graphs and tables, all clear and to the point. This book is a superb review and summary of the data on radiation risks

  1. Dose/volume–response relations for rectal morbidity using planned and simulated motion-inclusive dose distributions

    International Nuclear Information System (INIS)

    Thor, Maria; Apte, Aditya; Deasy, Joseph O.; Karlsdóttir, Àsa; Moiseenko, Vitali; Liu, Mitchell; Muren, Ludvig Paul

    2013-01-01

    Background and purpose: Many dose-limiting normal tissues in radiotherapy (RT) display considerable internal motion between fractions over a course of treatment, potentially reducing the appropriateness of using planned dose distributions to predict morbidity. Accounting explicitly for rectal motion could improve the predictive power of modelling rectal morbidity. To test this, we simulated the effect of motion in two cohorts. Materials and methods: The included patients (232 and 159 cases) received RT for prostate cancer to 70 and 74 Gy. Motion-inclusive dose distributions were introduced as simulations of random or systematic motion to the planned dose distributions. Six rectal morbidity endpoints were analysed. A probit model using the QUANTEC recommended parameters was also applied to the cohorts. Results: The differences in associations using the planned over the motion-inclusive dose distributions were modest. Statistically significant associations were obtained with four of the endpoints, mainly at high doses (55–70 Gy), using both the planned and the motion-inclusive dose distributions, primarily when simulating random motion. The strongest associations were observed for GI toxicity and rectal bleeding (Rs = 0.12–0.21; Rs = 0.11–0.20). Applying the probit model, significant associations were found for tenesmus and rectal bleeding (Rs = 0.13, p = 0.02). Conclusion: Equally strong associations with rectal morbidity were observed at high doses (>55 Gy), for the planned and the simulated dose distributions including in particular random rectal motion. Future studies should explore patient-specific descriptions of rectal motion to achieve improved predictive power

  2. The Effects of Low Dose Irradiation on Inflammatory Response Proteins in a 3D Reconstituted Human Skin Tissue Model

    Energy Technology Data Exchange (ETDEWEB)

    Varnum, Susan M.; Springer, David L.; Chaffee, Mary E.; Lien, Katie A.; Webb-Robertson, Bobbie-Jo M.; Waters, Katrina M.; Sacksteder, Colette A.

    2012-12-01

    Skin responses to moderate and high doses of ionizing radiation include the induction of DNA repair, apoptosis, and stress response pathways. Additionally, numerous studies indicate that radiation exposure leads to inflammatory responses in skin cells and tissue. However, the inflammatory response of skin tissue to low dose radiation (<10 cGy) is poorly understood. In order to address this, we have utilized a reconstituted human skin tissue model (MatTek EpiDerm FT) and assessed changes in 23 cytokines twenty-four and forty eight hours following treatment of skin with either 3 or 10 cGy low-dose of radiation. Three cytokines, IFN-γ, IL-2, MIP-1α, were significantly altered in response to low dose radiation. In contrast, seven cytokines were significantly altered in response to a high radiation dose of 200 cGy (IL-2, IL-10, IL-13, IFN-γ, MIP-1α, TNF α, and VEGF) or the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (G-CSF, GM-CSF, IL-1α, IL-8, MIP-1α, MIP-1β, RANTES). Additionally, radiation induced inflammation appears to have a distinct cytokine response relative to the non-radiation induced stressor, TPA. Overall, these results indicate that there are subtle changes in the inflammatory protein levels following exposure to low dose radiation and this response is a sub-set of what is seen following a high dose in a human skin tissue model.

  3. Dose response of fish oil versus safflower oil on graft arteriosclerosis in rabbit heterotopic cardiac allografts.

    Science.gov (United States)

    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

  4. Sex- and dose-dependent effects of calcium ion irradiation on behavioral performance of B6D2F1 mice during contextual fear conditioning training

    Science.gov (United States)

    Raber, Jacob; Weber, Sydney J.; Kronenberg, Amy; Turker, Mitchell S.

    2016-06-01

    The space radiation environment includes energetic charged particles that may impact behavioral and cognitive performance. The relationship between the dose and the ionization density of the various types of charged particles (expressed as linear energy transfer or LET), and cognitive performance is complex. In our earlier work, whole body exposure to 28Si ions (263 MeV/n, LET = 78keV / μ m ; 1.6 Gy) affected contextual fear memory in C57BL/6J × DBA2/J F1 (B6D2F1) mice three months following irradiation but this was not the case following exposure to 48Ti ions (1 GeV/n, LET = 107keV / μ m ; 0.2 or 0.4 Gy). As an increased understanding of the impact of charged particle exposures is critical for assessment of risk to the CNS of astronauts during and following missions, in this study we used 40Ca ion beams (942 MeV/n, LET = 90keV / μm) to determine the behavioral and cognitive effects for the LET region between that of Si ions and Ti ions. 40Ca ion exposure reduced baseline activity in a novel environment in a dose-dependent manner, which suggests reduced motivation to explore and/or a diminished level of curiosity in a novel environment. In addition, exposure to 40Ca ions had sex-dependent effects on response to shock. 40Ca ion irradiation reduced the response to shock in female, but not male, mice. In contrast, 40Ca ion irradiation did not affect fear learning, memory, or extinction of fear memory for either gender at the doses employed in this study. Thus 40Ca ion irradiation affected behavioral, but not cognitive, performance. The effects of 40Ca ion irradiation on behavioral performance are relevant, as a combination of novelty and aversive environmental stimuli is pertinent to conditions experienced by astronauts during and following space missions.

  5. Emission properties of thermoluminescence from natural quartz - blue and red TL response to absorbed dose

    International Nuclear Information System (INIS)

    Hashimoto, T.; Yokosaka, K.; Habuki, H.

    1987-01-01

    The TL spectrometry of natural quartz exposed to a gamma radiation dose of 8.8 kGy proved that the red TL, mainly from volcanically originated quartz, has a broad emission band with a peak around 620 nm, while the blue TL from plutonically originated quartz also has a broad emission band giving a peak around 470 nm. These typical red or blue intrinsic colours were also confirmed on the thermoluminescence colour images (TLCI). Exceptionally, a pegmatite quartz changed its TLCI colour from red to blue when the absorbed dose was increased. By using colour filter assemblies, all these quartz samples were shown to emit mainly blue and red TLs, which have distinctly different TL responses to the absorbed dose; the blue invariably showed a supralinearity relation between 1 and 10 kGy dose. For the purpose of dating, the use of red TL, is preferable. The red TL component is related to the impurity Eu content in quartz minerals. (author)

  6. Dose-response analysis of parotid gland function: what is the best measure of xerostomia?

    Science.gov (United States)

    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.

  7. Relationship between dose of emamectin benzoate and molting response of ovigerous American lobsters (Homarus americanus).

    Science.gov (United States)

    Waddy, S L; Merritt, V A; Hamilton-Gibson, M N; Aiken, D E; Burridge, L E

    2007-05-01

    A widely-prescribed treatment to control sea lice on cultured salmon is the administration of feed medicated with SLICE (active ingredient emamectin benzoate (EMB)). High doses of EMB can disrupt the molt cycle of ovigerous American lobsters, causing them to enter proecdysis prematurely and lose their attached eggs when the shell is cast. To determine the dose response to EMB, lobsters were forced to ingest doses that ranged from 0.05 to 0.39 microg g(-1). A significant proportion of lobsters given doses of 0.39 and 0.22 microg g(-1) (37% and 23%, respectively) molted prematurely, almost a year earlier than the control group. All the lobsters in the 0.05 and 0.12 microg g(-1) groups molted at the normal time and the mean time of molt was similar to that of the control group. Thus, the no-observed-effect level (NOEL) and lowest-observed-effect level (LOEL) of EMB on the molt cycle were 0.12 and 0.22 microg EMB g(-1) lobster, respectively. To acquire the LOEL, a 500-g lobster would have to consume 22 g of salmon feed medicated with SLICE at a level of 5 microg EMB g(-1) feed.

  8. Dose-dependent response of Trichoderma harzianum in improving drought tolerance in rice genotypes.

    Science.gov (United States)

    Pandey, Veena; Ansari, Mohammad W; Tula, Suresh; Yadav, Sandep; Sahoo, Ranjan K; Shukla, Nandini; Bains, Gurdeep; Badal, Shail; Chandra, Subhash; Gaur, A K; Kumar, Atul; Shukla, Alok; Kumar, J; Tuteja, Narendra

    2016-05-01

    This study demonstrates a dose-dependent response of Trichoderma harzianum Th-56 in improving drought tolerance in rice by modulating proline, SOD, lipid peroxidation product and DHN / AQU transcript level, and the growth attributes. In the present study, the effect of colonization of different doses of T. harzianum Th-56 strain in rice genotypes were evaluated under drought stress. The rice genotypes treated with increasing dose of T. harzianum strain Th-56 showed better drought tolerance as compared with untreated control plant. There was significant change in malondialdehyde, proline, higher superoxide dismutase level, plant height, total dry matter, relative chlorophyll content, leaf rolling, leaf tip burn, and the number of scorched/senesced leaves in T. harzianum Th-56 treated rice genotypes under drought stress. This was corroborated with altered expression of aquaporin and dehydrin genes in T. harzianum Th-56 treated rice genotypes. The present findings suggest that a dose of 30 g/L was the most effective in improving drought tolerance in rice, and its potential exploitation will contribute to the advancement of rice genotypes to sustain crop productivity under drought stress. Interaction studies of T. harzianum with three aromatic rice genotypes suggested that PSD-17 was highly benefitted from T. harzianum colonization under drought stress.

  9. 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

  10. 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)

  11. Radiation-induced attenuation in polarization maintaining fibers: low dose rate response, stress, and materials effects

    International Nuclear Information System (INIS)

    Gingerich, M.E.; Friebele, E.J.; Hickey, S.J.; Brambani, L.A.; Onstott, J.R.

    1989-01-01

    The loss induced in polarization-maintaining (PM) fibers by low dose rate <0.01 Gy/h, where 1 Gy = 100 rads(Si) radiation exposure has been found to vary from <0.4 to ∼6 dB/km-10 Gy, depending on the wavelength of measurement and the fiber. Correlations have been established between low dose rate response and the ''permanent'' induced loss determined by fitting the recovery of the induced loss following high dose rate exposure to nth-order kinetics. Using this technique, both 0.85- and 1.3-μm PM fibers have been found which show virtually no permanent incremental loss and would therefore appear to be resistant to low dose rate radiation environments. The asymmetric stress inherent in PM fibers has been shown to reduce the permanent induced loss, while the recovery of the radiation-induced attenuation was found to be enhanced in fibers with Ge-F-doped silica clads

  12. Dose-response relationships for chromosome aberrations in peripheral blood lymphocytes after whole- and partial-body irradiations. Pt. 1

    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.)

  13. Individual variation in paternal responses of virgin male California mice (Peromyscus californicus): behavioral and physiological correlates

    NARCIS (Netherlands)

    de Jong, T.R.; Korosi, A.; Harris, B.N.; Perea-Rodriguez, J.P.; Saltzman, W.

    2012-01-01

    California mice Peromyscus californicus are a rodent species in which fathers provide extensive paternal care; however, behavioral responses of virgin males toward conspecific neonates vary from paternal behavior to tolerance to infanticide. Indirect evidence suggests that paternal responses might

  14. Maximum likelihood estimation of dose-response parameters for therapeutic operating characteristic (TOC) analysis of carcinoma of the nasopharynx

    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

  15. Mathematical modeling improves EC50 estimations from classical dose-response curves.

    Science.gov (United States)

    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.

  16. 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)

  17. Response surfaces and sensitivity analyses for an environmental model of dose calculations

    Energy Technology Data Exchange (ETDEWEB)

    Iooss, Bertrand [CEA Cadarache, DEN/DER/SESI/LCFR, 13108 Saint Paul lez Durance, Cedex (France)]. E-mail: bertrand.iooss@cea.fr; Van Dorpe, Francois [CEA Cadarache, DEN/DTN/SMTM/LMTE, 13108 Saint Paul lez Durance, Cedex (France); Devictor, Nicolas [CEA Cadarache, DEN/DER/SESI/LCFR, 13108 Saint Paul lez Durance, Cedex (France)

    2006-10-15

    A parametric sensitivity analysis is carried out on GASCON, a radiological impact software describing the radionuclides transfer to the man following a chronic gas release of a nuclear facility. An effective dose received by age group can thus be calculated according to a specific radionuclide and to the duration of the release. In this study, we are concerned by 18 output variables, each depending of approximately 50 uncertain input parameters. First, the generation of 1000 Monte-Carlo simulations allows us to calculate correlation coefficients between input parameters and output variables, which give a first overview of important factors. Response surfaces are then constructed in polynomial form, and used to predict system responses at reduced computation time cost; this response surface will be very useful for global sensitivity analysis where thousands of runs are required. Using the response surfaces, we calculate the total sensitivity indices of Sobol by the Monte-Carlo method. We demonstrate the application of this method to one site of study and to one reference group near the nuclear research Center of Cadarache (France), for two radionuclides: iodine 129 and uranium 238. It is thus shown that the most influential parameters are all related to the food chain of the goat's milk, in decreasing order of importance: dose coefficient 'effective ingestion', goat's milk ration of the individuals of the reference group, grass ration of the goat, dry deposition velocity and transfer factor to the goat's milk.

  18. Behavioral Responses to Epidemics in an Online Experiment: Using Virtual Diseases to Study Human Behavior

    Science.gov (United States)

    Chen, Frederick; Griffith, Amanda; Cottrell, Allin; Wong, Yue-Ling

    2013-01-01

    We report the results of a study we conducted using a simple multiplayer online game that simulates the spread of an infectious disease through a population composed of the players. We use our virtual epidemics game to examine how people respond to epidemics. The analysis shows that people's behavior is responsive to the cost of self-protection, the reported prevalence of disease, and their experiences earlier in the epidemic. Specifically, decreasing the cost of self-protection increases the rate of safe behavior. Higher reported prevalence also raises the likelihood that individuals would engage in self-protection, where the magnitude of this effect depends on how much time has elapsed in the epidemic. Individuals' experiences in terms of how often an infection was acquired when they did not engage in self-protection are another factor that determines whether they will invest in preventive measures later on. All else being equal, individuals who were infected at a higher rate are more likely to engage in self-protective behavior compared to those with a lower rate of infection. Lastly, fixing everything else, people's willingness to engage in safe behavior waxes or wanes over time, depending on the severity of an epidemic: when prevalence is high, people are more likely to adopt self-protective measures as time goes by; when prevalence is low, a ‘self-protection fatigue’ effect sets in whereby individuals are less willing to engage in safe behavior over time. PMID:23326360

  19. No priming of the immune response in newborn Brown Norway rats dosed with ovalbumin in the mouth

    DEFF Research Database (Denmark)

    Madsen, Charlotte Bernhard; Pilegaard, Kirsten

    2003-01-01

    with ovalbumin and if this method could be used in an animal model for food allergy. Methods: Newborn Brown Norway rats were dosed with ovalbumin in the mouth (100 mug or 6 mg). As young adults, the animals were dosed by gavage for 35 days with 1 mg ovalbumin/day or once intraperitoneally with 100 mug. Control......E and IgG responses were decreased compared to the control groups, however, not always reaching statistical significance. A statistical significant decrease in the specific immune response was found in young adult rats dosed in the mouth as compared to by gavage. Conclusions: Dosing Brown Norway rats...

  20. Impact of different infliximab dose regimens on treatment response and drug survival in 462 patients with psoriatic arthritis

    DEFF Research Database (Denmark)

    Glintborg, Bente; Gudbjornsson, Bjorn; Krogh, Niels Steen

    2014-01-01

    Icelandic patients at baseline [median 3.1 (interquartile range 3.0-3.8) vs 2.3 (2.1-2.9) mg/kg, P drug survival than...... Icelandic patients (1183 vs 483 days). In univariate analyses stratified by country, time until dose escalation, response rates, drug survival and 1-year's disease activity were independent of starting dose. Drug survival was shorter among patients not receiving concomitant MTX. CONCLUSION: In clinical...... practice, > 70% of Icelandic and Danish PsA patients treated with infliximab received sustained doses below the 5 mg/kg every 8 weeks recommended in international guidelines. Lower starting doses did not affect drug survival or response....

  1. X-ray conditions and response characteristics of automatic dose control in cinematography

    International Nuclear Information System (INIS)

    Arai, Hiroaki

    1997-01-01

    X-ray characteristics including subject thickness (copper plate), tube voltage, tube current and irradiation time were measured at stability, with an automatic dose control x-ray generator for cineangiography. Regardless of subject thickness, it is possible that the energy input to the x-ray tube in one frame may be decreased. The automatic control response was measured after rapid fluctuation in subject thickness. Two inverter-type x-ray generators with different automatic control units were studied. The older control unit changes exposure dose by tube voltage and tube current, while the newer one changes exposure dose by tube voltage, tube current and irradiation time. The maximum rate of change in tube voltage is greater with the newer control unit. In addition, the actual tube current response of the newer control unit in increasing nominal value is faster than the older one. In the new control unit, for each pulse, irradiation is cut off by means of a signal that the exposure has reached the proper value. Thus given the same differential in subject thickness, the newer control unit resumed stability faster than the older one. (author)

  2. Adaptive response of the chicken embryo to low doses of x-irradiation

    International Nuclear Information System (INIS)

    Tempel, K.; Schleifer, S.

    1995-01-01

    Chicken embryos were x-irradiated in ovo with 5-30 cGy (=priming dose) at the 13th-15th day of development. After 3-48 h, brain- and liver-cell suspensions were x-irradiated in vitro with (challenge) doses of 4-32 Gy. Significantly less radiation damage was observed when the radiation response was measured by scheduled DNA synthesis, nucleoid sedimentation and viscosity of alkaline cell lysates 12-36 h after the priming exposure. In vivo, pre-irradiation with 10 cGy enhanced regeneration as evidenced by the DNA content of chicken embryo brain and liver 24 h following a challenge dose of 4 Gy. From nucleoid sedimentation analyses in brain and liver cells immediately after irradiation with 16 Gy and after a 30-min repair period in the presence of aphidicolin, dideoxythymidine and 3-aminobenzamide or in the absence of these DNA repair inhibitors, it is concluded that a reduction of the initial radiation damage is the dominant mechanism of the ''radio-adaptive'' response of the chicken embryo. Sedimentation of nucleoids from ethidium bromide (EB) (0.75-400 μg/ml)-treated cells suggests a higher tendency of ''radio-adapted'' cells to undergo positive DNA supercoiling in the presence of high EB concentrations. (orig.)

  3. Adaptive response induced by low doses of ionizing radiation in human lymphocytes

    International Nuclear Information System (INIS)

    Frati, Diego Libkind; Bunge, Maria M.

    2001-01-01

    The term adaptive response (AR) applies to the phenomenon of protection or enhanced repair induced by a small dose of a mutagenic agent. In order to determine the existence of AR in human lymphocytes for two different irradiation schemes, microcultures of blood from 4 donors were irradiated. Samples were exposed 24 hours (hr) after phytohemagglutinin stimulation to an adapting dose of 0,01 Gy and to a challenging dose of 1,5 Gy either 6 or 24 hr later (irradiation scheme 24+30 or 24+48, respectively). Gamma radiation from a 2,5 MeV Linac was used in all experiments. A cytogenetic analysis of unstable chromosome aberrations was applied as the endpoint. High inter-individual variability was found for the first irradiation scheme: one expressed AR, two did not and the last showed an apparent synergistic response. For the second irradiation scheme, low mitotic indices (MI) were found, suggesting a G2 arrest. When a series of harvesting times were applied for the last donor, normal MI were obtained only harvesting after 58 hr. An AR was found when harvesting at 72 hr but not at 58 hr. (author)

  4. Guidelines for application of chemical-specific adjustment factors in dose/concentration-response assessment

    International Nuclear Information System (INIS)

    Meek, M.E.; Renwick, A.; Ohanian, E.; Dourson, M.; Lake, B.; Naumann, B.D.; Vu, V.

    2002-01-01

    This manuscript addresses guidance in the use of kinetic and dynamic data to inform quantitatively extrapolations for interspecies differences and human variability in dose-response assessment developed in a project of the International Programme on Chemical Safety (IPCS) initiative on Harmonisation of Approaches to the Assessment of Risk from Exposure to Chemicals. The guidance has been developed and refined through a series of planning and technical meetings and larger workshops of a broad range of participants from academia, government agencies and the private sector. The guidance for adequacy of data for replacement of common defaults for interspecies differences and human variability is presented in the context of several generic categories including: determination of the active chemical species, choice of the appropriate metric (kinetic components) or endpoint (dynamic components) and nature of experimental data, the latter which includes reference to the relevance of population, route and dose and the adequacy of the number of subjects/samples. The principal objective of this guidance developed primarily as a resource for risk assessors, is to foster better understanding of the components of and criteria for adequacy of chemical-specific data to quantitate interspecies differences and human variability in kinetics and dynamics. It is anticipated that this guidance will also encourage the development of appropriate data and facilitate their incorporation in a consistent fashion in dose-response assessment for regulatory purposes (IPCS, 2001)

  5. X-ray conditions and response characteristics of automatic dose control in cinematography

    Energy Technology Data Exchange (ETDEWEB)

    Arai, Hiroaki [Cardiovascular Institute Hospital, Tokyo (Japan)

    1997-11-01

    X-ray characteristics including subject thickness (copper plate), tube voltage, tube current and irradiation time were measured at stability, with an automatic dose control x-ray generator for cineangiography. Regardless of subject thickness, it is possible that the energy input to the x-ray tube in one frame may be decreased. The automatic control response was measured after rapid fluctuation in subject thickness. Two inverter-type x-ray generators with different automatic control units were studied. The older control unit changes exposure dose by tube voltage and tube current, while the newer one changes exposure dose by tube voltage, tube current and irradiation time. The maximum rate of change in tube voltage is greater with the newer control unit. In addition, the actual tube current response of the newer control unit in increasing nominal value is faster than the older one. In the new control unit, for each pulse, irradiation is cut off by means of a signal that the exposure has reached the proper value. Thus given the same differential in subject thickness, the newer control unit resumed stability faster than the older one. (author)

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

    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

  7. Dose and time relationships in the endocrine response of the irradiated adult rat testis

    International Nuclear Information System (INIS)

    Delic, J.I.; Hendry, J.H.; Morris, I.D.; Shalet, S.M.

    1986-01-01

    The dose- and time-dependent responses for the interstitial and tubular compartments in irradiated adult rat testes are described. Leydig cell dysfunction, as indicated by increased serum LH (to a maximum of 385% of control after 5 Gy) and decreased serum T (to a minimum of 30% of control after 10 Gy), was observed at 8 weeks postirradiation. Subsequent recovery of Leydig cell function was then observed, so that after 9 months serum T was normal but LH was still marginally elevated. The dysfunction, with a threshold of about 4 to 5 Gy, was associated with a loss of Leydig cells from the testis. Spermatogenic damage was observed; after doses of 3 Gy and above a marked dose-response was recorded as assessed by counts of tubule cross sections exhibiting spermatogenesis. Reduced serum levels of androgen binding protein indicated Sertoli cell dysfunction at 8 weeks after 3 Gy and above, with values of less than one half of those seen in the controls. Serum FSH also was elevated to between 150% and 200% of control, and after 9 months closely reflected androgen binding protein changes. Unlike the Leydig cell, no recovery with time was observed for this aspect of Sertoli cell function

  8. Effects of clinically relevant doses of methyphenidate on spatial memory, behavioral sensitization and open field habituation: a time related study.

    Science.gov (United States)

    Haleem, Darakhshan Jabeen; Inam, Qurrat-ul-Aen; Haleem, Muhammad Abdul

    2015-03-15

    The psychostimulant methylphenidate (MPD) is a first-line drug for the treatment of attention deficit hyperactivity disorder (ADHD). Despite acceptable therapeutic efficacy, there is limited data regarding the long-term consequences of MPD exposure over extended periods. The present study concerns effects of clinically relevant doses of MPD, administered orally to rats for an extended period, on spatial memory, behavioral sensitization and habituation to an open field. Water maze test was used to monitor memory acquisition (2 h after training), retention (day next to training), extinction (1 week after training) and reconsolidation (weekly for 4 weeks). Administration of MPD at doses of 0.25-1.0 mg/kg improved memory acquisition, retention, reconsolidation and impaired memory extinction. Treatment with 0.25 and 0.5 mg/kg MPD for 6 weeks produced a sustained increase in motor activity but higher dose (1.0 mg/kg) elicited behavioral sensitization. High as well as low doses MPD impaired open field habituation. We conclude that clinically relevant doses of MPD enhance memory even if used for extended period. It is suggested that higher (1.0 mg/kg) clinically relevant doses of MPD, if used for extended period, may exacerbate hyperactivity and impulsivity associated with the disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. 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

  10. 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.

  11. Dose response effect of cement dust on respiratory muscles competence in cement mill workers.

    Science.gov (United States)

    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.

  12. Methods for extracting dose response curves fr