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.

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

Responsive web design with jQuery

CERN Document Server

Carlos, Gilberto

2013-01-01

Responsive Web Design with jQuery follows a standard tutorial-based approach, covering various aspects of responsive web design by building a comprehensive website.""Responsive Web Design with jQuery"" is aimed at web designers who are interested in building device-agnostic websites. You should have a grasp of standard HTML, CSS, and JavaScript development, and have a familiarity with graphic design. Some exposure to jQuery and HTML5 will be beneficial but isn't essential.

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

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.

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.

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

Angular and dose dependence of CR-39 neutron response for shape-selected tracks

CERN Document Server

Tam, N C; Lakosi, L

1999-01-01

A shape selection method corresponding to an energy discrimination was used to eliminate unwanted events disturbing evaluation of CR-39 detectors in detecting tracks induced by particles both of perpendicular and oblique incidence. The angular dependence of the response was examined, detecting fast neutrons from sup 2 sup 5 sup 2 Cf with shape selection technique at various angles and distances. Also, the CR-39 track detectors with the sup 2 sup 5 sup 2 Cf source were exposed to high gamma-intensity of a sup 6 sup 0 Co irradiation facility in the range 0.1 to 4.5 kGy, similar to the exposures inside spent fuel assemblies. Using the two functions the lower limit of burnup could be determined by the method.

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

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

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

Molecular mechanisms of the 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced inverted U-shaped dose responsiveness in anchorage independent growth and cell proliferation of human breast epithelial cells with stem cell characteristics

International Nuclear Information System (INIS)

Ahn, Nam-Shik; Hu, Hongbo; Park, Jin-Sung; Park, Joon-Suk; Kim, Jong-Sik; An, Sungwhan; Kong, Gu; Aruoma, Okezie I.; Lee, Yong-Soon; Kang, Kyung-Sun

2005-01-01

Although 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a variety of carcinogenic and noncarcinogenic effects in experimental animals, its role in human carcinogenicity remain controversial. A simian virus 40-immortalized cell line from normal human breast epithelial cells with stem cells and luminal characteristics (M13SV1) was used to study whether TCDD can induce AIG positive colony formation and cause increased cell numbers in a inverted U-shaped dose-response manner. TCDD activated Akt, ERK2, and increased the expression of CYP1A1, PAI-2, IL-lb mRNA, and ERK2 protein levels. TCDD was able to increased phosphorylation and expression of ERK2 in same dose-response manner as AIG positive colony formation. Thus, TCDD induced tumorigenicity in M13SV1, possibly through the phosphorylation of ERK2 and/or Akt. Further, cDNA microarray with 7448 sequence-verified clones was used to profile various gene expression patterns after treatment of TCDD. Three clear patterns could be delineated: genes that were dose-dependently up-regulated, genes expressed in either U-shape and/or inverted U-shape. The fact that these genes are intrinsically related to breast epithelial cell proliferation and survival clearly suggests that they may be involved in the TCDD-induced breast tumorigenesis

The induction by x rays of chromosome aberrations in male guinea-pigs, rabbits and golden hamsters. 3. Dose-response relationship after single doses of X-rays to spermatogonia

Energy Technology Data Exchange (ETDEWEB)

Lyon, M F; Cox, B D

1975-09-01

The induction by X-rays of translocations in spermatogonia was studied by cytological means in spermatocytes derived from them. In the rabbit and guinea-pig, hump-shaped dose-response curves were obtained, with a linear relationship at the low doses. The shapes of the curves were similar to those reported for the mouse, except that the maximum occurred at 600-700 rad in the mouse as opposed to 300 rad in the guinea-pig and rabbit. Unlike the guinea-pig and rabbit, the golden hamster showed a hump dose-response curve without a definite peak value and with little decrease in yield at high radiation doses. Over the low dose range 100-300 rad, the slopes of the curves of translocation yield were in the order: mouse (highest), rabbit, guinea-pig and hamster. Data on sterile periods suggested that the amount of spermatogonial killing in the rabbit and guinea-pig was as great or greater than in the mouse, and that in the golden hamster it was most severe. It is suggested that the differing shapes of the dose-response curves can be explained by a lower sensitivity to translocation induction in the test species and, also especially in the golden hamster, a greater sensitivity to cell killing. The possibility of extrapolating from these data to other species is discussed.

Radiation dose reduction in parasinus CT by spectral shaping

Energy Technology Data Exchange (ETDEWEB)

May, Matthias S.; Brand, Michael; Lell, Michael M.; Uder, Michael; Wuest, Wolfgang [University Hospital Erlangen, Department of Radiology, Erlangen (Germany); Sedlmair, Martin; Allmendinger, Thomas [Siemens Healthcare GmbH, Forchheim (Germany)

2017-02-15

Spectral shaping aims to narrow the X-ray spectrum of clinical CT. The aim of this study was to determine the image quality and the extent of radiation dose reduction that can be achieved by tin prefiltration for parasinus CT. All scans were performed with a third generation dual-source CT scanner. A study protocol was designed using 100 kV tube voltage with tin prefiltration (200 mAs) that provides image noise levels comparable to a low-dose reference protocol using 100 kV without spectral shaping (25 mAs). One hundred consecutive patients were prospectively enrolled and randomly assigned to the study or control group. All patients signed written informed consent. The study protocol was approved by the local Institutional Review Board and applies to the HIPAA. Subjective and objective image quality (attenuation values, image noise, and contrast-to-noise ratio (CNR)) were assessed. Radiation exposure was assessed as volumetric CT dose index, and effective dose was estimated. Mann-Whitney U test was performed for radiation exposure and for image noise comparison. All scans were of diagnostic image quality. Image noise in air, in the retrobulbar fat, and in the eye globe was comparable between both groups (all p > 0.05). CNR{sub eye} {sub globe/air} did not differ significantly between both groups (p = 0.7). Radiation exposure (1.7 vs. 2.1 mGy, p < 0.01) and effective dose (0.055 vs. 0.066 mSv, p < 0.01) were significantly reduced in the study group. Radiation dose can be further reduced by 17% for low-dose parasinus CT by tin prefiltration maintaining diagnostic image quality. (orig.)

Radiation dose reduction in parasinus CT by spectral shaping

International Nuclear Information System (INIS)

May, Matthias S.; Brand, Michael; Lell, Michael M.; Uder, Michael; Wuest, Wolfgang; Sedlmair, Martin; Allmendinger, Thomas

2017-01-01

Spectral shaping aims to narrow the X-ray spectrum of clinical CT. The aim of this study was to determine the image quality and the extent of radiation dose reduction that can be achieved by tin prefiltration for parasinus CT. All scans were performed with a third generation dual-source CT scanner. A study protocol was designed using 100 kV tube voltage with tin prefiltration (200 mAs) that provides image noise levels comparable to a low-dose reference protocol using 100 kV without spectral shaping (25 mAs). One hundred consecutive patients were prospectively enrolled and randomly assigned to the study or control group. All patients signed written informed consent. The study protocol was approved by the local Institutional Review Board and applies to the HIPAA. Subjective and objective image quality (attenuation values, image noise, and contrast-to-noise ratio (CNR)) were assessed. Radiation exposure was assessed as volumetric CT dose index, and effective dose was estimated. Mann-Whitney U test was performed for radiation exposure and for image noise comparison. All scans were of diagnostic image quality. Image noise in air, in the retrobulbar fat, and in the eye globe was comparable between both groups (all p > 0.05). CNR_e_y_e _g_l_o_b_e_/_a_i_r did not differ significantly between both groups (p = 0.7). Radiation exposure (1.7 vs. 2.1 mGy, p < 0.01) and effective dose (0.055 vs. 0.066 mSv, p < 0.01) were significantly reduced in the study group. Radiation dose can be further reduced by 17% for low-dose parasinus CT by tin prefiltration maintaining diagnostic image quality. (orig.)

Book received: Towards a Science of Art History: J. J. Tikkanen and Art Historical Scholarship in Europe and The shaping of Art History in Finland

OpenAIRE

Publications of the Society of Art History in Finland

2010-01-01

Publications of the Society of Art History in Finland: Towards a Science of Art History: J. J. Tikkanen and Art Historical Scholarship in Europe and The shaping of Art History in Finland, Helsinki 2007 with tables of contents.

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

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)

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

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.

Dose reduction in pulsed fluoroscopy by modifying the high-voltage pulse shape

International Nuclear Information System (INIS)

Sabau, M.N.; Phelps, G.

1988-01-01

This paper presents the dose reduction results in pulsed fluoroscopy by modifying the high-voltage pulse shape (HVPS). Since the HVPS in regular pulsed fluoroscopy has a long tail, the radiation pulse shape (RPS) is similar. Using specially designed circuitry in the high-voltage generator to produce a rectangular HVPS, and consequently a rectangular RPS, it was possible to obtain a reduction of up to 25% of patient exposure. This dose reduction obtained by cutting the long tail of RPS does not damage the image quality

Dose Measurements in a 20-J Repetitive Plasma Focus

Science.gov (United States)

Goudarzi, S.; Babaee, H.; Esmaeli, A.; Nasiri, A.; Mazandarani, A.

2018-02-01

In this article, the results of X-ray dose measurements executed using thermoluminescent dosimeters in experiments with a very small (20 J) repetitive plasma focus device named SORENA-1 are presented and analyzed. The working gas in these experiments was Argon. Also, pinch formation in experiments with this device has been observed. This device has been designed and constructed in Plasma and Nuclear Fusion Research School of Nuclear Science and Technology Research Institute of Iran. From these results, it is concluded that we can do experiments with this device using Ar as working gas all over the working days of year, and a good symmetry for measured dose around the device has been seen.

Modification of transmission dose algorithm for irregularly shaped radiation field and tissue deficit

Energy Technology Data Exchange (ETDEWEB)

Yun, Hyong Geon; Shin, Kyo Chul [Dankook Univ., College of Medicine, Seoul (Korea, Republic of); Huh, Soon Nyung; Woo, Hong Gyun; Ha, Sung Whan [Seoul National Univ., College of Medicine, Seoul (Korea, Republic of); Lee, Hyoung Koo [The Catholic Univ., College of Medicine, Seoul (Korea, Republic of)

2002-07-01

Algorithm for estimation of transmission dose was modified for use in partially blocked radiation fields and in cases with tissue deficit. The beam data was measured with flat solid phantom in various conditions of beam block. And an algorithm for correction of transmission dose in cases of partially blocked radiation field was developed from the measured data. The algorithm was tested in some clinical settings with irregular shaped field. Also, another algorithm for correction of transmission dose for tissue deficit was developed by physical reasoning. This algorithm was tested in experimental settings with irregular contours mimicking breast cancer patients by using multiple sheets of solid phantoms. The algorithm for correction of beam block could accurately reflect the effect of beam block, with error within {+-}1.0%, both with square fields and irregularly shaped fields. The correction algorithm for tissue deficit could accurately reflect the effect of tissue deficit with errors within {+-}1.0% in most situations and within {+-}3.0% in experimental settings with irregular contours mimicking breast cancer treatment set-up. Developed algorithms could accurately estimate the transmission dose in most radiation treatment settings including irregularly shaped field and irregularly shaped body contour with tissue deficit in transmission dosimetry.

Modification of transmission dose algorithm for irregularly shaped radiation field and tissue deficit

International Nuclear Information System (INIS)

Yun, Hyong Geon; Shin, Kyo Chul; Huh, Soon Nyung; Woo, Hong Gyun; Ha, Sung Whan; Lee, Hyoung Koo

2002-01-01

Algorithm for estimation of transmission dose was modified for use in partially blocked radiation fields and in cases with tissue deficit. The beam data was measured with flat solid phantom in various conditions of beam block. And an algorithm for correction of transmission dose in cases of partially blocked radiation field was developed from the measured data. The algorithm was tested in some clinical settings with irregular shaped field. Also, another algorithm for correction of transmission dose for tissue deficit was developed by physical reasoning. This algorithm was tested in experimental settings with irregular contours mimicking breast cancer patients by using multiple sheets of solid phantoms. The algorithm for correction of beam block could accurately reflect the effect of beam block, with error within ±1.0%, both with square fields and irregularly shaped fields. The correction algorithm for tissue deficit could accurately reflect the effect of tissue deficit with errors within ±1.0% in most situations and within ±3.0% in experimental settings with irregular contours mimicking breast cancer treatment set-up. Developed algorithms could accurately estimate the transmission dose in most radiation treatment settings including irregularly shaped field and irregularly shaped body contour with tissue deficit in transmission dosimetry

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

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

Skull base chordomas: analysis of dose-response characteristics

International Nuclear Information System (INIS)

Niemierko, Andrzej; Terahara, Atsuro; Goitein, Michael

1997-01-01

parameters of the time-dose-response relationship for the analyzed group of patients. For example, the maximum likelihood estimates of surviving fraction at 2Gy (SF 2 ) are 0.47 with 95% confidence limits of [0.45-0.49] for male and 0.53 [0.51-0.55] for female, with the coefficient of inter-patient variation in SF 2 of 4.3%. The density of clonogens was estimated to be 10 8.2 clonogens per cubic centimeter. In effect, the slope of the dose-response curve, γ 50 , was estimated to be 2.7 [1.9-3.2] for both male and female, and the ED 50 doses to be 67Gy and 73Gy respectively. Skull base chordomas of the female patients seemed to be not only more resistant to radiation but also recurring faster than that for male patients (the maximum likelihood estimates of the Weibull shape parameter β are 2.6 for female and 1.7 for male patients). Conclusions: This analysis revealed several clinically important characteristics of radioresponsiveness of skull base chordomas. The comprehensive patient data obtained using three-dimensional treatment planning system allowed us to demonstrate and quantify the existence of dose-response and dose-volume relationships. In consequence, we are able to estimate prospectively the individual's probability of staying recurrence-free and her/his overall survival characteristics as a function of the applied three-dimensional dose distribution and time after treatment. Based on the analysis our treatment protocols have been modified to account for differences in radiosensitivity between female and male patients

Interactive dose shaping - efficient strategies for CPU-based real-time treatment planning

International Nuclear Information System (INIS)

Ziegenhein, P; Kamerling, C P; Oelfke, U

2014-01-01

Conventional intensity modulated radiation therapy (IMRT) treatment planning is based on the traditional concept of iterative optimization using an objective function specified by dose volume histogram constraints for pre-segmented VOIs. This indirect approach suffers from unavoidable shortcomings: i) The control of local dose features is limited to segmented VOIs. ii) Any objective function is a mathematical measure of the plan quality, i.e., is not able to define the clinically optimal treatment plan. iii) Adapting an existing plan to changed patient anatomy as detected by IGRT procedures is difficult. To overcome these shortcomings, we introduce the method of Interactive Dose Shaping (IDS) as a new paradigm for IMRT treatment planning. IDS allows for a direct and interactive manipulation of local dose features in real-time. The key element driving the IDS process is a two-step Dose Modification and Recovery (DMR) strategy: A local dose modification is initiated by the user which translates into modified fluence patterns. This also affects existing desired dose features elsewhere which is compensated by a heuristic recovery process. The IDS paradigm was implemented together with a CPU-based ultra-fast dose calculation and a 3D GUI for dose manipulation and visualization. A local dose feature can be implemented via the DMR strategy within 1-2 seconds. By imposing a series of local dose features, equal plan qualities could be achieved compared to conventional planning for prostate and head and neck cases within 1-2 minutes. The idea of Interactive Dose Shaping for treatment planning has been introduced and first applications of this concept have been realized.

Exercise, oxidants, and antioxidants change the shape of the bell-shaped hormesis curve

Directory of Open Access Journals (Sweden)

Zsolt Radak

2017-08-01

Full Text Available It is debated whether exercise-induced ROS production is obligatory to cause adaptive response. It is also claimed that antioxidant treatment could eliminate the adaptive response, which appears to be systemic and reportedly reduces the incidence of a wide range of diseases. Here we suggest that if the antioxidant treatment occurs before the physiological function-ROS dose-response curve reaches peak level, the antioxidants can attenuate function. On the other hand, if the antioxidant treatment takes place after the summit of the bell-shaped dose response curve, antioxidant treatment would have beneficial effects on function. We suggest that the effects of antioxidant treatment are dependent on the intensity of exercise, since the adaptive response, which is multi pathway dependent, is strongly influenced by exercise intensity. It is further suggested that levels of ROS concentration are associated with peak physiological function and can be extended by physical fitness level and this could be the basis for exercise pre-conditioning. Physical inactivity, aging or pathological disorders increase the sensitivity to oxidative stress by altering the bell-shaped dose response curve.

SU-E-J-273: Simulation of the Radiation Response of Hypoxic Tumors

Energy Technology Data Exchange (ETDEWEB)

Espinoza, I [Pontificia Universidad Catolica de Chile, Santiago (Chile); Peschke, P; Karger, C [German Cancer Research Center (DKFZ), Heidelberg (Germany)

2014-06-01

Purpose: In radiotherapy, it is important to predict the response of tumour to irradiation prior to the treatment. Mathematical modelling of tumour control probability (TCP) based on the dose distribution, medical imaging and other biological information may help to improve this prediction and to optimize the treatment plan. The aim of this work is to develop an image based 3D multiscale radiobiological model, which describes the growth and the response to radiotherapy of hypoxic tumors. Methods: The computer model is based on voxels, containing tumour, normal (including capillary) and dead cells. Killing of tumour cells due to irradiation is calculated by the Linear Quadratic Model (extended for hypoxia), and the proliferation and resorption of cells are modelled by exponential laws. The initial shape of the tumours is taken from CT images and the initial vascular and cell density information from PET and/or MR images. Including the fractionation regime and the physical dose distribution of the radiation treatment, the model simulates the spatial-temporal evolution of the tumor. Additionally, the dose distribution may be biologically optimized. Results: The model describes the appearance of hypoxia during tumour growth and the reoxygenation processes during radiotherapy. Among other parameters, the TCP is calculated for different dose distributions. The results are in accordance with published results. Conclusion: The simulation model may contribute to the understanding of the influence of biological parameters on tumor response during treatment, and specifically on TCP. It may be used to implement dose-painting approaches. Experimental and clinical validation is needed. This study is supported by a grant from the Ministry of Education of Chile, Programa Mece Educacion Superior (2)

SU-E-J-273: Simulation of the Radiation Response of Hypoxic Tumors

International Nuclear Information System (INIS)

Espinoza, I; Peschke, P; Karger, C

2014-01-01

Purpose: In radiotherapy, it is important to predict the response of tumour to irradiation prior to the treatment. Mathematical modelling of tumour control probability (TCP) based on the dose distribution, medical imaging and other biological information may help to improve this prediction and to optimize the treatment plan. The aim of this work is to develop an image based 3D multiscale radiobiological model, which describes the growth and the response to radiotherapy of hypoxic tumors. Methods: The computer model is based on voxels, containing tumour, normal (including capillary) and dead cells. Killing of tumour cells due to irradiation is calculated by the Linear Quadratic Model (extended for hypoxia), and the proliferation and resorption of cells are modelled by exponential laws. The initial shape of the tumours is taken from CT images and the initial vascular and cell density information from PET and/or MR images. Including the fractionation regime and the physical dose distribution of the radiation treatment, the model simulates the spatial-temporal evolution of the tumor. Additionally, the dose distribution may be biologically optimized. Results: The model describes the appearance of hypoxia during tumour growth and the reoxygenation processes during radiotherapy. Among other parameters, the TCP is calculated for different dose distributions. The results are in accordance with published results. Conclusion: The simulation model may contribute to the understanding of the influence of biological parameters on tumor response during treatment, and specifically on TCP. It may be used to implement dose-painting approaches. Experimental and clinical validation is needed. This study is supported by a grant from the Ministry of Education of Chile, Programa Mece Educacion Superior (2)

A water-responsive shape memory ionomer with permanent shape reconfiguration ability

Science.gov (United States)

Bai, Yongkang; Zhang, Jiwen; Tian, Ran; Chen, Xin

2018-04-01

In this work, a water-responsive shape memory ionomer with high toughness was fabricated by cross-linking hyaluronic acid sodium (HAS) and polyvinyl alcohol (PVA) through coordination interactions. The strong Fe3+-carboxyl (from HAS) coordination interactions served as main physical cross-linking points for the performance of water-responsive shape memory, which associated with the flexibility of PVA chain producing excellent mechanical properties of this ionomer. The optimized ionomer was not only able to recover to its original shape within just 22 s by exposing to water, but exhibited high tensile strength up to 35.4 MPa and 4 times higher tractility than the ionomer without PVA. Moreover, the ionomers can be repeatedly programed to various new permanent shapes on demand due to the reversible physical interactions, which still performed complete and fast geometric recovery under stimuli even after 4 cycles of reprograming with 3 different shapes. The excellent shape memory and strong mechanical behaviors make our ionomers significant and promising smart materials for variety of applications.

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.)

Electromagnetic response of non-trivially shaped superconductors in external magnetic fields and with applied currents

International Nuclear Information System (INIS)

Cabral, Leonardo Ribeiro Eulalio; Aguiar, Jose Albino Oliveira de

2002-01-01

Full text: The study of the electromagnetic response of high-T c superconductors is essential for future technological applications. Such materials are hard type II superconductors, where the mixed state (a state characterized by quantized normal flux tubes - also called vortices - immersed in a superconductor phase) occupies most of the phase diagram. Therefore, the electromagnetic properties are dictated by the vortex dynamics in these materials. One has also to consider the presence of structural defects and thermal effects, which turn the vortex dynamics very complex. These difficulties may be overcome throughout a macroscopic description, also known as continuum approximation, of the electromagnetic fields in superconductors, obtained from critical state models and constitutive relations E = E(j) and H = H(B) (where E is the electric field generated by moving vortices, j the current density, B the induction - related to the local density of vortices - and H the reversible magnetic field that is in equilibrium with B). In superconductors with negligible demagnetization factors, such as long cylinders and bars with applied magnetic fields and/or currents along their longer dimensions, the Meissner state and the flux penetration is quite well understood. However, the actual specimen shape plays an important role on the electromagnetic behavior of superconductors. Numerical methods are often employed, since such cases are hard to treat analytically. In this work we studied the electromagnetic response of superconductors with various shapes. The Meissner state is obtained for thin curved strips and long cylinders with arbitrary cross-section, in perpendicular field and with applied currents. The flux penetration is numerically calculated for thin curved strips for the Bean (j c =const.) and the Kim (j c (B) = j c0 /(1 + βB)) models. (author)

Kinetic and dose dependencies of the SOS-induction in E.coli K-12 (uvrA) cells exposed to different UV doses

International Nuclear Information System (INIS)

Komova, O.V.; Kandiano, E.S.; Malavina, G.; )

2000-01-01

Kinetic and dose dependencies of the SOS-induction in E. coli (uvrA) cells exposed to UV light were investigated. below 2 J/m 2 the rate of the SOS-induction increased with dose. Maximal level of the SOS-response was proportional to the UV dose. Pyrimidine dimers were necessary for the induction. In the dose range 2-10 J/m 2 the rate of SOS-induction decreased with dose. Dose-maximum response curve was non-linear. Pyrimidine dimers were not required for the induction. nature of the molecular events leading to the SOS-induction at low and high doses was discussed [ru

Biostatistical approaches for modeling U-shaped dose-response curves and study design considerations in assessing the biological effects of low doses

International Nuclear Information System (INIS)

Downs, T.

1992-01-01

The demonstration of hormetic effects is rendered difficult for a number of reasons: The spontaneous rate must be large enough for a difference to be detectable. In contrast with detrimental effects, there is a limited range of doses over which beneficial effects are likely to be found. Publication bias hampers publication of low-dose beneficial effects and discourages research in the area. Some scientists actually believe that hormetic effects are contary to reason. All these factors contribute to lessen the chances of detecting hormetic effects through synthesis of the scientific literature. The extra statistical power obtained from mathematical modeling is not available for hormetic studies when appropriate models are not available. Even a simple statistical device such as a test for linear trend does not work well for U-shaped data. The first part of this two-part chapter deals with the probabilities of determining qualitatively what kinds of health effects may result from exposures to substances, and the second part with characterizing quantitative relationships between such health effects and exposures. The health effects may be beneficial in some situations, and detrimental in others

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.

Dose-response and failure pattern for bulky or barrel-shaped stage IB cervical cancer treated by combined photon irradiation and extrafascial hysterectomy

International Nuclear Information System (INIS)

Maruyama, Y.; van Nagell, J.R.; Yoneda, J.; Donaldson, E.; Gallion, H.H.; Higgins, R.; Powell, D.; Kryscio, R.; Berner, B.

1989-01-01

From 1975 to 1987, 80 patients with bulky or barrel-shaped Stage IB cervical cancer were treated with preoperative irradiation and Cs-137 intracavitary implant therapy, before a planned extrafascial abdominal hysterectomy, using a consistent treatment policy. Of the hysterectomy specimens obtained, 37% were positive histologically at 89 +/- 2.3 days after the start of radiotherapy and at 4 to 6 weeks after the completion of radiation therapy. Sixty-three percent were negative after a total external and internal cervix irradiation dose of 9642 cGy at point T. The average point A dose contributed by intracavitary therapy was 2104 cGy. The survival rate at 5 years was 84%: At 10 years the survival rate was 78%. The failure pattern was analyzed for patients who had positive and negative specimens. The patients with positive specimens failed pelvically or pelvically and distantly. Patients with negative specimens failed in extrapelvic or distant metastatic sites. Preoperative radiotherapy led to excellent local and pelvic control of tumor, and the failures became predominantly distant metastases. The combined radiosurgical therapy was tolerated well and allowed surgical staging of disease. This permitted earlier and selective consideration of adjunctive therapy (i.e., paraaortic irradiation, chemotherapy, or chemoradiotherapy). The dose-response data give insight into the effects of photon radiotherapy on bulky or barrel Stage IB cervical cancers and correlate histologic status with failure pattern, outcome, and long-term survival

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.

Study of a wave power generator system using an air turbine having improved J-shaped blades; Kairyo J gatayoku kuki turbine wo mochiita haryoku hatsuden sochi no kenkyu

Energy Technology Data Exchange (ETDEWEB)

Honma, T; Omata, K; Kojima, N [Meiji University, Tokyo (Japan)

1997-11-25

An improved J-shaped blade, in which a J-shaped blade is combined with a small-size Savonius blade, has been developed, to further improve efficiency of an air turbine for wave power generator systems. A prototype model of stationary wave power generator has been developed using the improved blade, to confirm its power generation characteristics by tests in a water tank and small-scale ocean tests. The results are compared with the characteristics of the units with conventional blades. The air turbine unit with the improved blade shows an efficiency of 13 to 35%, which is higher by 10 to 20% than that of the turbine with a J-shaped blade and by 20 to 70% than that of the one with a Savonius blade, more noted at low speed of rotation. It is therefore considered that the turbine with the improved blade is suited for sea areas having a relatively low wave height. It is also considered that efficiency can be further enhanced, when one or more guide vanes are provided around the blade. 2 refs., 12 figs.

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.

Low-dose Norfloxacin-treated leptospires induce less IL-1β release in J774A.1 cells following discrepant leptospiral gene expression.

Science.gov (United States)

Cao, Yongguo; Xie, Xufeng; Zhang, Wenlong; Wu, Dianjun; Tu, Changchun

2018-06-01

Currently, accumulating evidence is challenging subtherapeutic therapy. Low-dose Norfloxacin (Nor) has been reported to suppress the immune response and worsen leptospirosis. In this study, we investigated the influence of low-dose Nor (0.03 μg/ml, 0.06 μg/ml, 0.125 μg/ml) on leptospiral gene expression and analyzed the immunomodulatory effects of low-dose Nor-treated leptospires in J774A.1 cells. To study the expression profiles of low-dose Nor-treated leptospires, we chose LipL71/LipL21 as reference genes determined by the geNorm applet in this experiment. The results showed that low-dose Nor up-regulated the expression of FlaB and inhibited the expression of 16S rRNA, LipL32, LipL41, Loa22, KdpA, and KdpB compared with the untreated leptospires. These results indicated that low-dose Nor could regulate leptospiral gene expression. Using RT-PCR, the gene expression of IL-1β and TNF-α in J774A.1 cells was detected. Nor-treated leptospires induced higher expression levels of both IL-1β and TNF-α. However, when analyzed by ELISA, the release of mature IL-1β was reduced compared with that observed in cells induced with no Nor-treated leptospires, although the TNF-α protein level showed no significant change. Our study indicated that the gene expression of leptospires could be modulated by low-dose Nor, which induced less IL-1β release in J774A.1 cells. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

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

Kinetic and dose dependences of the SOS-induction in E.coli K-12 (uvrA) cells exposed to the different UV doses

International Nuclear Information System (INIS)

Komova, O.V.; Kandiano, E.S.; Malavya, G.

1999-01-01

The kinetic and dose dependences of the SOS-induction in E.coli (uvrA) cells exposed to UV light were investigated. Below 2 J/m 2 the rate of the SOS-induction increased with dose. The maximal level of the SOS-response was proportional to the UV dose. Pyrimidine dimers were necessary for the induction. In the dose range 2-10 J/m 2 the rate of the SOS-induction decreased with dose. The dose-response curve was non-linear. Pyrimidine dimers were not required for the induction. The nature of the molecular events leading to the SOS-induction at low and high UV doses was discussed. (author)

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

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

The J-shape association of ethanol intake with total homocysteine concentrations: the ATTICA study

Directory of Open Access Journals (Sweden)

Pitsavos Christos

2004-10-01

Full Text Available Abstract Background Epidemiological studies suggest a non-monotonic effect of alcohol consumption on cardiovascular risk, while there is strong evidence concerning the involvement of homocysteine levels on thrombosis. The aim of this work was to evaluate the association between usual ethanol consumption and homocysteine levels, in cardiovascular disease free adults. Methods From May 2001 to December 2002 we randomly enrolled 1514 adult men and 1528 women, without any evidence of cardiovascular disease, stratified by age – gender (census 2001, from the greater area of Athens, Greece. Among the variables ascertained we measured the daily ethanol consumption and plasma homocysteine concentrations. Results Data analysis revealed a J-shape association between ethanol intake (none, 48 gr per day and total homocysteine levels (mean ± standard deviation among males (13 ± 3 vs. 11 ± 3 vs. 14 ± 4 vs. 18 ± 5 vs. 19 ± 3 μmol/L, respectively, p Conclusion We observed a J-shape relationship between homocysteine concentrations and the amount of ethanol usually consumed.

Estimation of computed tomography dose in various phantom shapes and compositions

Energy Technology Data Exchange (ETDEWEB)

Lee, Chang Lae [Dept. of Radiological Science, Yonsei University, Seoul (Korea, Republic of)

2017-03-15

The purpose of this study was to investigate CTDI (computed tomography dose index at center) for various phantom shapes, sizes, and compositions by using GATE (geant4 application for tomographic emission) simulations. GATE simulations were performed for various phantom shapes (cylinder, elliptical, and hexagonal prism PMMA phantoms) and phantom compositions (water, PMMA, polyethylene, polyoxymethylene) with various diameters (1-50 cm) at various kVp and mAs levels. The CTDI100center values of cylinder, elliptical, and hexagonal prism phantom at 120 kVp, 200 mAs resulted in 11.1, 13.4, and 12.2 mGy, respectively. The volume is the same, but CTDI{sub 100center} values are different depending on the type of phantom. The water, PMMA, and polyoxymethylene phantom CTDI{sub 100center} values were relatively low as the material density increased. However, in the case of Polyethylene, the CTDI{sub 100center} value was higher than that of PMMA at diameters exceeding 15 cm (CTDI{sub 100center} : 35.0 mGy). And a diameter greater than 30 cm (CTDI{sub 100center} : 17.7 mGy) showed more CTDI{sub 100center} than Water. We have used limited phantoms to evaluate CT doses. In this study, CTDI{sub 100center} values were estimated and simulated by GATE simulation according to the material and shape of the phantom. CT dosimetry can be estimated more accurately by using various materials and phantom shapes close to human body.

Radiosensitive xrs-5 and parental CHO cells show identical DNA neutral filter elution dose-response: implications for a relationship between cell radiosensitivity and induction of DNA double-strand breaks

International Nuclear Information System (INIS)

Iliakis, George; Okayasu, Ryuichi; Seaner, Robert

1988-01-01

The purpose of this work was to investigate a possible correlation between DNA elution dose-response and cell radiosensitivity. For this purpose neutral (pH 9.6) DNA filter elution dose-response curves were measured with radiosensitive xrs-5 and the parental Chinese hamster ovary (CHO) cells in the logarithmic and plateau phase of growth. No difference was observed between the two cell types in the DNA elution dose-response curves either in logarithmic or plateau phase, despite the dramatic differences in cell radiosensitivity. This observation indicates that the shape of the DNA elution dose-response curve and the shape of the cell survival curve are not causally related. It is proposed that the shoulder observed in the DNA elution dose-response curve reflects either partial release of DNA from chromatin, or cell cycle-specific alterations in the physicochemical properties of the DNA. (author)

bg/sup J//bg/sup J/:W/W/sup v/ bone marrow chimera. A model for studying stem cell regulation

Energy Technology Data Exchange (ETDEWEB)

Patt, H M; Maloney, M A

1978-01-01

In studies with bg/sup J//bg/sup J/:W/W/sup v/ chimeric mice, we used the beige neutrophil marker as a criterion of W/W/sup v/ marrow replacement by implanted bg/sup J//bg/sup J/ stem cells. Data from a 50-fold range of inoculum doses and a 2 y period of observation indicate a hyperbolic pattern of replacement expressed as a log dose-response relationship. The saturating effect with increasing inoculum dose was interpreted as reflecting random initial stem cell seeding in bone marrow coupled with a decreasing efficiency of colonization by migration. From the statistics of random sampling and the exponential decrease of the 63% replacement dose with time, we estimate that W/W/sup v/ marrow contains about 2600 stem cell regulatory volumes of about 10/sup 8/ ..mu../sup 3/ (50 cell diameters) each, a dimension consistent with concepts of short-range cell-cell interactions. Our observations suggest that each regulatory volume is essentially self-contained and that stem cell migration is generally restricted to contiguous volumes.

The shapes of the radiation dose-mutation response curves in drosophila: Mechanisms and implications

International Nuclear Information System (INIS)

Abrahamson, S.; DeJongh, C.; Meyer, H.U.

1981-01-01

This chapter proposes that radiation induced mutations, namely sex-linked recessive lethals in Drosophila and forward mutations at specific loci in Drosophila, mammals and lower eucaryotes, are the result of two sub-lesions or hits, induced by either single ionization tracks or by the interaction of two independent tracks for low LET radiations, when the dose is delivered in an acute fashion. Utilizes the well recognized linear quadratic expression Y=C+αD+βD 2 , where C is the spontaneous frequency of events scored and α and β represent the coefficients of the dose. Concludes that for low LET radiations, X or gamma rays, the linear-quadratic model can be used to predict the genetic response of germ cells and somatic cells to a variety of radiation regimes. Points out that the point of inflection in the curve, α/β value, can be determined specifically by target dimensions which vary with respect to DNA content. Considers the difference in RBE values observed for different species to be a reflection of their different target sizes

Evaluation of axillary dose coverage following whole breast radiotherapy: Variation with the breast volume and shape

International Nuclear Information System (INIS)

Aguiar, Artur; Gomes Pereira, Helena; Azevedo, Isabel; Gomes, Luciano

2015-01-01

Objective: To evaluate the axillary dose coverage in patients treated with tridimensional whole breast radiotherapy (3D-WBRT), according to the breast volume and shape in treatment position. Background: Several studies have demonstrated an insufficient dose contribution to the axillary levels, using 3D-WBRT, remaining unclear whether the breast volume and shape can influence it. Materials and methods: We retrospectively delineated the axillary levels on planning CT-images of 100 patients, treated with 3D-WBRT along 2012 in our institution. To estimate the shape we established an anatomic CT-based interval, defined as the Thoracic Extent (TE). The breast volume matched its CTV. Mean dose levels and V95 (volume receiving at least 95% of the prescribed dose) were evaluated. Results: Mean axillary level I (A1), II (A2) and III (A3) volume was 56.1 cc, 16.5 cc and 18.9 cc, respectively, and mean doses were 43.9 Gy, 38.6 Gy and 19.5 Gy. For breast volumes of <800 cc, 800–999 cc, 1000–1199 cc and >1200 cc, mean A1 V95 was 38%, 51%, 61.2% and 57.2% whereas median A2 V95 was 8.3%, 13.4%, 19.4% and 28% respectively. Regarding shape, where the breast relative position to the TE was categorized in intervals between 31% and 40%, 41% and 50%, 51% and 60%, and 61% and 70%, mean A1 V95 was 38.7%, 43.1%, 51.1% and 77.3% whereas mean A2 V95 was 6.1%, 11.2%, 17.1% and 37% respectively. Conclusions: We observed inadequate dose coverage to all axillary levels, even after applying a sub-analysis accounting for different breast volumes and shapes. Although higher doses were associated with the more voluminous and pendulous breasts, axillary coverage with 3D-WBRT seems to be inefficient, regardless of the breast morphology

Systematic review and meta-analysis of reduction in all-cause mortality from walking and cycling and shape of dose response relationship.

Science.gov (United States)

Kelly, Paul; Kahlmeier, Sonja; Götschi, Thomas; Orsini, Nicola; Richards, Justin; Roberts, Nia; Scarborough, Peter; Foster, Charlie

2014-10-24

Walking and cycling have shown beneficial effects on population risk of all-cause mortality (ACM). This paper aims to review the evidence and quantify these effects, adjusted for other physical activity (PA). We conducted a systematic review to identify relevant studies. Searches were conducted in November 2013 using the following health databases of publications: Embase (OvidSP); Medline (OvidSP); Web of Knowledge; CINAHL; SCOPUS; SPORTDiscus. We also searched reference lists of relevant texts and reviews. Eligible studies were prospective cohort design and reporting walking or cycling exposure and mortality as an outcome. Only cohorts of individuals healthy at baseline were considered eligible. Extracted data included study population and location, sample size, population characteristics (age and sex), follow-up in years, walking or cycling exposure, mortality outcome, and adjustment for other co-variables. We used random-effects meta-analyses to investigate the beneficial effects of regular walking and cycling. Walking (18 results from 14 studies) and cycling (8 results from 7 studies) were shown to reduce the risk of all-cause mortality, adjusted for other PA. For a standardised dose of 11.25 MET.hours per week (or 675 MET.minutes per week), the reduction in risk for ACM was 11% (95% CI = 4 to 17%) for walking and 10% (95% CI = 6 to 13%) for cycling. The estimates for walking are based on 280,000 participants and 2.6 million person-years and for cycling they are based on 187,000 individuals and 2.1 million person-years. The shape of the dose-response relationship was modelled through meta-analysis of pooled relative risks within three exposure intervals. The dose-response analysis showed that walking or cycling had the greatest effect on risk for ACM in the first (lowest) exposure interval. The analysis shows that walking and cycling have population-level health benefits even after adjustment for other PA. Public health approaches would have the biggest impact

Dose-response effect of photobiomodulation therapy on neuromuscular economy during submaximal running.

Science.gov (United States)

Dellagrana, Rodolfo André; Rossato, Mateus; Sakugawa, Raphael Luiz; Lazzari, Caetano Decian; Baroni, Bruno Manfredini; Diefenthaeler, Fernando

2018-02-01

The purpose of this study was to verify the photobiomodulation therapy (PBMT) effects with different doses on neuromuscular economy during submaximal running tests. Eighteen male recreational runners participate in a randomized, double-blind, and placebo-controlled trial, which each participant was submitted to the same testing protocol in five conditions: control, placebo, and PBMT with doses of 15, 30, and 60 J per site (14 sites in each lower limb). The submaximal running was performed at 8 and 9 km h -1 during 5 min for each velocity. Muscle activation of the vastus lateralis (VL), vastus medialis (VM), rectus femoris (RF), biceps femoris (BF), and gastrocnemius lateralis (GL) was collected during the last minute of each running test. The root mean square (RMS) was normalized by maximal isometric voluntary contraction (MIVC) performed a priori in an isokinetic dynamometer. The RMS sum of all muscles (RMS LEG ) was considered as main neuromuscular economy parameter. PBMT with doses of 15, 30, and 60 J per site [33 diodes = 5 lasers (850 nm), 12 LEDs (670 nm), 8 LEDs (880 nm), and 8 LEDs (950 nm)] or placebo applications occurred before running tests. For the statistical analysis, the effect size was calculated. Moreover, a qualitative inference was used to determine the magnitude of differences between groups. Peak torque and RMS during MIVCs showed small effect sizes. According to magnitude-based inference, PBMT with dose of 15 J per site showed possibly and likely beneficial effects on neuromuscular economy during running at 8 and 9 km h -1 , respectively. On other hand, PBMT with doses of 30 and 60 J per site showed possible beneficial effects only during running at 9 km h -1 . We concluded that PBMT improve neuromuscular economy and the best PBMT dose was 15 J per site (total dose of 420 J).

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)

Performance of long J-shaped coils in large and giant intracranial aneurysms: an in vitro study

International Nuclear Information System (INIS)

Tokunaga, K.; Tanaka, N.; Sugiu, K.; Levrier, O.; Martin, J.B.; Ruefenacht, D.A.

2002-01-01

We evaluated the performance of long straight coils (Detach-18 trademark J-shaped coils) in large and giant in-vitro aneurysms. The coils consisted of a distal semicircular part 7 or 15 mm in diameter and a proximal 70 cm straight part having three types of stiffness: soft, standard, and stiff. We first investigated the ease of passage through a microcatheter in a realistic cerebral vessel model. Second, we made silicone models simulating lateral-type aneurysms of various spherical dome diameters (12, 15, 20 and 30 mm) and neck sizes (3-10 mm; dome-to-neck ratio approximately 3:1) and connected them to a pulsating circulatory pump. We evaluated the anchoring and folding patterns of the coils, stability of the microcatheter and coils in the aneurysm, and smoothness of delivery and retrieval of coils. Third, we compared the conformability of a coil in a large, irregular aneurysm with that of a spiral coil. The long J-shaped coils were easily advanced and retrieved through a microcatheter in a tortuous vessel model. In 12 mm spherical aneurysms, each coil made a complex framework, and knot formation or damage to the coil during withdrawal was often observed. In 15 mm aneurysms, the coils were all easily delivered and retrieved; standard-stiffness coils adapted best to this size. In 20 mm aneurysms, frameworks were less complex but still good with a standard or stiff coil, but those with soft coil were unstable and changed significantly within 3 min of detachment due to gravity and pulsatile flow. In 30 mm aneurysms, soft coils filled only the lower part during introduction, whereas a stiff coil still made a favourable framework. Conformability of a long J-shaped coil was superior to that of a spiral coil in a large, irregular aneurysm. Long J-shaped coils conform well to various configurations of large and giant aneurysms and can shorten procedures since a larger implant volume can be delivered with a single coil. Their principle of action may promote more favourable

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

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

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...

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)

SIMS analyses of ultra-low-energy B ion implants in Si: Evaluation of profile shape and dose accuracy

International Nuclear Information System (INIS)

Magee, C.W.; Hockett, R.S.; Bueyueklimanli, T.H.; Abdelrehim, I.; Marino, J.W.

2007-01-01

Numerous experimental studies for near-surface analyses of B in Si have shown that the B distribution within the top few nanometers is distorted by secondary ion mass spectrometry (SIMS) depth profiling with O 2 -flooding or normal incidence O 2 bombardment. Furthermore, the presence of surface oxide affects the X j determination as well as B profile shape when SIMS analyses are conducted while fully oxidizing the analytical area. Nuclear techniques such as elastic recoil detection (ERD), nuclear reaction analysis (NRA), and high-resolution Rutherford backscattering spectrometry (HR-RBS), are known to provide a profile shape near the surface that is free of artifacts. Comparisons with SIMS analyses have shown that SIMS analyses without fully oxidizing the analytical area agree well with these techniques at sufficiently high concentrations (where the nuclear techniques are applicable). The ability to measure both the B profile and an oxide marker with this non-oxidizing SIMS technique also allows accurate positioning of the B profile with respect to the SiO 2 /Si interface. This SIMS analysis protocol has been used to study the differences in near-surface dopant distribution for plasma-based implants. This study specifically focuses on measuring near-surface profile shapes as well as total implant doses for ultra-shallow B implants in Si especially those made with high peak B concentrations

Dose-shaping using targeted sparse optimization

International Nuclear Information System (INIS)

Sayre, George A.; Ruan, Dan

2013-01-01

functions. In particular, E tot sparse -optimized plans for the pancreas case and head-and-neck case exhibited substantially improved sparing of the spinal cord and parotid glands, respectively, while maintaining or improving sparing for other OARs and markedly improving PTV homogeneity. Plan deliverability for E tot sparse -optimized plans was shown to be better than their associated clinical plans, according to the two-dimensional modulation index.Conclusions: These results suggest that our formulation may be used to improve dose-shaping and OAR-sparing for complicated disease sites, such as the pancreas or head and neck. Furthermore, our objective function and constraints are linear and constitute a linear program, which converges to the global minimum quickly, and can be easily implemented in treatment planning software. Thus, the authors expect fast translation of our method to the clinic where it may have a positive impact on plan quality for challenging disease sites

Dose-shaping using targeted sparse optimization.

Science.gov (United States)

Sayre, George A; Ruan, Dan

2013-07-01

(sparse)-optimized plans for the pancreas case and head-and-neck case exhibited substantially improved sparing of the spinal cord and parotid glands, respectively, while maintaining or improving sparing for other OARs and markedly improving PTV homogeneity. Plan deliverability for E tot (sparse)-optimized plans was shown to be better than their associated clinical plans, according to the two-dimensional modulation index. These results suggest that our formulation may be used to improve dose-shaping and OAR-sparing for complicated disease sites, such as the pancreas or head and neck. Furthermore, our objective function and constraints are linear and constitute a linear program, which converges to the global minimum quickly, and can be easily implemented in treatment planning software. Thus, the authors expect fast translation of our method to the clinic where it may have a positive impact on plan quality for challenging disease sites.

Stochastic basis for curve shape, RBE and temporal dependence

International Nuclear Information System (INIS)

Bond, V.P.

1982-01-01

This paper uses biophysical-microdosimetric quantities, measured in a physical surrogate or phantom cell, to explain the shape of absorbed dose-quantal cell response curves, the role of radiation quality and the influence of dose rate. Responses expected are explored first in simple autonomous cell systems, followed by increasingly-complex systems. Complications seen with increasingly-complex systems appear to be confined largely to the higher dose and dose rate ranges

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

Centering Ability of ProTaper Next and WaveOne Classic in J-Shape Simulated Root Canals.

Science.gov (United States)

Troiano, Giuseppe; Dioguardi, Mario; Cocco, Armando; Giuliani, Michele; Fabiani, Cristiano; D'Alessandro, Alfonso; Ciavarella, Domenico; Lo Muzio, Lorenzo

Introduction . The aim of this study was to evaluate and compare the shaping and centering ability of ProTaper Next (PTN; Dentsply Maillefer, Ballaigues, Switzerland) and WaveOne Classic systems (Dentsply Maillefer) in simulated root canals. Methods . Forty J-shaped canals in resin blocks were assigned to two groups ( n = 20 for each group). Photographic method was used to record pre- and postinstrumentation images. After superimposition, centering and shaping ability were recorded at 9 different levels from the apex using the software Autocad 2013 (Autodesk Inc., San Rafael, USA). Results . Shaping procedures with ProTaper Next resulted in a lower amount of resin removed at each reference point level. In addition, the pattern of centering ability improved after the use of ProTaper Next in 8 of 9 measurement points. Conclusions . Within the limitations of this study, shaping procedures with ProTaper Next instruments demonstrated a lower amount of resin removed and a better centering ability than WaveOne Classic system.

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

Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life.

Science.gov (United States)

Zuardi, Antonio W; Rodrigues, Natália P; Silva, Angélica L; Bernardo, Sandra A; Hallak, Jaime E C; Guimarães, Francisco S; Crippa, José A S

2017-01-01

The purpose of this study was to investigate whether the anxiolytic effect of cannabidiol (CBD) in humans follows the same pattern of an inverted U-shaped dose-effect curve observed in many animal studies. Sixty healthy subjects of both sexes aged between 18 and 35 years were randomly assigned to five groups that received placebo, clonazepam (1 mg), and CBD (100, 300, and 900 mg). The subjects were underwent a test of public speaking in a real situation (TPSRS) where each subject had to speak in front of a group formed by the remaining participants. Each subject completed the anxiety and sedation factors of the Visual Analog Mood Scale and had their blood pressure and heart rate recorded. These measures were obtained in five experimental sessions with 12 volunteers each. Each session had four steps at the following times (minutes) after administration of the drug/placebo, as time 0: -5 (baseline), 80 (pre-test), 153 (speech), and 216 (post-speech). Repeated-measures analyses of variance showed that the TPSRS increased the subjective measures of anxiety, heart rate, and blood pressure. Student-Newman-Keuls test comparisons among the groups in each phase showed significant attenuation in anxiety scores relative to the placebo group in the group treated with clonazepam during the speech phase, and in the clonazepam and CBD 300 mg groups in the post-speech phase. Clonazepam was more sedative than CBD 300 and 900 mg and induced a smaller increase in systolic and diastolic blood pressure than CBD 300 mg. The results confirmed that the acute administration of CBD induced anxiolytic effects with a dose-dependent inverted U-shaped curve in healthy subjects, since the subjective anxiety measures were reduced with CBD 300 mg, but not with CBD 100 and 900 mg, in the post-speech phase.

Inverted U-Shaped Dose-Response Curve of the Anxiolytic Effect of Cannabidiol during Public Speaking in Real Life

Directory of Open Access Journals (Sweden)

Antonio W. Zuardi

2017-05-01

Full Text Available The purpose of this study was to investigate whether the anxiolytic effect of cannabidiol (CBD in humans follows the same pattern of an inverted U-shaped dose-effect curve observed in many animal studies. Sixty healthy subjects of both sexes aged between 18 and 35 years were randomly assigned to five groups that received placebo, clonazepam (1 mg, and CBD (100, 300, and 900 mg. The subjects were underwent a test of public speaking in a real situation (TPSRS where each subject had to speak in front of a group formed by the remaining participants. Each subject completed the anxiety and sedation factors of the Visual Analog Mood Scale and had their blood pressure and heart rate recorded. These measures were obtained in five experimental sessions with 12 volunteers each. Each session had four steps at the following times (minutes after administration of the drug/placebo, as time 0: -5 (baseline, 80 (pre-test, 153 (speech, and 216 (post-speech. Repeated-measures analyses of variance showed that the TPSRS increased the subjective measures of anxiety, heart rate, and blood pressure. Student-Newman-Keuls test comparisons among the groups in each phase showed significant attenuation in anxiety scores relative to the placebo group in the group treated with clonazepam during the speech phase, and in the clonazepam and CBD 300 mg groups in the post-speech phase. Clonazepam was more sedative than CBD 300 and 900 mg and induced a smaller increase in systolic and diastolic blood pressure than CBD 300 mg. The results confirmed that the acute administration of CBD induced anxiolytic effects with a dose-dependent inverted U-shaped curve in healthy subjects, since the subjective anxiety measures were reduced with CBD 300 mg, but not with CBD 100 and 900 mg, in the post-speech phase.

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

Shape-Morphing Materials from Stimuli-Responsive Hydrogel Hybrids.

Science.gov (United States)

Jeon, Seog-Jin; Hauser, Adam W; Hayward, Ryan C

2017-02-21

The formation of well-defined and functional three-dimensional (3D) structures by buckling of thin sheets subjected to spatially nonuniform stresses is common in biological morphogenesis and has become a subject of great interest in synthetic systems, as such programmable shape-morphing materials hold promise in areas including drug delivery, biomedical devices, soft robotics, and biomimetic systems. Given their ability to undergo large changes in swelling in response to a wide variety of stimuli, hydrogels have naturally emerged as a key type of material in this field. Of particular interest are hybrid systems containing rigid inclusions that can define both the anisotropy and spatial nonuniformity of swelling as well as nanoparticulate additives that can enhance the responsiveness and functionality of the material. In this Account, we discuss recent progress in approaches to achieve well-defined shape morphing in hydrogel hybrids. First, we provide an overview of materials and methods that facilitate fabrication of such systems and outline the geometry and mechanics behind shape morphing of thin sheets. We then discuss how patterning of stiff inclusions within soft responsive hydrogels can be used to program both bending and swelling, thereby providing access to a wide array of complex 3D forms. The use of discretely patterned stiff regions to provide an effective composite response offers distinct advantages in terms of scalability and ease of fabrication compared with approaches based on smooth gradients within a single layer of responsive material. We discuss a number of recent advances wherein control of the mechanical properties and geometric characteristics of patterned stiff elements enables the formation of 3D shapes, including origami-inspired structures, concatenated helical frameworks, and surfaces with nonzero Gaussian curvature. Next, we outline how the inclusion of functional elements such as nanoparticles can enable unique pathways to programmable

Dose-shaping using targeted sparse optimization

Energy Technology Data Exchange (ETDEWEB)

Sayre, George A.; Ruan, Dan [Department of Radiation Oncology, University of California - Los Angeles School of Medicine, 200 Medical Plaza, Los Angeles, California 90095 (United States)

2013-07-15

's spatial dose distribution than conventional objective functions. In particular, E{sub tot}{sup sparse}-optimized plans for the pancreas case and head-and-neck case exhibited substantially improved sparing of the spinal cord and parotid glands, respectively, while maintaining or improving sparing for other OARs and markedly improving PTV homogeneity. Plan deliverability for E{sub tot}{sup sparse}-optimized plans was shown to be better than their associated clinical plans, according to the two-dimensional modulation index.Conclusions: These results suggest that our formulation may be used to improve dose-shaping and OAR-sparing for complicated disease sites, such as the pancreas or head and neck. Furthermore, our objective function and constraints are linear and constitute a linear program, which converges to the global minimum quickly, and can be easily implemented in treatment planning software. Thus, the authors expect fast translation of our method to the clinic where it may have a positive impact on plan quality for challenging disease sites.

Low-Dose Contrast-Enhanced Breast CT Using Spectral Shaping Filters: An Experimental Study.

Science.gov (United States)

Makeev, Andrey; Glick, Stephen J

2017-12-01

Iodinated contrast-enhanced X-ray imaging of the breast has been studied with various modalities, including full-field digital mammography (FFDM), digital breast tomosynthesis (DBT), and dedicated breast CT. Contrast imaging with breast CT has a number of advantages over FFDM and DBT, including the lack of breast compression, and generation of fully isotropic 3-D reconstructions. Nonetheless, for breast CT to be considered as a viable tool for routine clinical use, it would be desirable to reduce radiation dose. One approach for dose reduction in breast CT is spectral shaping using X-ray filters. In this paper, two high atomic number filter materials are studied, namely, gadolinium (Gd) and erbium (Er), and compared with Al and Cu filters currently used in breast CT systems. Task-based performance is assessed by imaging a cylindrical poly(methyl methacrylate) phantom with iodine inserts on a benchtop breast CT system that emulates clinical breast CT. To evaluate detectability, a channelized hoteling observer (CHO) is used with sums of Laguerre-Gauss channels. It was observed that spectral shaping using Er and Gd filters substantially increased the dose efficiency (defined as signal-to-noise ratio of the CHO divided by mean glandular dose) as compared with kilovolt peak and filter settings used in commercial and prototype breast CT systems. These experimental phantom study results are encouraging for reducing dose of breast CT, however, further evaluation involving patients is needed.

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

Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests.

Science.gov (United States)

Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Palermo-Neto, J

2009-06-01

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P open field test.

Verticalization of behavior elicited by dopaminergic mobilization is qualitatively different between C57BL/6J and DBA/2J mice.

Science.gov (United States)

Tirelli, E; Witkin, J M

1994-10-01

Behavioral effects of dopaminergic stimulation were evaluated in C57BL/6J mice and compared to the effects occurring in DBA/2J mice, an inbred strain with reduced densities of striatal dopamine receptors. Effects of apomorphine (0.5-64 mg/kg) alone and in combination with cocaine (30 mg/kg) were assessed using a time-sampling technique that classified climbing and leaning in separate categories. Locomotion was also assessed in a separate experiment. Climbing occurred in DBA/2J mice only at doses of apomorphine that were 16 times higher than the smallest effective dose in C57BL/6J mice; nevertheless, relative to baseline values, effects were fairly comparable. By contrast, whereas DBA/2J mice showed dose-dependent leaning under apomorphine, C57BL/6J mice exhibited little leaning even at doses not producing climbing, and only after the highest apomorphine dose was leaning significantly increased. Apomorphine was equipotent in inducing gnawing across strains, although somewhat less efficacious in DBA/2J mice. When given alone, cocaine produced significant climbing, but not leaning or gnawing, in either strain. Whereas cocaine potentiated apomorphine-induced climbing and gnawing in both strains, apomorphine-induced leaning was not consistently changed by cocaine in either strain. These effects were not indirectly due to hyperkinesia, since neither apomorphine alone nor apomorphine and cocaine in combination was stimulant; apomorphine alone reduced locomotor activity and attenuated cocaine-induced hyperkinesia. The present data do not support a unitary, purely quantitative, account of insensitivity to dopaminergic stimulation based upon low densities of striatal dopamine receptors in DBA/2J mice. Rather, this constellation of results is suggestive of qualitative interstrain dissimilarities in dopaminergic responsiveness that could reflect organizational differences in receptor populations.

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)

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

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

Hydration and transparency of the rabbit cornea irradiated with UVB-doses of 0.25 J/cm(2) and 0.5 J/cm(2) compared with equivalent UVB radiation exposure reaching the human cornea from sunlight.

Science.gov (United States)

Cejka, Cestmír; Ardan, Taras; Sirc, Jakub; Michálek, Jiří; Beneš, Jiří; Brůnová, Blanka; Rosina, Jozef

2011-07-01

Exposure of the cornea to UV radiation from sunlight evokes intraocular inflammation, photokeratitis. Photokeratitis is caused by UVB radiation. It is accompanied by changes of corneal hydration and light absorption. The aim of this study was to examine the effect of two UVB doses on corneal optics in rabbits and to compare these UVB doses with the equivalent exposure of UVB radiation reaching the human cornea from sunlight. Rabbit corneas were irradiated with a daily UVB dose of 0.25 J/cm(2) or 0.5 J/cm(2) for 4 days. One day after finishing the irradiations the rabbits were sacrificed and corneal light absorption measured using our spectrophotometrical method. Corneal hydration was examined using an ultrasonic Pachymeter every experimental day before the irradiation procedure and the last day before sacrificing the animals. Changes in corneal optics appeared after the repeated exposure of the cornea to a UVB dose of 0.25 J/ cm(2) and massively increased after the repeated exposure of the cornea to a UVB dose of 0.5 J/cm(2). The first significant changes in corneal hydration appeared after a single exposure of the cornea to a UVB dose of 0.25 J/cm(2). Changes in corneal hydration appeared after the exposure of the rabbit cornea to a single UVB dose equivalent to 2.6 hours of solar UVB radiation reaching the human cornea, as measured by UVB sensors embedded in the eyes of mannequin heads facing the sun on a beach at noon in July. Repeated exposure of the rabbit cornea to the same UVB dose evoked profound changes in corneal optics. Although comparison of experimental and outdoor conditions are only approximate, the results in rabbits point to the danger for the human eye from UVB radiation when short stays in sunlight are repeated for several consecutive days without UV protection.

Coffee intake and the incident risk of cognitive disorders: A dose-response meta-analysis of nine prospective cohort studies.

Science.gov (United States)

Wu, Lei; Sun, Dali; He, Yao

2017-06-01

Previous epidemiological studies have provided inconsistent conclusions on the impact of coffee consumption in the developing of cognitive disorders. However, no previous meta-analysis has pooled the evidence from the prospective cohort studies to assess the influence of coffee drinking and its potential dose-response patterns on the risk of developing cognitive disorders specifically. Two databases (PubMed and Embase) were searched for evidence of cohort studies from inception to February 2016. We used a generic inverse-variance method with a random-effects model to pool the fully adjusted relative risks (RRs) and the corresponding 95% confidence intervals (CIs). In the dose-response analyses, a generalized least-squares trend estimation model was applied to computing the study-specific slopes. Nine prospective cohort studies involving 34,282 participants were included in our study. The duration of follow-up years ranged from 1.3 to 28. Compared with coffee was inversely linked with the occurrence of cognitive disorders (i.e., Alzheimer's disease, dementia, cognitive decline, and cognitive impairment), and the pooled RR (95% CI) was 0.82 (0.71, 0.94) with evidence of non-significant heterogeneity (I 2  = 25%). Non-significant differences were presented for the association between coffee consumption (>3 vs. coffee consumption. A "J-shaped" association was presented between coffee intake and incident cognitive disorders, with the lowest risk of incident cognitive disorders at a daily consumption level of 1-2 cups of coffee. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Cancer Control Related to Stimulation of Immunity by Low-Dose Radiation

OpenAIRE

Liu, Shu-Zheng

2006-01-01

Previous studies showed that low dose radiation (LDR) could stimulate the immune system in both animal and human populations. This paper reviews the present status of relevant research as support to the use of LDR in clinical practice for cancer prevention and treatment. It has been demonstrated that radiation-induced changes in immune activity follows an inverse J-shaped curve, i.e., low dose stimulation and high dose suppression. The stimulation of immunity by LDR concerns most anticancer p...

Disparity in Cutaneous Pigmentary Response to LED vs Halogen Incandescent Visible Light: Results from a Single Center, Investigational Clinical Trial Determining a Minimal Pigmentary Visible Light Dose.

Science.gov (United States)

Soleymani, Teo; Cohen, David E; Folan, Lorcan M; Okereke, Uchenna R; Elbuluk, Nada; Soter, Nicholas A

2017-11-01

Background: While most of the attention regarding skin pigmentation has focused on the effects of ultraviolet radiation, the cutaneous effects of visible light (400 to 700nm) are rarely reported. The purpose of this study was to investigate the cutaneous pigmentary response to pure visible light irradiation, examine the difference in response to different sources of visible light irradiation, and determine a minimal pigmentary dose of visible light irradiation in melanocompetent subjects with Fitzpatrick skin type III - VI. The study was designed as a single arm, non-blinded, split-side dual intervention study in which subjects underwent visible light irradiation using LED and halogen incandescent light sources delivered at a fluence of 0.14 Watts/cm2 with incremental dose progression from 20 J/cm2 to 320 J/cm2. Pigmentation was assessed by clinical examination, cross-polarized digital photography, and analytic colorimetry. Immediate, dose-responsive pigment darkening was seen with LED light exposure in 80% of subjects, beginning at 60 Joules. No pigmentary changes were seen with halogen incandescent light exposure at any dose in any subject. This study is the first to report a distinct difference in cutaneous pigmentary response to different sources of visible light, and the first to demonstrate cutaneous pigment darkening from visible LED light exposure. Our findings raise the concern that our increasing daily artificial light surroundings may have clandestine effects on skin biology. J Drugs Dermatol. 2017;16(11):1105-1110..

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.)

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.

Reconfigurable photonic crystals enabled by pressure-responsive shape-memory polymers

Science.gov (United States)

Fang, Yin; Ni, Yongliang; Leo, Sin-Yen; Taylor, Curtis; Basile, Vito; Jiang, Peng

2015-01-01

Smart shape-memory polymers can memorize and recover their permanent shape in response to an external stimulus (for example, heat). They have been extensively exploited for a wide spectrum of applications ranging from biomedical devices to aerospace morphing structures. However, most of the existing shape-memory polymers are thermoresponsive and their performance is hindered by heat-demanding programming and recovery steps. Although pressure is an easily adjustable process variable such as temperature, pressure-responsive shape-memory polymers are largely unexplored. Here we report a series of shape-memory polymers that enable unusual ‘cold' programming and instantaneous shape recovery triggered by applying a contact pressure at ambient conditions. Moreover, the interdisciplinary integration of scientific principles drawn from two disparate fields—the fast-growing photonic crystal and shape-memory polymer technologies—enables fabrication of reconfigurable photonic crystals and simultaneously provides a simple and sensitive optical technique for investigating the intriguing shape-memory effects at nanoscale. PMID:26074349

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...

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

The effect of electron collimator leaf shape on the build-up dose in narrow electron MLC fields

International Nuclear Information System (INIS)

Vatanen, T; Vaeaenaenen, A; Lahtinen, T; Traneus, E

2009-01-01

Previously, we have found that the build-up dose from abutting narrow electron beams formed with unfocussed electron multi-leaf collimator (eMLC) steal leaves was higher than with the respective open field. To investigate more closely the effect of leaf material and shape on dose in the build-up region, straight, round (radius 1.5 cm) and leaf ends with a different front face angle of α (leaf front face pointing towards the beam axis at an angle of 90 - α) made of steel, brass and tungsten were modelled using the BEAMnrc code. Based on a treatment head simulation of a Varian 2100 C/D linac, depth-dose curves and profiles in water were calculated for narrow 6, 12 and 20 MeV eMLC beams (width 1.0 cm, length 10 cm) at source-to-surface distances (SSD) of 102 and 105 cm. The effects of leaf material and front face angle were evaluated based on electron fluence, angle and energy spectra. With a leaf front face angle of 15 deg., the dose in the build-up region of the 6 MeV field varied between 91 and 100%, while for straight and round leaf shapes the dose varied between 89 and 100%. The variation was between 94 and 100% for 12 and 20 MeV. For abutting narrow 6 MeV fields with total field size 5 x 10 cm 2 , the build-up doses at 5 mm depth for the face angle 15 deg. and straight and round leaf shapes were 96% and 86% (SSD 102 cm) and 89% and 85% (SSD 105 cm). With higher energies, the effect of eMLC leaf shape on dose at 5 mm was slight (3-4% units with 12 MeV) and marginal with 20 MeV. The fluence, energy and angle spectra for total and leaf scattered electrons were practically the same for different leaf materials with 6 MeV. With high energies, the spectra for tungsten were more peaked due to lower leaf transmission. Compared with straight leaf ends, the face angle of 15 deg. and round leaf ends led to a 1 mm (for 6 MeV) and between 1 and 5 mm (12 and 20 MeV at a SSD of 105 cm) decrease of therapeutic range and increase of the field size, respectively. However

Architecture of a minimal signaling pathway explains the T-cell response to a 1 million-fold variation in antigen affinity and dose

Science.gov (United States)

Lever, Melissa; Lim, Hong-Sheng; Kruger, Philipp; Nguyen, John; Trendel, Nicola; Abu-Shah, Enas; Maini, Philip Kumar; van der Merwe, Philip Anton

2016-01-01

T cells must respond differently to antigens of varying affinity presented at different doses. Previous attempts to map peptide MHC (pMHC) affinity onto T-cell responses have produced inconsistent patterns of responses, preventing formulations of canonical models of T-cell signaling. Here, a systematic analysis of T-cell responses to 1 million-fold variations in both pMHC affinity and dose produced bell-shaped dose–response curves and different optimal pMHC affinities at different pMHC doses. Using sequential model rejection/identification algorithms, we identified a unique, minimal model of cellular signaling incorporating kinetic proofreading with limited signaling coupled to an incoherent feed-forward loop (KPL-IFF) that reproduces these observations. We show that the KPL-IFF model correctly predicts the T-cell response to antigen copresentation. Our work offers a general approach for studying cellular signaling that does not require full details of biochemical pathways. PMID:27702900

Implications of tissue target-cell survival-curve shape for values of split-dose recovery doses: late versus early effects

International Nuclear Information System (INIS)

Redpath, J.L.; Peel, D.M.; Hopewell, J.W.

1984-01-01

Recent data from this laboratory on split-dose recovery for early and late effects in pig skin are consistent with the linear-quadratic model for cell survival, and with relative cell survival-curve shapes for early- and late-effect target cells where the early-effect cells have an intially steeper and straighter survival-curve than the late-effect cells. (author)

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.)

Low Dose Radiation Response Curves, Networks and Pathways in Human Lymphoblastoid Cells Exposed from 1 to 10 cGy of Acute Gamma Radiation

Energy Technology Data Exchange (ETDEWEB)

Wyrobek, A. J.; Manohar, C. F.; Nelson, D. O.; Furtado, M. R.; Bhattacharya, M. S.; Marchetti, F.; Coleman, M.A.

2011-04-18

We investigated the low dose dependency of the transcriptional response of human cells to characterize the shape and biological functions associated with the dose response curve and to identify common and conserved functions of low dose expressed genes across cells and tissues. Human lymphoblastoid (HL) cells from two unrelated individuals were exposed to graded doses of radiation spanning the range of 1-10 cGy were analyzed by transcriptome profiling, qPCR and bioinformatics, in comparison to sham irradiated samples. A set of {approx}80 genes showed consistent responses in both cell lines; these genes were associated with homeostasis mechanisms (e.g., membrane signaling, molecule transport), subcellular locations (e.g., Golgi, and endoplasmic reticulum), and involved diverse signal transduction pathways. The majority of radiation-modulated genes had plateau-like responses across 1-10 cGy, some with suggestive evidence that transcription was modulated at doses below 1 cGy. MYC, FOS and TP53 were the major network nodes of the low-dose response in HL cells. Comparison our low dose expression findings in HL cells with those of prior studies in mouse brain after whole body exposure, in human keratinocyte cultures, and in endothelial cells cultures, indicates that certain components of the low dose radiation response are broadly conserved across cell types and tissues, independent of proliferation status.

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.

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.

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

International Nuclear Information System (INIS)

Preston, D.L.; McConney, M.E.; Awa, A.A.; Ohtaki, Kazuo; Itoh, Masahiro; Honda, Takeo.

1989-05-01

Cytogenetic data, derived from cultured lymphocytes of atomic bomb survivors and controls in the ABCC-RERF Adult Health Study cohort, have been analyzed to determine differences in the dose-response relationships for chromosome aberrations between the T65D and DS86 dose estimates and to assess differences between Hiroshima and Nagasaki. For a linear dose-response model, the average percentage of cells with at least one chromosome aberration increases less rapidly with dose in Nagasaki than in Hiroshima. The magnitude of the intercity difference in the percentage of cells with aberrations per gray is less for DS86 than for T65D, though the difference is statistically significant for both kerma and bone marrow dose with either dosimetry. The percentage of cells with aberrations per gray for DS86 kerma estimates is about 60 % greater than the corresponding T65D slope. Analyses to test nonlinearity in the dose-response function indicate significant departures (p<.001) from linearity, using both dosimetries for both kerma and marrow dose. Therefore, comparative results are presented for a range of RBE relationships under various linear (L) and linearquadratic linear (LQ-L) models. As an illustrative result, if one assumes an LQ-L model similar to models reported in the cytogenetic literature, with a limiting RBE of 20 at zero dose, the DS86 slope (the percentage of cells with aberrations per sievert) is 120 % greater than the corresponding T65D value. (J.P.N.)

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

Application of Key Events Dose Response Framework to defining the upper intake level of leucine in young men.

Science.gov (United States)

Pencharz, Paul B; Russell, Robert M

2012-12-01

Leucine is sold in large doses in health food stores and is ingested by weight-training athletes. The safety of ingestion of large doses of leucine is unknown. Before designing chronic high-dose leucine supplementation experiments, we decided to determine the effect of graded doses of leucine in healthy participants. The Key Events Dose Response Framework is an organizational and analytical framework that dissects the various biologic steps (key events) that occur between exposure to a substance and an eventual adverse effect. Each biologic event is looked at for its unique dose-response characteristics. For nutrients, there are a number of biologic homeostatic mechanisms that work to keep circulating/tissue levels in a safe, nontoxic range. If a response mechanism at a particular key event is especially vulnerable and easily overwhelmed, this is known as a determining event, because this event drives the overall slope or shape of the dose-response relationship. In this paper, the Key Events Dose Framework has been applied to the problem of leucine toxicity and leucine's tolerable upper level. After analyzing the experimental data vis a vis key events for leucine leading to toxicity, it became evident that the rate of leucine oxidation was the determining event. A dose-response study has been conducted to graded intakes of leucine in healthy human adult male volunteers. All participants were started at the mean requirement level of leucine [50 mg/(kg · d)] and the highest leucine intake was 1250 mg/( kg · d), which is 25 times the mean requirement. No gut intolerance was seen. Blood glucose fell progressively but remained within normal values without any changes in plasma insulin. Maximal leucine oxidation levels occurred at an intake of 550 mg leucine/( kg · d), after which plasma leucine progressively increased and plasma ammonia also increased in response to leucine intakes >500 mg/( kg · d). Thus, the "key determining event" appears to be when the

A reverse J-shaped association between serum 25-hydroxyvitamin D and cardiovascular disease mortality - the CopD-study

DEFF Research Database (Denmark)

Durup, Darshana; Jørgensen, Henrik Løvendahl; Christensen, Jane

2015-01-01

myocardial mortality in a non-linear, reverse J-shaped manner, with highest risk at lower levels. Whether this was a causal or associational finding cannot be determined from our data. There is a need for randomized clinical trials which include information on the effects of 25-hydroxyvitamin D levels above...

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

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)

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

Shape Control of Responsive Building Envelopes

DEFF Research Database (Denmark)

Foged, Isak Worre; Kirkegaard, Poul Henning; Christensen, Jesper Thøger

2010-01-01

The present paper considers shape control of adaptive architectural structures for improvement of structural performance by recognizing changes in their environments and loads, adapting to meet goals, and using past events to improve future performance or maintain serviceability. The general scop...... environmental system to a primary structural system joint into a collective behavioral system equipment with an actuator system is presented....... alternatives. The adaptive structure is a proposal for a responsive building envelope which is an idea of a first level operational framework for present and future investigations towards performance based responsive architectures through a set of responsive typologies. A mock-up concept of a secondary...

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.)

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

Reducing Conservatism of Analytic Transient Response Bounds via Shaping Filters

Science.gov (United States)

Kwan, Aiyueh; Bedrossian, Nazareth; Jan, Jiann-Woei; Grigoriadis, Karolos; Hua, Tuyen (Technical Monitor)

1999-01-01

Recent results show that the peak transient response of a linear system to bounded energy inputs can be computed using the energy-to-peak gain of the system. However, analytically computed peak response bound can be conservative for a class of class bounded energy signals, specifically pulse trains generated from jet firings encountered in space vehicles. In this paper, shaping filters are proposed as a Methodology to reduce the conservatism of peak response analytic bounds. This Methodology was applied to a realistic Space Station assembly operation subject to jet firings. The results indicate that shaping filters indeed reduce the predicted peak response bounds.

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)

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

Interpretation of the margin of exposure for genotoxic carcinogens - elicitation of expert knowledge about the form of the dose response curve at human relevant exposures.

Science.gov (United States)

Boobis, Alan; Flari, Villie; Gosling, John Paul; Hart, Andy; Craig, Peter; Rushton, Lesley; Idahosa-Taylor, Ehi

2013-07-01

The general approach to risk assessment of genotoxic carcinogens has been to advise reduction of exposure to "as low as reasonably achievable/practicable" (ALARA/P). However, whilst this remains the preferred risk management option, it does not provide guidance on the urgency or extent of risk management actions necessary. To address this, the "Margin of Exposure" (MOE) approach has been proposed. The MOE is the ratio between the point of departure for carcinogenesis and estimated human exposure. However, interpretation of the MOE requires implicit or explicit consideration of the shape of the dose-response curve at human relevant exposures. In a structured elicitation exercise, we captured expert opinion on available scientific evidence for low dose-response relationships for genotoxic carcinogens. This allowed assessment of: available evidence for the nature of dose-response relationships at human relevant exposures; the generality of judgments about such dose-response relationships; uncertainties affecting judgments on the nature of such dose-response relationships; and whether this last should differ for different classes of genotoxic carcinogens. Elicitation results reflected the variability in experts' views on the form of the dose-response curve for low dose exposure and major sources of uncertainty affecting the assumption of a linear relationship. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comment on “Shape transition of unstrained flattest single-walled carbon nanotubes under pressure” [J. Appl. Phys. 115, 044512 (2014)

Energy Technology Data Exchange (ETDEWEB)

Vassilev, Vassil M., E-mail: vasilvas@imbm.bas.bg; Djondjorov, Peter A., E-mail: padjon@imbm.bas.bg [Institute of Mechanics, Bulgarian Academy of Sciences Acad. G. Bonchev Str., Block 4, Sofia 1113 (Bulgaria); Mladenov, Ivaïlo M., E-mail: mladenov@bio21.bas.bg [Institute of Biophysics and Biomedical Engineering, Bulgarian Academy of Sciences Acad. G. Bonchev Str., Block 21, Sofia 1113 (Bulgaria)

2015-05-21

Recently, Mu et al. [J. Appl. Phys. 115, 044512 (2014)] have developed an analytic approach to describe some special shapes of a single-wall carbon nanotube (SWCNT) under hydrostatic pressure. These authors have found approximate analytic expressions for the parametric equations of the tube cross section profile and its curvature at the convex-to-concave transition pressure using a shell-like 2D continuum model describing the shapes of such nanotubes. In this comment, we provide additional insight into this problem taking into account the exact analytic representation of the shapes that a SWCNT attains when subjected to hydrostatic pressure according to the very same continuum model.

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.

Reproductive factors, menopausal hormone therapies and primary liver cancer risk: a systematic review and dose-response meta-analysis of observational studies.

Science.gov (United States)

Zhong, Guo-Chao; Liu, Yan; Chen, Nan; Hao, Fa-Bao; Wang, Kang; Cheng, Jia-Hao; Gong, Jian-Ping; Ding, Xiong

2016-12-01

A striking gender disparity in the incidence and outcome of primary liver cancer (PLC) has been well recognized. Mounting evidence from basic research suggests that hormonal factors may be involved in the gender disparity of PLC. Whether hormonal exposures in human subjects are associated with PLC risk is largely unknown. Whether reproductive factors and use of menopausal hormone therapies (MHTs) in women are associated with PLC risk remains controversial. We conducted this study to clarify this issue. PubMed and EMBASE were searched to July, 2016 for studies published in English or Chinese. Observational studies (cohort, nested case-control and case-control) that provided risk estimates of reproductive factors, MHTs and PLC risk were eligible. The quality of included studies was determined based on the Newcastle-Ottawa quality assessment scale. Summary risk ratios (RRs) were calculated using a random-effects model. Dose-response analysis was conducted where possible. Fifteen peer-reviewed studies, involving 1795 PLC cases and 2 256 686 women, were included. Overall meta-analyses on parity and PLC risk did not find any significant associations; however, when restricting to studies with PLC cases ≥100, increasing parity was found to be significantly associated with a decreased risk of PLC [RR for the highest versus lowest parity 0.67, 95% CI 0.52, 0.88; RR for parous versus nulliparous 0.71, 95% CI 0.53, 0.94; RR per one live birth increase 0.93, 95% CI 0.88, 0.99]. A J-shaped relationship between parity and PLC risk was identified (P non-linearity  Parity is associated with PLC risk in a J-shaped dose-response pattern. Late age at menarche and ever use of MHT are associated with a reduced risk of PLC, whereas there is no association of ever use of ET and EPT, age at first birth, or spontaneous and induced abortion with PLC risk. Compared to women with no history of oophorectomy, those with a history of oophorectomy are at an increased risk of PLC. Our findings

Prognostic value of body mass index in transcatheter aortic valve implantation: A "J"-shaped curve.

Science.gov (United States)

González-Ferreiro, Rocío; Muñoz-García, Antonio J; López-Otero, Diego; Avanzas, Pablo; Pascual, Isaac; Alonso-Briales, Juan H; Trillo-Nouche, Ramiro; Pun, Federico; Jiménez-Navarro, Manuel F; Hernández-García, José M; Morís, César; González Juanatey, José R

2017-04-01

We aimed to determine whether body mass index (BMI) is a prognostic indicator for long-term, all-cause mortality in patients undergoing transcatheter aortic valve implantation (TAVI). Obesity in patients with established cardiovascular disease has previously been identified as an indicator of good prognosis, a phenomenon known as the "obesity paradox". The prognostic significance of BMI in patients with severe aortic stenosis (AoS) undergoing TAVI is a matter of current debate, as published studies are scarce and their results conflicting. This is an observational, retrospective study involving 770 patients who underwent TAVI for AoS. The cohort was divided into three groups based on their BMI: normal weight (≥18.5 to value=0.036]). After adjustment by logistic EuroSCORE, being overweight was found to be an independent protective factor against mortality (HR: 0.63 [95% CI: 0.42 to 0.94], p=0.024). This was not the case for obesity (HR: 0.92 [95% CI: 0.63 to 1.35], p=0.664). We therefore describe for the first time, a "J-shaped" regression curve describing the relationship between BMI and mortality. BMI is a predictive factor of all-cause mortality in AoS patients undergoing TAVI. This relationship takes the form of a "J-shaped" curve in which overweight patients are associated with the lowest mortality rate at follow-up. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

SU-E-J-270: Study of PET Response to HDR Brachytherapy of Rectal Cancer

Energy Technology Data Exchange (ETDEWEB)

Hobbs, R; Le, Y; Armour, E; Efron, J; Azad, N; Wahl, R; Gearhart, S; Herman, J [Johns Hopkins University, Baltimore, MD (United States)

2014-06-01

Purpose: Dose-response studies in radiation therapy are typically using single response values for tumors across ensembles of tumors. Using the high dose rate (HDR) treatment plan dose grid and pre- and post-therapy FDG-PET images, we look for correlations between voxelized dose and FDG uptake response in individual tumors. Methods: Fifteen patients were treated for localized rectal cancer using 192Ir HDR brachytherapy in conjunction with surgery. FDG-PET images were acquired before HDR therapy and 6–8 weeks after treatment (prior to surgery). Treatment planning was done on a commercial workstation and the dose grid was calculated. The two PETs and the treatment dose grid were registered to each other using non-rigid registration. The difference in PET SUV values before and after HDR was plotted versus absorbed radiation dose for each voxel. The voxels were then separated into bins for every 400 cGy of absorbed dose and the bin average values plotted similarly. Results: Individual voxel doses did not correlate with PET response; however, when group into tumor subregions corresponding to dose bins, eighty percent of the patients showed a significant positive correlation (R2 > 0) between PET uptake difference in the targeted region and the absorbed dose. Conclusion: By considering larger ensembles of voxels, such as organ average absorbed dose or the dose bins considered here, valuable information may be obtained. The dose-response correlations as measured by FDG-PET difference potentially underlines the importance of FDG-PET as a measure of response, as well as the value of voxelized information.

FMRI evidence of 'mirror' responses to geometric shapes.

Science.gov (United States)

Press, Clare; Catmur, Caroline; Cook, Richard; Widmann, Hannah; Heyes, Cecilia; Bird, Geoffrey

2012-01-01

Mirror neurons may be a genetic adaptation for social interaction. Alternatively, the associative hypothesis proposes that the development of mirror neurons is driven by sensorimotor learning, and that, given suitable experience, mirror neurons will respond to any stimulus. This hypothesis was tested using fMRI adaptation to index populations of cells with mirror properties. After sensorimotor training, where geometric shapes were paired with hand actions, BOLD response was measured while human participants experienced runs of events in which shape observation alternated with action execution or observation. Adaptation from shapes to action execution, and critically, observation, occurred in ventral premotor cortex (PMv) and inferior parietal lobule (IPL). Adaptation from shapes to execution indicates that neuronal populations responding to the shapes had motor properties, while adaptation to observation demonstrates that these populations had mirror properties. These results indicate that sensorimotor training induced populations of cells with mirror properties in PMv and IPL to respond to the observation of arbitrary shapes. They suggest that the mirror system has not been shaped by evolution to respond in a mirror fashion to biological actions; instead, its development is mediated by stimulus-general processes of learning within a system adapted for visuomotor control.

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.

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...

Chronic low-dose UVA irradiation induces local suppression of contact hypersensitivity, Langerhans cell depletion and suppressor cell activation in C3H/HeJ mice

International Nuclear Information System (INIS)

Bestak, Rosa; Halliday, G.M.

1996-01-01

It has previously been demonstrated that chronic low-dose solar-simulated UV radiation could induce both local and systemic immunosuppression as well as tolerance to a topically applied hapten. In this study, we have used a chronic low-dose UV-irradiation protocol to investigate the effects of UVA on the skin immune system of C3H/HeJ mice. Irradiation with UVA+B significantly suppressed the local and systemic primary contact hypersensitivity (CHS) response to the hapten 2,4,6-trinitrochlorobenzene. Furthermore, UVA+B reduced Langerhans cell (LC) and dendritic epidermal T cell (DETC) densities in chronically UV-irradiated mice. Ultraviolet A irradiation induced local, but not systemic, immunosuppression and reduced LC (32%) but not DETC from the epidermis compared to the shaved control animals. Treatment of mice with both UVA+B and UVA radiation also induced an impaired secondary CHS response, and this tolerance was transferable with spleen cells. (Author)

Second Solid Cancers After Radiation Therapy: A Systematic Review of the Epidemiologic Studies of the Radiation Dose-Response Relationship

Energy Technology Data Exchange (ETDEWEB)

Berrington de Gonzalez, Amy, E-mail: berringtona@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Gilbert, Ethel; Curtis, Rochelle; Inskip, Peter; Kleinerman, Ruth; Morton, Lindsay; Rajaraman, Preetha; Little, Mark P. [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

2013-06-01

Rapid innovations in radiation therapy techniques have resulted in an urgent need for risk projection models for second cancer risks from high-dose radiation exposure, because direct observation of the late effects of newer treatments will require patient follow-up for a decade or more. However, the patterns of cancer risk after fractionated high-dose radiation are much less well understood than those after lower-dose exposures (0.1-5 Gy). In particular, there is uncertainty about the shape of the dose-response curve at high doses and about the magnitude of the second cancer risk per unit dose. We reviewed the available evidence from epidemiologic studies of second solid cancers in organs that received high-dose exposure (>5 Gy) from radiation therapy where dose-response curves were estimated from individual organ-specific doses. We included 28 eligible studies with 3434 second cancer patients across 11 second solid cancers. Overall, there was little evidence that the dose-response curve was nonlinear in the direction of a downturn in risk, even at organ doses of ≥60 Gy. Thyroid cancer was the only exception, with evidence of a downturn after 20 Gy. Generally the excess relative risk per Gray, taking account of age and sex, was 5 to 10 times lower than the risk from acute exposures of <2 Gy among the Japanese atomic bomb survivors. However, the magnitude of the reduction in risk varied according to the second cancer. The results of our review provide insights into radiation carcinogenesis from fractionated high-dose exposures and are generally consistent with current theoretical models. The results can be used to refine the development of second solid cancer risk projection models for novel radiation therapy techniques.

Fast-Response-Time Shape-Memory-Effect Foam Actuators

Science.gov (United States)

Jardine, Peter

2010-01-01

Bulk shape memory alloys, such as Nitinol or CuAlZn, display strong recovery forces undergoing a phase transformation after being strained in their martensitic state. These recovery forces are used for actuation. As the phase transformation is thermally driven, the response time of the actuation can be slow, as the heat must be passively inserted or removed from the alloy. Shape memory alloy TiNi torque tubes have been investigated for at least 20 years and have demonstrated high actuation forces [3,000 in.-lb (approximately equal to 340 N-m) torques] and are very lightweight. However, they are not easy to attach to existing structures. Adhesives will fail in shear at low-torque loads and the TiNi is not weldable, so that mechanical crimp fits have been generally used. These are not reliable, especially in vibratory environments. The TiNi is also slow to heat up, as it can only be heated indirectly using heater and cooling must be done passively. This has restricted their use to on-off actuators where cycle times of approximately one minute is acceptable. Self-propagating high-temperature synthesis (SHS) has been used in the past to make porous TiNi metal foams. Shape Change Technologies has been able to train SHS derived TiNi to exhibit the shape memory effect. As it is an open-celled material, fast response times were observed when the material was heated using hot and cold fluids. A methodology was developed to make the open-celled porous TiNi foams as a tube with integrated hexagonal ends, which then becomes a torsional actuator with fast response times. Under processing developed independently, researchers were able to verify torques of 84 in.-lb (approximately equal to 9.5 Nm) using an actuator weighing 1.3 oz (approximately equal to 37 g) with very fast (less than 1/16th of a second) initial response times when hot and cold fluids were used to facilitate heat transfer. Integrated structural connections were added as part of the net shape process, eliminating

Ultraviolet Radiation Induces Dose-Dependent Pigment Dispersion in Crustacean Chromatophores

OpenAIRE

Gouveia, Glauce Ribeiro; Lopes, Thaís Martins; Neves, Carla Amorim; Nery, Luiz Eduardo Maia; Trindade, Gilma Santos

2004-01-01

Pigment dispersion in chromatophores as a response to UV radiation was investigated in two species of crustaceans, the crab Chasmagnathus granulata and the shrimp Palaemonetes argentinus. Eyestalkless crabs and shrimps maintained on either a black or a white background were irradiated with different UV bands. In eyestalkless crabs the significant minimal effective dose inducing pigment dispersion was 0.42 J/cm2 for UVA and 2.15 J/cm2 for UVB. Maximal response was achieved with 10.0 J/cm...

Phase I trial of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 for androgen-independent prostate cancer.

Science.gov (United States)

Milowsky, Matthew I; Nanus, David M; Kostakoglu, Lale; Vallabhajosula, Shankar; Goldsmith, Stanley J; Bander, Neil H

2004-07-01

To determine the maximum-tolerated dose (MTD), toxicity, human antihuman antibody (HAHA) response, pharmacokinetics, organ dosimetry, targeting, and preliminary efficacy of yttrium-90-labeled anti-prostate-specific membrane antigen monoclonal antibody J591 ((90)Y-J591) in patients with androgen-independent prostate cancer (PC). Patients with androgen-independent PC and evidence of disease progression received indium-111-J591 for pharmacokinetic and biodistribution determinations followed 1 week later by (90)Y-J591 at five dose levels: 5, 10, 15, 17.5, and 20 mCi/m(2). Patients were eligible for up to three re-treatments if platelet and neutrophil recovery was satisfactory. Twenty-nine patients with androgen-independent PC received (90)Y-J591, four of whom were re-treated. Dose limiting toxicity (DLT) was seen at 20 mCi/m(2), with two patients experiencing thrombocytopenia with non-life-threatening bleeding episodes requiring platelet transfusions. The 17.5-mCi/m(2) dose level was determined to be the MTD. No re-treated patients experienced DLT. Nonhematologic toxicity was not dose limiting. Targeting of known sites of bone and soft tissue metastases was seen in the majority of patients. No HAHA response was seen. Antitumor activity was seen, with two patients experiencing 85% and 70% declines in prostate-specific antigen (PSA) levels lasting 8 and 8.6 months, respectively, before returning to baseline. Both patients had objective measurable disease responses. An additional six patients (21%) experienced PSA stabilization. The recommended dose for (90)Y-J591 is 17.5 mCi/m(2). Acceptable toxicity, excellent targeting of known sites of PC metastases, and biologic activity in patients with androgen-independent PC warrant further investigation of (90)Y-J591 in the treatment of patients with PC.

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.

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

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

National Research Council Canada - National Science Library

Vallabhajosula, Shankar

2007-01-01

Phase I dose escalation studies with 177Lu-DOTA-huJ591 using dose fractionation regimen will be performed in patients with PCa and who have recurrent and/or metastatic disease. The 177Lu dose (20-45 mCi/m2...

Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination With Docetaxel

National Research Council Canada - National Science Library

Vallabhajosula, Shankar

2006-01-01

Phase I dose escalation studies with 177Lu-DOTA-huJ591 using dose fractionation regimen will be performed in patients with PCa and who have recurrent and/or metastatic disease. The 177Lu dose (20-45 mCi/m2...

FMRI evidence of 'mirror' responses to geometric shapes.

Directory of Open Access Journals (Sweden)

Clare Press

Full Text Available Mirror neurons may be a genetic adaptation for social interaction. Alternatively, the associative hypothesis proposes that the development of mirror neurons is driven by sensorimotor learning, and that, given suitable experience, mirror neurons will respond to any stimulus. This hypothesis was tested using fMRI adaptation to index populations of cells with mirror properties. After sensorimotor training, where geometric shapes were paired with hand actions, BOLD response was measured while human participants experienced runs of events in which shape observation alternated with action execution or observation. Adaptation from shapes to action execution, and critically, observation, occurred in ventral premotor cortex (PMv and inferior parietal lobule (IPL. Adaptation from shapes to execution indicates that neuronal populations responding to the shapes had motor properties, while adaptation to observation demonstrates that these populations had mirror properties. These results indicate that sensorimotor training induced populations of cells with mirror properties in PMv and IPL to respond to the observation of arbitrary shapes. They suggest that the mirror system has not been shaped by evolution to respond in a mirror fashion to biological actions; instead, its development is mediated by stimulus-general processes of learning within a system adapted for visuomotor control.

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.

Methods to Analyze Bone Regenerative Response to Different rhBMP-2 Doses in Rabbit Craniofacial Defects

Science.gov (United States)

2014-02-28

Ruggiero, S., Fantasia, J., Burakoff, R., Moorji, S.M., Paric, E., et al. Sonic hedgehog gene enhanced tissue engineering for bone regeneration. Gene Ther...discectomy and fusion: a case study. Spine J 7, 235, 2007. 8. Zara, J.N., Siu, R.K., Zhang, X., Shen, J., Ngo, R., Lee, M., et al. High doses of bone

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

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

Dose and dose rate monitor

International Nuclear Information System (INIS)

Novakova, O.; Ryba, J.; Slezak, V.; Svobodova, B.; Viererbl, L.

1984-10-01

The methods are discussea of measuring dose rate or dose using a scintillation counte. A plastic scintillator based on polystyrene with PBD and POPOP activators and coated with ZnS(Ag) was chosen for the projected monitor. The scintillators were cylindrical and spherical in shape and of different sizes; black polypropylene tubes were chosen as the best case for the probs. For the counter with different plastic scintillators, the statistical error 2σ for natural background was determined. For determining the suitable thickness of the ZnS(Ag) layer the energy dependence of the counter was measured. Radioisotopes 137 Cs, 241 Am and 109 Cd were chosen as radiation sources. The best suited ZnS(Ag) thickness was found to be 0.5 μm. Experiments were carried out to determine the directional dependence of the detector response and the signal to noise ratio. The temperature dependence of the detector response and its compensation were studied, as were the time stability and fatigue manifestations of the photomultiplier. The design of a laboratory prototype of a dose rate and dose monitor is described. Block diagrams are given of the various functional parts of the instrument. The designed instrument is easiiy portable, battery powered, measures dose rates from natural background in the range of five orders, i.e., 10 -2 to 10 3 nGy/s, and allows to determine a dose of up to 10 mGy. Accouracy of measurement in the energy range of 50 keV to 1 MeV is better than +-20%. (E.S.)

Harnessing the theoretical foundations of the exponential and beta-Poisson dose-response models to quantify parameter uncertainty using Markov Chain Monte Carlo.

Science.gov (United States)

Schmidt, Philip J; Pintar, Katarina D M; Fazil, Aamir M; Topp, Edward

2013-09-01

Dose-response models are the essential link between exposure assessment and computed risk values in quantitative microbial risk assessment, yet the uncertainty that is inherent to computed risks because the dose-response model parameters are estimated using limited epidemiological data is rarely quantified. Second-order risk characterization approaches incorporating uncertainty in dose-response model parameters can provide more complete information to decisionmakers by separating variability and uncertainty to quantify the uncertainty in computed risks. Therefore, the objective of this work is to develop procedures to sample from posterior distributions describing uncertainty in the parameters of exponential and beta-Poisson dose-response models using Bayes's theorem and Markov Chain Monte Carlo (in OpenBUGS). The theoretical origins of the beta-Poisson dose-response model are used to identify a decomposed version of the model that enables Bayesian analysis without the need to evaluate Kummer confluent hypergeometric functions. Herein, it is also established that the beta distribution in the beta-Poisson dose-response model cannot address variation among individual pathogens, criteria to validate use of the conventional approximation to the beta-Poisson model are proposed, and simple algorithms to evaluate actual beta-Poisson probabilities of infection are investigated. The developed MCMC procedures are applied to analysis of a case study data set, and it is demonstrated that an important region of the posterior distribution of the beta-Poisson dose-response model parameters is attributable to the absence of low-dose data. This region includes beta-Poisson models for which the conventional approximation is especially invalid and in which many beta distributions have an extreme shape with questionable plausibility. © Her Majesty the Queen in Right of Canada 2013. Reproduced with the permission of the Minister of the Public Health Agency of Canada.

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

Proton dose distribution measurements using a MOSFET detector with a simple dose-weighted correction method for LET effects.

Science.gov (United States)

Kohno, Ryosuke; Hotta, Kenji; Matsuura, Taeko; Matsubara, Kana; Nishioka, Shie; Nishio, Teiji; Kawashima, Mitsuhiko; Ogino, Takashi

2011-04-04

We experimentally evaluated the proton beam dose reproducibility, sensitivity, angular dependence and depth-dose relationships for a new Metal Oxide Semiconductor Field Effect Transistor (MOSFET) detector. The detector was fabricated with a thinner oxide layer and was operated at high-bias voltages. In order to accurately measure dose distributions, we developed a practical method for correcting the MOSFET response to proton beams. The detector was tested by examining lateral dose profiles formed by protons passing through an L-shaped bolus. The dose reproducibility, angular dependence and depth-dose response were evaluated using a 190 MeV proton beam. Depth-output curves produced using the MOSFET detectors were compared with results obtained using an ionization chamber (IC). Since accurate measurements of proton dose distribution require correction for LET effects, we developed a simple dose-weighted correction method. The correction factors were determined as a function of proton penetration depth, or residual range. The residual proton range at each measurement point was calculated using the pencil beam algorithm. Lateral measurements in a phantom were obtained for pristine and SOBP beams. The reproducibility of the MOSFET detector was within 2%, and the angular dependence was less than 9%. The detector exhibited a good response at the Bragg peak (0.74 relative to the IC detector). For dose distributions resulting from protons passing through an L-shaped bolus, the corrected MOSFET dose agreed well with the IC results. Absolute proton dosimetry can be performed using MOSFET detectors to a precision of about 3% (1 sigma). A thinner oxide layer thickness improved the LET in proton dosimetry. By employing correction methods for LET dependence, it is possible to measure absolute proton dose using MOSFET detectors.

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.

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

The Effects of Low Dose-Rate Ionizing Radiation on the Shapes of Transients in the LM124 Operational Amplifier

Science.gov (United States)

Buchner, Stephen; McMorrow, Dale; Roche, Nicholas; Dusseau, Laurent; Pease, Ron L.

2008-01-01

Shapes of single event transients (SETs) in a linear bipolar circuit (LM124) change with exposure to total ionizing dose (TID) radiation. SETs shape changes are a direct consequence of TID-induced degradation of bipolar transistor gain. A reduction in transistor gain causes a reduction in the drive current of the current sources in the circuit, and it is the lower drive current that most affects the shapes of large amplitude SETs.

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.

Mandibular second molar exhibiting a unique "Y-" and "J-" "shaped" root canal anatomy diagnosed using cone-beam computed tomographic scanning: A case report.

Science.gov (United States)

Parashar, Saumya-Rajesh; Kowsky, R Dinesh; Natanasabapathy, Velmurugan

2017-01-01

This article aims to report a unique case with aberrant root canal anatomy exhibiting "Y-" and "J"-shaped canal pattern in a mandibular second molar. Anatomic complexities may pose challenges for endodontic treatment. Before performing endodontic treatment, the clinician should be aware of the internal anatomy of the tooth being treated and should recognize anatomic aberrations if present. Presence of unusual anatomy may call for modifications in treatment planning. This report describes in detail about a mandibular second molar tooth associated with two paramolar tubercles having a peculiar "Y-" and "J-"shaped canal anatomy detected with the aid of cone beam computed tomography, which has never been reported in the dental literature. The proposed treatment protocol for the endodontic management of the same has also been discussed.

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)

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

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

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.

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.

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)

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

International Nuclear Information System (INIS)

Little, Mark P.; Stovall, Marilyn; Smith, Susan A.; Kleinerman, Ruth A.

2013-01-01

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

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

Chemical risk factors responsible for the formation of wedge-shaped lesions

Directory of Open Access Journals (Sweden)

Perić Dejan

2015-01-01

Full Text Available Introduction: Non-carious tooth substances loss pose a major health problem of a modern man. The literature often collectively describes all non-carious lesions and is therefore difficult to compare results obtained by different authors. Chemical factors are one of the predisposing factors responsible for the formation of wedge-shaped erosions. Aim: Examination of chemical risk factors as one of the predisposing causes responsible for the formation of wedge-shaped lesions. Method: We examined 62 patients with wedge-shaped erosions (mean age 45.52 ± 12.03 years, 58.1% of men and 60 patients without erosions in the control group (mean age 34.40 ± 9.28 years, 60% men . The entire examination was completed by using a questionnaire at the Dental Clinic of the University of Pristina - Kosovska Mitrovica. salivary pH was measured by the pH meter. Results: The results show that the wedge-shaped lesions often occur equally in both men and women. Considerably often it might appear in older people but can also occur in teenagers. Patients with wedge-shaped erosion have increased acidity of saliva, a heightened sense of acid in the mouth and consume a lot more carbonated drinks compared to patients without erosions. Conclusion: Wedge-shaped lesions are more common in people older than 40 years. Taking into account the results obtained in this study it can be concluded that the chemical risk factors truly fall within the predisposing factors that may be responsible for the creation of wedge-shaped erosions.

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".

Maximum likelihood estimation for cytogenetic dose-response curves

International Nuclear Information System (INIS)

Frome, E.L; DuFrain, R.J.

1983-10-01

In vitro dose-response curves are used to describe the relation between the yield of dicentric chromosome aberrations and radiation dose for human lymphocytes. The dicentric yields follow the Poisson distribution, and the expected yield depends on both the magnitude and the temporal distribution of the dose for low LET radiation. A general dose-response model that describes this relation has been obtained by Kellerer and Rossi using the theory of dual radiation action. The yield of elementary lesions is kappa[γd + g(t, tau)d 2 ], where t is the time and d is dose. The coefficient of the d 2 term is determined by the recovery function and the temporal mode of irradiation. Two special cases of practical interest are split-dose and continuous exposure experiments, and the resulting models are intrinsically nonlinear in the parameters. A general purpose maximum likelihood estimation procedure is described and illustrated with numerical examples from both experimental designs. Poisson regression analysis is used for estimation, hypothesis testing, and regression diagnostics. Results are discussed in the context of exposure assessment procedures for both acute and chronic human radiation exposure

Maximum likelihood estimation for cytogenetic dose-response curves

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.

Fast-ion response to energetic-particle-driven MHD activity in Heliotron J

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, S.; Yamamoto, S.; Mizuuchi, T.; Nagasaki, K.; Okada, H.; Minami, T.; Hanatani, K.; Konoshima, S.; Ohshima, S.; Toushi, K.; Sano, F. [Institute of Advanced Energy, Kyoto University, Gokasho, Uji (Japan); Nagaoka, K.; Suzuki, Y.; Takeiri, Y.; Yokoyama, M. [National Institute for Fusion Science, Toki, Gifu (Japan); Murakami, S. [Graduate School of Engineering, Kyoto University, Kyoto (Japan); Lee, H.Y.; Nakamura, Y.; Hosaka, K. [Graduate School of Energy Science, Kyoto University, Gokasho, Uji (Japan)

2010-08-15

In Heliotron J, low magnetic shear configuration, instabilities with frequency chirping in the frequency range of Alfven eigenmodes have been observed in tangentially injected neutral beam plasmas. These modes are induced by energetic-particle driven magnetohydrodynamic (MHD) instabilities such as global Alfven eigenmode or energetic particle mode. A hybrid directional Langmuir probe system has been installed into Heliotron J to investigate the response of fast-ion fluxes to the MHD modes. A high coherent response of the ion flux to the bursting modes has been observed not only by the co-directed probe but also by the counter-directed one. A linear correlation between the response of the co-directed ion flux and the mode amplitude has been found. The radial profile of the response of the co-directed ions has decreased with the minor radius and has not been obtained significantly outside last closed flux surface. These results indicate that the fast-ion response is due to a resonant convective oscillation. The ion flux response of the counter-directed probe has appeared in the growth phase of the mode burst. Its phase relation is different from that of co-directed one and magnetic probe located at the Heliotron J vacuum vessel. Two candidates of the detected ion flux of the counter-directed probe have been discussed. (copyright 2010 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim) (orig.)

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

A dose of nature: Tree cover, stress reduction, and gender differences

Science.gov (United States)

Bin Jiang; Chun-Yen Chang; William C. Sullivan

2014-01-01

Although it is well established that exposure to nearby nature can help reduce stress in individuals, the shape of the dose-response curve is entirely unclear. To establish this dose-response curve, we recruited 160 individuals for a laboratory experiment. Participants engaged in the Trier Social Stress Test (TSST) to induce psychological stress, and were then randomly...

Introduction to benchmark dose methods and U.S. EPA's benchmark dose software (BMDS) version 2.1.1

International Nuclear Information System (INIS)

Davis, J. Allen; Gift, Jeffrey S.; Zhao, Q. Jay

2011-01-01

Traditionally, the No-Observed-Adverse-Effect-Level (NOAEL) approach has been used to determine the point of departure (POD) from animal toxicology data for use in human health risk assessments. However, this approach is subject to substantial limitations that have been well defined, such as strict dependence on the dose selection, dose spacing, and sample size of the study from which the critical effect has been identified. Also, the NOAEL approach fails to take into consideration the shape of the dose-response curve and other related information. The benchmark dose (BMD) method, originally proposed as an alternative to the NOAEL methodology in the 1980s, addresses many of the limitations of the NOAEL method. It is less dependent on dose selection and spacing, and it takes into account the shape of the dose-response curve. In addition, the estimation of a BMD 95% lower bound confidence limit (BMDL) results in a POD that appropriately accounts for study quality (i.e., sample size). With the recent advent of user-friendly BMD software programs, including the U.S. Environmental Protection Agency's (U.S. EPA) Benchmark Dose Software (BMDS), BMD has become the method of choice for many health organizations world-wide. This paper discusses the BMD methods and corresponding software (i.e., BMDS version 2.1.1) that have been developed by the U.S. EPA, and includes a comparison with recently released European Food Safety Authority (EFSA) BMD guidance.

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)

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

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

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

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.)

Magnetic-Responsive Microparticles that Switch Shape at 37 °C

Directory of Open Access Journals (Sweden)

Koichiro Uto

2017-11-01

Full Text Available Shape-memory polymers have seen tremendous research efforts driven by the need for better drug carries and biomedical devices. In contrast to these advancements, fabrication of shape-memory particles which actuate at body temperature remains scarce. We developed a shape-memory microparticle system with dynamically tunable shapes under physiological temperature. Temperature-responsive poly(ε-caprolactone (PCL microparticles were successfully prepared by an in situ oil-in-water (o/w emulsion polymerization technique using linear telechelic and tetra-branched PCL macromonomers. By optimizing the mixing ratios of branched PCL macromonomers, the crystal-amorphous transition temperature was adjusted to the biological relevant temperature. The particles with a disk-like temporal shape were achieved by compression. The shape recovery from the disk to spherical shape was also realized at 37 °C. We also incorporated magnetic nanoparticles within the PCL microparticles, which can be remote-controllable by a magnet, in such a way that they can be actuated and manipulated in a controlled way.

Linear dose response curves in fungi and tradescantia

International Nuclear Information System (INIS)

Unrau, P.

1999-07-01

Tradescantia Clone 02 data suggests that linear non-threshold dose responses are expected to the lowest doses and dose rates of low linear energy transfer (LET) radiation. This is likely to be true for other living organisms even though Clone 02 is radiation sensitive. It is concluded that Clone 02 is partially defective in the RAD 6 pathway for the repair of DNA interstrand cross-links (ISCL) and other loss of coding damage (LCD), based on its cross sensitivities to EMS and ionizing radiation. Tradescantia Clone 02 data showing linear non-threshold induction of somatic genetic events in part reflects the repair deficiency of this Clone. More DNA damage is repaired by recombinational mechanisms in Clone 02 than would occur in a wild-type strain. Two important classes of DNA lesions are induced by ionizing radiation in DNA - double strand breaks (DSB) which are repaired by recombination mechanisms, and loss of coding information damage (LCD), which is repaired by error prone mechanisms but may also be a substrate for recombinational repair. Based on data from yeast, there are two different repair pathways which deal with these differing lesions with different somatic genetic consequences. From yeast, yield cross sections can be derived and applied to DNA damage and repair in Tradescantia. For Clone 02, per lesion, more visible genetic events are scored than in wild-type strains. In a radiation-derived sub-clone, Clone 0106, which is more variable than Clone 02, even more events occur per lesion. This derivative clone, plus breeding experiments, indicate that Clone 02 is heterozygous, or a 'carrier' for a mutant version of a gene in the Tradescantia RAD 6 repair pathway. Clone 02 is, therefore, much like a Fanconi's anemia carrier in a human population, while the Clone 0106 derivative is much like a homozygous Fanconi's anemia patient, with respect to its response to ionizing radiation damage. Two anomalies in its dose response curves for 'pink' loss of

Linear dose response curves in fungi and tradescantia

Energy Technology Data Exchange (ETDEWEB)

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

1999-07-15

Tradescantia Clone 02 data suggests that linear non-threshold dose responses are expected to the lowest doses and dose rates of low linear energy transfer (LET) radiation. This is likely to be true for other living organisms even though Clone 02 is radiation sensitive. It is concluded that Clone 02 is partially defective in the RAD 6 pathway for the repair of DNA interstrand cross-links (ISCL) and other loss of coding damage (LCD), based on its cross sensitivities to EMS and ionizing radiation. Tradescantia Clone 02 data showing linear non-threshold induction of somatic genetic events in part reflects the repair deficiency of this Clone. More DNA damage is repaired by recombinational mechanisms in Clone 02 than would occur in a wild-type strain. Two important classes of DNA lesions are induced by ionizing radiation in DNA - double strand breaks (DSB) which are repaired by recombination mechanisms, and loss of coding information damage (LCD), which is repaired by error prone mechanisms but may also be a substrate for recombinational repair. Based on data from yeast, there are two different repair pathways which deal with these differing lesions with different somatic genetic consequences. From yeast, yield cross sections can be derived and applied to DNA damage and repair in Tradescantia. For Clone 02, per lesion, more visible genetic events are scored than in wild-type strains. In a radiation-derived sub-clone, Clone 0106, which is more variable than Clone 02, even more events occur per lesion. This derivative clone, plus breeding experiments, indicate that Clone 02 is heterozygous, or a 'carrier' for a mutant version of a gene in the Tradescantia RAD 6 repair pathway. Clone 02 is, therefore, much like a Fanconi's anemia carrier in a human population, while the Clone 0106 derivative is much like a homozygous Fanconi's anemia patient, with respect to its response to ionizing radiation damage. Two anomalies in its dose response curves for &apos

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.

SU-E-T-96: Energy Dependence of the New GafChromic- EBT3 Film's Dose Response-Curve.

Science.gov (United States)

Chiu-Tsao, S; Massillon-Jl, G; Domingo-Muñoz, I; Chan, M

2012-06-01

To study and compare the dose response curves of the new GafChromic EBT3 film for megavoltage and kilovoltage x-ray beams, with different spatial resolution. Two sets of EBT3 films (lot#A101711-02) were exposed to each x-ray beam (6MV, 15MV and 50kV) at 8 dose values (50-3200cGy). The megavoltage beams were calibrated per AAPM TG-51 protocol while the kilovoltage beam was calibrated following the TG-61 using an ionization chamber calibrated at NIST. Each film piece was scanned three consecutive times in the center of Epson 10000XL flatbed scanner in transmission mode, landscape orientation, 48-bit color at two separate spatial resolutions of 75 and 300 dpi. The data were analyzed using ImageJ and, for each scanned image, a region of interest (ROI) of 2×2cm 2 at the field center was selected to obtain the mean pixel value with its standard deviation in the ROI. For each energy, dose value and spatial resolution, the average netOD and its associated uncertainty were determined. The Student's t-test was performed to evaluate the statistical differences between the netOD/dose values of the three energy modalities, with different color channels and spatial resolutions. The dose response curves for the three energy modalities were compared in three color channels with 75 and 300dpi. Weak energy dependence was found. For doses above 100cGy, no statistical differences were observed between 6 and 15MV beams, regardless of spatial resolution. However, statistical differences were observed between 50kV and the megavoltage beams. The degree of energy dependence (from MV to 50kV) was found to be function of color channel, dose level and spatial resolution. The dose response curves for GafChromic EBT3 films were found to be weakly dependent on the energy of the photon beams from 6MV to 50kV. The degree of energy dependence varies with color channel, dose and spatial resolution. GafChromic EBT3 films were supplied by Ashland Corp. This work was partially supported by DGAPA

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

International Nuclear Information System (INIS)

Raabe, O.G.

1988-01-01

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

Dose response 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

The shape of dose-effect curves for diploid yeast cells irradiated with ionizing particles

International Nuclear Information System (INIS)

Pohlit, W.

1975-01-01

In a cybernetic model for the radiation reactions in eukaryotic cells, after irradiation they are assumed to be in one of three states: (a) viable cells; (b) with repairable damage; and (c) with irreparable damage. Two biological counter reactions with certain time constants can be observed: (i) recovery from sublethal damage; and (ii) repair of potential lethal damage. The shape of the dose-effect curve is influenced in a characteristic way by the different occupation of these states of the cells and by the time constants of the biological counter reactions. The biochemical analysis of the biological counter reactions, recovery and repair, has shown that both are linked together by the energy pool in the cell. In this way changes in the slope of the dose-effect curve due to different metabolic states of the cells can be understood quantitatively. Also the complicated dependence of survival cells on the absorbed dose rate over a wide range can be explained quantitatively. (author)

Effect of low dose radiation on apoptosis in mouse spleen

International Nuclear Information System (INIS)

Chen Dong; Liu Jiamei; Chen Aijun; Liu Shuzheng

1999-01-01

Objective: To study the effect of whole body irradiation (WBI) with different doses of X-ray on apoptosis in mouse spleen. Methods: Time course changes and dose-effect relationship of apoptosis in mouse spleen induced by WBI were observed with transmission electron microscopy (TEM) qualitatively and TUNEL method semi-quantitatively. Results: Many typical apoptotic lymphocytes were found by TEM in mouse spleen after WBI with 2 Gy. No marked alterations of ultrastructure were found following WBI with 0.075 Gy. It was observed by TUNEL that the apoptosis of splenocytes increased after high dose radiation and decreased following low dose radiation (LDR). The dose-effect relationship of radiation-induced apoptosis showed a J-shaped curve. Conclusion: The effect of different doses of ionizing radiation on apoptosis in mouse spleen was distinct. And the decrease of apoptosis after LDR is considered a manifestation of radiation hormesis

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...

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.

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.

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

Dose dependence on stochastic radiobiological effect in radiation risk estimation

International Nuclear Information System (INIS)

Komochkov, M.M.

1999-01-01

The analysis of the results in dose -- effect relationship observation has been carried out on the cell and organism levels, with the aim to obtain more precise data on the risk coefficients at low doses. The results are represented by two contrasting groups of dose dependence on effect: a downwards concave and a J-shaped curve. Both types of dependence are described by the equation solutions of an assumed unified protective mechanism, which comprises two components: constitutive and adaptive or inducible ones. The latest data analysis of the downwards concave dependence curves shows a considerable underestimation of radiation risk in all types of cancer, except leukemia, for a number of critical groups in a population, at low doses comparing to the ICRP recommendations. With the dose increase, the decrease of the effect value per dose unit is observed. It may be possibly related to the switching of the activity of the adaptive protective mechanism, with some threshold dose values being exceeded

Optimization of the beam shaping assembly in the D-D neutron generators-based BNCT using the response matrix method.

Science.gov (United States)

Kasesaz, Y; Khalafi, H; Rahmani, F

2013-12-01

Optimization of the Beam Shaping Assembly (BSA) has been performed using the MCNP4C Monte Carlo code to shape the 2.45 MeV neutrons that are produced in the D-D neutron generator. Optimal design of the BSA has been chosen by considering in-air figures of merit (FOM) which consists of 70 cm Fluental as a moderator, 30 cm Pb as a reflector, 2mm (6)Li as a thermal neutron filter and 2mm Pb as a gamma filter. The neutron beam can be evaluated by in-phantom parameters, from which therapeutic gain can be derived. Direct evaluation of both set of FOMs (in-air and in-phantom) is very time consuming. In this paper a Response Matrix (RM) method has been suggested to reduce the computing time. This method is based on considering the neutron spectrum at the beam exit and calculating contribution of various dose components in phantom to calculate the Response Matrix. Results show good agreement between direct calculation and the RM method. Copyright © 2013 Elsevier Ltd. All rights reserved.

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)

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...

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.

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

Significance of the evaluation of radiation dose at the site boundary

International Nuclear Information System (INIS)

Takitani, Koichi

2013-01-01

Nuclear Regulation Authority, Japan, is drawing up new regulation standards for the light water reactors. The focal point of the new regulation drawing is how 'the safeguard against the release of radioactive materials at possible severe accident' should be shaped up. Checking the radiation dose rate at the site boundary is indispensable for the evaluation of the efficiency of measures against the severe accident. 'Avoiding radiation hazard on habitants' should be included in the regulation. The critical dose may be 100mSv for whole body and 1000mSv for the children's thyroid gland. (J.P.N.)

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)

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

Energy Technology Data Exchange (ETDEWEB)

Little, Mark P., E-mail: mark.little@nih.gov [Radiation Epidemiology Branch, National Cancer Institute, Rockville, Maryland (United States); Stovall, Marilyn; Smith, Susan A. [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Kleinerman, Ruth A. [Radiation Epidemiology Branch, National Cancer Institute, Rockville, Maryland (United States)

2013-02-01

Purpose: To assess the shape of the dose response for various cancer endpoints and modifiers by age and time. Methods and Materials: Reanalysis of the US peptic ulcer data testing for heterogeneity of radiogenic risk by cancer endpoint (stomach, pancreas, lung, leukemia, all other). Results: There are statistically significant (P<.05) excess risks for all cancer and for lung cancer and borderline statistically significant risks for stomach cancer (P=.07), and leukemia (P=.06), with excess relative risks Gy{sup -1} of 0.024 (95% confidence interval [CI] 0.011, 0.039), 0.559 (95% CI 0.221, 1.021), 0.042 (95% CI -0.002, 0.119), and 1.087 (95% CI -0.018, 4.925), respectively. There is statistically significant (P=.007) excess risk of pancreatic cancer when adjusted for dose-response curvature. General downward curvature is apparent in the dose response, statistically significant (P<.05) for all cancers, pancreatic cancer, and all other cancers (ie, other than stomach, pancreas, lung, leukemia). There are indications of reduction in relative risk with increasing age at exposure (for all cancers, pancreatic cancer), but no evidence for quadratic variations in relative risk with age at exposure. If a linear-exponential dose response is used, there is no significant heterogeneity in the dose response among the 5 endpoints considered or in the speed of variation of relative risk with age at exposure. The risks are generally consistent with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers. Conclusions: There are excess risks for various malignancies in this data set. Generally there is a marked downward curvature in the dose response and significant reduction in relative risk with increasing age at exposure. The consistency of risks with those observed in the Japanese atomic bomb survivors and in groups of nuclear workers implies that there may be little sparing effect of fractionation of dose or low-dose-rate exposure.

Radiotherapy Dose Fractionation under Parameter Uncertainty

International Nuclear Information System (INIS)

Davison, Matt; Kim, Daero; Keller, Harald

2011-01-01

In radiotherapy, radiation is directed to damage a tumor while avoiding surrounding healthy tissue. Tradeoffs ensue because dose cannot be exactly shaped to the tumor. It is particularly important to ensure that sensitive biological structures near the tumor are not damaged more than a certain amount. Biological tissue is known to have a nonlinear response to incident radiation. The linear quadratic dose response model, which requires the specification of two clinically and experimentally observed response coefficients, is commonly used to model this effect. This model yields an optimization problem giving two different types of optimal dose sequences (fractionation schedules). Which fractionation schedule is preferred depends on the response coefficients. These coefficients are uncertainly known and may differ from patient to patient. Because of this not only the expected outcomes but also the uncertainty around these outcomes are important, and it might not be prudent to select the strategy with the best expected outcome.

Developing responsive web applications with Ajax and jQuery

CERN Document Server

Patel, Sandeep Kumar

2014-01-01

This book is a standard tutorial for web application developers presented in a comprehensive, step-by-step manner to explain the nuances involved. It has an abundance of code and examples supporting explanations of each feature. This book is intended for Java developers wanting to create rich and responsive applications using AJAX. Basic experience of using jQuery is assumed.

Uniform dose compensation using field within a field technique in T-shaped irradiation for esophageal cancer

International Nuclear Information System (INIS)

Murakami, Ryuji; Sugahara, Takeshi; Baba, Yuji; Yamashita, Yasuyuki

2003-01-01

We devised a uniform compensation method to improve dose distribution using the field within a field technique in T-shaped irradiation for esophageal cancer. Isodose curves and dose volume histograms (DVH) of the esophagus in the treatment volume were examined in ten patients treated for esophageal cancers. For the DVH analysis, the prescription dose was 40 Gy to the center of the treatment volume, and the volume ratio of the esophagus receiving within ±5% of the prescription dose (38-42 Gy) was regarded as an index of dose homogeneity (V±5%). The peak dose in the conventional antero-posterior opposed fields irradiation existed at the clavicular level, and the 90% isodose curve crossing the esophagus almost corresponded to the top level of the aortic arch. When 40 Gy is irradiated, the maximum dose of the esophagus and V±5% were 45.55±0.55 Gy and 59.7±13.2% respectively. The dose distribution of the esophagus became relatively homogeneous when a 10% dose was added using the field within a field technique to the area under the bottom level of the aortic arch, and the maximum dose and V±5% were 42.53±0.94 Gy and 91.7±7.1% respectively. A 10% and more overdose area existed at the clavicular level in the conventional antero-posterior opposed fields irradiation. A relatively homogeneous dose distribution could be obtained using the field within a field technique. (author)

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

Comments on 'Reconsidering the definition of a dose-volume histogram'-dose-mass histogram (DMH) versus dose-volume histogram (DVH) for predicting radiation-induced pneumonitis

International Nuclear Information System (INIS)

Mavroidis, Panayiotis; Plataniotis, Georgios A; Gorka, Magdalena Adamus; Lind, Bengt K

2006-01-01

In a recently published paper (Nioutsikou et al 2005 Phys. Med. Biol. 50 L17) the authors showed that the use of the dose-mass histogram (DMH) concept is a more accurate descriptor of the dose delivered to lung than the traditionally used dose-volume histogram (DVH) concept. Furthermore, they state that if a functional imaging modality could also be registered to the anatomical imaging modality providing a functional weighting across the organ (functional mass) then the more general and realistic concept of the dose-functioning mass histogram (D[F]MH) could be an even more appropriate descriptor. The comments of the present letter to the editor are in line with the basic arguments of that work since their general conclusions appear to be supported by the comparison of the DMH and DVH concepts using radiobiological measures. In this study, it is examined whether the dose-mass histogram (DMH) concept deviated significantly from the widely used dose-volume histogram (DVH) concept regarding the expected lung complications and if there are clinical indications supporting these results. The problem was investigated theoretically by applying two hypothetical dose distributions (Gaussian and semi-Gaussian shaped) on two lungs of uniform and varying densities. The influence of the deviation between DVHs and DMHs on the treatment outcome was estimated by using the relative seriality and LKB models using the Gagliardi et al (2000 Int. J. Radiat. Oncol. Biol. Phys. 46 373) and Seppenwoolde et al (2003 Int. J. Radiat. Oncol. Biol. Phys. 55 724) parameter sets for radiation pneumonitis, respectively. Furthermore, the biological equivalent of their difference was estimated by the biologically effective uniform dose (D-bar) and equivalent uniform dose (EUD) concepts, respectively. It is shown that the relation between the DVHs and DMHs varies depending on the underlying cell density distribution and the applied dose distribution. However, the range of their deviation in terms of

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...

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

Dose evaluation and risk estimation for secondary cancer in contralateral breast and a study of correlation between thorax shape and dose to organs at risk following tangentially breast irradiation during deep inspiration breath-hold and free breathing

International Nuclear Information System (INIS)

Johansen, Safora; Vikstroem, Johan; Blihovde Hjelstuen, Mari Helene; Mjaaland, Ingvil; Dybvik, Kjell Ivar; Olsen, Dag Rune

2011-01-01

Purpose: To assess the impact of using breathing adapted radiotherapy on contralateral breast (CB) dose, to relate the thorax shape with the dose to the organs at risk (OARs) and to predict the risk for induced malignancies in CB using linear and non-linear models, following tangential irradiation of breast. Material and methods. Sixteen patients with stage I-II breast cancer treatment planned with tangential fields using deep inspiration breath hold (DIBH) and free breathing (FB) techniques were included in this analysis. The dose results mainly based on DVH analysis were compared. Four parameters were defined to describe thoracic shape. Excess relative risk (ERR) for cancer induction in CB, employing linear and non-linear models was calculated. Results. Average CB volumes exposed to a dose of 1 Gy is 1.3 times higher in DIBH plans than in FB plans. No significant difference in average V3Gy and V5Gy for DIBH and FB plans is observed. The average mean CB dose for DIBH and FB plans is 0.33 and 0.28 Gy, respectively. No correlation between thorax shape parameters and mean OARs dose is observed. The estimated average mean ERR with linear model is lower in FB plans (0.12) than for the DIBH plans (0.14). The estimated ERR with non-linear model is 0.14 for DIBH plans and 0.15 for FB plans. Conclusion. No significant difference in CB dose between DIBH and FB plans is observed. The four thorax shape parameters defined in this study can not be related to the dose at OARs using DIBH and FB radiation techniques. The ERR estimates for secondary CB cancer are nearly the same for FB and DIBH planning when using a linear and non-linear risk prediction models

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.

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

Thermomechanical Methodology for Stabilizing Shape Memory Alloy (SMA) Response

Science.gov (United States)

Padula, Santo A., II (Inventor)

2016-01-01

Methods and apparatuses for stabilizing the strain-temperature response for a shape memory alloy are provided. To perform stabilization of a second sample of the shape memory alloy, a first sample of the shape memory alloy is selected for isobaric treatment and the second sample is selected for isothermal treatment. When applying the isobaric treatment to the first sample, a constant stress is applied to the first sample. Temperature is also cycled from a minimum temperature to a maximum temperature until a strain on the first sample stabilizes. Once the strain on the first sample stabilizes, the isothermal treatment is performed on the second sample. During isothermal treatment, different levels of stress on the second sample are applied until a strain on the second sample matches the stabilized strain on the first sample.

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.

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

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

Constraining Cometary Crystal Shapes from IR Spectral Features

Science.gov (United States)

Wooden, D. H.; Lindsay, S.; Harker, D. E.; Kelley, M. S.; Woodward, C. E.; Murphy, J. R.

2013-12-01

forsterite crystal shapes (equant, b-platelets, c-platelets, b-colums - excluding a- and c-columns) derived from our modeling [17] of comet Hale-Bopp, compared to laboratory synthesis experiments [18], suggests that these crystals are high temperature condensates. By observing and modeling the crystalline features in comet ISON, we may constrain forsterite crystal shape(s) and link to their formation temperature(s) and environment(s). References: [1] Campins, H., Ryan, E.V. 1989. ApJ, 341, 1059 [2] Crovisier, J., et al. 1997. Science, 275, 1904 [3] Wooden, D.H., et al. 1999. ApJ, 517, 1034 [4] Wooden, D.H., et al. 2004. ApJL, 612, L77 [5] Harker, D.E., et al. 2002. ApJ, 580, 579 [6] --. 2004, ApJ, 615, 1081 [7] Lisse, C.M., et al. 2006. Icarus 195, 941-944. [8] Lisse, C.M., et.al. 2007. Icarus 191, 223-240. [9] Kelley, M.S., et al. 2010, LPSC, 41, #2375 [10] Harker, D.E., et al. 2011, AJ, 141, 26 [11] Draine, B.T., & Flatau, P.J. 1994, J. Opt. Soc. Am. A, 11, 1491 [12] Draine, B.T., & Flatau, P.J. 2008, J. Opt. Soc. Am. A, 25, 2693 [13] Fabian, D., et al., 2001, A&A, 378, 228 [14] Tamanai, A., et al. 2006. ApJ, 648, L147 [15] Tamanai, A., et al. 2009. ASP Conf. Ser., 414, 438 [16] Koike, C., et al. 2010. ApJ, 709, 983 [17] Lindsay, S.S., et al. 2013, ApJ, 766, 54 [18] Tsuchiyama, A. 1998. Mineralogical J., 20, 59 [19] Kobatake, H., et al., 2008. Icarus, 198, 208 [20] Takigawa, A., et al.. 2009. ApJL, 707, L97

Optimized choice of method for determining proliferation response of peripheral lymphocytes to mitogens in low dose irradiation with cyclotron fast neutrons

International Nuclear Information System (INIS)

Refka, Z.; Svec, M.; Aganov, P.; Svoboda, V.; Podzimek, F.

1989-01-01

Heparinized venous blood sampled from seven donors was irradiated with doses of 0.1; 0.25; 0.5; 1.0; 2.0 and 3.0 Gy of fast neutrons of a mean energy of 7.6 MeV using the U 120 M isochronous cyclotron. A non-irradiated control sample was also prepared. A lymphoblastic transformation test was conducted with both the intact and irradiated samples. The samples were cultivated in the RPMI-1640 medium with and without a mitogen addition, this in five time variants, viz., for 48, 72, 90, 96 and 120 hours. The proliferation was monitored of lymphocytes stimulated with mitogens PHA, CON-A and PWM in dependence on the time of cultivation and on the radiation dose. The dose dependent relative response was also studied of the irradiated lymphocytes. (E.J.). 8 figs., 1 tab., 18 refs

Late biological effects of ionizing radiation as influenced by dose, dose rate, age at exposure, and genetic sensitivity to neoplastic transformation

International Nuclear Information System (INIS)

Spalding, J.F.; Prine, J.R.; Tietjen, G.L.

1978-01-01

A most comprehensive investigation is in progress at the Los Alamos Scientific Laboratory to study the late biological effects of whole-body exposure to gamma irradiation as they may be influenced by total dose, dose rate, age at exposure, and genetic background. Strain C57B1/6J mice of four age groups (newborn, 2, 6, and 15 months) were given five doses (20, 60, 180, 540, and 1620 rad) of gamma rays, with each dose being delivered at six dose rates (0.7, 2.1, 6.3, 18.9, 56.7 rad/day and 25 rad/min). Forty to sixty mice were used in each of the approximately 110 dose/dose-rate and age combinations. The study was done in two replications with an equal number of mice per replication. Strain RF/J mice were used in a companion study to investigate the influence of genetic background on the type and magnitude of effect. Results of the first and second replications of the 15-month-old age group and data on the influence of genetic background on biological response have been completed, and the results show no significant life shortening within the dose and dose-rate range used

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

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)

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.

Shape optimization and sensitivity of compliant beams for prescribed load-displacement response

NARCIS (Netherlands)

Radaelli, G.; Herder, J.L.

2016-01-01

This paper presents the shape optimization of a compliant beam for prescribed load-displacements response. The analysis of the design is based on the isogeometric analysis framework for an enhanced fidelity between designed and analysed shape. The sensitivities used for an improved optimization

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

Science.gov (United States)

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

2014-03-01

Monk parrots (Myiopsitta monachus) are susceptible to atherosclerosis, a progressive disease characterized by the formation of plaques in the arteries accompanied by underlying chronic inflammation. The family of n-3 fatty acids, especially eicosapentaenoic acid (20:5n-3, EPA) and docosahexaenoic acid (22:6n-3, DHA), have consistently been shown to reduce atherosclerotic risk factors in humans and other mammals. Some avian species have been observed to convert α-linolenic acid (18:3n-3, ALA) to EPA and DHA (Htin et al. in Arch Geflugelk 71:258-266, 2007; Petzinger et al. in J Anim Physiol Anim Nutr, 2013). Therefore, the metabolic effects of including flaxseed oil, as a source of ALA, in the diet at three different levels (low, medium, and high) on the lipid metabolism of Monk parrots was evaluated through measuring plasma total cholesterol (TC), free cholesterol (FC), triacylglycerols (TAG), and phospholipid fatty acids. Feed intake, body weight, and body condition score were also assessed. Thus the dose and possible saturation response of increasing dietary ALA at constant linoleic acid (18:2n-6, LNA) concentration on lipid metabolism in Monk parrots (M. monachus) was evaluated. Calculated esterified cholesterol in addition to plasma TC, FC, and TAG were unaltered by increasing dietary ALA. The high ALA group had elevated levels of plasma phospholipid ALA, EPA, and docosapentaenoic acid (DPAn-3, 22:5n-3). The medium and high ALA groups had suppressed plasma phospholipid 20:2n-6 and adrenic acid (22:4n-6, ADA) compared to the low ALA group. When the present data were combined with data from a previous study (Petzinger et al. in J Anim Physiol Anim Nutr, 2013) a dose response to dietary ALA was observed when LNA was constant. Plasma phospholipid ALA, EPA, DPAn-3, DHA, and total n-3 were positively correlated while 20:2n-6, di-homo-gamma-linoleic acid (20:3n-6Δ7), arachidonic acid (20:4n-6), ADA, and total n-6 were inversely correlated with dietary en% ALA.

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

Ultraviolet radiation induces dose-dependent pigment dispersion in crustacean chromatophores.

Science.gov (United States)

Gouveia, Glauce Ribeiro; Lopes, Thaís Martins; Neves, Carla Amorim; Nery, Luiz Eduardo Maia; Trindade, Gilma Santos

2004-10-01

Pigment dispersion in chromatophores as a response to UV radiation was investigated in two species of crustaceans, the crab Chasmagnathus granulata and the shrimp Palaemonetes argentinus. Eyestalkless crabs and shrimps maintained on either a black or a white background were irradiated with different UV bands. In eyestalkless crabs the significant minimal effective dose inducing pigment dispersion was 0.42 J/cm(2) for UVA and 2.15 J/cm(2) for UVB. Maximal response was achieved with 10.0 J/cm(2) UVA and 8.6 J/cm(2) UVB. UVA was more effective than UVB in inducing pigment dispersion. Soon after UV exposure, melanophores once again reached the initial stage of pigment aggregation after 45 min. Aggregated erythrophores of shrimps adapted to a white background showed significant pigment dispersion with 2.5 J/cm(2) UVA and 0.29 J/cm(2) UVC. Dispersed erythrophores of shrimps adapted to a black background did not show any significant response to UVA, UVB or UVC radiation. UVB did not induce any significant pigment dispersion in shrimps adapted to either a white or a black background. As opposed to the tanning response, which only protects against future UV exposure, the pigment dispersion response could be an important agent protecting against the harmful effects of UV radiation exposure.

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)

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)

Detecting the Subtle Shape Differences in Hemodynamic Responses at the Group Level

Directory of Open Access Journals (Sweden)

Gang eChen

2015-10-01

Full Text Available The nature of the hemodynamic response (HDR is still not fully understood due to the multifaceted processes involved. Aside from the overall amplitude, the response may vary across cognitive states, tasks, brain regions, and subjects with respect to characteristics such as rise and fall speed, peak duration, undershoot shape, and overall duration. Here we demonstrate that the fixed-shape or adjusted-shape methods may fail to detect some shape subtleties. In contrast, the estimated-shape method (ESM through multiple basis functions can provide the opportunity to identify some subtle shape differences and achieve higher statistical power at both individual and group levels. Previously, some dimension reduction approaches focused on the peak magnitude, or made inferences based on the area under the curve or interaction, which can lead to potential misidentifications. By adopting a generic framework of multivariate modeling (MVM, we showcase a hybrid approach that is validated by simulations and real data. Unlike the few analyses that were limited to main effect, two- or three-way interactions, we extend the approach to an inclusive platform that is more adaptable than the conventional GLM, achieving a practical equipoise among representation, false positive control, statistical power, and modeling flexibility.

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

On the shock response of the shape memory alloy, NiTi

International Nuclear Information System (INIS)

Millett, J.C.F.; Bourne, N.K.; Stevens, G.S.; Gray, G.T. III

2002-01-01

There has been recent interest in the behaviour of the shape-memory alloy NiTi since it undergoes a stress-induced phase change at a low stress value. It has been additionally noted that the NiTi does not appear to exhibit a Hugoniot elastic limit (HEL) in the way normally associated with other metals. In order to investigate the possible mechanisms operating to give rise to these effects, a series of plate impact experiments have been conducted in order to probe the material's response to shock. In particular attention has been paid to determination of the material Hugoniot in order to ascertain whether the observed features of the response may be explained. A series of other shots where shaped waves are applied are described in order to probe the lower rate response

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

fMRI Evidence of ‘Mirror’ Responses to Geometric Shapes

Science.gov (United States)

Press, Clare; Catmur, Caroline; Cook, Richard; Widmann, Hannah; Heyes, Cecilia; Bird, Geoffrey

2012-01-01

Mirror neurons may be a genetic adaptation for social interaction [1]. Alternatively, the associative hypothesis [2], [3] proposes that the development of mirror neurons is driven by sensorimotor learning, and that, given suitable experience, mirror neurons will respond to any stimulus. This hypothesis was tested using fMRI adaptation to index populations of cells with mirror properties. After sensorimotor training, where geometric shapes were paired with hand actions, BOLD response was measured while human participants experienced runs of events in which shape observation alternated with action execution or observation. Adaptation from shapes to action execution, and critically, observation, occurred in ventral premotor cortex (PMv) and inferior parietal lobule (IPL). Adaptation from shapes to execution indicates that neuronal populations responding to the shapes had motor properties, while adaptation to observation demonstrates that these populations had mirror properties. These results indicate that sensorimotor training induced populations of cells with mirror properties in PMv and IPL to respond to the observation of arbitrary shapes. They suggest that the mirror system has not been shaped by evolution to respond in a mirror fashion to biological actions; instead, its development is mediated by stimulus-general processes of learning within a system adapted for visuomotor control. PMID:23251653

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

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

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)

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).

Liver perfusion CT during hepatic arteriography for the hepatocellular carcinoma: Dose reduction and quantitative evaluation for normal- and ultralow-dose protocol

Energy Technology Data Exchange (ETDEWEB)

Watanabe, Shingo [Department of Radiology, Dokkyo Medical University Koshigaya Hospital, 2-1-50, Minami-Koshigaya, Koshigaya-shi, Saitama 343-8555 (Japan); Katada, Yoshiaki, E-mail: yoshiaki@dokkyomed.ac.jp [Department of Radiology, Dokkyo Medical University Koshigaya Hospital, 2-1-50, Minami-Koshigaya, Koshigaya-shi, Saitama 343-8555 (Japan); Gohkyu, Masaki; Nakajima, Masahiro; Kawabata, Hideyuki; Nozaki, Miwako [Department of Radiology, Dokkyo Medical University Koshigaya Hospital, 2-1-50, Minami-Koshigaya, Koshigaya-shi, Saitama 343-8555 (Japan)

2012-12-15

Objectives: The purpose of this study was to investigate whether substantial reduction of the computed tomography (CT) dose is possible in liver CT perfusion imaging by comparing the results of ultralow-dose CT perfusion imaging with those of conventional CT perfusion imaging the same patients and under the same conditions. Materials and methods: The study was composed following two parts: computer simulation and patients study. In computer simulation, noise was added to the images so that the standard deviation (SD) of the CT values in the liver parenchyma became various values using ImageJ. Time density curves (TDCs) were created from the simulated data, and the influence of difference in the SDs on the shapes of the TDCs was investigated. In the patient study, CT perfusion during intra-arterial injection was performed in 30 consecutive patients undergoing transcatheter arterial chemoembolization. CT perfusion images were acquired twice, at 100 mA (CTDI{sub vol}, 300 mGy) for normal and at 20 mA (CTDI{sub vol}, 60 mGy) for the ultralow radiation doses, under the same conditions. Results: No change was observed in the shape of the TDCs and peak values in the analysis of simulation images. A very good correlation was observed between the normal- and ultralow-dose CT images for all analyzed values (R{sup 2} = 0.9885 for blood flow, 0.9269 for blood volume, and 0.8424 for mean transit time). Conclusions: Our results demonstrated that there was no significant difference in the analysis results of perfusion CT between ultralow-dose CT performed using 20% of the conventional dose and normal-dose CT perfusion.

Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors.

Science.gov (United States)

Milowsky, Matthew I; Nanus, David M; Kostakoglu, Lale; Sheehan, Christine E; Vallabhajosula, Shankar; Goldsmith, Stanley J; Ross, Jeffrey S; Bander, Neil H

2007-02-10

Based on prostate-specific membrane antigen (PSMA) expression on the vasculature of solid tumors, we performed a phase I trial of antibody J591, targeting the extracellular domain of PSMA, in patients with advanced solid tumor malignancies. This was a proof-of-principle evaluation of PSMA as a potential neovascular target. The primary end points were targeting,toxicity, maximum-tolerated dose, pharmacokinetics (PK), and human antihuman antibody (HAHA) response. Patients had advanced solid tumors previously shown to express PSMA on the neovasculature. They received 111Indium (111ln)-J591 for scintigraphy and PK, followed 2 weeks later by J591 with a reduced amount of 111In for additional PK measurements. J591 dose levels were 5, 10, 20, 40, and 80 mg. The protocol was amended for six weekly administrations of unchelated J591. Patients with a response or stable disease were eligible for re-treatment. Immunohistochemistry assessed PSMA expression in tumor tissues. Twenty-seven patients received monoclonal antibody (mAb) J591. Treatment was well tolerated. Twenty (74%) of 27 patients had at least one area of known metastatic disease targeted by 111In-J591, with positive imaging seen in patients with kidney, bladder, lung, breast, colorectal, and pancreatic cancers, and melanoma. Seven of 10 patient specimens available for immunohistochemical assessment of PSMA expression in tumor-associated vasculature demonstrated PSMA staining. No HAHA response was seen. Three patients of 27 with stable disease received re-treatment. Acceptable toxicity and excellent targeting of known sites of metastases were demonstrated in patients with multiple solid tumor types, highlighting a potential role for the anti-PSMA antibody J591 as a vascular-targeting agent.

Low dose irradiation does not stimulate in vivo primary antibody response in specific-pathogen-free mice

International Nuclear Information System (INIS)

Kamisaku, H.; Sado, T.; Muto, M.; Pongpiachan, P.; Magnemi, U.

1991-01-01

Recent studies from other laboratories indicated that exposure of mice to low dose radiation resulted in the enhancement of primary anti-SRBC PFC response in mice. We have repeated these experiments using four strains of mice that are known to differ in radiosensitivity of immune response potential in vivo. In one study mice were exposed to 2.5-25 cGy of X-rays. Nine hours later they were injected with SRBC and the number of PFCs per spleen was assessed individually at 4.5 days. The results indicated no evidence for the enhancement of PFC response at all exposure levels examined. In another study, groups of C57BL/6J mice were immunized with SRBC and exposed to 0, 150, or 300 cGy of X-rays 2 days later. Numbers of direct as well as indirect PFCs per spleen were then assessed individually at frequent intervals thereafter. The results indicated that exposure of mice to 150 cGy resulted in a significant increase in the number of indirect PFCs assessed at day 11 after SRBC injection, or 9 days after radiation exposure. Dose-response analysis of radiation-induced enhancement of indirect PFC response by this protocol indicated that only after exposure to 150 and 300 cGy for C57BL/6 and C3H/He strain, respectively, a significant enhancement of indirect PFC response was demonstrated. Flow cytometric analysis of spleen cells from these animals indicated that CD4+/CD+ cell ratios increased rapidly during the first three days after radiation exposure, followed by a rapid decline, suggesting that relative proportion of helper/inducer as compared to cytotoxic/suppressor T cell subset changed rapidly in favor of the former shortly after radiation exposure and possibly contributed to the observed enhancement of indirect PFC response. (author)

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...

SU-E-J-274: Responses of Medulloblastoma Cells to Radiation Dosimetric Parameters in Intensity-Modulated Radiation Therapy

International Nuclear Information System (INIS)

Park, J; Park, J; Rogalla, S; Contag, C; Woo, D; Lee, D; Park, H; Suh, T

2015-01-01

Purpose: To evaluate radiation responses of the medulloblastoma cell line Daoy in intensity-modulated radiation therapy (IMRT), quantitative variations to variable radiation dosimetic parameters were tracked by bioluminescent images (BLIs). Methods: The luciferase and green fluorescent protein positive Daoy cells were cultured on dishes. The medulloblastoma cells irradiated to different dose rate, interval of fractionated doses, field margin and misalignment, and dose uniformity in IMRT were monitored using bioluminescent images. The cultured cells were placed into a dedicated acrylic phantom to deliver intensity-modulated fluences and calculate accurate predicted dose distribution. The radiation with dose rate from 0.5 Gy/min to 15 Gy/min was irradiated by adjusting monitor unit per minute and source-to-surface distances. The intervals of fractionated dose delivery were changed considering the repair time of double strand breaks (DSB) revealed by straining of gamma-H2AX.The effect of non-uniform doses on the cells were visualized by registering dose distributions and BLIs. The viability according to dosimetric parameters was correlated with bioluminescent intensities for cross-check of radiation responses. Results: The DSB and cell responses due to the first fractionated dose delivery significantly affected final tumor control rather than other parameters. The missing tumor volumes due to the smaller field margin than the tumor periphery or field misalignment caused relapse of cell responses on BLIs. The dose rate and gradient had effect on initial responses but could not bring out the distinguishable killing effect on cancer cells. Conclusion: Visualized and quantified bioluminescent images were useful to correlate the dose distributions with spatial radiation effects on cells. This would derive the effective combination of dose delivery parameters and fractionation. Radiation responses in particular IMRT configuration could be reflected to image based-dose re-optimization

On the approximation of crack shapes found during inservice inspection

International Nuclear Information System (INIS)

Bhate, S.R.; Chawla, D.S.; Kushwaha, H.S.

1997-01-01

This paper addresses the characterization of axial internal flaw found during inservice inspection of a pipe. J-integral distribution for various flaw shapes is obtained using line spring finite, element method. The peak J-value and its distribution across the crack is found to be characteristic feature of each shape. The triangular shape yields peak J-value away from the center, the point of depth. The elliptic approximation results in large overestimate of J-value for unsymmetric flaws. Triangular approximation is recommended for such flaws so that further service can be obtained from the component

On the approximation of crack shapes found during inservice inspection

Energy Technology Data Exchange (ETDEWEB)

Bhate, S.R.; Chawla, D.S.; Kushwaha, H.S. [Bhabha Atomic Research Centre, Bombay (India)] [and others

1997-04-01

This paper addresses the characterization of axial internal flaw found during inservice inspection of a pipe. J-integral distribution for various flaw shapes is obtained using line spring finite, element method. The peak J-value and its distribution across the crack is found to be characteristic feature of each shape. The triangular shape yields peak J-value away from the center, the point of depth. The elliptic approximation results in large overestimate of J-value for unsymmetric flaws. Triangular approximation is recommended for such flaws so that further service can be obtained from the component.

Arsenic-induced dose-dependent modulation of the NF-κB/IL-6 axis in thymocytes triggers differential immune responses

International Nuclear Information System (INIS)

Choudhury, Sreetama; Gupta, Payal; Ghosh, Sayan; Mukherjee, Sudeshna; Chakraborty, Priyanka; Chatterji, Urmi; Chattopadhyay, Sreya

2016-01-01

Highlights: • We for the first time explicitly show that arsenic exposure causes morphological damage to the thymus and results in heightened death of thymocytes. • Our data suggests that arsenic-induced apoptosis occurs due to increase in cellular oxidative and nitrosative stress. • We have for the first time established a non-classical role of NF-κB, correlating it with increase in FoxP3 expression. • The % of CD4+ CD25+ T cells were high and expression of FoxP3 has also increased at higher doses of arsenic indicating an nTreg bias. - Abstract: Arsenic contamination of drinking water is a matter of global concern. Arsenic intake impairs immune responses and leads to a variety of pathological conditions including cancer. In order to understand the intricate tuning of immune responses elicited by chronic exposure to arsenic, a mouse model was established by subjecting mice to different environmentally relevant concentrations of arsenic in drinking water for 30 days. Detailed study of the thymus, a primary immune organ, revealed arsenic-mediated tissue damage in both histological specimens and scanning electron micrographs. Analysis of molecular markers of apoptosis by Western blot revealed a dose-dependent activation of the apoptotic cascade. Enzymatic assays supported oxidative stress as an instigator of cell death. Interestingly, assessment of inflammatory responses revealed disparity in the NF-κB/IL-6/STAT3 axis, where it was found that in animals consuming higher amounts of arsenic NF-κB activation did not lead to the classical IL-6 upregulation response. This deviation from the canonical pathway was accompanied with a significant rise in numbers of CD4+ CD25+ FoxP3 expressing cells in the thymus. The cytokine profile of the animals exposed to higher doses of arsenic also indicated an immune-suppressed milieu, thus validating that arsenic shapes the immune environment in context to its dose of exposure and that at higher doses it leads to immune

Low-dose CT of the paranasal sinuses. Minimizing X-ray exposure with spectral shaping

Energy Technology Data Exchange (ETDEWEB)

Wuest, Wolfgang [Friedrich-Alexander-University Erlangen-Nuremberg, Radiological Institute, Erlangen (Germany); Radiological Institute, Erlangen (Germany); May, Matthias; Saake, Marc; Brand, Michael; Uder, Michael; Lell, Michael [Friedrich-Alexander-University Erlangen-Nuremberg, Radiological Institute, Erlangen (Germany)

2016-11-15

Shaping the energy spectrum of the X-ray beam has been shown to be beneficial in low-dose CT. This study's aim was to investigate dose and image quality of tin filtration at 100 kV for pre-operative planning in low-dose paranasal CT imaging in a large patient cohort. In a prospective trial, 129 patients were included. 64 patients were randomly assigned to the study protocol (100 kV with additional tin filtration, 150mAs, 192 x 0.6-mm slice collimation) and 65 patients to the standard low-dose protocol (100 kV, 50mAs, 128 x 0.6-mm slice collimation). To assess the image quality, subjective parameters were evaluated using a five-point scale. This scale was applied on overall image quality and contour delineation of critical anatomical structures. All scans were of diagnostic image quality. Bony structures were of good diagnostic image quality in both groups, soft tissues were of sufficient diagnostic image quality in the study group because of a high level of noise. Radiation exposure was very low in both groups, but significantly lower in the study group (CTDI{sub vol} 1.2 mGy vs. 4.4 mGy, p < 0.001). Spectral optimization (tin filtration at 100 kV) allows for visualization of the paranasal sinus with sufficient image quality at a very low radiation exposure. (orig.)

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

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...

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.

Thermo-Mechanical Methodology for Stabilizing Shape Memory Alloy Response

Science.gov (United States)

Padula, Santo

2013-01-01

This innovation is capable of significantly reducing the amount of time required to stabilize the strain-temperature response of a shape memory alloy (SMA). Unlike traditional stabilization processes that take days to weeks to achieve stabilized response, this innovation accomplishes stabilization in a matter of minutes, thus making it highly useful for the successful and practical implementation of SMA-based technologies in real-world applications. The innovation can also be applied to complex geometry components, not just simple geometries like wires or rods.

Morphological differences in the response of mouse small intestine to radiobiologically equivalent doses of X and neutron irradiation

International Nuclear Information System (INIS)

Carr, K.E.; Hamlet, R.; Nias, A.H.; Watt, C.

1984-01-01

A scale has been developed to describe the effects of radiation on small intestinal villi. The scale has been used to compare the damage done to the villi in the period 0-5 days after irradiation by X-irradiation or neutron irradiation, using 10 Gy X-rays and 5 Gy neutrons, doses which are radiobiologically equivalent when assessed by the microcolony assay method. Use of the scale indicates that the damage done to the villi by neutrons is greater than that produced by X-rays. This has implications for the interpretation of radiobiological equivalent doses (R.B.E.). Resin light microscopy and transmission electron microscopy (T.E.M.) have also been used to examine small intestinal damage after 10 Gy X-irradiation and 5 Gy neutron irradiation. Differences include variations in crypt shape, mitotic activity and the proportion of crypts which are heavily parasitised. As well as the differences in villous shape which have been reflected in the different values on the scoring system, there are also variations in the response of the constituent cells of the epithelial compartment of the villi. In general, the effect of the neutron irradiation is more severe than that of the X-rays, particularly as would be suggested by a simple quantitation of crypt regeneration

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.

Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis.

Science.gov (United States)

Crippa, Alessio; Discacciati, Andrea; Larsson, Susanna C; Wolk, Alicja; Orsini, Nicola

2014-10-15

Several studies have analyzed the relationship between coffee consumption and mortality, but the shape of the association remains unclear. We conducted a dose-response meta-analysis of prospective studies to examine the dose-response associations between coffee consumption and mortality from all causes, cardiovascular disease (CVD), and all cancers. Pertinent studies, published between 1966 and 2013, were identified by searching PubMed and by reviewing the reference lists of the selected articles. Prospective studies in which investigators reported relative risks of mortality from all causes, CVD, and all cancers for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Twenty-one prospective studies, with 121,915 deaths and 997,464 participants, met the inclusion criteria. There was strong evidence of nonlinear associations between coffee consumption and mortality for all causes and CVD (P for nonlinearity Coffee consumption was not associated with cancer mortality. Findings from this meta-analysis indicate that coffee consumption is inversely associated with all-cause and CVD mortality. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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)

Response functions for computing absorbed dose to skeletal tissues from photon irradiation-an update

Energy Technology Data Exchange (ETDEWEB)

Johnson, Perry B; Bahadori, Amir A [Nuclear and Radiological Engineering, University of Florida, Gainesville, FL 32611 (United States); Eckerman, Keith F [Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831 (United States); Lee, Choonsik [Radiation Epidemiology Branch, National Cancer Institute, Bethesda, MD 20892 (United States); Bolch, Wesley E, E-mail: wbolch@ufl.edu [Nuclear and Radiological/Biomedical Engineering, University of Florida, Gainesville, FL 32611 (United States)

2011-04-21

A comprehensive set of photon fluence-to-dose response functions (DRFs) is presented for two radiosensitive skeletal tissues-active and total shallow marrow-within 15 and 32 bone sites, respectively, of the ICRP reference adult male. The functions were developed using fractional skeletal masses and associated electron-absorbed fractions as reported for the UF hybrid adult male phantom, which in turn is based upon micro-CT images of trabecular spongiosa taken from a 40 year male cadaver. The new DRFs expand upon both the original set of seven functions produced in 1985, and a 2007 update calculated under the assumption of secondary electron escape from spongiosa. In this study, it is assumed that photon irradiation of the skeleton will yield charged particle equilibrium across all spongiosa regions at energies exceeding 200 keV. Kerma coefficients for active marrow, inactive marrow, trabecular bone and spongiosa at higher energies are calculated using the DRF algorithm setting the electron-absorbed fraction for self-irradiation to unity. By comparing kerma coefficients and DRF functions, dose enhancement factors and mass energy-absorption coefficient (MEAC) ratios for active marrow to spongiosa were derived. These MEAC ratios compared well with those provided by the NIST Physical Reference Data Library (mean difference of 0.8%), and the dose enhancement factors for active marrow compared favorably with values calculated in the well-known study published by King and Spiers (1985 Br. J. Radiol. 58 345-56) (mean absolute difference of 1.9 percentage points). Additionally, dose enhancement factors for active marrow were shown to correlate well with the shallow marrow volume fraction (R{sup 2} = 0.91). Dose enhancement factors for the total shallow marrow were also calculated for 32 bone sites representing the first such derivation for this target tissue.

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...

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)

Mechanisms and biological importance of photon-induced bystander responses. Do they have an impact on low-dose radiation responses

International Nuclear Information System (INIS)

Tomita, Masanori; Maeda, Munetoshi

2015-01-01

Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced by-stander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. (author)

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

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

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.

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

HDL and CER-001 Inverse-Dose Dependent Inhibition of Atherosclerotic Plaque Formation in apoE-/- Mice: Evidence of ABCA1 Down-Regulation.

Science.gov (United States)

Tardy, Claudine; Goffinet, Marine; Boubekeur, Nadia; Cholez, Guy; Ackermann, Rose; Sy, Gavin; Keyserling, Constance; Lalwani, Narendra; Paolini, John F; Dasseux, Jean-Louis; Barbaras, Ronald; Baron, Rudi

2015-01-01

CER-001 is a novel engineered HDL-mimetic comprised of recombinant human apoA-I and charged phospholipids that was designed to mimic the beneficial properties of nascent pre-ß HDL. In this study, we have evaluated the dose-dependent regulation of ABCA1 expression in vitro and in vivo in the presence of CER-001 and native HDL (HDL3). CER-001 induced cholesterol efflux from J774 macrophages in a dose-dependent manner similar to natural HDL. A strong down-regulation of the ATP-binding cassette A1 (ABCA1) transporter mRNA (- 50%) as well as the ABCA1 membrane protein expression (- 50%) was observed at higher doses of CER-001 and HDL3 compared to non-lipidated apoA-I. In vivo, in an apoE-/- mouse "flow cessation model," in which the left carotid artery was ligatured to induce local inflammation, the inhibition of atherosclerotic plaque burden progression in response to a dose-range of every-other-day CER-001 or HDL in the presence of a high-fat diet for two weeks was assessed. We observed a U-shaped dose-response curve: inhibition of the plaque total cholesterol content increased with increasing doses of CER-001 or HDL3 up to a maximum inhibition (- 51%) at 5 mg/kg; however, as the dose was increased above this threshold, a progressively less pronounced inhibition of progression was observed, reaching a complete absence of inhibition of progression at doses of 20 mg/kg and over. ABCA1 protein expression in the same atherosclerotic plaque was decreased by-45% and-68% at 50 mg/kg for CER-001 and HDL respectively. Conversely, a-12% and 0% decrease in ABCA1 protein expression was observed at the 5 mg/kg dose for CER-001 and HDL respectively. These data demonstrate that high doses of HDL and CER-001 are less effective at slowing progression of atherosclerotic plaque in apoE-/- mice compared to lower doses, following a U-shaped dose-response curve. A potential mechanism for this phenomenon is supported by the observation that high doses of HDL and CER-001 induce a rapid and

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)

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

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

Radiation-induced changes in breathing frequency and lung histology of C57BL/6J mice are time- and dose-dependent

Energy Technology Data Exchange (ETDEWEB)

Eldh, T.; Heinzelmann, F.; Velalakan, A. [Univ. Hospital of Tuebingen (Germany). Dept. of Radiation Oncology; Budach, W. [Duesseldorf Univ. (Germany). Dept. of Radiation Oncology; Belka, C. [Univ. Hospital of Tuebingen (Germany). Dept. of Radiation Oncology; Muenchen Univ. (Germany). Dept. of Radiation Oncology; Jendrossek, V. [Univ. Hospital of Tuebingen (Germany). Dept. of Radiation Oncology; Duisburg-Essen Univ., Essen (DE). Inst. of Cell Biology (Cancer Research)

2012-03-15

Pneumonitis and fibrosis constitute serious adverse effects of radiotherapy in the thoracic region. In this study, time-course and dose-dependence of clinically relevant parameters of radiation-induced lung injury in C57BL/6J mice were analyzed. A well-characterized disease model is necessary for the analysis of the cellular and molecular mechanisms using genetically modified mice. C57BL/6J mice received single dose right hemithorax irradiation with 12.5 or 22.5 Gy. Body weight and breathing frequency were recorded as parameters for health impairment. Lung tissue was collected over 24 weeks for histological analysis. Hemithorax irradiation with 12.5 or 22.5 Gy induced biphasic breathing impairment with the first increase between days 7 and 70. Although breathing impairment was more pronounced in the 22.5 Gy group, it was accompanied in both dose groups by pneumonitis-associated histological changes. A second rise in breathing frequency ratios became visible starting on day 70 with a steady increase until day 210. Again, breathing was more strongly affected in the 22.5 Gy group. However, breathing impairment coincided only in the 22.5 Gy group with a significant increase in collagen deposition in the lung tissue by day 210. Tissue inflammation and fibrosis were observed in the irradiated and the shielded lungs, pointing toward involvement of systemic effects. Hemithorax irradiation induces time-dependent pneumonitis and fibrosis in C57BL/6J mice. While hemithorax irradiation with 12.5 Gy is sufficient to induce lung inflammation, it is below the threshold for collagen deposition and fibrosis development by day 210.

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

How age, sex and genotype shape the stress response.

Science.gov (United States)

Novais, Ashley; Monteiro, Susana; Roque, Susana; Correia-Neves, Margarida; Sousa, Nuno

2017-02-01

Exposure to chronic stress is a leading pre-disposing factor for several neuropsychiatric disorders as it often leads to maladaptive responses. The response to stressful events is heterogeneous, underpinning a wide spectrum of distinct changes amongst stress-exposed individuals'. Several factors can underlie a different perception to stressors and the setting of distinct coping strategies that will lead to individual differences on the susceptibility/resistance to stress. Beyond the factors related to the stressor itself, such as intensity, duration or predictability, there are factors intrinsic to the individuals that are relevant to shape the stress response, such as age, sex and genetics. In this review, we examine the contribution of such intrinsic factors to the modulation of the stress response based on experimental rodent models of response to stress and discuss to what extent that knowledge can be potentially translated to humans.

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

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)

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

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

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

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.

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

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.

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)

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.

Late biological effects of ionizing radiation as influenced by dose, dose rate, age at exposure and genetic sensitivity to neoplastic transformation

International Nuclear Information System (INIS)

Spalding, J.F.; Prine, J.R.; Tietjen, G.L.

1978-01-01

A most comprehensive investigation is in progress at the Los Alamos Scientific Laboratory to study the late biological effects of whole-body exposure to gamma irradiation as they may be influenced by total dose, dose rate, age at exposure and genetic background. Strain C57B1/6J mice of four age groups (newborn, 2, 6 and l5 months) were given five doses (20, 60, 180, 540, and 1620 rads) of gamma rays, with each dose being delivered at six dose rates (0.7, 2.1, 6.3, 18.9, 56.7 rads/day and 25 rads/min). Forty to sixty mice were used in each of the approximately 119 dose/dose-rate and age combinations. The study was done in two replications with an equal number of mice per replicaton. Strain RF/J mice were used in a companion study to investigate the influence of genetic background on the type and magnitude of effect. Results of the first and second replications of the l5-month-old age group and data on the influence of genetic background on biological response have been completed, and the results show no significant life shortening within the dose and dose-rate range used. It was also concluded that radiaton-induced neoplastic transformaton was significantly greater in mice with a known genetic sensitivity to neoplastic disease than in mammals which do not normally have a significant incidence of tumours. (author)

Association of Escherichia coli J5-specific serum antibody responses with clinical mastitis outcome for J5 vaccinate and control dairy cattle.

Science.gov (United States)

Wilson, David J; Mallard, Bonnie A; Burton, Jeanne L; Schukken, Ynte H; Grohn, Yrjo T

2009-02-01

Dairy cattle in two commercial Holstein herds were randomly selected to be vaccinated twice with J5, at approximately 60 days and 28 days before the expected calving date, or to be untreated controls. Based on whether milk production changed following clinical mastitis or whether cows were culled or died within 30 days after onset, 51 mastitis cases were classified as severe or mild. J5-specific antibody responses were evaluated by enzyme-linked immunosorbent assay of all 32 severe and 19 mild cases. The amounts of J5-specific immunoglobulin M (IgM), IgG1, and IgG2 antibodies in sera from the 27 J5 vaccinates were compared with those of the 24 controls. At drying off (before J5 vaccination), all cows had similar amounts of J5-specific antibody. Immediately after calving (approximately 28 days after the second vaccination), J5 vaccinates had significantly higher production of J5-specific IgG1 and IgG2 than controls. When cows were tested following clinical mastitis, none of the three antibody classes differed significantly between the controls and the vaccinates. Vaccinates that contracted Escherichia coli mastitis had 75% less milk loss than controls. The cows that contracted clinical mastitis later in lactation, the unvaccinated controls, and those infected with E. coli had more milk loss following mastitis. The hazards of being culled for all reasons and of being culled for mastitis were significantly lower for J5 vaccinates. Vaccination with J5 was associated with protection against milk production loss and culling following clinical mastitis, and it was also significantly associated with changes in J5-specific IgM, IgG1, and IgG2 antibodies in sera of vaccinated cows.

Polydopamine Particle-Filled Shape-Memory Polyurethane Composites with Fast Near-Infrared Light Responsibility.

Science.gov (United States)

Yang, Li; Tong, Rui; Wang, Zhanhua; Xia, Hesheng

2018-03-25

A new kind of fast near-infrared (NIR) light-responsive shape-memory polymer composites was prepared by introducing polydopamine particles (PDAPs) into commercial shape-memory polyurethane (SMPU). The toughness and strength of the polydopamine-particle-filled polyurethane composites (SMPU-PDAPs) were significantly enhanced with the addition of PDAPs due to the strong interface interaction between PDAPs and polyurethane segments. Owing to the outstanding photothermal effect of PDAPs, the composites exhibit a rapid light-responsive shape-memory process in 60 s with a PDAPs content of 0.01 wt%. Due to the excellent dispersion and convenient preparation method, PDAPs have great potential to be used as high-efficiency and environmentally friendly fillers to obtain novel photoactive functional polymer composites. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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).

Dose-response evaluation after Yttrium-90 resin microsphere radio-embolization of breast cancer liver metastases

International Nuclear Information System (INIS)

Gnesin, S.; Verdun, F.R.; Baechler, S.; Boubacker, A.; Adib, S.; Cherbuin, N.; Prior, J.O.; Bize, P.; Denys, A.

2015-01-01

Full text of publication follows. Aim: Yttrium-90 resin microsphere radio-embolization is a valuable therapeutic option in metastatic breast cancer patients with progressive disease refractory to chemotherapy. The goal of this study was to evaluate the dose-response relationship of liver metastasis based on a 3D voxelized 90 Y PET dosimetry. Materials and methods: we studied the dose-response relationship of twelve hepatic lesions in four selected patients with metastatic breast cancer who underwent 90 Y radio-embolization (Sirtex SIR-Spheres Pty Ltd.). The administered activity ranged from 1 to 1.3 GBq. Ten days before treatment, patients underwent a baseline 18 F-FDG PET/CT. The determination of the 90 Y-microsphere activity to administer for treatment was based on the BSA method refined with the partition model derived from a 99m Tc-MAA SPECT/CT performed a week prior to radio-embolization. Within 24 hours after treatment, 90 Y TOF PET/CT imaging was performed. A follow-up 18 F-FDG PET/CT was performed 1 month after the treatment to evaluate the response to radio-embolization. For each patient, 3D voxelized dose-maps were obtained from the post-treatment 90 Y TOF PET/CT. A volume of interest (VOI) was drawn for each selected hepatic lesion using the baseline 18 F-FDG PET/CT. To obtain dose-volume histogram (DVH) for each lesion, image co-registration and VOI masks were generated using the PMOD 3.4 software and then exported in Matlab for dose calculation. Furthermore, the average absorbed dose in lesions was corrected for PVE effects by multiplication for appropriate (phantom-based) recovery coefficients according to the lesion size. Early metabolic lesion response was assessed in terms of variation in the maximum standard uptake value (ΔSUVmax) between baseline and follow-up 18 F-FDG PET/CT. The average absorbed dose for each lesion was associated with the respective metabolic response. Results: for the 12 selected lesions, the average volume was 35 cm 3

variations in dimensions and shape of thoracic cage with aging

African Journals Online (AJOL)

the rib cage dimensions, the shape and cross- ..... Figure 6: CT axial section of thorax, showing the internal thoracic dimensions and shape at different age .... Dean J, Koehler R, Schleien C, Michael J, Chantarojanasiri T, Rogers M, Traystman ...

Fast Response Shape Memory Effect Titanium Nickel (TiNi) Foam Torque Tubes

Science.gov (United States)

Jardine, Peter

2014-01-01

Shape Change Technologies has developed a process to manufacture net-shaped TiNi foam torque tubes that demonstrate the shape memory effect. The torque tubes dramatically reduce response time by a factor of 10. This Phase II project matured the actuator technology by rigorously characterizing the process to optimize the quality of the TiNi and developing a set of metrics to provide ISO 9002 quality assurance. A laboratory virtual instrument engineering workbench (LabVIEW'TM')-based, real-time control of the torsional actuators was developed. These actuators were developed with The Boeing Company for aerospace applications.

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

Photobiomodulation delays the onset of skeletal muscle fatigue in a dose-dependent manner.

Science.gov (United States)

Larkin-Kaiser, Kelly A; Borsa, Paul A; Baweja, Harsimran S; Moore, Molly A; Tillman, Mark D; George, Steven Z; Christou, Evangelos A

2016-09-01

Photobiomodulation (PBM) therapy has been implicated as an effective ergogenic aid to delay the onset of muscle fatigue. The purpose of this study was to examine the dose-response ergogenic properties of PBM therapy and its ability to prolong time to task failure by enhancing muscle activity and delaying the onset of muscle fatigue using a static positioning task. Nine participants (24.3 ± 4.9 years) received three doses of near-infrared (NIR) light therapy randomly on three separate sessions (sham, 240, and 480 J). For the positioning task, participants held a 30 % one-repetition maximum (1-RM) load using the index finger until volitional fatigue. Surface electromyography (sEMG) of the first dorsal interosseous muscle was recorded for the length of the positioning task. Outcomes included time to task failure (TTF), muscle fatigue, movement accuracy, motor output variability, and muscle activity (sEMG). The 240-J dose significantly extended TTF by 26 % (p = 0.032) compared with the sham dose. TTF for the 240-J dose was strongly associated with a decrease in muscle fatigue (R (2) = 0.54, p = 0.024). Our findings show that a 240-J dose of NIR light therapy is efficacious in delaying the onset and extent of muscle fatigue during submaximal isometric positioning tasks. Our findings suggest that NIR light therapy may be used as an ergogenic aid during functional tasks or post-injury rehabilitation.

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

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

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

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.

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.

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

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

Effect of extended exposure of low-dose radiation on autoimmune diseases of immunologically depressed MRL/MpJ-gld/gld mice

International Nuclear Information System (INIS)

Ootsuyama, A.; Okazaki, R.; Norimura, T.

2000-01-01

We analyzed alterations of splenic T cell subpopulations and amelioration of autoimmune disease of MRL/MpJ-gld/gld mice (MRL/gld mice) after the extended exposure to low-dose radiation (LDR). Four-month old MRL/gld mice were exposed to 0.05, 0.2 and 0.5 Gy/day for 4 weeks (5 days/week) with a total dose of 1, 4 and 10 Gy, respectively. The mice irradiated with 0.2 and 0.5 Gy/day showed an obvious decrease in the proportions of splenic CD4 - CD8 - T cells and remission of their autoimmune disease. In the mice irradiated with 0.2 Gy/day, apoptotic cells were found in the white pulp of the spleen after the last irradiation, but not in that of the treated MRL/MpJ-+/+ mice (MRL/wild type mice). It seems that the accumulated CD4 - CD8 - T cells are more sensitive to radiation than other T cell subpopulations and prone to apoptosis, and efficient elimination of abnormal CD4 - CD8 - T cells by radiation-induced apoptosis may lead to the amelioration of autoimmune disease. (author)

On the common mechanism for initiation of different effects of low doses of ionizing radiations

International Nuclear Information System (INIS)

Ehjdus, L.Kh.

1996-01-01

Main regularities of different endpoints of ionizing radiation low dose effects (adaptive response, stimulation of proliferation, special radiosensitivity of lymphoid cells, and others) have been examined. It has been shown that these endpoints have a commonness for the dose interval, the shape of the dose-response curve, the reverse effect of dose rate, non-specificity toward initiating agents, and others. An explanation is suggested for the common mechanism of the initiation of all the studied low dose effects, basing on the theory of the non-specific reaction of cell to external influences. It is concluded that initiation of the low dose effects is conditioned by radiation induced damage of functions of plasmic and internal membranes

Multi-stimulus-responsive shape-memory polymer nanocomposite network cross-linked by cellulose nanocrystals.

Science.gov (United States)

Liu, Ye; Li, Ying; Yang, Guang; Zheng, Xiaotong; Zhou, Shaobing

2015-02-25

In this study, we developed a thermoresponsive and water-responsive shape-memory polymer nanocomposite network by chemically cross-linking cellulose nanocrystals (CNCs) with polycaprolactone (PCL) and polyethylene glycol (PEG). The nanocomposite network was fully characterized, including the microstructure, cross-link density, water contact angle, water uptake, crystallinity, thermal properties, and static and dynamic mechanical properties. We found that the PEG[60]-PCL[40]-CNC[10] nanocomposite exhibited excellent thermo-induced and water-induced shape-memory effects in water at 37 °C (close to body temperature), and the introduction of CNC clearly improved the mechanical properties of the mixture of both PEG and PCL polymers with low molecular weights. In addition, Alamar blue assays based on osteoblasts indicated that the nanocomposites possessed good cytocompatibility. Therefore, this thermoresponsive and water-responsive shape-memory nanocomposite could be potentially developed into a new smart biomaterial.

Dose response on the 110 °C thermoluminescence peak of un-heated, synthetic Merck quartz

Energy Technology Data Exchange (ETDEWEB)

Kaya Keleş, Şule, E-mail: sule.kaya@ankara.edu.tr; Meriç, Niyazi; Polymeris, George S.

2016-07-15

Studies on 110 °C TL peak have been carried out using natural quartz from different origins and synthetic quartz produced by different suppliers. The interest in quartz is due to its usage in dating and retrospective dosimetry as a main material; both synthetic and natural types of quartz yield the 110 °C TL peak in their glow curve. In most studies to understand the physical mechanism behind the TL system, synthetic quartz samples are used and there are many investigations about dose response, in both low and high radiation dose region. In these studies generally synthetic quartz samples produced by Sawyer Research Products are used and the studies showed that both heated and un-heated synthetic quartz samples have intense supra-linear responses. Supra-linearity was enhanced by applying a pre-irradiation while several models have been developed towards an explanation to these supra-linearity effects. In this study commercially available synthetic Merck quartz was used. Different combinations of optical filters were used to obtain dose response curves upto 266 Gy and the effect of pre-dose to these dose response curves was studied. Un-pre-dosed Merck quartz samples dose supra-linearity index is below 1 independently on the optical filters; so Merck quartz showed linear or sub-linear dose response.

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)

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

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.)

Dose-responses for mortality from cerebrovascular and heart diseases in atomic bomb survivors: 1950-2003

Energy Technology Data Exchange (ETDEWEB)

Schoellnberger, Helmut [Helmholtz Zentrum Muenchen, Department of Radiation Sciences, Institute of Radiation Protection, Neuherberg (Germany); Federal Office for Radiation Protection, Department of Radiation Protection and the Environment, Neuherberg (Germany); Eidemueller, Markus; Simonetto, Cristoforo; Kaiser, Jan Christian [Helmholtz Zentrum Muenchen, Department of Radiation Sciences, Institute of Radiation Protection, Neuherberg (Germany); Cullings, Harry M. [Radiation Effects Research Foundation, Department of Statistics, Hiroshima (Japan); Neff, Frauke [Staedtisches Klinikum Muenchen and Technical University of Munich, Institute of Pathology, Munich (Germany)

2018-03-15

The scientific community faces important discussions on the validity of the linear no-threshold (LNT) model for radiation-associated cardiovascular diseases at low and moderate doses. In the present study, mortalities from cerebrovascular diseases (CeVD) and heart diseases from the latest data on atomic bomb survivors were analyzed. The analysis was performed with several radio-biologically motivated linear and nonlinear dose-response models. For each detrimental health outcome one set of models was identified that all fitted the data about equally well. This set was used for multi-model inference (MMI), a statistical method of superposing different models to allow risk estimates to be based on several plausible dose-response models rather than just relying on a single model of choice. MMI provides a more accurate determination of the dose response and a more comprehensive characterization of uncertainties. It was found that for CeVD, the dose-response curve from MMI is located below the linear no-threshold model at low and medium doses (0-1.4 Gy). At higher doses MMI predicts a higher risk compared to the LNT model. A sublinear dose-response was also found for heart diseases (0-3 Gy). The analyses provide no conclusive answer to the question whether there is a radiation risk below 0.75 Gy for CeVD and 2.6 Gy for heart diseases. MMI suggests that the dose-response curves for CeVD and heart diseases in the Lifespan Study are sublinear at low and moderate doses. This has relevance for radiotherapy treatment planning and for international radiation protection practices in general. (orig.)

Low dose effects detected by micronucleus assay in lymphocytes

International Nuclear Information System (INIS)

Koeteles, G.J.; Bojtor, I.; Kubasova, T.; Horvath, G.

1997-01-01

The effects of low doses of X-rays between 0.01 and 1 Gy were studied on whole blood samples of various individuals using the cytokinesis-blocked lymphocyte micronucleus assay as an endpoint. The adaptive response could be induced in G 0 cells by 0.01 Gy followed by 1 Gy challenging dose within a time period of 8 hours, in vitro. The probability distribution of micronucleus increments in those samples which had received very low doses in the range 0.01-0.05 Gy proved to be of asymmetrical type (i.e. lognormal) -very likely to the same shape which has been verified for unirradiated (control) population - while the variable turned to be normally distributed at or above 1 Gy. Profound changes have been experienced in the main characteristics of the linear dose - response relationship and in regression parameters, as well, when successively lessened dose ranges were studied toward 0.01 Gy. In the range below ∼ 0.2 Gy the response were found to be unrelated to the absorbed dose. These findings suggest that in (very) low dose range a higher attention should be needed to biological parameters like repair, protective mechanisms and antioxidant capacities, rather than to the absorbed radiation energy only. (author)

'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

Low Dose Suppression of Neoplastic Transformation in Vitro

Energy Technology Data Exchange (ETDEWEB)

John Leslie Redpath

2012-05-01

This grant was to study the low dose suppression of neoplastic transformation in vitro and the shape of the dose-response curve at low doses and dose-rates of ionizing radiation. Previous findings had indicated a suppression of transformation at dose <10cGy of low-LET radiation when delivered at high dose-rate. The present study indicates that such suppression extends out to doses in excess of 100cGy when the dose (from I-125 photons) is delivered at dose-rates as low as 0.2 mGy/min and out to in excess of {approx}25cGy the highest dose studied at the very low dose-rate of 0.5 mGy/day. We also examined dose-rate effects for high energy protons (which are a low-LET radiation) and suppression was evident below {approx}10cGy for high dose-rate delivery and at least out to 50cGy for low dose-rate (20cGy/h) delivery. Finally, we also examined the effect of low doses of 1 GeV/n iron ions (a high-LET radiation) delivered at high dose-rate on transformation at low doses and found a suppression below {approx}10cGy that could be attributable to an adaptive response in bystander cells induced by the associated low-LET delta rays. These results have implications for cancer risk assessment at low doses.

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

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.

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.

A thermoluminescence study of mineral silicates extracted from herbs in the dose range 0.5–5 Gy

International Nuclear Information System (INIS)

Della Monaca, Sara; Fattibene, Paola; Bortolin, Emanuela

2013-01-01

The presence of silicates in many personal objects suggests their potential use at low dose as fortuitous dosimeter in an accidental radiological exposure, when conventional dosimetry is not available. The goal of the present work is the dosimetric characterization of mineral silicates extracted from the plant Hibiscus Sabdariffa L, known as Jamaica flower, in the dose range 0.5–5 Gy. By studying the radiation-induced signal in time, the temperature integration region between 210 °C and 250 °C was found to be the most stable and also reduced the effects of thermal fading in the dose reconstruction process; the dose response curve was linear between 0.5 Gy and 5 Gy. By checking the change in sensitivity after repeated exposures to ionizing radiations and to high temperature heating, no variation in the glow curve shape or peak intensities were detected. To eliminate a pre-existing background signal, all the characterization measurements were performed with aliquots “annealed” by a preliminary readout of the TL. - Highlights: • Glow curves change in shape and intensity just in the first 3 days after irradiation. • The dose response is linear in the dose range 0.5–5 Gy. • The curve shape or intensity don't change after repeated exposures and heatings. • Encouraging results were obtained in the dose recovery test

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)

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...

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

Earthquake Response of Reinforced Concrete Building Retrofitted with Geopolymer Concrete and X-shaped Metallic Damper

Science.gov (United States)

Madheswaran, C. K.; Prakash vel, J.; Sathishkumar, K.; Rao, G. V. Rama

2017-06-01

A three-storey half scale reinforced concrete (RC) building is fixed with X-shaped metallic damper at the ground floor level, is designed and fabricated to study its seismic response characteristics. Experimental studies are carried out using the (4 m × 4 m) tri-axial shake-table facility to evaluate the seismic response of a retrofitted RC building with open ground storey (OGS) structure using yielding type X-shaped metallic dampers (also called as Added Damping and Stiffness-ADAS elements) and repairing the damaged ground storey columns using geopolymer concrete composites. This elasto-plastic device is normally incorporated within the frame structure between adjacent floors through chevron bracing, so that they efficiently enhance the overall energy dissipation ability of the seismically deficient frame structure under earthquake loading. Free vibration tests on RC building without and with yielding type X-shaped metallic damper is carried out. The natural frequencies and mode shapes of RC building without and with yielding type X-shaped metallic damper are determined. The retrofitted reinforced concrete building is subjected to earthquake excitations and the response from the structure is recorded. This work discusses the preparation of test specimen, experimental set-up, instrumentation, method of testing of RC building and the response of the structure. The metallic damper reduces the time period of the structure and displacement demands on the OGS columns of the structure. Nonlinear time history analysis is performed using structural analysis package, SAP2000.

A simulation study of a C-shaped in-beam PET system for dose verification in carbon ion therapy

International Nuclear Information System (INIS)

Jung An, Su; Beak, Cheol-Ha; Lee, Kisung; Hyun Chung, Yong

2013-01-01

The application of hadrons such as carbon ions is being developed for the treatment of cancer. The effectiveness of such a technique is due to the eligibility of charged particles in delivering most of their energy near the end of the range, called the Bragg peak. However, accurate verification of dose delivery is required since misalignment of the hadron beam can cause serious damage to normal tissue. PET scanners can be utilized to track the carbon beam to the tumor by imaging the trail of the hadron-induced positron emitters in the irradiated volume. In this study, we designed and evaluated (through Monte Carlo simulations) an in-beam PET scanner for monitoring patient dose in carbon beam therapy. A C-shaped PET and a partial-ring PET were designed to avoid interference between the PET detectors and the therapeutic carbon beam delivery. Their performance was compared with that of a full-ring PET scanner. The C-shaped, partial-ring, and full-ring scanners consisted of 14, 12, and 16 detector modules, respectively, with a 30.2 cm inner diameter for brain imaging. Each detector module was composed of a 13×13 array of 4.0 mm×4.0 mm×20.0 mm LYSO crystals and four round 25.4 mm diameter PMTs. To estimate the production yield of positron emitters such as 10 C, 11 C, and 15 O, a cylindrical PMMA phantom (diameter, 20 cm; thickness, 20 cm) was irradiated with 170, 290, and 350 AMeV 12 C beams using the GATE code. Phantom images of the three types of scanner were evaluated by comparing the longitudinal profile of the positron emitters, measured along the carbon beam as it passed a simulated positron emitter distribution. The results demonstrated that the development of a C-shaped PET scanner to characterize carbon dose distribution for therapy planning is feasible.

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

International Nuclear Information System (INIS)

Upton, Arthur C.

2002-01-01

In recent decades, it has been customary, for radiation protection purposes, to assume that the overall risk of radiation- included 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 question, 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 advancing 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 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 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 ore plausible than the linear-nonthreshold model, although other dose-response relationships cannot be excluded. (author)

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.

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.

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)

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

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

Low-dose effect on blood chromosomes

International Nuclear Information System (INIS)

Pohl-Rueling, J.

1992-01-01

Linear dose response relationships of biological effects at low doses are experimentally and theoretically disputed. Structural chromosome aberration rates at doses ranging from normal background exposures up to about 30 mGy/yr in vivo and up to 50 mGy in vitro were investigated by the author and other scientists. Results are comparable and dose effect curves reveal following shapes; within the normal burden and up to 2-10 mGy/yr in vivo rates they increase sharply to about 3-6 times the lowest values; subsequent doses either from natural, occupational or accidental exposures up to about 30 mGy/yr yield either constant aberration rates, assuming a plateau, or perhaps even a decrease. In vitro experiments show comparable results up to 50 mGy. Other biological effects seem to have similar dose dependencies. The non-linearity of low-dose effects can be explained by induction of repair enzymes at certain damage to the DNA. This hypothesis is sustained experimentally and theoretically by several papers in literature. (author). 14 refs., 5 figs

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

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

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

Polylactide-based polyurethane shape memory nanocomposites (Fe3O4/PLAUs) with fast magnetic responsiveness

International Nuclear Information System (INIS)

Gu, Shu-Ying; Jin, Sheng-Peng; Gao, Xie-Feng; Mu, Jian

2016-01-01

Polylactide-based polyurethane shape memory nanocomposites (Fe 3 O 4 /PLAUs) with fast magnetic responsiveness are presented. For the purpose of fast response and homogeneous dispersion of magnetic nanoparticles, oleic acid was used to improve the dispersibility of Fe 3 O 4 nanoparticles in a polymer matrix. A homogeneous distribution of Fe 3 O 4 nanoparticles in the polymer matrix was obtained for nanocomposites with low Fe 3 O 4 loading content. A small agglomeration was observed for nanocomposites with 6 wt% and 9 wt% loading content, leading to a small decline in the mechanical properties. PLAU and its nanocomposites have glass transition around 52 °C, which can be used as the triggering temperature. PLAU and its nanocomposites have shape fixity ratios above 99%, shape recovery ratios above 82% for the first cycle and shape recovery ratios above 91% for the second cycle. PLAU and its nanocomposites also exhibit a fast water bath or magnetic responsiveness. The magnetic recovery time decreases with an increase in the loading content of Fe 3 O 4 nanoparticles due to an improvement in heating performance for increased weight percentage of fillers. The nanocomposites have fast responses in an alternating magnetic field and have potential application in biomedical areas such as intravascular stent. (paper)

X-ray dose response of calcite—A comprehensive analysis for optimal application in TL dosimetry

International Nuclear Information System (INIS)

Kalita, J.M.; Wary, G.

2016-01-01

Highlights: • Effect of annealing temperature on TL signal of calcite has been studied. • Specific annealing treatment for optimal dose response has been evaluated. • The dose response of natural calcite has been analyzed quantitatively. - Abstract: The effect of various annealing treatments on dosimetric characteristics of orange calcite (CaCO_3) mineral has been studied in detail. Quantitative analysis on the dose response shows that the 573 K annealed sample showed sublinear dose response from 10 mGy to 1 Gy. The fading and reproducibility of this sample are also good enough for dosimetric application. However, a specific annealing treatment after irradiation shows some significant improvements in the dosimetric characteristics of the sample. The 773 K pre-annealed sample, after X-ray irradiation post-annealing at 340 K for 6 min provides linear dose response from 10 mGy to 3.60 Gy, very less fading and good reproducibility. Moreover, this sample after post-annealing at 380 K for 6 min shows linear dose response from 10 mGy to 5.40 Gy when analyzed from the ∼408 K thermoluminescence (TL) glow peak. Analysis of TL glow curves confirmed that the 1.30 eV trap center in calcite crystal is the most effective trapping site for dosimetric application.

X-ray dose response of calcite—A comprehensive analysis for optimal application in TL dosimetry

Energy Technology Data Exchange (ETDEWEB)

Kalita, J.M., E-mail: jitukalita09@gmail.com; Wary, G.

2016-09-15

Highlights: • Effect of annealing temperature on TL signal of calcite has been studied. • Specific annealing treatment for optimal dose response has been evaluated. • The dose response of natural calcite has been analyzed quantitatively. - Abstract: The effect of various annealing treatments on dosimetric characteristics of orange calcite (CaCO{sub 3}) mineral has been studied in detail. Quantitative analysis on the dose response shows that the 573 K annealed sample showed sublinear dose response from 10 mGy to 1 Gy. The fading and reproducibility of this sample are also good enough for dosimetric application. However, a specific annealing treatment after irradiation shows some significant improvements in the dosimetric characteristics of the sample. The 773 K pre-annealed sample, after X-ray irradiation post-annealing at 340 K for 6 min provides linear dose response from 10 mGy to 3.60 Gy, very less fading and good reproducibility. Moreover, this sample after post-annealing at 380 K for 6 min shows linear dose response from 10 mGy to 5.40 Gy when analyzed from the ∼408 K thermoluminescence (TL) glow peak. Analysis of TL glow curves confirmed that the 1.30 eV trap center in calcite crystal is the most effective trapping site for dosimetric application.

Heritability of Wing Size and Shape of the Rice and Corn Strains of Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae).

Science.gov (United States)

Cañas-Hoyos, N; Márquez, E J; Saldamando-Benjumea, C I

2016-08-01

Spodoptera frugiperda (J.E. Smith) (Lepidoptera: Noctuidae) represents a pest of economic importance in all Western Hemisphere. This polyphagous species has diverged into two populations that have been mainly recognized with various mitochondrial and nuclear molecular markers and named "the rice" and "the corn" strains. In Colombia, both strains have evolved prezygotic and postzygotic isolation. They differ in tolerance to Bacillus thuringiensis (Cry1Ac and Cry1Ab endotoxins) and the insecticides lambda-cyhalothrin and methomyl. In 2014, a wing morphometric analysis made in 159 individuals from a colony showed that both strains significantly differ in wing shape. The species also exhibits sexual dimorphism in the rice strain as in females wing size is larger than in males. Here, we continued this work with another wing morphometric approach in laboratory-reared strains to calculate wing size and shape heritabilities using a full-sib design and in wild populations to determine if this method distinguishes these strains. Our results show that male heritabilities of both traits were higher than female ones. Wild populations were significantly different in wing shape and size. These results suggest that wing morphometrics can be used as an alternative method to molecular markers to differentiate adults from laboratory-reared populations and wild populations of this pest, particularly in males of this species. Finally, Q ST values obtained for wing size and shape further demonstrated that both strains are genetically differentiated in nature.

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)

Mechanical properties and shape memory effect of thermal-responsive polymer based on PVA

Science.gov (United States)

Lin, Liulan; Zhang, Lingfeng; Guo, Yanwei

2018-01-01

In this study, the effect of content of glutaraldehyde (GA) on the shape memory behavior of a shape memory polymer based on polyvinyl alcohol chemically cross-linked with GA was investigated. Thermal-responsive shape memory composites with three different GA levels, GA-PVA (3 wt%, 5 wt%, 7 wt%), were prepared by particle melting, mold forming and freeze-drying technique. The mechanical properties, thermal properties and shape memory behavior were measured by differential scanning calorimeter, physical bending test and cyclic thermo-mechanical test. The addition of GA to PVA led to a steady shape memory transition temperature and an improved mechanical compressive strength. The composite with 5 wt% of GA exhibited the best shape recoverability. Further increase in the crosslinking agent content of GA would reduce the recovery force and prolong the recovery time due to restriction in the movement of the soft PVA chain segments. These results provide important information for the study on materials in 4D printing.

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.

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

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)

Dose-response for X-ray induction of myeloid leukaemia in male CBA/H mice

Energy Technology Data Exchange (ETDEWEB)

Mole, R H; Papworth, D G; Corp, M J [Medical Research Council, Harwell (UK). Radiobiological Research Unit

1983-02-01

The form of the dose-response for induction of malignant diseases in vivo by ionizing radiation is not yet established in spite of its scientific interest and its practical importance. Considerably extended observations have confirmed that the dose-response for acute myeloid leukaemia induced in male CBA/H mice by X-ray exposure is highly curvilinear. The dose-response was well fitted by the expression aD/sup 2/esup(-..gamma..D) (D = dose) in agreement with induction at the cellular level in proportion to D/sup 2/ over the whole dose range 0.25-6.0 Gy. The factor esup(-..gamma..D) accounts for the inescapable concomitant inactivating action of the inducing irradiation. The quantitative aspects of induction of myeloid leukaemia by ionizing radiation are unlike the induction of genetic mutation or cell inactivation and suggest that interaction of two adjoining cells is an essential element in radiation leukaemogenesis.

Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females

International Nuclear Information System (INIS)

Silasi, Greg; Diaz-Heijtz, Rochellys; Besplug, Jill; Rodriguez-Juarez, Rocio; Titov, Viktor; Kolb, Bryan; Kovalchuk, Olga

2004-01-01

Radiation exposure is known to have profound effects on the brain, leading to precursor cell dysfunction and debilitating cognitive declines [Nat. Med. 8 (2002) 955]. Although a plethora of data exist on the effects of high radiation doses, the effects of low-dose irradiation, such as ones received during repetitive diagnostic and therapeutic exposures, are still under-investigated [Am. J. Otolaryngol. 23 (2002) 215; Proc. Natl. Acad. Sci. USA 97 (2000) 889; Curr. Opin. Neurol. 16 (2003) 129]. Furthermore, most studies of the biological effects of ionizing radiation have been performed using a single acute dose, while clinically and environmentally relevant exposures occur predominantly under chronic/repetitive conditions. Here, we have used a mouse model to compare the effects of chronic/repetitive and acute low-dose radiation (LDR) exposure (0.5 Gy) to ionizing radiation on the brain in vivo. We examined the LDR effects on p42/44 MAPK (ERK1/ERK2), CaMKII, and AKT signaling-the interconnected pathways that have been previously shown to be crucial for neuronal survival upon irradiation. We report perturbations in ERK1/2, AKT, and CREB upon acute and chronic/repetitive low-dose exposure in the hippocampus and frontal cortex of mice. These studies were paralleled by the analysis of radiation effects on neurogenesis and cellular proliferation. Repetitive exposure had a much more pronounced effect on cellular signaling and neurogenesis than acute exposure. These results suggest that studies of single acute exposures might be limited in terms of their predictive value. We also present the first evidence of sex differences in radiation-induced signaling in the hippocampus and frontal cortex. We show the role of estrogens in brain radiation responses and discuss the implications of the observed changes

Magnetic field influences on the lateral dose response functions of photon-beam detectors: MC study of wall-less water-filled detectors with various densities.

Science.gov (United States)

Looe, Hui Khee; Delfs, Björn; Poppinga, Daniela; Harder, Dietrich; Poppe, Björn

2017-06-21

The distortion of detector reading profiles across photon beams in the presence of magnetic fields is a developing subject of clinical photon-beam dosimetry. The underlying modification by the Lorentz force of a detector's lateral dose response function-the convolution kernel transforming the true cross-beam dose profile in water into the detector reading profile-is here studied for the first time. The three basic convolution kernels, the photon fluence response function, the dose deposition kernel, and the lateral dose response function, of wall-less cylindrical detectors filled with water of low, normal and enhanced density are shown by Monte Carlo simulation to be distorted in the prevailing direction of the Lorentz force. The asymmetric shape changes of these convolution kernels in a water medium and in magnetic fields of up to 1.5 T are confined to the lower millimetre range, and they depend on the photon beam quality, the magnetic flux density and the detector's density. The impact of this distortion on detector reading profiles is demonstrated using a narrow photon beam profile. For clinical applications it appears as favourable that the magnetic flux density dependent distortion of the lateral dose response function, as far as secondary electron transport is concerned, vanishes in the case of water-equivalent detectors of normal water density. By means of secondary electron history backtracing, the spatial distribution of the photon interactions giving rise either directly to secondary electrons or to scattered photons further downstream producing secondary electrons which contribute to the detector's signal, and their lateral shift due to the Lorentz force is elucidated. Electron history backtracing also serves to illustrate the correct treatment of the influences of the Lorentz force in the EGSnrc Monte Carlo code applied in this study.

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

SU-E-J-158: Experimental Investigation of Proton Radiography Based On Time-Resolved Dose Measurements

Energy Technology Data Exchange (ETDEWEB)

Testa, M; Paganetti, H; Lu, H-M [Massachusetts General Hospital ' Harvard Medical School, Boston, MA (United States); Doolan, P [University College London (United Kingdom); H, Bentefour E [IBA, Warrenville, IL (United States)

2014-06-01

Purpose: To use proton radiography for i) in-vivo range verification of the brain fields of medulloblastoma patients in order to reduce the exit dose to the cranial skin and thus the risk of permanent alopecia; ii) for performing patient specific optimization of the calibration from CT-Hounsfield units to proton relative stopping power in order to minimize uncertainties of proton rang Methods: We developed and tested a prototype proton radiography system based on a single-plane scintillation screen coupled with a fast CCD camera (1ms sampling rate, 0.29x0.29 mm{sup 2} pixel size, 30×30 cm{sup 2} field of view). The method is based on the principle that, for passively scattered beams, the radiological depth of any point in the plateau of a spread-out Bragg-Peak (SOBP) can be inferred from the time-pattern of the dose rate measurements. We performed detector characterization measurements using complex-shape homogeneous phantoms and an Alderson phanto Results: Detector characterization tests confirmed the robustness of the technique. The results of the phantom measurements are encouraging in terms of achievable accuracy of the water equivalent thickness. A technique to minimize the degradation of spatial resolution due to multiple Coulomb scattering is discussed. Our novel radiographic technique is rapid (100 ms) and simultaneous over the whole field. The dose required to produce one radiograph, with the current settings, is ∼3 cG Conclusion: The results obtained with this simple and innovative radiography method are promising and motivate further development of technique. The system requires only a single-plane 2D dosimeter and it uses the clinical beam for a fraction of second with low dose to the patient.

Comparison of Dose Response Models for Predicting Normal Tissue Complications from Cancer Radiotherapy: Application in Rat Spinal Cord

Energy Technology Data Exchange (ETDEWEB)

Adamus-Górka, Magdalena; Mavroidis, Panayiotis, E-mail: panayiotis.mavroidis@ki.se; Lind, Bengt K.; Brahme, Anders [Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm S-17176 (Sweden)

2011-05-18

Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ{sup 2}-distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint.

Comparison of Dose Response Models for Predicting Normal Tissue Complications from Cancer Radiotherapy: Application in Rat Spinal Cord

International Nuclear Information System (INIS)

Adamus-Górka, Magdalena; Mavroidis, Panayiotis; Lind, Bengt K.; Brahme, Anders

2011-01-01

Seven different radiobiological dose-response models have been compared with regard to their ability to describe experimental data. The first four models, namely the critical volume, the relative seriality, the inverse tumor and the critical element models are mainly based on cell survival biology. The other three models: the Lyman (Gaussian distribution), the parallel architecture and the Weibull distribution models are semi-empirical and rather based on statistical distributions. The maximum likelihood estimation was used to fit the models to experimental data and the χ 2 -distribution, AIC criterion and F-test were applied to compare the goodness-of-fit of the models. The comparison was performed using experimental data for rat spinal cord injury. Both the shape of the dose-response curve and the ability of handling the volume dependence were separately compared for each model. All the models were found to be acceptable in describing the present experimental dataset (p > 0.05). For the white matter necrosis dataset, the Weibull and Lyman models were clearly superior to the other models, whereas for the vascular damage case, the Relative Seriality model seems to have the best performance although the Critical volume, Inverse tumor, Critical element and Parallel architecture models gave similar results. Although the differences between many of the investigated models are rather small, they still may be of importance in indicating the advantages and limitations of each particular model. It appears that most of the models have favorable properties for describing dose-response data, which indicates that they may be suitable to be used in biologically optimized intensity modulated radiation therapy planning, provided a proper estimation of their radiobiological parameters had been performed for every tissue and clinical endpoint

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.

Adverse impact of multileaf collimator field shaping on lens dose in children with acute leukemia receiving cranial irradiation

International Nuclear Information System (INIS)

Kalapurakal, John A.; Sathiaseelan, Vythialingam; Bista, Tomasz C.; Marymont, Maryanne H.

2000-01-01

Purpose: This study was designed to investigate the impact of multileaf collimator (MLC) on lens dose in children with leukemia undergoing cranial irradiation. Methods and Materials: This is a prospective study utilizing three common cranial irradiation techniques. Technique A uses a half-beam, nondivergent radiation field. Technique B has the anterior divergent field edge at the lateral bony canthus. Technique C is similar to B, but with a field collimator angle. Thermoluminescent dosimeter (TLD) lens dose measurements were obtained in children and phantom with all three techniques. Results: Seventeen children were studied. Lens dose measurements were obtained in 14 children with technique A using MLC and blocks. In 7 of 14 children, dose measurements were obtained with MLC only. One child was treated with technique B and 2 children were treated with C, with MLC ± blocks. In all 3 techniques, with MLC alone, the lens dose increased by 64%, 119%, and 72%, respectively. Similar results were obtained in phantom. Conclusion: This study demonstrates that independent of irradiation technique, additional custom blocking is required to maximally protect the lens with MLC shaped fields. This is due to the lack of conformity between MLC and the desired field edge at the lateral bony canthus

Effect of the shape and size of dosimeters on the response of solid state/EPR dosimetry

International Nuclear Information System (INIS)

Yordanov, Nicola D.; Fabisiak, Slawomir; Lagunov, Oleg

2006-01-01

The influence of the shape and size of dosimeters used in solid state-EPR (SS/EPR) dosimetry on their response is reported. It is shown that for commonly used cylindrical (rod) shaped dosimeters of equal height, prepared of low (ε=<3) dielectric constant materials, linearity between their volume and the EPR response is observed when their diameter varies between 3 and 5mm. Further increase of the dosimeter's diameter is not recommended since the increased penetration of the dosimeter material into the electric component of the microwave field in the EPR cavity increases the dielectric losses and decreases the EPR response. In an attempt to improve the sensitivity of the SS/EPR dosimetry we have prepared and tested new, flat-shaped, dosimeters of low (ε∼2) dielectric constant materials which were found to exhibit: (i) linear EPR response within 1-5mm thickness; (ii) higher sensitivity than cylindrical dosimeters at equal sample volume; (iii) increased by ca. 270% EPR sensitivity at 5mm thickness compared to the cylindrical dosimeters with the same diameter (ca. 1.7 times increased sample volume). Using flat shape dosimeters of suitable size provides 2.7 times higher EPR sensitivity of single estimation

Dose-rate and humidity effects upon the gamma-radiation response of nylon-based radiachromic film dosimeters

International Nuclear Information System (INIS)

Gehringer, P.; Eschweiler, H.; Proksch, E.

1979-10-01

At dose-rates typical for 60 Co gamma irradiation sources, the radiation response of hexahydroxyethyl pararosaniline cyanide/ 50μm nylon radiachromic films is dependent upon dose-rate as well as upon the moisture content of the films, or the relative humidity of the surrounding atmosphere, respectively. Under equilibrium moisture conditions, the response measured at 606 nm 24 hours after end of irradiation shows its highest dose-rate dependence at about 32 % r.h. A decrease in dose-rate from 2.8 to 0.039 Gy.s -1 results in a decrease in response by 17%. At higher humidities, the sensitivity of the film as well as the rate dependence decreases and at 86% r.h. no discernible dose-rate effect could be found. At lower humidities than 32% a flat maximum in response follows. At nominal 0% r.h. a second absorption band at 412 nm appears which is converted completely to an additional 606 nm absorption by exposure to a humid atmosphere. After that procedure the resultant response is somewhat lower than but shows almost the same dose-rate dependence as at 32% r.h. or else to eliminate the dose-rate effect by an extrapolation procedure based on the fact that the rate dependence vanishes at zero dose. (author)

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.

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.

SU-E-J-105: Stromal-Epithelial Responses to Fractionated Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Qayyum, M [Little Company of Mary Hospital, Ever Green Park, IL (United States)

2014-06-01

Purpose: The stromal-epithelial-cell interactions that are responsible for directing normal breast-tissue development and maintenance play a central role in the progression of breast cancer. In the present study, we developed three-dimensional (3-D) cell co-cultures used to study cancerous mammary cell responses to fractionated radiotherapy. In particular, we focused on the role of the reactive stroma in determining the therapeutic ratio for postsurgical treatment. Methods: Cancerous human mammary epithelial cells were cultured in a 3-D collagen matrix with human fibroblasts stimulated by various concentrations of transforming growth factor beta 1 (TGF-β1). These culture samples were designed to model the post-lumpectomy mammary stroma in the presence of residual cancer cells. We tracked over time the changes in medium stiffness, fibroblast-cell activation (conversion to cancer activated fibroblasts (CAF)), and proliferation of both cell types under a variety of fractionated radiotherapy protocols. Samples were exposed to 6 MV X-rays from a linear accelerator in daily fraction sizes of 90, 180 and 360 cGy over five days in a manner consistent with irradiation exposure during radiotherapy. Results: We found in fractionation studies with fibroblasts and CAF that higher doses per fraction may be more effective early on in deactivating cancer-harboring cellular environments. Higher-dose fraction schemes inhibit contractility in CAF and prevent differentiation of fibroblasts, thereby metabolically uncoupling tumor cells from their surrounding stroma. Yet, over a longer time period, the higher dose fractions may slow wound healing and increase ECM stiffening that could stimulate proliferation of surviving cancer cells. Conclusion: The findings suggest that dose escalation to the region with residual disease can deactivate the reactive stroma, thus minimizing the cancer promoting features of the cellular environment. Large-fraction irradiation may be used to sterilize

SU-E-J-105: Stromal-Epithelial Responses to Fractionated Radiotherapy

International Nuclear Information System (INIS)

Qayyum, M

2014-01-01

Purpose: The stromal-epithelial-cell interactions that are responsible for directing normal breast-tissue development and maintenance play a central role in the progression of breast cancer. In the present study, we developed three-dimensional (3-D) cell co-cultures used to study cancerous mammary cell responses to fractionated radiotherapy. In particular, we focused on the role of the reactive stroma in determining the therapeutic ratio for postsurgical treatment. Methods: Cancerous human mammary epithelial cells were cultured in a 3-D collagen matrix with human fibroblasts stimulated by various concentrations of transforming growth factor beta 1 (TGF-β1). These culture samples were designed to model the post-lumpectomy mammary stroma in the presence of residual cancer cells. We tracked over time the changes in medium stiffness, fibroblast-cell activation (conversion to cancer activated fibroblasts (CAF)), and proliferation of both cell types under a variety of fractionated radiotherapy protocols. Samples were exposed to 6 MV X-rays from a linear accelerator in daily fraction sizes of 90, 180 and 360 cGy over five days in a manner consistent with irradiation exposure during radiotherapy. Results: We found in fractionation studies with fibroblasts and CAF that higher doses per fraction may be more effective early on in deactivating cancer-harboring cellular environments. Higher-dose fraction schemes inhibit contractility in CAF and prevent differentiation of fibroblasts, thereby metabolically uncoupling tumor cells from their surrounding stroma. Yet, over a longer time period, the higher dose fractions may slow wound healing and increase ECM stiffening that could stimulate proliferation of surviving cancer cells. Conclusion: The findings suggest that dose escalation to the region with residual disease can deactivate the reactive stroma, thus minimizing the cancer promoting features of the cellular environment. Large-fraction irradiation may be used to sterilize

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

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

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)

Shape-dependent Surface Energetics of Nanocrystalline TiO2

International Nuclear Information System (INIS)

Park, T.J.; Wong, S.; Levchenko, A.A.; Zhou, H.; Navrotsky, A.

2010-01-01

We report the direct determination of surface enthalpies for nanophase TiO 2 anatase with different morphologies derived from drop solution calorimetry in a molten sodium molybdate (3Na 2 Ol·4MoO 3 ) solvent at 702 C. The energetics of surface hydration has been measured using a Calvet microcalorimeter coupled with a gas dosing system. The surface enthalpies of hydrated surfaces for anatase TiO 2 nanoparticles, nanowires and sea-urchin-like assemblies are 0.51 ± 0.05, 1.07 ± 0.28, and 1.29 ± 0.16 J m -2 , respectively, whereas those of anhydrous surfaces are 0.74 ± 0.04, 1.24 ± 0.28, and 1.41 ± 0.16 J m -2 , respectively. The trend in TiO 2 , which shows higher surface enthalpies for more complex nanostructures, is consistent with that reported in ZnO. The shape-dependent surface enthalpy at the nanoscale level is discussed in terms of exposed surface structures. The enthalpies of hydration appear to be similar for all morphologies.

Shape-dependent Surface Energetics of Nanocrystalline TiO2

Energy Technology Data Exchange (ETDEWEB)

Park, T.J.; Wong, S.; Levchenko, A.A.; Zhou, H.; Navrotsky, A.

2010-10-21

We report the direct determination of surface enthalpies for nanophase TiO{sub 2} anatase with different morphologies derived from drop solution calorimetry in a molten sodium molybdate (3Na{sub 2}Ol{center_dot}4MoO{sub 3}) solvent at 702 C. The energetics of surface hydration has been measured using a Calvet microcalorimeter coupled with a gas dosing system. The surface enthalpies of hydrated surfaces for anatase TiO{sub 2} nanoparticles, nanowires and sea-urchin-like assemblies are 0.51 {+-} 0.05, 1.07 {+-} 0.28, and 1.29 {+-} 0.16 J m{sup -2}, respectively, whereas those of anhydrous surfaces are 0.74 {+-} 0.04, 1.24 {+-} 0.28, and 1.41 {+-} 0.16 J m{sup -2}, respectively. The trend in TiO{sub 2}, which shows higher surface enthalpies for more complex nanostructures, is consistent with that reported in ZnO. The shape-dependent surface enthalpy at the nanoscale level is discussed in terms of exposed surface structures. The enthalpies of hydration appear to be similar for all morphologies.

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.

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.

'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

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...

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:…

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

FERMI LARGE AREA TELESCOPE OBSERVATIONS OF GAMMA-RAY PULSARS PSR J1057-5226, J1709-4429, AND J1952+3252

International Nuclear Information System (INIS)

Abdo, A. A.; Ajello, M.; Bechtol, K.; Berenji, B.; Borgland, A. W.; Bouvier, A.; Buehler, R.; Antolini, E.; Bonamente, E.; Baldini, L.; Bellazzini, R.; Bregeon, J.; Brez, A.; Ballet, J.; Barbiellini, G.; Baring, M. G.; Bastieri, D.; Brigida, M.; Bruel, P.; Burnett, T. H.

2010-01-01

The Fermi Large Area Telescope (LAT) data have confirmed the pulsed emission from all six high-confidence gamma-ray pulsars previously known from the EGRET observations. We report results obtained from the analysis of 13 months of LAT data for three of these pulsars (PSR J1057-5226, PSR J1709-4429, and PSR J1952+3252) each of which had some unique feature among the EGRET pulsars. The excellent sensitivity of LAT allows more detailed analysis of the evolution of the pulse profile with energy and also of the variation of the spectral shape with phase. We measure the cutoff energy of the pulsed emission from these pulsars for the first time and provide a more complete picture of the emission mechanism. The results confirm some, but not all, of the features seen in the EGRET data.

Exosomes carring gag/env of ALV-J possess negative effect on immunocytes.

Science.gov (United States)

Wang, Guihua; Wang, Zhenzhen; Zhuang, Pingping; Zhao, Xiaomin; Cheng, Ziqiang

2017-11-01

J subgroup avian leukosis virus (ALV-J) is an exogenous retrovirus of avian. A key feature of ALV-J infection is leading to severe immunosuppressive characteristic of diseases. Viral components of retrovirus were reported closely associated with immunosuppression, and several similarities between exosomes and retrovirus preparations have lead to the hypotheses of retrovirus hijacker exosomes pathway. In this study, we purified exosomes from DF-1 cells infected and uninfected by ALV-J. Electron microscopy and mass spectrometry (MS) analysis showed that ALV-J not only increased the production of exosomes from ALV-J infected DF-1 cells (Exo-J) but also stimulated some proteins expression, especially ALV-J components secreted in exosomes. Immunosuppressive domain peptide (ISD) of envelope subunit transmembrane (TM) and gag of ALV-J were secreted in Exo-J. It has been reported that HIV gag was budded from endosome-like domains of the T cell plasma membrane. But env protein was first detected in exosomes from retrovirus infected cells. We found that Exo-J caused negative effects on splenocytes in a dose-dependant manner by flow cytometric analysis. And low dose of Exo-J activated immune activity of splenocytes, while high dose possessed immunosuppressive properties. Interestingly, Exo-J has no significant effects on the immunosuppression induced by ALV-J, and the immunosuppressive effects induced by Exo-J lower than that by ALV-J. Taken together, our data indicated that Exo-J supplied a microenvironment for the replication and transformation of ALV-J. Copyright © 2017. Published by Elsevier Ltd.

Bovine Leukemia Virus Infection in Dairy Cattle: Effect on Serological Response to Immunization against J5 Escherichia coli Bacterin

Directory of Open Access Journals (Sweden)

Ronald J. Erskine

2011-01-01

Full Text Available Thirteen bovine leukemia virus- (BLV- negative and 22 BLV-positive Holstein cows were immunized with J5 Escherichia coli bacterin at dry off, three weeks before calving, during the second week after calving, and three weeks after the third immunization. Serum was collected before the initial immunization, immediately before the third and fourth immunizations, and 21 days after the fourth immunization. Anti-J5 E. coli IgM, IgG1, and IgG2 titers were determined by ELISA. Anti-J5 E. coli IgM titers did not differ significantly (P=.98 between groups. Increases in anti-J5 E. coli IgG1 titers were higher in the BLV-negative cows (P=.057. Geometric mean anti-J5 E. coli IgG2 titers increased fourfold in the BLV-negative cows, which was significantly higher (P=.007 than the twofold increase in the BLV-positive cows. Cattle infected with BLV may have impaired serologic responses following immunization with J5 bacterin, and response may differ according to antibody isotype.

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.

Dose-dependent optically stimulated luminescence of synthetic quartz at room temperature

International Nuclear Information System (INIS)

Kale, Y.D.; Gandhi, Y.H.; Gartia, R.K.

2008-01-01

Physical conditions such as annealing temperature, duration of annealing, ionizing radiation, etc., play a significant role in the applications of optically stimulated luminescence (OSL) dating as well as OSL dosimetry. Many efforts are made to understand the effect of these physical parameters on quartz specimens owing to its use in such applications. Such factors induce changes in OSL decay pattern. The definite correlation between color centers and luminescence sensitivity can be established on account of such pre-treatments to the specimen. The purpose of present investigations is to study the effect of ionizing radiation under identical physical conditions on OSL properties measured at room temperature. The shapes of decay curve and dose-response data are considered for this purpose. This study can reveal the changes in color centers in response to the pre-conditions to the specimen. It was found that the OSL decay remains slow and OSL properties change systematically with the rise in beta dose up to a critical dose; however, it changes the pattern when the beta exposure to the specimen was increased higher than the critical dose. This critical dose was found to be different for different temperature of annealing. The shape of decay curve up to the critical dose was also studied by considering the difference of OSL intensities between two successive durations from the observed OSL decay data. The results are explained based on the changes in available shallow traps during OSL measurement at room temperature with changes in pre-conditions to the specimens. The results also have been confirmed with the corresponding changes in ESR signals

Shape Memory Investigation of α-Keratin Fibers as Multi-Coupled Stimuli of Responsive Smart Materials

Directory of Open Access Journals (Sweden)

Xueliang Xiao

2017-03-01

Full Text Available Like the water responsive shape memory (SM effect of β-keratin bird feathers, α-keratin hairs either existing broadly in nature are found responsive to many types of coupled stimuli in SM behaviors. In this article, α-keratin hairs were investigated for the combined stimuli of thermo-solvent, solvent-solvent, and UV (radiation-reductant sensitive SM abilities. The related netpoints and switches from the hair molecular networks were identified. The experimental results showed that α-keratin hairs manifested a higher ability of shape fixation under thermal stimulus followed with the stimuli of solvent and UV-radiation. Shape recovery from the hair with a temporarily fixed shape showed a higher recovery ability using solvent than the stimuli of heat and UV-radiation. The effects of coupled stimuli on hair’s shape fixation and recovery and on variations of the crystal, disulfide, and hydrogen bonds were studied systematically. A structural network model was thereafter proposed to interpret the multi-coupled stimuli sensitive SM of α-keratin hair. This original study is expected to provide inspiration for exploring other natural fibers to reveal related smart functions and for making more types of remarkable adapted synthetic materials.

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

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

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)

Effects of Differing Response-Force Requirements on Food-Maintained Responding in C57BL/6J Mice

Science.gov (United States)

Zarcone, Troy J.; Chen, Rong; Fowler, Stephen C.

2009-01-01

The effect of force requirements on response effort was examined using inbred C57BL/6J mice trained to press a disk with their snout. Lateral peak forces greater than 2 g were defined as responses (i.e., all responses above the measurement threshold). Different, higher force requirements were used to define criterion responses (a subclass of all…

Dosimetry of irregular shaped fields of β rays

International Nuclear Information System (INIS)

Supe, S.J.; Datta, S.

1976-01-01

The feasibility of using various shapes and sizes of field limiting devices and collimators with β-ray eye applicators has necessitated the study of dosimetry for these fields. A method of calculating surface and depth doses for any shaped field from the data for circular fields is presented. The depth dose evaluation is based on a measured dose function which is defined as the dose rate at a particular depth for a particular circular field. The evaluated values for the surface and depth dose were compared with experimentally obtained values for three non-circular fields. The good agreement in these data indicates the practicability of the method suggested. (author)

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.

Complex, non-monotonic dose-response curves with multiple maxima: Do we (ever) sample densely enough?

Science.gov (United States)

Cvrčková, Fatima; Luštinec, Jiří; Žárský, Viktor

2015-01-01

We usually expect the dose-response curves of biological responses to quantifiable stimuli to be simple, either monotonic or exhibiting a single maximum or minimum. Deviations are often viewed as experimental noise. However, detailed measurements in plant primary tissue cultures (stem pith explants of kale and tobacco) exposed to varying doses of sucrose, cytokinins (BA or kinetin) or auxins (IAA or NAA) revealed that growth and several biochemical parameters exhibit multiple reproducible, statistically significant maxima over a wide range of exogenous substance concentrations. This results in complex, non-monotonic dose-response curves, reminiscent of previous reports of analogous observations in both metazoan and plant systems responding to diverse pharmacological treatments. These findings suggest the existence of a hitherto neglected class of biological phenomena resulting in dose-response curves exhibiting periodic patterns of maxima and minima, whose causes remain so far uncharacterized, partly due to insufficient sampling frequency used in many studies.

Latest developments on fibered MOPA in mJ range with hollow-core fiber beam delivery and fiber beam shaping used as seeder for large scale laser facilities (Conference Presentation)

Science.gov (United States)

Gleyze, Jean-François; Scol, Florent; Perrin, Arnaud; Gouriou, Pierre; Valentin, Constance; Bouwmans, Géraud; Hugonnot, Emmanuel

2017-05-01

The Laser Megajoule (LMJ) is a French large scale laser facility dedicated to inertial fusion and plasma physics research. LMJ front-ends are based on fiber laser technology at nanojoule range [1]. Scaling the energy of those fiber seeders to the millijoule range is a way to upgrade LMJ's front ends architecture and could also be used as seeder for lasers for ELI project for example. However, required performances are so restrictive (optical-signal-to-noise ratio higher than 50 dB, temporally-shaped nanosecond pulses and spatial single-mode top-hat beam output) that such fiber systems are very tricky to build. High-energy fiber amplifiers In 2015, we have demonstrated, an all-fiber MOPA prototype able to produce a millijoule seeder, but unfortunately not 100% conform for all LMJ's performances. A major difficulty was to manage the frequency modulation used to avoid stimulated Brillouin scattering, to amplitude modulation (FM-AM) conversion, this limits the energy at 170µJ. For upgrading the energy to the millijoule range, it's necessary to use an amplifier with a larger core fiber. However, this fiber must still be flexible; polarization maintaining and exhibit a strictly single-mode behaviour. We are thus developing a new amplifier architecture based on an Yb-doped tapered fiber: its core diameter is from a narrow input to a wide output (MFD 8 to 26 µm). A S² measurement on a 2,5m long tapered fiber rolled-up on 22 cm diameter confirmed that this original geometry allows obtaining strictly single-mode behaviour. In a 1 kHz repetition rate regime, we already obtain 750 µJ pulses, and we are on the way to mJ, respecting LMJ performances. Beam delivery In LMJ architecture the distance between the nanojoule fiber seeder and the amplifier stages is about 16 m. Beam delivery is achieved with a standard PM fiber, such a solution is no longer achievable with hundreds of kilowatt peak powers. An efficient way to minimize nonlinear effects is to use hollow-core (HC

Late follow up results after J - 131 therapy of toxic multi-nodular goiter

International Nuclear Information System (INIS)

Petrovski, Z.

2015-01-01

Full text of publication follows. Objective: the aim of this study was to analyze success of radioiodine therapy in patients with toxic multi-nodular goiter (TMG). Methods: The group of 43 patients (36 females / 7 males, aged 47 ± 11 yrs, range 27 - 75 yrs) with TMG were treated with radioiodine. 28 patients were treated with one dose, 12 patients with two doses and 7 patients with three and more doses according to Marinelli's formula. The administered activity of J -131 was established basing on radioiodine uptake and goiter size ( median 555 MBq, range: 370 - 1100 MBq). Patients were evaluated by clinical and thyroid examination of TSH, FT4, FT3 after 1 - 3 months. Thyroid scintigraphy was performed 3 months after radioiodine therapy. Prior to treatment with J -131 all patients were treated with antithyroid medications, who were suspended 4 - 7 days and restarted one week after J - 131 therapy. Results: in 76,8% (33/43) patients there was control of disease after the first J -131 dose and in 95,2% (40/43) patients after the second and more doses. At 20 years of follow up, there were 84,4% (36/43) patients euthyroid, 13,9% (6/43) patients hypothyroid and 4,6% (2/43) patients hyperthyroid. Reduction of gland weight were in 74,4% (32/43) patients. During 20 years of follow up no adverse side effects were observed after J - 131 therapy. Conclusion: radioiodine therapy is the right choice of treatment for toxic multi-nodular goiter and single dose of J -131 is successful in most of the cases. A single higher radioiodine dose diminishes the need for additional J -131 therapy, without increasing of developing hypothyroidism. (authors)

Feasibility of spectral shaping for detection and quantification of coronary calcifications in ultra-low dose CT

Energy Technology Data Exchange (ETDEWEB)

Vonder, Marleen; Pelgrim, Gert Jan; Vliegenthart, Rozemarijn [University of Groningen, University Medical Center Groningen, Department of Radiology, Groningen (Netherlands); University of Groningen, University Medical Center Groningen, Center for Medical Imaging North-East Netherlands (CMI-NEN), Groningen (Netherlands); Huijsse, Sevrin E.M.; Greuter, Marcel J.W. [University of Groningen, University Medical Center Groningen, Department of Radiology, Groningen (Netherlands); Meyer, Mathias; Henzler, Thomas [Heidelberg University, Institute of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim, University Medical Center Mannheim, Heidelberg (Germany); Flohr, Thomas G. [Siemens Healthcare GmbH, Computed Tomography, Forchheim (Germany); Oudkerk, Matthijs [University of Groningen, University Medical Center Groningen, Center for Medical Imaging North-East Netherlands (CMI-NEN), Groningen (Netherlands)

2017-05-15

To evaluate detectability and quantification of coronary calcifications for CT with a tin filter for spectral shaping. Phantom inserts with 100 small and 9 large calcifications, and a moving artificial artery with 3 calcifications (speed 0-30 mm/s) were placed in a thorax phantom simulating different patient sizes. The phantom was scanned in high-pitch spiral mode at 100 kVp with tin filter (Sn100 kVp), and at a reference of 120 kVp, with electrocardiographic (ECG) gating. Detectability and quantification of calcifications were analyzed for standard (130 HU) and adapted thresholds. Sn100 kVp yielded lower detectability of calcifications (9 % versus 12 %, p = 0.027) and lower Agatston scores (p < 0.008), irrespective of calcification, patient size and speed. Volume scores of the moving calcifications for Sn100 kVp at speed 10-30 mm/s were lower (p < 0.001), while mass scores were similar (p = 0.131). For Sn100 kVp with adapted threshold of 117 HU, detectability (p = 1.000) and Agatston score (p > 0.206) were similar to 120 kVp. Spectral shaping resulted in median dose reduction of 62.3 % (range 59.0-73.4 %). Coronary calcium scanning with spectral shaping yields lower detectability of calcifications and lower Agatston scores compared to 120 kVp scanning, for which a HU threshold correction should be developed. (orig.)

When Legitimacy Shapes Environmentally Responsible Behaviors: Considering Exposure to University Sustainability Initiatives

Science.gov (United States)

Watson, Lesley; Hegtvedt, Karen A.; Johnson, Cathryn; Parris, Christie L.; Subramanyam, Shruthi

2017-01-01

This study examines how perceptions of the legitimacy of university sustainability efforts--support by the administration (authorization) or from students' peers (endorsement)--as well as the physical context in which students live, matter in shaping students' environmentally responsible behaviors (ERBs). Using survey data collected from…