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Sample records for biologically based dose

  1. Biologically based modelling and simulation of carcinogenesis at low doses

    International Nuclear Information System (INIS)

    Ouchi, Noriyuki B.

    2003-01-01

    The process of the carcinogenesis is studied by computer simulation. In general, we need a large number of experimental samples to detect mutations at low doses, but in practice it is difficult to get such a large number of data. To satisfy the requirements of the situation at low doses, it is good to study the process of carcinogenesis using biologically based mathematical model. We have mainly studied it by using as known as 'multi-stage model'; the model seems to get complicated, as we adopt the recent new findings of molecular biological experiments. Moreover, the basic idea of the multi-stage model is based on the epidemiologic data of log-log variation of cancer incidence with age, it seems to be difficult to compare with experimental data of irradiated cell culture system, which has been increasing in recent years. Taking above into consideration, we concluded that we had better make new model with following features: 1) a unit of the target system is a cell, 2) the new information of the molecular biology can be easily introduced, 3) having spatial coordinates for checking a colony formation or tumorigenesis. In this presentation, we will show the detail of the model and some simulation results about the carcinogenesis. (author)

  2. The biological bases of the dose-effect relationship

    International Nuclear Information System (INIS)

    Lafuma, J.

    2001-01-01

    In radiation protection, the recent data in epidemiology, in animal experimentation and on the base researches are no more compatible with a linear dose-effect relationship without threshold and do not account for the radiological risks at low doses. The cancers should be accelerated by radiations as any pathology linked to the ageing and for which threshold exit. Relative to the genetic risk it is known today that the natural exposure that lasts for several generations has not lead excess of hereditary illness as it was to be feared in 1959 for several countries. Considering that for populations the exposure levels induced by human activities have already been, under these ones of average natural exposures the genetic risk can be negligible and it is the somatic risk alone, with its thresholds that has to be into account. (N.C.)

  3. Biologically effective dose distribution based on the linear quadratic model and its clinical relevance

    International Nuclear Information System (INIS)

    Lee, Steve P.; Leu, Min Y.; Smathers, James B.; McBride, William H.; Parker, Robert G.; Withers, H. Rodney

    1995-01-01

    Purpose: Radiotherapy plans based on physical dose distributions do not necessarily entirely reflect the biological effects under various fractionation schemes. Over the past decade, the linear-quadratic (LQ) model has emerged as a convenient tool to quantify biological effects for radiotherapy. In this work, we set out to construct a mechanism to display biologically oriented dose distribution based on the LQ model. Methods and Materials: A computer program that converts a physical dose distribution calculated by a commercially available treatment planning system to a biologically effective dose (BED) distribution has been developed and verified against theoretical calculations. This software accepts a user's input of biological parameters for each structure of interest (linear and quadratic dose-response and repopulation kinetic parameters), as well as treatment scheme factors (number of fractions, fractional dose, and treatment time). It then presents a two-dimensional BED display in conjunction with anatomical structures. Furthermore, to facilitate clinicians' intuitive comparison with conventional fractionation regimen, a conversion of BED to normalized isoeffective dose (NID) is also allowed. Results: Two sample cases serve to illustrate the application of our tool in clinical practice. (a) For an orthogonal wedged pair of x-ray beams treating a maxillary sinus tumor, the biological effect at the ipsilateral mandible can be quantified, thus illustrates the so-called 'double-trouble' effects very well. (b) For a typical four-field, evenly weighted prostate treatment using 10 MV x-rays, physical dosimetry predicts a comparable dose at the femoral necks between an alternate two-fields/day and four-fields/day schups. However, our BED display reveals an approximate 21% higher BED for the two-fields/day scheme. This excessive dose to the femoral necks can be eliminated if the treatment is delivered with a 3:2 (anterio-posterior/posterio-anterior (AP

  4. The biological bases of the dose-effect relationship; Les bases biologiques de la relation dose-effet

    Energy Technology Data Exchange (ETDEWEB)

    Lafuma, J

    2001-06-01

    In radiation protection, the recent data in epidemiology, in animal experimentation and on the base researches are no more compatible with a linear dose-effect relationship without threshold and do not account for the radiological risks at low doses. The cancers should be accelerated by radiations as any pathology linked to the ageing and for which threshold exit. Relative to the genetic risk it is known today that the natural exposure that lasts for several generations has not lead excess of hereditary illness as it was to be feared in 1959 for several countries. Considering that for populations the exposure levels induced by human activities have already been, under these ones of average natural exposures the genetic risk can be negligible and it is the somatic risk alone, with its thresholds that has to be into account. (N.C.)

  5. A phenomenological biological dose model for proton therapy based on linear energy transfer spectra.

    Science.gov (United States)

    Rørvik, Eivind; Thörnqvist, Sara; Stokkevåg, Camilla H; Dahle, Tordis J; Fjaera, Lars Fredrik; Ytre-Hauge, Kristian S

    2017-06-01

    The relative biological effectiveness (RBE) of protons varies with the radiation quality, quantified by the linear energy transfer (LET). Most phenomenological models employ a linear dependency of the dose-averaged LET (LET d ) to calculate the biological dose. However, several experiments have indicated a possible non-linear trend. Our aim was to investigate if biological dose models including non-linear LET dependencies should be considered, by introducing a LET spectrum based dose model. The RBE-LET relationship was investigated by fitting of polynomials from 1st to 5th degree to a database of 85 data points from aerobic in vitro experiments. We included both unweighted and weighted regression, the latter taking into account experimental uncertainties. Statistical testing was performed to decide whether higher degree polynomials provided better fits to the data as compared to lower degrees. The newly developed models were compared to three published LET d based models for a simulated spread out Bragg peak (SOBP) scenario. The statistical analysis of the weighted regression analysis favored a non-linear RBE-LET relationship, with the quartic polynomial found to best represent the experimental data (P = 0.010). The results of the unweighted regression analysis were on the borderline of statistical significance for non-linear functions (P = 0.053), and with the current database a linear dependency could not be rejected. For the SOBP scenario, the weighted non-linear model estimated a similar mean RBE value (1.14) compared to the three established models (1.13-1.17). The unweighted model calculated a considerably higher RBE value (1.22). The analysis indicated that non-linear models could give a better representation of the RBE-LET relationship. However, this is not decisive, as inclusion of the experimental uncertainties in the regression analysis had a significant impact on the determination and ranking of the models. As differences between the models were

  6. WE-B-304-02: Treatment Planning Evaluation and Optimization Should Be Biologically and Not Dose/volume Based

    International Nuclear Information System (INIS)

    Deasy, J.

    2015-01-01

    The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor control probability (TCP) with an acceptable normal tissue complication probability (NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. It has been suggested that treatment planning evaluation and optimization would be more effective if they were biologically and not dose/volume based, and this is the claim debated in this month’s Point/Counterpoint. After a brief overview of biologically and DVH based treatment planning by the Moderator Colin Orton, Joseph Deasy (for biological planning) and Charles Mayo (against biological planning) will begin the debate. Some of the arguments in support of biological planning include: this will result in more effective dose distributions for many patients DVH-based measures of plan quality are known to have little predictive value there is little evidence that either D95 or D98 of the PTV is a good predictor of tumor control sufficient validated outcome prediction models are now becoming available and should be used to drive planning and optimization Some of the arguments against biological planning include: several decades of experience with DVH-based planning should not be discarded we do not know enough about the reliability and errors associated with biological models the radiotherapy community in general has little direct experience with side by side comparisons of DVH vs biological metrics and outcomes it is unlikely that a clinician would accept extremely cold regions in a CTV or hot regions in a PTV, despite having acceptable TCP values Learning Objectives: To understand dose/volume based treatment planning and its potential limitations To understand biological metrics such as EUD, TCP, and NTCP To understand biologically based treatment planning and its potential limitations

  7. Dose estimation by biological methods

    International Nuclear Information System (INIS)

    Guerrero C, C.; David C, L.; Serment G, J.; Brena V, M.

    1997-01-01

    The human being is exposed to strong artificial radiation sources, mainly of two forms: the first is referred to the occupationally exposed personnel (POE) and the second, to the persons that require radiological treatment. A third form less common is by accidents. In all these conditions it is very important to estimate the absorbed dose. The classical biological dosimetry is based in the dicentric analysis. The present work is part of researches to the process to validate the In situ Fluorescent hybridation (FISH) technique which allows to analyse the aberrations on the chromosomes. (Author)

  8. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose response (BBDR) Model***

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (HPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the 1-IPT axis. Model calibrations, carried out by adjusting key model...

  9. Evaluation of iodide deficiency in the lactating rat and pup using a biologically based dose-response model

    Science.gov (United States)

    A biologically-based dose response (BBDR) model for the hypothalamic-pituitary thyroid (BPT) axis in the lactating rat and nursing pup was developed to describe the perturbations caused by iodide deficiency on the HPT axis. Model calibrations, carried out by adjusting key model p...

  10. Research toward the development of a biologically based dose response assessment for inorganic arsenic carcinogenicity: A progress report

    International Nuclear Information System (INIS)

    Clewell, Harvey J.; Thomas, Russell S.; Gentry, P. Robinan; Crump, Kenny S.; Kenyon, Elaina M.; El-Masri, Hisham A.; Yager, Janice W.

    2007-01-01

    Cancer risk assessments for inorganic arsenic have been based on human epidemiological data, assuming a linear dose response below the range of observation of tumors. Part of the reason for the continued use of the linear approach in arsenic risk assessments is the lack of an adequate biologically based dose response (BBDR) model that could provide a quantitative basis for an alternative nonlinear approach. This paper describes elements of an ongoing collaborative research effort between the CIIT Centers for Health Research, the U.S. Environmental Protection Agency, ENVIRON International, and EPRI to develop BBDR modeling approaches that could be used to inform a nonlinear cancer dose response assessment for inorganic arsenic. These efforts are focused on: (1) the refinement of physiologically based pharmacokinetic (PBPK) models of the kinetics of inorganic arsenic and its metabolites in the mouse and human; (2) the investigation of mathematical solutions for multi-stage cancer models involving multiple pathways of cell transformation; (3) the review and evaluation of the literature on the dose response for the genomic effects of arsenic; and (4) the collection of data on the dose response for genomic changes in the urinary bladder (a human target tissue for arsenic carcinogenesis) associated with in vivo drinking water exposures in the mouse as well as in vitro exposures of both mouse and human cells. An approach is proposed for conducting a biologically based margin of exposure risk assessment for inorganic arsenic using the in vitro dose response for the expression of genes associated with the obligatory precursor events for arsenic tumorigenesis

  11. Detection of base damage in DNA in human blood exposed to ionizing radiation at biologically relevant doses

    International Nuclear Information System (INIS)

    Loon, A.A.W.M. van; Lohman, P.H.M.; Groenendijk, R.H.; Schans, G.P. van der; Baan, R.A.

    1991-01-01

    The alkaline elution technique for the detection of DNA damage has been adapted to allow application on unlabelled blood cells. Both the induction and subsequent repair have been studied of two classes of DNA damage, viz. single-strand breaks and base damage recognized by the γ-endonuclease activity in a cell-free extract of Micrococcus luteus bacteria. The high sensitivity of the assay permitted the measurement of induction and repair of base damage after in vitro exposure of full blood under aerobic conditions to biologically relevant doses of γ-rays (1.5-4.5 Gy). After a radiation dose of 3 Gy about 50% of the base damage was removed within 1.5 h of repair. Base damage could still be detected at 24h after exposure to 15 Gy. (author)

  12. Isobio software: biological dose distribution and biological dose volume histogram from physical dose conversion using linear-quadratic-linear model.

    Science.gov (United States)

    Jaikuna, Tanwiwat; Khadsiri, Phatchareewan; Chawapun, Nisa; Saekho, Suwit; Tharavichitkul, Ekkasit

    2017-02-01

    To develop an in-house software program that is able to calculate and generate the biological dose distribution and biological dose volume histogram by physical dose conversion using the linear-quadratic-linear (LQL) model. The Isobio software was developed using MATLAB version 2014b to calculate and generate the biological dose distribution and biological dose volume histograms. The physical dose from each voxel in treatment planning was extracted through Computational Environment for Radiotherapy Research (CERR), and the accuracy was verified by the differentiation between the dose volume histogram from CERR and the treatment planning system. An equivalent dose in 2 Gy fraction (EQD 2 ) was calculated using biological effective dose (BED) based on the LQL model. The software calculation and the manual calculation were compared for EQD 2 verification with pair t -test statistical analysis using IBM SPSS Statistics version 22 (64-bit). Two and three-dimensional biological dose distribution and biological dose volume histogram were displayed correctly by the Isobio software. Different physical doses were found between CERR and treatment planning system (TPS) in Oncentra, with 3.33% in high-risk clinical target volume (HR-CTV) determined by D 90% , 0.56% in the bladder, 1.74% in the rectum when determined by D 2cc , and less than 1% in Pinnacle. The difference in the EQD 2 between the software calculation and the manual calculation was not significantly different with 0.00% at p -values 0.820, 0.095, and 0.593 for external beam radiation therapy (EBRT) and 0.240, 0.320, and 0.849 for brachytherapy (BT) in HR-CTV, bladder, and rectum, respectively. The Isobio software is a feasible tool to generate the biological dose distribution and biological dose volume histogram for treatment plan evaluation in both EBRT and BT.

  13. Biological Effects of Low-Dose Exposure

    CERN Document Server

    Komochkov, M M

    2000-01-01

    On the basis of the two-protection reaction model an analysis of stochastic radiobiological effects of low-dose exposure of different biological objects has been carried out. The stochastic effects are the results published in the last decade: epidemiological studies of human cancer mortality, the yield of thymocyte apoptosis of mice and different types of chromosomal aberrations. The results of the analysis show that as dependent upon the nature of biological object, spontanous effect, exposure conditions and radiation type one or another form dose - effect relationship is realized: downwards concave, near to linear and upwards concave with the effect of hormesis included. This result testifies to the incomplete conformity of studied effects of 1990 ICRP recomendations based on the linear no-threshold hypothesis about dose - effect relationship. Because of this the methodology of radiation risk estimation recomended by ICRP needs more precisian and such quantity as collective dose ought to be classified into...

  14. Doses due to tritium releases by NET - data base and relevant parameters on biological tritium behaviour

    International Nuclear Information System (INIS)

    Diabate, S.; Strack, S.

    1990-12-01

    This study gives an overview on the current knowledge about the behaviour of tritium in plants and in food chains in order to evaluate the ingestion pathway modelling of existing computer codes for dose estimations. The tritium uptake and retention by plants standing at the beginning of the food chains is described. The different chemical forms of tritium, which may be released into the atmosphere (HT, HTO and tritiated organics), and incorporation of tritium into organic material of plants are considered. Uptake and metabolism of tritiated compounds in animals and man are reviewed with particular respect to organically bound tritium and its significance for dose estimations. Some basic remarks on tritium toxicity are also included. Furthermore, a choice of computer codes for dose estimations due to chronic or accidental tritium releases has been compared with respect to the ingestion pathway. (orig.) [de

  15. Quantitative global sensitivity analysis of a biologically based dose-response pregnancy model for the thyroid endocrine system.

    Science.gov (United States)

    Lumen, Annie; McNally, Kevin; George, Nysia; Fisher, Jeffrey W; Loizou, George D

    2015-01-01

    A deterministic biologically based dose-response model for the thyroidal system in a near-term pregnant woman and the fetus was recently developed to evaluate quantitatively thyroid hormone perturbations. The current work focuses on conducting a quantitative global sensitivity analysis on this complex model to identify and characterize the sources and contributions of uncertainties in the predicted model output. The workflow and methodologies suitable for computationally expensive models, such as the Morris screening method and Gaussian Emulation processes, were used for the implementation of the global sensitivity analysis. Sensitivity indices, such as main, total and interaction effects, were computed for a screened set of the total thyroidal system descriptive model input parameters. Furthermore, a narrower sub-set of the most influential parameters affecting the model output of maternal thyroid hormone levels were identified in addition to the characterization of their overall and pair-wise parameter interaction quotients. The characteristic trends of influence in model output for each of these individual model input parameters over their plausible ranges were elucidated using Gaussian Emulation processes. Through global sensitivity analysis we have gained a better understanding of the model behavior and performance beyond the domains of observation by the simultaneous variation in model inputs over their range of plausible uncertainties. The sensitivity analysis helped identify parameters that determine the driving mechanisms of the maternal and fetal iodide kinetics, thyroid function and their interactions, and contributed to an improved understanding of the system modeled. We have thus demonstrated the use and application of global sensitivity analysis for a biologically based dose-response model for sensitive life-stages such as pregnancy that provides richer information on the model and the thyroidal system modeled compared to local sensitivity analysis.

  16. Quantitative global sensitivity analysis of a biologically based dose-response pregnancy model for the thyroid endocrine system

    Directory of Open Access Journals (Sweden)

    Annie eLumen

    2015-05-01

    Full Text Available A deterministic biologically based dose-response model for the thyroidal system in a near-term pregnant woman and the fetus was recently developed to evaluate quantitatively thyroid hormone perturbations. The current work focuses on conducting a quantitative global sensitivity analysis on this complex model to identify and characterize the sources and contributions of uncertainties in the predicted model output. The workflow and methodologies suitable for computationally expensive models, such as the Morris screening method and Gaussian Emulation processes, were used for the implementation of the global sensitivity analysis. Sensitivity indices, such as main, total and interaction effects, were computed for a screened set of the total thyroidal system descriptive model input parameters. Furthermore, a narrower sub-set of the most influential parameters affecting the model output of maternal thyroid hormone levels were identified in addition to the characterization of their overall and pair-wise parameter interaction quotients. The characteristic trends of influence in model output for each of these individual model input parameters over their plausible ranges were elucidated using Gaussian Emulation processes. Through global sensitivity analysis we have gained a better understanding of the model behavior and performance beyond the domains of observation by the simultaneous variation in model inputs over their range of plausible uncertainties. The sensitivity analysis helped identify parameters that determine the driving mechanisms of the maternal and fetal iodide kinetics, thyroid function and their interactions, and contributed to an improved understanding of the system modeled. We have thus demonstrated the use and application of global sensitivity analysis for a biologically based dose-response model for sensitive life-stages such as pregnancy that provides richer information on the model and the thyroidal system modeled compared to local

  17. On the sensitivity of IMRT dose optimization to the mathematical form of a biological imaging-based prescription function

    International Nuclear Information System (INIS)

    Bowen, Stephen R; Bentzen, Soeren M; Jeraj, Robert; Flynn, Ryan T

    2009-01-01

    Voxel-based prescriptions of deliberately non-uniform dose distributions based on molecular imaging, so-called dose painting or theragnostic radiation therapy, require specification of a transformation that maps the image data intensities to prescribed doses. However, the functional form of this transformation is currently unknown. An investigation into the sensitivity of optimized dose distributions resulting from several possible prescription functions was conducted. Transformations between the radiotracer activity concentrations from Cu-ATSM PET images, as a surrogate of tumour hypoxia, and dose prescriptions were implemented to yield weighted distributions of prescribed dose boosts in high uptake regions. Dose escalation was constrained to reflect clinically realistic whole tumour doses and constant normal tissue doses. Optimized heterogeneous dose distributions were found by minimizing a voxel-by-voxel quadratic objective function in which all tumour voxels were given equal weight. Prescriptions based on a polynomial mapping function were found to be least constraining on their optimized plans, while prescriptions based on a sigmoid mapping function were the most demanding to deliver. A prescription formalism that fixed integral dose was less sensitive to errors in the choice of the mapping function than one that boosted integral dose. Integral doses to normal tissue and critical structures were insensitive to the shape of the prescription function. Planned target dose conformity improved with smaller beamlet dimensions until the inherent spatial resolution of the functional image was matched. Clinical implementation of dose painting depends on advances in absolute quantification of functional images and improvements in delivery techniques over smaller spatial scales.

  18. Dose-volume and biological-model based comparison between helical tomotherapy and (inverse-planned) IMAT for prostate tumours

    International Nuclear Information System (INIS)

    Iori, Mauro; Cattaneo, Giovanni Mauro; Cagni, Elisabetta; Fiorino, Claudio; Borasi, Gianni; Riccardo, Calandrino; Iotti, Cinzia; Fazio, Ferruccio; Nahum, Alan E.

    2008-01-01

    Background and purpose: Helical tomotherapy (HT) and intensity-modulated arc therapy (IMAT) are two arc-based approaches to the delivery of intensity-modulated radiotherapy (IMRT). Through plan comparisons we have investigated the potential of IMAT, both with constant (conventional or IMAT-C) and variable (non-conventional or IMAT-NC, a theoretical exercise) dose-rate, to serve as an alternative to helical tomotherapy. Materials and methods: Six patients with prostate tumours treated by HT with a moderately hypo-fractionated protocol, involving a simultaneous integrated boost, were re-planned as IMAT treatments. A method for IMAT inverse-planning using a commercial module for static IMRT combined with a multi-leaf collimator (MLC) arc-sequencing was developed. IMAT plans were compared to HT plans in terms of dose statistics and radiobiological indices. Results: Concerning the planning target volume (PTV), the mean doses for all PTVs were similar for HT and IMAT-C plans with minimum dose, target coverage, equivalent uniform dose (EUD) and tumour control probability (TCP) values being generally higher for HT; maximum dose and degree of heterogeneity were instead higher for IMAT-C. In relation to organs at risk, mean doses and normal tissue complication probability (NTCP) values were similar between the two modalities, except for the penile bulb where IMAT was significantly better. Re-normalizing all plans to the same rectal toxicity (NTCP = 5%), the HT modality yielded higher TCP than IMAT-C but there was no significant difference between HT and IMAT-NC. The integral dose with HT was higher than that for IMAT. Conclusions: with regards to the plan analysis, the HT is superior to IMAT-C in terms of target coverage and dose homogeneity within the PTV. Introducing dose-rate variation during arc-rotation, not deliverable with current linac technology, the simulations result in comparable plan indices between (IMAT-NC) and HT

  19. Mathematical simulation of biologically equivalent doses for LDR-HDR

    International Nuclear Information System (INIS)

    Slosarek, K.; Zajusz, A.

    1996-01-01

    Based on the LQ model examples of biologically equivalent doses LDR, HDR and external beams were calculated. The biologically equivalent doses for LDR were calculated by appending to the LQ model the corrector for the time of repair of radiation sublethal damages. For radiation continuously delivered at a low dose rate the influence of sublethal damage repair time changes on biologically equivalent doses were analysed. For fractionated treatment with high dose rate the biologically equivalent doses were calculated by adding to the LQ model the formula of accelerated repopulation. For total biologically equivalent dose calculation for combine LDR-HDR-Tele irradiation examples are presented with the use of different parameters of the time of repair of sublethal damages and accelerated repopulation. The calculations performed show, that the same biologically equivalent doses can be obtained for different parameters of cell kinetics changes during radiation treatment. It also shows, that during biologically equivalent dose calculations for different radiotherapy schedules, ignorance of cell kinetics parameters can lead to relevant errors

  20. Biology of dose rate in brachytherapy

    International Nuclear Information System (INIS)

    Brenner, David J.

    1995-01-01

    Purpose: This course is designed for practitioners and beginners in brachytherapy. The aim is to review biological principles underlying brachytherapy, to understand why current treatment regimes are the way they are, and to discuss what the future may hold in store. Brachytherapy has a long history. It was suggested as long ago as 1903 by Alexander Graham Bell, and the optimal application of this technique has been a subject of debate ever since. 'Brachy' means 'short', and the essential features of conventional brachytherapy are: positioning of the source a short distance from, or in, the tumor, allowing good dose distributions; short overall treatment times, to counter tumor repopulation; low dose rate, enabling a good therapeutic advantage between tumor control and damage to late-responding tissue. The advantages of good dose distributions speak for themselves; in some situations, as we shall see, computer-based dose optimization can be used to improve them still further. The advantages of short overall times stem from the fact that accelerated repopulation of the tumor typically begins a few weeks after the start of a radiation treatment. If all the radiation can be crammed in before that time, the risks of tumor repopulation can be considerably reduced. In fact even external-beam radiotherapy is moving in this direction, with the use of highly accelerated protocols. The advantages of low dose rate stem from the differential response to fractionation of early- and late-responding tissues. Essentially, lowering the dose rate spares late-responding tissue more than it does early-responding tissue such as tumors. We shall also discuss some recent innovations in the context of the general principles that have been outlined. For example, High dose rate brachytherapy, particularly for the uterine cervix: Does it work? If so, when and why? Use of Ir-192 sources, with a half life of 70 days: Should corrections be made for changing biological effectiveness as the dose

  1. Clinically Applicable Monte Carlo–based Biological Dose Optimization for the Treatment of Head and Neck Cancers With Spot-Scanning Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wan Chan Tseung, Hok Seum, E-mail: wanchantseung.hok@mayo.edu; Ma, Jiasen; Kreofsky, Cole R.; Ma, Daniel J.; Beltran, Chris

    2016-08-01

    Purpose: Our aim is to demonstrate the feasibility of fast Monte Carlo (MC)–based inverse biological planning for the treatment of head and neck tumors in spot-scanning proton therapy. Methods and Materials: Recently, a fast and accurate graphics processor unit (GPU)–based MC simulation of proton transport was developed and used as the dose-calculation engine in a GPU-accelerated intensity modulated proton therapy (IMPT) optimizer. Besides dose, the MC can simultaneously score the dose-averaged linear energy transfer (LET{sub d}), which makes biological dose (BD) optimization possible. To convert from LET{sub d} to BD, a simple linear relation was assumed. By use of this novel optimizer, inverse biological planning was applied to 4 patients, including 2 small and 1 large thyroid tumor targets, as well as 1 glioma case. To create these plans, constraints were placed to maintain the physical dose (PD) within 1.25 times the prescription while maximizing target BD. For comparison, conventional intensity modulated radiation therapy (IMRT) and IMPT plans were also created using Eclipse (Varian Medical Systems) in each case. The same critical-structure PD constraints were used for the IMRT, IMPT, and biologically optimized plans. The BD distributions for the IMPT plans were obtained through MC recalculations. Results: Compared with standard IMPT, the biologically optimal plans for patients with small tumor targets displayed a BD escalation that was around twice the PD increase. Dose sparing to critical structures was improved compared with both IMRT and IMPT. No significant BD increase could be achieved for the large thyroid tumor case and when the presence of critical structures mitigated the contribution of additional fields. The calculation of the biologically optimized plans can be completed in a clinically viable time (<30 minutes) on a small 24-GPU system. Conclusions: By exploiting GPU acceleration, MC-based, biologically optimized plans were created for

  2. Strategies for Biologic Image-Guided Dose Escalation: A Review

    International Nuclear Information System (INIS)

    Sovik, Aste; Malinen, Eirik; Olsen, Dag Rune

    2009-01-01

    There is increasing interest in how to incorporate functional and molecular information obtained by noninvasive, three-dimensional tumor imaging into radiotherapy. The key issues are to identify radioresistant regions that can be targeted for dose escalation, and to develop radiation dose prescription and delivery strategies providing optimal treatment for the individual patient. In the present work, we review the proposed strategies for biologic image-guided dose escalation with intensity-modulated radiation therapy. Biologic imaging modalities and the derived images are discussed, as are methods for target volume delineation. Different dose escalation strategies and techniques for treatment delivery and treatment plan evaluation are also addressed. Furthermore, we consider the need for response monitoring during treatment. We conclude with a summary of the current status of biologic image-based dose escalation and of areas where further work is needed for this strategy to become incorporated into clinical practice

  3. Biological effective dose studies in carcinoma of uterine cervix

    International Nuclear Information System (INIS)

    Yadav, Poonam; Ramasubramanian, V.

    2008-01-01

    Cancer of cervix is the second most common cancer worldwide among women. Several treatments related protocols of radiotherapy have been followed over few decades in its treatment for evaluating the response. These physical doses varying on the basics of fractionation size, dose rate and total dose needed to be indicated as biological effective dose (BED) to rationalize these treatments. The curative potential of radiation therapy in the management of carcinoma of the cervix is greatly enhanced by the use of intracavitary brachytherapy. Successful brachytherapy requires the high radiation dose to be delivered to the tumor where as minimum radiation dose reach to surrounding normal tissue. Present study is aimed to evaluate biologically effective dose in patients receiving high dose-rate brachytherapy plus external beam radiotherapy based on tumor cell proliferation values in cancer of the cervix patients. The study includes 30 patients' data as a retrospective analysis. In addition determine extent of a dose-response relationship existing between the biological effective dose at Point A and the bladder and rectum and the clinical outcomes

  4. SU-C-202-04: Adapting Biologically Optimized Dose Escalation Based On Mid-Treatment PET/CT for Non-Small-Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, P; Kuo, L; Yorke, E; Hu, Y; Lockney, N; Mageras, G; Deasy, J; Rimner, A [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2016-06-15

    Purpose: To develop a biological modeling strategy which incorporates the response observed on the mid-treatment PET/CT into a dose escalation design for adaptive radiotherapy of non-small-cell lung cancer. Method: FDG-PET/CT was acquired midway through standard fractionated treatment and registered to pre-treatment planning PET/CT to evaluate radiation response of lung cancer. Each mid-treatment PET voxel was assigned the median SUV inside a concentric 1cm-diameter sphere to account for registration and imaging uncertainties. For each voxel, the planned radiation dose, pre- and mid-treatment SUVs were used to parameterize the linear-quadratic model, which was then utilized to predict the SUV distribution after the full prescribed dose. Voxels with predicted post-treatment SUV≥2 were identified as the resistant target (response arm). An adaptive simultaneous integrated boost was designed to escalate dose to the resistant target as high as possible, while keeping prescription dose to the original target and lung toxicity intact. In contrast, an adaptive target volume was delineated based only on the intensity of mid-treatment PET/CT (intensity arm), and a similar adaptive boost plan was optimized. The dose escalation capability of the two approaches was compared. Result: Images of three patients were used in this planning study. For one patient, SUV prediction indicated complete response and no necessary dose escalation. For the other two, resistant targets defined in the response arm were multifocal, and on average accounted for 25% of the pre-treatment target, compared to 67% in the intensity arm. The smaller response arm targets led to a 6Gy higher mean target dose in the adaptive escalation design. Conclusion: This pilot study suggests that adaptive dose escalation to a biologically resistant target predicted from a pre- and mid-treatment PET/CT may be more effective than escalation based on the mid-treatment PET/CT alone. More plans and ultimately clinical

  5. Biological evidence of low ionizing radiation doses

    International Nuclear Information System (INIS)

    Mirsch, Johanna

    2017-01-01

    Throughout life, every person is constantly exposed to different types of ionising radiation, without even noticing the exposure. The mean radiation exposure for people living in Germany amounts to approximately 4 mSv per year and encompasses the exposure from natural and man-made sources. The risks associated with exposure to low doses of radiation are still the subject of intense and highly controversial discussions, emphasizing the social relevance of studies investigating the effects of low radiation doses. In this thesis, DNA double-strand breaks (DSBs) were analyzed within three projects covering different aspects. DSBs are among the most hazardous DNA lesions induced by ionizing radiation, because this type of damage can easily lead to the loss of genetic information. Consequently, the DSB presents a high risk for the genetic integrity of the cell. In the first project, extensive results uncovered the track structure of charged particles in a biological model tissue. This provided the first biological data that could be used for comparison with data that were measured or predicted using theoretical physical dosimetry methods and mathematical simulations. Charged particles contribute significantly to the natural radiation exposure and are used increasingly in cancer radiotherapy because they are more efficient in tumor cell killing than X- or γ-rays. The difference in the biological effects of high energy charged particles compared with X- or γ-rays is largely determined by the spatial distribution of their energy deposition and the track structure inducing a three-dimensional damage pattern in living cells. This damage pattern consists of cells directly hit by the particle receiving a high dose and neighboring cells not directly hit by primary particles but exposed to far-reaching secondary electrons (δ-electrons). These cells receive a much lower dose deposition in the order of a few mGy. The radial dose distribution of single particle tracks was

  6. Low dose irradiation and biological defense mechanisms

    International Nuclear Information System (INIS)

    Sugahara, Tsutomu; Sagan, L.A.; Aoyama, Takashi

    1992-01-01

    It has been generally accepted in the context of radiation protection that ionizing radiation has some adverse effect even at low doses. However, epidemiological studies of human populations cannot definitively show its existence or absence. Furthermore, recent studies of populations living in areas of different background radiation levels reported some decrease in adverse health effects at high background levels. Genetic studies of atomic bomb survivors failed to produce statistically significant findings on the mutagenic effects of ionizing radiation. A British study however, suggests that a father's exposure to low dose radiation on the job may increase his children's risk of leukemia. On the other hand, many experimental studies have raised the possibility that low doses of ionizing radiation may not be harmful or may even produce stimulating or adaptive responses. The term 'hormesis' has come to be used to describe these phenomena produced by low doses of ionizing radiation when they were beneficial for the organisms studied. At the end of the International Conference on Low Dose Irradiation one conclusion appeared to be justified: radiation produces an adaptive response, though it is not universally detected yet. The conference failed to obtain any consensus on risk assessment at low doses, but raised many problems to be dealt with by future studies. The editors therefore believe that the Proceedings will be useful for all scientists and people concerned with radiation protection and the biological effects of low-dose irradiation

  7. Evaluation of perturbations in serum thyroid hormones during human pregnancy due to dietary iodide and perchlorate exposure using a biologically based dose-response model.

    Science.gov (United States)

    Lumen, Annie; Mattie, David R; Fisher, Jeffrey W

    2013-06-01

    A biologically based dose-response model (BBDR) for the hypothalamic pituitary thyroid (HPT) axis was developed in the near-term pregnant mother and fetus. This model was calibrated to predict serum levels of iodide, total thyroxine (T4), free thyroxine (fT4), and total triiodothyronine (T3) in the mother and fetus for a range of dietary iodide intake. The model was extended to describe perchlorate, an environmental and food contaminant, that competes with the sodium iodide symporter protein for thyroidal uptake of iodide. Using this mode-of-action framework, simulations were performed to determine the daily ingestion rates of perchlorate that would be associated with hypothyroxinemia or onset of hypothyroidism for varying iodide intake. Model simulations suggested that a maternal iodide intake of 75 to 250 µg/day and an environmentally relevant exposure of perchlorate (~0.1 µg/kg/day) did not result in hypothyroxinemia or hypothyroidism. For a daily iodide-sufficient intake of 200 µg/day, the dose of perchlorate required to reduce maternal fT4 levels to a hypothyroxinemic state was estimated at 32.2 µg/kg/day. As iodide intake was lowered to 75 µg/day, the model simulated daily perchlorate dose required to cause hypothyroxinemia was reduced by eightfold. Similarly, the perchlorate intake rates associated with the onset of subclinical hypothyroidism ranged from 54.8 to 21.5 µg/kg/day for daily iodide intake of 250-75 µg/day. This BBDR-HPT axis model for pregnancy provides an example of a novel public health assessment tool that may be expanded to address other endocrine-active chemicals found in food and the environment.

  8. 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)

  9. Normal tissue dose-effect models in biological dose optimisation

    International Nuclear Information System (INIS)

    Alber, M.

    2008-01-01

    Sophisticated radiotherapy techniques like intensity modulated radiotherapy with photons and protons rely on numerical dose optimisation. The evaluation of normal tissue dose distributions that deviate significantly from the common clinical routine and also the mathematical expression of desirable properties of a dose distribution is difficult. In essence, a dose evaluation model for normal tissues has to express the tissue specific volume effect. A formalism of local dose effect measures is presented, which can be applied to serial and parallel responding tissues as well as target volumes and physical dose penalties. These models allow a transparent description of the volume effect and an efficient control over the optimum dose distribution. They can be linked to normal tissue complication probability models and the equivalent uniform dose concept. In clinical applications, they provide a means to standardize normal tissue doses in the face of inevitable anatomical differences between patients and a vastly increased freedom to shape the dose, without being overly limiting like sets of dose-volume constraints. (orig.)

  10. Application of biological dose concept in dose optimization for conformal radiotherapy of prostate carcinoma

    International Nuclear Information System (INIS)

    Li Yunhai; Liao Yuan; Zhou Lijun; Pan Ziqiang; Feng Yan

    2003-01-01

    Objective: On basis of physical dose optimization, LQ model was used to investigate the difference between the curves of biological effective dose and physical isodose. The influence of applying the biological dose concept on three dimensional conformal radiotherapy of prostate carcinoma was discussed. Methods: Four treatment plannings were designed for physical dose optimization: three fields, four-box fields, five fields and six fields. Target dose uniformity and protection of the critical tissue-rectum were used as the principal standard for designing the treatment planning. Biological effective dose (BED) was calculated by LQ model. The difference between the BED curve drawn in the central layer and the physical isodose curve was studied. The difference between the adjusted physical dose (APD) and the physical dose was also studied. Results: Five field planning was the best in target dose uniformity and protection of the critical tissue-rectum. The physical dose was uniform in the target, but the biological effective doses revealed great discrepancy in the biological model. Adjusted physical dose distribution also displayed larger discrepancy than the physical dose unadjusted. Conclusions: Intensified Modulated Radiotherapy (IMRT) technique with inversion planning using biological dose concept may be much more advantageous to reach a high tumor control probability and low normal tissue complication probability

  11. A new method for dosing uranium in biological media

    International Nuclear Information System (INIS)

    Henry, Ph.; Kobisch, Ch.

    1964-01-01

    This report describes a new method for dosing uranium in biological media based on measurement of alpha activity. After treatment of the sample with a mineral acid, the uranium is reduced to the valency four by trivalent titanium and is precipitated as phosphate in acid solution. The uranium is then separated from the titanium by precipitation as UF 4 with lanthanum as carrier. A slight modification, unnecessary in the case of routine analyses, makes it possible to eliminate other possible alpha emitters (thorium and transuranic elements). (authors) [fr

  12. Biological effects of low-dose ionizing radiation exposure

    International Nuclear Information System (INIS)

    Reinoehl-Kompa, Sabine; Baldauf, Daniela; Heller, Horst

    2009-01-01

    The report on the meeting of the Strahlenschutzkommission 2007 concerning biological effects of low-dose ionizing radiation exposure includes the following contributions: Adaptive response. The importance of DNA damage mechanisms for the biological efficiency of low-energy photons. Radiation effects in mammography: the relative biological radiation effects of low-energy photons. Radiation-induced cataracts. Carcinomas following prenatal radiation exposure. Intercellular apoptosis induction and low-dose irradiation: possible consequences for the oncogenesis control. Mechanistic models for the carcinogenesis with radiation-induced cell inactivation: application to all solid tumors in the Japanese atomic bomb survivors. Microarrays at low radiation doses. Mouse models for the analysis of biological effects of low-dose ionizing radiation. The bystander effect: observations, mechanisms and implications. Lung carcinoma risk of Majak workers - modeling of carcinogenesis and the bystander effect. Microbeam studies in radiation biology - an overview. Carcinogenesis models with radiation-induced genomic instability. Application to two epidemiological cohorts.

  13. Predicted allowable doses to normal organs for biologically targeted radiotherapy

    International Nuclear Information System (INIS)

    O'Donoghue, J.A.; Wheldon, T.E.; Western Regional Hospital Board, Glasgow

    1988-01-01

    The authors have used Dale's extension to the ''linear quadratic'' (LQ) model (Dale, 1985) to evaluate ''equivalent doses'' in cases involving exponentially decaying dose rates. This analysis indicates that the dose-rate effect will be a significant determinant of allowable doses to organs such as liver, kidney and lung. These organ tolerance doses constitute independent constraints on the therapeutic intensity of biologically targeted radiotherapy in exactly the same way as for conventional external beam radiotherapy. In the context of marrow rescue they will in all likelihood constitute the dose-limiting side-effects and thus be especially important. (author)

  14. Towards biologically conformal radiation therapy (BCRT): Selective IMRT dose escalation under the guidance of spatial biology distribution

    International Nuclear Information System (INIS)

    Yang Yong; Xing Lei

    2005-01-01

    It is well known that the spatial biology distribution (e.g., clonogen density, radiosensitivity, tumor proliferation rate, functional importance) in most tumors and sensitive structures is heterogeneous. Recent progress in biological imaging is making the mapping of this distribution increasingly possible. The purpose of this work is to establish a theoretical framework to quantitatively incorporate the spatial biology data into intensity modulated radiation therapy (IMRT) inverse planning. In order to implement this, we first derive a general formula for determining the desired dose to each tumor voxel for a known biology distribution of the tumor based on a linear-quadratic model. The desired target dose distribution is then used as the prescription for inverse planning. An objective function with the voxel-dependent prescription is constructed with incorporation of the nonuniform dose prescription. The functional unit density distribution in a sensitive structure is also considered phenomenologically when constructing the objective function. Two cases with different hypothetical biology distributions are used to illustrate the new inverse planning formalism. For comparison, treatments with a few uniform dose prescriptions and a simultaneous integrated boost are also planned. The biological indices, tumor control probability (TCP) and normal tissue complication probability (NTCP), are calculated for both types of plans and the superiority of the proposed technique over the conventional dose escalation scheme is demonstrated. Our calculations revealed that it is technically feasible to produce deliberately nonuniform dose distributions with consideration of biological information. Compared with the conventional dose escalation schemes, the new technique is capable of generating biologically conformal IMRT plans that significantly improve the TCP while reducing or keeping the NTCPs at their current levels. Biologically conformal radiation therapy (BCRT

  15. TU-AB-BRC-02: Accuracy Evaluation of GPU-Based OpenCL Carbon Monte Carlo Package (goCMC) in Biological Dose and Microdosimetry in Comparison to FLUKA Simulations

    Energy Technology Data Exchange (ETDEWEB)

    Taleei, R; Peeler, C; Qin, N; Jiang, S; Jia, X [UT Southwestern Medical Center, Dallas, TX (United States)

    2016-06-15

    Purpose: One of the most accurate methods for radiation transport is Monte Carlo (MC) simulation. Long computation time prevents its wide applications in clinic. We have recently developed a fast MC code for carbon ion therapy called GPU-based OpenCL Carbon Monte Carlo (goCMC) and its accuracy in physical dose has been established. Since radiobiology is an indispensible aspect of carbon ion therapy, this study evaluates accuracy of goCMC in biological dose and microdosimetry by benchmarking it with FLUKA. Methods: We performed simulations of a carbon pencil beam with 150, 300 and 450 MeV/u in a homogeneous water phantom using goCMC and FLUKA. Dose and energy spectra for primary and secondary ions on the central beam axis were recorded. Repair-misrepair-fixation model was employed to calculate Relative Biological Effectiveness (RBE). Monte Carlo Damage Simulation (MCDS) tool was used to calculate microdosimetry parameters. Results: Physical dose differences on the central axis were <1.6% of the maximum value. Before the Bragg peak, differences in RBE and RBE-weighted dose were <2% and <1%. At the Bragg peak, the differences were 12.5% caused by small range discrepancy and sensitivity of RBE to beam spectra. Consequently, RBE-weighted dose difference was 11%. Beyond the peak, RBE differences were <20% and primarily caused by differences in the Helium-4 spectrum. However, the RBE-weighted dose agreed within 1% due to the low physical dose. Differences in microdosimetric quantities were small except at the Bragg peak. The simulation time per source particle with FLUKA was 0.08 sec, while goCMC was approximately 1000 times faster. Conclusion: Physical doses computed by FLUKA and goCMC were in good agreement. Although relatively large RBE differences were observed at and beyond the Bragg peak, the RBE-weighted dose differences were considered to be acceptable.

  16. Cytogenetic biological dosimetry. Dose estimative in accidental exposure

    International Nuclear Information System (INIS)

    Santos, O.R. dos; Campos, I.M.A. de.

    1988-01-01

    The methodology of cytogenetic biological dosimetry is studied. The application in estimation of dose in five cases of accidental exposure is reported. An hematological study and culture of lymphocytes is presented. (M.A.C.) [pt

  17. The relative biological effectiveness of out-of-field dose

    International Nuclear Information System (INIS)

    Balderson, Michael; Koger, Brandon; Kirkby, Charles

    2016-01-01

    Purpose: using simulations and models derived from existing literature, this work investigates relative biological effectiveness (RBE) for out-of-field radiation and attempts to quantify the relative magnitudes of different contributing phenomena (spectral, bystander, and low dose hypersensitivity effects). Specific attention is paid to external beam radiotherapy treatments for prostate cancer. Materials and methods: using different biological models that account for spectral, bystander, and low dose hypersensitivity effects, the RBE was calculated for different points moving radially out from isocentre for a typical single arc VMAT prostate case. The RBE was found by taking the ratio of the equivalent dose with the physical dose. Equivalent doses were calculated by determining what physical dose would be necessary to produce the same overall biological effect as that predicted using the different biological models. Results: spectral effects changed the RBE out-of-field less than 2%, whereas response models incorporating low dose hypersensitivity and bystander effects resulted in a much more profound change of the RBE for out-of-field doses. The bystander effect had the largest RBE for points located just outside the edge of the primary radiation beam in the cranial caudal (z-direction) compared to low dose hypersensitivity and spectral effects. In the coplanar direction, bystander effect played the largest role in enhancing the RBE for points up to 8.75 cm from isocentre. Conclusions: spectral, bystander, and low dose hypersensitivity effects can all increase the RBE for out-of-field radiation doses. In most cases, bystander effects seem to play the largest role followed by low dose hypersensitivity. Spectral effects were unlikely to be of any clinical significance. Bystander, low dose hypersensitivity, and spectral effect increased the RBE much more in the cranial caudal direction (z-direction) compared with the coplanar directions. (paper)

  18. Radiation research contracts: Biological effects of small radiation doses

    Energy Technology Data Exchange (ETDEWEB)

    Hug, O [International Atomic Energy Agency, Division of Health, Safety and Waste Disposal, Vienna (Austria)

    1959-04-15

    To establish the maximum permissible radiation doses for occupational and other kinds of radiation exposure, it is necessary to know those biological effects which can be produced by very small radiation doses. This particular field of radiation biology has not yet been sufficiently explored. This holds true for possible delayed damage after occupational radiation exposure over a period of many years as well as for acute reactions of the organism to single low level exposures. We know that irradiation of less than 25 Roentgen units (r) is unlikely to produce symptoms of radiation sickness. We have, however, found indications that even smaller doses may produce certain instantaneous reactions which must not be neglected

  19. Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

    Energy Technology Data Exchange (ETDEWEB)

    Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States)

    2013-05-15

    Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

  20. Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions

    International Nuclear Information System (INIS)

    Zeng Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A.; Trofimov, Alexei

    2013-01-01

    Purpose: Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. Methods: For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor

  1. Maximizing the biological effect of proton dose delivered with scanned beams via inhomogeneous daily dose distributions.

    Science.gov (United States)

    Zeng, Chuan; Giantsoudi, Drosoula; Grassberger, Clemens; Goldberg, Saveli; Niemierko, Andrzej; Paganetti, Harald; Efstathiou, Jason A; Trofimov, Alexei

    2013-05-01

    Biological effect of radiation can be enhanced with hypofractionation, localized dose escalation, and, in particle therapy, with optimized distribution of linear energy transfer (LET). The authors describe a method to construct inhomogeneous fractional dose (IFD) distributions, and evaluate the potential gain in the therapeutic effect from their delivery in proton therapy delivered by pencil beam scanning. For 13 cases of prostate cancer, the authors considered hypofractionated courses of 60 Gy delivered in 20 fractions. (All doses denoted in Gy include the proton's mean relative biological effectiveness (RBE) of 1.1.) Two types of plans were optimized using two opposed lateral beams to deliver a uniform dose of 3 Gy per fraction to the target by scanning: (1) in conventional full-target plans (FTP), each beam irradiated the entire gland, (2) in split-target plans (STP), beams irradiated only the respective proximal hemispheres (prostate split sagittally). Inverse planning yielded intensity maps, in which discrete position control points of the scanned beam (spots) were assigned optimized intensity values. FTP plans preferentially required a higher intensity of spots in the distal part of the target, while STP, by design, employed proximal spots. To evaluate the utility of IFD delivery, IFD plans were generated by rearranging the spot intensities from FTP or STP intensity maps, separately as well as combined using a variety of mixing weights. IFD courses were designed so that, in alternating fractions, one of the hemispheres of the prostate would receive a dose boost and the other receive a lower dose, while the total physical dose from the IFD course was roughly uniform across the prostate. IFD plans were normalized so that the equivalent uniform dose (EUD) of rectum and bladder did not increase, compared to the baseline FTP plan, which irradiated the prostate uniformly in every fraction. An EUD-based model was then applied to estimate tumor control probability

  2. Dose prescription complexity versus tumor control probability in biologically conformal radiotherapy

    International Nuclear Information System (INIS)

    South, C. P.; Evans, P. M.; Partridge, M.

    2009-01-01

    The technical feasibility and potential benefits of voxel-based nonuniform dose prescriptions for biologically heterogeneous tumors have been widely demonstrated. In some cases, an ''ideal'' dose prescription has been generated by individualizing the dose to every voxel within the target, but often this voxel-based prescription has been discretized into a small number of compartments. The number of dose levels utilized and the methods used for prescribing doses and assigning tumor voxels to different dose compartments have varied significantly. The authors present an investigation into the relationship between the complexity of the dose prescription and the tumor control probability (TCP) for a number of these methods. The linear quadratic model of cell killing was used in conjunction with a number of modeled tumors heterogeneous in clonogen density, oxygenation, or proliferation. Models based on simple mathematical functions, published biological data, and biological image data were investigated. Target voxels were assigned to dose compartments using (i) simple rules based on the initial biological distribution, (ii) iterative methods designed to maximize the achievable TCP, or (iii) methods based on an ideal dose prescription. The relative performance of the simple rules was found to depend on the form of heterogeneity of the tumor, while the iterative and ideal dose methods performed comparably for all models investigated. In all cases the maximum achievable TCP was approached within the first few (typically two to five) compartments. Results suggest that irrespective of the pattern of heterogeneity, the optimal dose prescription can be well approximated using only a few dose levels but only if both the compartment boundaries and prescribed dose levels are well chosen.

  3. Biological-based and physical-based optimization for biological evaluation of prostate patient's plans

    Science.gov (United States)

    Sukhikh, E.; Sheino, I.; Vertinsky, A.

    2017-09-01

    Modern modalities of radiation treatment therapy allow irradiation of the tumor to high dose values and irradiation of organs at risk (OARs) to low dose values at the same time. In this paper we study optimal radiation treatment plans made in Monaco system. The first aim of this study was to evaluate dosimetric features of Monaco treatment planning system using biological versus dose-based cost functions for the OARs and irradiation targets (namely tumors) when the full potential of built-in biological cost functions is utilized. The second aim was to develop criteria for the evaluation of radiation dosimetry plans for patients based on the macroscopic radiobiological criteria - TCP/NTCP. In the framework of the study four dosimetric plans were created utilizing the full extent of biological and physical cost functions using dose calculation-based treatment planning for IMRT Step-and-Shoot delivery of stereotactic body radiation therapy (SBRT) in prostate case (5 fractions per 7 Gy).

  4. Review of low dose-rate epidemiological studies and biological mechanisms of dose-rate effects on radiation induced carcinogenesis

    International Nuclear Information System (INIS)

    Iwasaki, Toshiyasu; Otsuka, Kensuke; Yoshida, Kazuo

    2015-01-01

    Radiation protection system adopts the linear non-threshold model with using dose and dose-rate effectiveness factor (DDREF). The dose-rate range where DDREF is applied is below 100 mGy per hour, and it is regarded that there are no dose-rate effects at very low dose rate, less than of the order of 10 mGy per year, even from the biological risk evaluation model based on cellular and molecular level mechanisms for maintenance of genetic integrity. Among low dose-rate epidemiological studies, studies of residents in high natural background areas showed no increase of cancer risks at less than about 10 mGy per year. On the other hand, some studies include a study of the Techa River cohort suggested the increase of cancer risks to the similar degree of Atomic bomb survivor data. The difference of those results was supposed due to the difference of dose rate. In 2014, International Commission on Radiological Protection opened a draft report on stem cell biology for public consultations. The report proposed a hypothesis based on the new idea of stem cell competition as a tissue level quality control mechanism, and suggested that it could explain the dose-rate effects around a few milligray per year. To verify this hypothesis, it would be needed to clarify the existence and the lowest dose of radiation-induced stem cell competition, and to elucidate the rate of stem cell turnover and radiation effects on it. As for the turnover, replenishment of damaged stem cells would be the important biological process. It would be meaningful to collect the information to show the difference of dose rates where the competition and the replenishment would be the predominant processes. (author)

  5. Biological indicators for radiation absorbed dose: a review

    International Nuclear Information System (INIS)

    Paul, S.F.D.; Venkatachalam, P.; Jeevanram, R.K.

    1996-01-01

    Biological dosimetry has an important role to play in assessing the cumulative radiation exposure of persons working with radiation and also in estimating the true dose received during accidents involving external and internal exposure. Various biodosimetric methods have been tried to estimate radiation dose for the above purposes. Biodosimetric methods include cytogenetic, immunological and mutational assays. Each technique has certain advantages and disadvantages. We present here a review of each technique, the actual method used for detection of dose, the sensitivity of detection and its use in long term studies. (author)

  6. A Paradigm Shift in Low Dose Radiation Biology

    Directory of Open Access Journals (Sweden)

    Z. Alatas

    2015-08-01

    Full Text Available When ionizing radiation traverses biological material, some energy depositions occur and ionize directly deoxyribonucleic acid (DNA molecules, the critical target. A classical paradigm in radiobiology is that the deposition of energy in the cell nucleus and the resulting damage to DNA are responsible for the detrimental biological effects of radiation. It is presumed that no radiation effect would be expected in cells that receive no direct radiation exposure through nucleus. The risks of exposure to low dose ionizing radiation are estimated by extrapolating from data obtained after exposure to high dose radiation. However, the validity of using this dose-response model is controversial because evidence accumulated over the past decade has indicated that living organisms, including humans, respond differently to low dose radiation than they do to high dose radiation. Moreover, recent experimental evidences from many laboratories reveal the fact that radiation effects also occur in cells that were not exposed to radiation and in the progeny of irradiated cells at delayed times after radiation exposure where cells do not encounter direct DNA damage. Recently, the classical paradigm in radiobiology has been shifted from the nucleus, specifically the DNA, as the principal target for the biological effects of radiation to cells. The universality of target theory has been challenged by phenomena of radiation-induced genomic instability, bystander effect and adaptive response. The new radiation biology paradigm would cover both targeted and non-targeted effects of ionizing radiation. The mechanisms underlying these responses involve biochemical/molecular signals that respond to targeted and non-targeted events. These results brought in understanding that the biological response to low dose radiation at tissue or organism level is a complex process of integrated response of cellular targets as well as extra-cellular factors. Biological understanding of

  7. 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

  8. PET imaging for the quantification of biologically heterogeneous tumours: measuring the effect of relative position on image-based quantification of dose-painting targets

    International Nuclear Information System (INIS)

    McCall, Keisha C; Barbee, David L; Kissick, Michael W; Jeraj, Robert

    2010-01-01

    measurement of contrast recovery values which were larger than 30%. However, the magnitudes of the errors were found to depend on the size of the sphere and method of image reconstruction. The error values from standard OSEM images of the 5 mm diameter sphere were 20-35%, and for the 10 mm diameter sphere were 5-10%. The position-dependent variation of contrast recovery can result in changes in spatial distribution within images of heterogeneous tumours. In experiments simulating random set-up errors during imaging of two HN patients, the expectation value of the correlation was ∼1.0 for these tumours; however, Pearson correlation coefficient values as low as 0.8 were observed. Moreover, variations within the images can drastically change the delineation of biological target volumes. The errors in target delineation were more prominent in very heterogeneous tumours. As an example, in a pair of images with a correlation of 0.8, there was a 36% change in the volume of the dose-painting target delineated at 50%-of-max-SUV (ROI 50% ). The results of these studies indicate that the contrast recovery and spatial distributions of tracer within PET images are susceptible to changes in the position of the patient/tumour at the time of imaging. As such, random set-up errors in HN patients can result in reduced correlation between subsequent image-studies of the same tumour.

  9. WE-B-304-00: Point/Counterpoint: Biological Dose Optimization

    International Nuclear Information System (INIS)

    2015-01-01

    The ultimate goal of radiotherapy treatment planning is to find a treatment that will yield a high tumor control probability (TCP) with an acceptable normal tissue complication probability (NTCP). Yet most treatment planning today is not based upon optimization of TCPs and NTCPs, but rather upon meeting physical dose and volume constraints defined by the planner. It has been suggested that treatment planning evaluation and optimization would be more effective if they were biologically and not dose/volume based, and this is the claim debated in this month’s Point/Counterpoint. After a brief overview of biologically and DVH based treatment planning by the Moderator Colin Orton, Joseph Deasy (for biological planning) and Charles Mayo (against biological planning) will begin the debate. Some of the arguments in support of biological planning include: this will result in more effective dose distributions for many patients DVH-based measures of plan quality are known to have little predictive value there is little evidence that either D95 or D98 of the PTV is a good predictor of tumor control sufficient validated outcome prediction models are now becoming available and should be used to drive planning and optimization Some of the arguments against biological planning include: several decades of experience with DVH-based planning should not be discarded we do not know enough about the reliability and errors associated with biological models the radiotherapy community in general has little direct experience with side by side comparisons of DVH vs biological metrics and outcomes it is unlikely that a clinician would accept extremely cold regions in a CTV or hot regions in a PTV, despite having acceptable TCP values Learning Objectives: To understand dose/volume based treatment planning and its potential limitations To understand biological metrics such as EUD, TCP, and NTCP To understand biologically based treatment planning and its potential limitations

  10. 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

  11. The biological effects of low doses of radiation: medical, biological and ecological aspects

    International Nuclear Information System (INIS)

    Gun-Aajav, T.; Ajnai, L.; Manlaijav, G.

    2007-01-01

    Full text: The results of recent studies show that low doses of radiation make many different structural and functional changes in a cell and these changes are preserved for a long time. This phenomenon is called as effects of low doses of radiation in biophysics, radiation biology and radiation medicine. The structural and functional changes depend on doses and this dependence has non-linear and bimodal behaviour. More detail, the radiation effect goes up and reaches its maximum (Low doses maximum) in low doses region, then it goes down and takes its stationary means (there is a negative effect in a few cases). With increases in doses and with further increases it goes up. It is established that low dose's maximum depends on physiological state of a biological object, radiation quality and dose rate. During the experiments another special date was established. This specialty is that many different physical and chemical factors are mutually connected and have synergetic behaviour. At present, researches are concentrating their attention on the following three directions: 1. Direct and indirect interaction of radiation's low doses: 2. Interpretation of its molecular mechanism, regulation of the positive effects and elaboration of ways o removing negative effects: 3. Application of the objective research results into practice. In conclusion the authors mention the current concepts on interpretation of low doses effect mechanism, forward their own views and emphasize the importance of considering low doses effects in researches of environmental radiation pollution, radiation medicine and radiation protection. (author)

  12. Biological dosimetry: chromosomal aberration analysis for dose assessment

    International Nuclear Information System (INIS)

    1986-01-01

    In view of the growing importance of chromosomal aberration analysis as a biological dosimeter, the present report provides a concise summary of the scientific background of the subject and a comprehensive source of information at the technical level. After a review of the basic principles of radiation dosimetry and radiation biology basic information on the biology of lymphocytes, the structure of chromosomes and the classification of chromosomal aberrations are presented. This is followed by a presentation of techniques for collecting blood, storing, transporting, culturing, making chromosomal preparations and scaring of aberrations. The physical and statistical parameters involved in dose assessment are discussed and examples of actual dose assessments taken from the scientific literature are given

  13. Confectionery-based dose forms.

    Science.gov (United States)

    Tangso, Kristian J; Ho, Quy Phuong; Boyd, Ben J

    2015-01-01

    Conventional dosage forms such as tablets, capsules and syrups are prescribed in the normal course of practice. However, concerns about patient preferences and market demands have given rise to the exploration of novel unconventional dosage forms. Among these, confectionery-based dose forms have strong potential to overcome compliance problems. This report will review the availability of these unconventional dose forms used in treating the oral cavity and for systemic drug delivery, with a focus on medicated chewing gums, medicated lollipops, and oral bioadhesive devices. The aim is to stimulate increased interest in the opportunities for innovative new products that are available to formulators in this field, particularly for atypical patient populations.

  14. Biological impact of high-dose and dose-rate radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Maliev, V.; Popov, D. [Russian Academy of Science, Vladicaucas (Russian Federation); Jones, J.; Gonda, S. [NASA -Johnson Space Center, Houston (United States); Prasad, K.; Viliam, C.; Haase, G. [Antioxida nt Research Institute, Premier Micronutrient Corporation, Novato (United States); Kirchin, V. [Moscow State Veterinary and Biotechnology Acade my, Moscow (Russian Federation); Rachael, C. [University Space Research Association, Colorado (United States)

    2006-07-01

    Experimental anti-radiation vaccine is a power tool of immune - prophylaxis of the acute radiation disease. Existing principles of treatment of the acute radiation dis ease are based on a correction of developing patho-physiological and biochemical processes within the first days after irradiation. Protection from radiation is built on the general principles of immunology and has two main forms - active and passive immunization. Active immunization by the essential radiation toxins of specific radiation determinant (S.D.R.) group allows significantly reduce the lethality and increase duration of life among animals that are irradiated by lethal and sub-lethal doses of gamma radiation.The radiation toxins of S.D.R. group have antigenic properties that are specific for different forms of acute radiation disease. Development of the specific and active immune reaction after intramuscular injection of radiation toxins allows optimize a manifestation of a clinical picture and stabilize laboratory parameters of the acute radiation syndromes. Passive immunization by the anti-radiation serum or preparations of immune-globulins gives a manifestation of the radioprotection effects immediately after this kind of preparation are injected into organisms of mammals. Providing passive immunization by preparations of anti-radiations immune-globulins is possible in different periods of time after radiation. Providing active immunization by preparations of S.D.R. group is possible only to achieve a prophylaxis goal and form the protection effects that start to work in 18 - 35 days after an injection of biological active S.D.R. substance has been administrated. However active and passive immunizations by essential anti-radiation toxins and preparations of gamma-globulins extracted from a hyper-immune serum of a horse have significantly different medical prescriptions for application and depend on many factors like a type of radiation, a power of radiation, absorption doses, a time of

  15. Biological impact of high-dose and dose-rate radiation exposure

    International Nuclear Information System (INIS)

    Maliev, V.; Popov, D.; Jones, J.; Gonda, S.; Prasad, K.; Viliam, C.; Haase, G.; Kirchin, V.; Rachael, C.

    2006-01-01

    Experimental anti-radiation vaccine is a power tool of immune - prophylaxis of the acute radiation disease. Existing principles of treatment of the acute radiation dis ease are based on a correction of developing patho-physiological and biochemical processes within the first days after irradiation. Protection from radiation is built on the general principles of immunology and has two main forms - active and passive immunization. Active immunization by the essential radiation toxins of specific radiation determinant (S.D.R.) group allows significantly reduce the lethality and increase duration of life among animals that are irradiated by lethal and sub-lethal doses of gamma radiation.The radiation toxins of S.D.R. group have antigenic properties that are specific for different forms of acute radiation disease. Development of the specific and active immune reaction after intramuscular injection of radiation toxins allows optimize a manifestation of a clinical picture and stabilize laboratory parameters of the acute radiation syndromes. Passive immunization by the anti-radiation serum or preparations of immune-globulins gives a manifestation of the radioprotection effects immediately after this kind of preparation are injected into organisms of mammals. Providing passive immunization by preparations of anti-radiations immune-globulins is possible in different periods of time after radiation. Providing active immunization by preparations of S.D.R. group is possible only to achieve a prophylaxis goal and form the protection effects that start to work in 18 - 35 days after an injection of biological active S.D.R. substance has been administrated. However active and passive immunizations by essential anti-radiation toxins and preparations of gamma-globulins extracted from a hyper-immune serum of a horse have significantly different medical prescriptions for application and depend on many factors like a type of radiation, a power of radiation, absorption doses, a time of

  16. Patterns of Care for Biologic-Dosing Outliers and Nonoutliers in Biologic-Naive Patients with Rheumatoid Arthritis.

    Science.gov (United States)

    Delate, Thomas; Meyer, Roxanne; Jenkins, Daniel

    2017-08-01

    Although most biologic medications for patients with rheumatoid arthritis (RA) have recommended fixed dosing, actual biologic dosing may vary among real-world patients, since some patients can receive higher (high-dose outliers) or lower (low-dose outliers) doses than what is recommended in medication package inserts. To describe the patterns of care for biologic-dosing outliers and nonoutliers in biologic-naive patients with RA. This was a retrospective, longitudinal cohort study of patients with RA who were not pregnant and were aged ≥ 18 and 110% of the approved dose in the package insert at any time during the study period. Baseline patient profiles, treatment exposures, and outcomes were collected during the 180 days before and up to 2 years after biologic initiation and compared across index biologic outlier groups. Patients were followed for at least 1 year, with a subanalysis of those patients who remained as members for 2 years. This study included 434 RA patients with 1 year of follow-up and 372 RA patients with 2 years of follow-up. Overall, the vast majority of patients were female (≈75%) and had similar baseline characteristics. Approximately 10% of patients were outliers in both follow-up cohorts. ETN patients were least likely to become outliers, and ADA patients were most likely to become outliers. Of all outliers during the 1-year follow-up, patients were more likely to be a high-dose outlier (55%) than a low-dose outlier (45%). Median 1- and 2-year adjusted total biologic costs (based on wholesale acquisition costs) were higher for ADA and ETA nonoutliers than for IFX nonoutliers. Biologic persistence was highest for IFX patients. Charlson Comorbidity Index score, ETN and IFX index biologic, and treatment with a nonbiologic disease-modifying antirheumatic drug (DMARD) before biologic initiation were associated with becoming high- or low-dose outliers (c-statistic = 0.79). Approximately 1 in 10 study patients with RA was identified as a

  17. Dose rate effect models for biological reaction to ionizing radiation in human cell lines

    International Nuclear Information System (INIS)

    Magae, Junji; Ogata, Hiromitsu

    2008-01-01

    , suggesting that dose rate effect predicted by MOE model is dependent on DNA repair system. Dose rate effect in a resting normal fibroblast cultured in serum-depleted medium also followed MOE model. In contrast, dose-rate effect was observed in these cell lines deficient of DNA repair system, when they were cultured for more than several month. This dose rate effect did not fit MOE model, and followed a model based on elimination of damaged cells. In conclusion, dose rate effect in growth inhibition and micronucleus formation in cultured cell lines is dependent on dose rate and irradiation time: In higher range of dose rates and short irradiation time, biological effect is determined by dose but not dose rate, and dose rate effect is not observed. In middle range of dose rates and irradiation time, dose rate effect is dependent on DNA repair system, and follows MOE model. In low range of dose-rates and irradiation time longer than several months, dose rate effect is mainly dependent on elimination of damaged cells, and biological effect is determined by dose rate rather than total dose. Our results suggest that dose rate and irradiation time should be included in estimation of long-term radiation risk at low dose rates. (author)

  18. Biological dose estimation for accidental supra-high dose gamma-ray exposure

    International Nuclear Information System (INIS)

    Chen, Y.; Yan, X.K.; Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K.

    2011-01-01

    To correctly estimate the biological dose of victims accidentally exposed to a very high dose of 60 Co gamma-ray, a new dose-effect curve of chromosomal dicentrics/multicentrics and rings in the supra-high dose range was established. Peripheral blood from two healthy men was irradiated in vitro with doses of 60 Co gamma-rays ranging from 6 to 22 Gy at a dose rate of 2.0 Gy/min. Lymphocytes were concentrated, cultured and harvested at 52 h, 68 h and 72 h. The numbers of dic + r were counted. The dose-effect curves were established and validated using comparisons with doses from the Tokai-mura accident and were then applied to two victims of supra-high dose exposure accident. The results indicated that there were no significant differences in chromosome aberration frequency among the different culture times from 52 h to 72 h. The 6-22 Gy dose-effect curve was fitted to a linear quadratic model Y = -2.269 + 0.776D - 7.868 x l0 -3 D 2 . Using this mathematic model, the dose estimates were similar to data from Tokai-mura which were estimated by PCC ring. Whole body average doses of 9.7 Gy and 18.1 Gy for two victims in the Jining accident were satisfactorily given. We established and successfully applied a new dose-effect curve of chromosomal dicentrics plus ring (dic + r) after 6-22 Gy γ-irradiation from a supra-high dose 60 Co gamma-ray accident.

  19. Biological effect of Pulsed Dose Rate brachytherapy with stepping sources

    International Nuclear Information System (INIS)

    Limbergen, Erik F.M. van; Fowler, Jack F.

    1996-01-01

    Purpose: To explore the possible increase of radiation effect in tissues irradiated by pulsed brachytherapy (PDR), for local tissue dose-rates between those 'averaged over the whole pulse' and the instantaneous high dose rates close to the dwell positions. An earlier publication (Fowler and Mount 1992) had shown that, for dose rates (averaged for the duration of the pulse) up to 3 Gy/h, little change of isoeffect doses from continuous low dose rate (CLDR) are expected, unless larger doses per fraction than 1 Gy are used, and especially if components of very rapid repair are present with half-times of less than about 0.5 hours. However, local and transient dose rates close to stepping sources can be up to several Gy per minute. Methods: Calculations were done assuming the linear quadratic formula for radiation damage, in which only the dose-squared term is subject to repair, at a constant exponential rate. The formula developed by Dale for fractionated low-dose-rate radiotherapy was used. A constant overall time of 140 hours and constant total dose of 70 Gy were assumed throughout, the continuous low dose-rate of 0.5 Gy/h (CLDR) providing the unitary standard effects for each PDR condition. Effects of dose-rates ranging from 4 Gy/h to 120 Gy/h (HDR at 2 Gy/min) were studied, and T (1(2)) from 4 minutes to 1.5 hours. Results: Curves are presented relating the ratio of increased biological effect (proportional to log cell kill) calculated for PDR relative to CLDR. Ratios as high as 1.5 can be found for large doses per pulse (> 1 Gy) at high instantaneous dose-rates if T (1(2)) in tissues is as short as a few minutes. The major influences on effect are dose per pulse, half-time of repair in the tissue, and - when T (1(2)) is short - the instantaneous dose-rate. Maximum ratios of PDR/CLDR effect occur when the dose-rate is such that pulse duration is approximately equal to T (1(2)) of repair. Results are presented for late-responding tissues, the differences from CLDR

  20. Modelling the Influence of Shielding on Physical and Biological Organ Doses

    CERN Document Server

    Ballarini, Francesca; Ferrari, Alfredo; Ottolenghi, Andrea; Pelliccioni, Maurizio; Scannicchio, Domenico

    2002-01-01

    Distributions of "physical" and "biological" dose in different organs were calculated by coupling the FLUKA MC transport code with a geometrical human phantom inserted into a shielding box of variable shape, thickness and material. While the expression "physical dose" refers to the amount of deposited energy per unit mass (in Gy), "biological dose" was modelled with "Complex Lesions" (CL), clustered DNA strand breaks calculated in a previous work based on "event-by-event" track-structure simulations. The yields of complex lesions per cell and per unit dose were calculated for different radiation types and energies, and integrated into a version of FLUKA modified for this purpose, allowing us to estimate the effects of mixed fields. As an initial test simulation, the phantom was inserted into an aluminium parallelepiped and was isotropically irradiated with 500 MeV protons. Dose distributions were calculated for different values of the shielding thickness. The results were found to be organ-dependent. In most ...

  1. Biological effects of low doses of radiation at low dose rate

    International Nuclear Information System (INIS)

    1996-05-01

    The purpose of this report was to examine available scientific data and models relevant to the hypothesis that induction of genetic changes and cancers by low doses of ionizing radiation at low dose rate is a stochastic process with no threshold or apparent threshold. Assessment of the effects of higher doses of radiation is based on a wealth of data from both humans and other organisms. 234 refs., 26 figs., 14 tabs

  2. Dose addition models based on biologically-relevant reductions in fetal testosterone accurately predict postnatal reproductive tract alterations by a phthalate mixture in rats

    Science.gov (United States)

    Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the curren...

  3. Treatment planning for heavy ion radiotherapy: calculation and optimization of biologically effective dose

    International Nuclear Information System (INIS)

    Kraemer, M.; Scholz, M.

    2000-09-01

    We describe a novel approach to treatment planning for heavy ion radiotherapy based on the local effect model (LEM) which allows to calculate the biologically effective dose not only for the target region but for the entire irradiation volume. LEM is ideally suited to be used as an integral part of treatment planning code systems for active dose shaping devices like the GSI raster scan system. Thus, it has been incorporated into our standard treatment planning system for ion therapy (TRiP). Single intensity modulated fields can be optimized with respect to homogeneous biologically effective dose. The relative biological effectiveness (RBE) is calculated separately for each voxel of the patient CT. Our radiobiologically oriented code system is in use since 1995 for the planning of irradiation experiments with cell cultures and animals such as rats and minipigs. Since 1997 it is in regular and successful use for patient treatment planning. (orig.)

  4. Biological effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Gonzalez, A.J.

    1994-01-01

    Few weeks ago, when the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) submitted to the U.N. General Assembly the UNSCEAR 1994 report, the international community had at its disposal a broad view of the biological effects of low doses of ionizing radiation. The 1994 report (272 pages) specifically addressed the epidemiological studies of radiation carcinogenesis and the adaptive responses to radiation in cells and organisms. The report was aimed to supplement the UNSCEAR 1993 report to the U.N. General Assembly- an extensive document of 928 pages-which addressed the global levels of radiation exposing the world population, as well as some issues on the effects of ionizing radiation, including: mechanisms of radiation oncogenesis due to radiation exposure, influence of the level of dose and dose rate on stochastic effects of radiation, hereditary effects of radiation effects on the developing human brain, and the late deterministic effects in children. Those two UNSCEAR reports taken together provide an impressive overview of current knowledge on the biological effects of ionizing radiation. This article summarizes the essential issues of both reports, although it cannot cover all available information. (Author)

  5. Reduced biological effect of e-cigarette aerosol compared to cigarette smoke evaluated in vitro using normalized nicotine dose and RNA-seq-based toxicogenomics

    OpenAIRE

    Haswell, Linsey E.; Baxter, Andrew; Banerjee, Anisha; Verrastro, Ivan; Mushonganono, Jessica; Adamson, Jason; Thorne, David; Ga?a, Marianna; Minet, Emmanuel

    2017-01-01

    Electronic cigarettes (e-cigarettes) use has increased globally and could potentially offer a lower risk alternative to cigarette smoking. Here, we assessed the transcriptional response of a primary 3D airway model acutely exposed to e-cigarette aerosol and cigarette (3R4F) smoke. Aerosols were generated with standard intense smoking regimens with careful consideration for dose by normalizing the exposures to nicotine. Two e-cigarette aerosol dilutions were tested for equivalent and higher ni...

  6. Biological dose assessment of 15 victims in Haerbin radiation accident

    International Nuclear Information System (INIS)

    Liu, Jian-xiang; Huang, Min-yan; Ruan, Jian-lei; Bai, Yu-shu; Xu, Su

    2008-01-01

    Full text: a) On July 5 and 8, 2005, Two patients with bone marrow suppression were successively hospitalized by the First Affiliated Hospital of Haerbin Medical University. Examination results showed that the patients seemed to get suspicious radiation disease. On July 13, 2005, a radioactive source was found in the patients' dwelling. The radiation source is Iridium-192 with 0.5 Ci(1.85 x 10 10 Bq) radioactivity. The radiation source is a metal bar which is a kind of radioactive industrial detection source for welding. The source is currently stored in the urban radioactive waste storehouse of Heilongjiang province. After finding the radioactive source on July 13, The Haerbin municipal government initiated an emergency response plan and developed medical rescue, radioactive source examination and case detection through organizing ministries involving health, environmental protection and public security. After receiving a report at 17:00 on July 14, 2005, Chinese Ministry of Health immediately sent experts to the spot for investigation, dose estimation and direction of patients' rescue. Health authority carried out physical examination twice on 113 residents within 30 meters to the source, among which 4 got radiation sickness, 5 showed abnormal hemotogram, and others showed no abnormal response. Of 4 patients with radiation sickness, one 81 year old patient has died of severe bone marrow form of sub acute radiation sickness coupled with lung infection and prostrate apparatus at 13:00 on Oct., 20. Two children have been treated in Beitaiping Road Hospital in Beijing, another patient has been treated in local hospital. b) Biological dosimetry using conventional chromosome aberration analysis in human peripheral blood lymphocytes has been shown as a reliable and useful tool in medical management of radiation accident victims. Peripheral blood lymphocytes of the victims were cultured using conventional culture medium with colchicine added at the beginning. Chromosome

  7. Dose inhomogeneities at various levels of biological organization

    International Nuclear Information System (INIS)

    Bond, V.P.

    1988-01-01

    Dose inhomogeneities in both tumor and normal tissue, inherent to the application of boron neutron capture therapy (BNCT), can be the result not only of ununiform distribution of 10 B at various levels of biological organization, but also of the distribution of the thermal neutrons and of the energy depositions from more energetic neutrons and other radiations comprising the externally-applied beams. The severity of the problems resulting from such inhomogeneities, and approaches to evaluating them, are illustrated by three examples, at the macro, micro and intermediate levels

  8. Biological effective doses in the intracavitary high dose rate brachytherapy of cervical cancer

    Directory of Open Access Journals (Sweden)

    Y. Sobita Devi

    2011-12-01

    Full Text Available Purpose: The aim of this study is to evaluate the decrease of biological equivalent dose and its correlation withlocal/loco-regional control of tumour in the treatment of cervical cancer when the strength of the Ir-192 high dose rate(HDR brachytherapy (BT source is reduced to single, double and triple half life in relation to original strength of10 Ci (~ 4.081 cGy x m2 x h–1. Material and methods: A retrospective study was carried out on 52 cervical cancer patients with stage II and IIItreated with fractionated HDR-BT following external beam radiation therapy (EBRT. International Commission onRadiation Units and Measurement (ICRU points were defined according to ICRU Report 38, using two orthogonal radiographimages taken by Simulator (Simulix HQ. Biologically effective dose (BED was calculated at point A for diffe -rent Ir-192 source strength and its possible correlation with local/loco-regional tumour control was discussed. Result: The increase of treatment time per fraction of dose due to the fall of dose rate especially in HDR-BT of cervicalcancer results in reduction in BED of 2.59%, 7.02% and 13.68% with single, double and triple half life reduction ofsource strength, respectively. The probabilities of disease recurrence (local/loco-regional within 26 months are expectedas 0.12, 0.12, 0.16, 0.39 and 0.80 for source strength of 4.081, 2.041, 1.020, 0.510 and 0.347 cGy x m2 x h–1, respectively.The percentages of dose increase required to maintain the same BED with respect to initial BED were estimated as1.71, 5.00, 11.00 and 15.86 for the dose rate of 24.7, 12.4, 6.2 and 4.2 Gy/hr at point A, respectively. Conclusions: This retrospective study of cervical cancer patients treated with HDR-BT at different Ir-192 sourcestrength shows reduction in disease free survival according to the increase in treatment time duration per fraction.The probable result could be associated with the decrease of biological equivalent dose to point A. Clinical

  9. Imprecision in estimates of dose from ingested 137Cs due to variability in human biological characteristics

    International Nuclear Information System (INIS)

    Schwarz, G.; Dunning, D.E. Jr.

    1982-01-01

    An attempt has been made to quantify the variability in human biological parameters determining dose to man from ingestion of a unit activity of soluble 137 Cs and the resulting imprecision in the predicted total-body dose commitment. The analysis is based on an extensive review of the literature along with the application of statistical methods to determine parameter variability, correlations between parameters, and predictive imprecision. The variability in the principal biological parameters (biological half-time and total-body mass) involved can be described by a geometric standard deviation of 1.2-1.5 for adults and 1.6-1.9 for children/ adolescents of age 0.1-18 yr. The estimated predictive imprecision (using a Monte Carlo technique) in the total-body dose commitment from ingested 137 Cs can be described by a geometric standard deviation on the order of 1.3-1.4, meaning that the 99th percentile of the predicted distribution of dose is within approximately 2.1 times the mean value. The mean dose estimate is 0.009 Sv/MBq (34 mrem/μ Ci) for children/adolescents and 0.01 Sv/MBq (38 mrem/μ Ci) for adults. Little evidence of age dependence in the total-body dose from ingested 137 Cs is observed. (author)

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

    Science.gov (United States)

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

  11. 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

  12. Exposures at low doses and biological effects of ionizing radiations

    International Nuclear Information System (INIS)

    Masse, R.

    2000-01-01

    Everyone is exposed to radiation from natural, man-made and medical sources, and world-wide average annual exposure can be set at about 3.5 mSv. Exposure to natural sources is characterised by very large fluctuations, not excluding a range covering two orders of magnitude. Millions of inhabitants are continuously exposed to external doses as high as 10 mSv per year, delivered at low dose rates, very few workers are exposed above the legal limit of 50 mSv/year, and referring to accidental exposures, only 5% of the 116 000 people evacuated following the Chernobyl disaster encountered doses above 100 mSv. Epidemiological survey of accidentally, occupationally or medically exposed groups have revealed radio-induced cancers, mostly following high dose-rate exposure levels, only above 100 mSv. Risk coefficients were derived from these studies and projected into linear models of risk (linear non-threshold hypothesis: LNT), for the purpose of risk management following exposures at low doses and low dose-rates. The legitimacy of this approach has been questioned, by the Academy of sciences and the Academy of medicine in France, arguing: that LNT was not supported by Hiroshima and Nagasaki studies when neutron dose was revisited; that linear modelling failed to explain why so many site-related cancers were obviously nonlinearly related to the dose, and especially when theory predicted they ought to be; that no evidence could be found of radio-induced cancers related to natural exposures or to low exposures at the work place; and that no evidence of genetic disease could be shown from any of the exposed groups. Arguments were provided from cellular and molecular biology helping to solve this issue, all resulting in dismissing the LNT hypothesis. These arguments included: different mechanisms of DNA repair at high and low dose rate; influence of inducible stress responses modifying mutagenesis and lethality; bystander effects allowing it to be considered that individual

  13. Effect of edema, relative biological effectiveness, and dose heterogeneity on prostate brachytherapy

    International Nuclear Information System (INIS)

    Wang, Jian Z.; Mayr, Nina A.; Nag, Subir; Montebello, Joseph; Gupta, Nilendu; Samsami, Nina; Kanellitsas, Christos

    2006-01-01

    Many factors influence response in low-dose-rate (LDR) brachytherapy of prostate cancer. Among them, edema, relative biological effectiveness (RBE), and dose heterogeneity have not been fully modeled previously. In this work, the generalized linear-quadratic (LQ) model, extended to account for the effects of edema, RBE, and dose heterogeneity, was used to assess these factors and their combination effect. Published clinical data have shown that prostate edema after seed implant has a magnitude (ratio of post- to preimplant volume) of 1.3-2.0 and resolves exponentially with a half-life of 4-25 days over the duration of the implant dose delivery. Based on these parameters and a representative dose-volume histogram (DVH), we investigated the influence of edema on the implant dose distribution. The LQ parameters (α=0.15 Gy -1 and α/β=3.1 Gy) determined in earlier studies were used to calculate the equivalent uniform dose in 2 Gy fractions (EUD 2 ) with respect to three effects: edema, RBE, and dose heterogeneity for 125 I and 103 Pd implants. The EUD 2 analysis shows a negative effect of edema and dose heterogeneity on tumor cell killing because the prostate edema degrades the dose coverage to tumor target. For the representative DVH, the V 100 (volume covered by 100% of prescription dose) decreases from 93% to 91% and 86%, and the D 90 (dose covering 90% of target volume) decrease from 107% to 102% and 94% of prescription dose for 125 I and 103 Pd implants, respectively. Conversely, the RBE effect of LDR brachytherapy [versus external-beam radiotherapy (EBRT) and high-dose-rate (HDR) brachytherapy] enhances dose effect on tumor cell kill. In order to balance the negative effects of edema and dose heterogeneity, the RBE of prostate brachytherapy was determined to be approximately 1.2-1.4 for 125 I and 1.3-1.6 for 103 Pd implants. These RBE values are consistent with the RBE data published in the literature. These results may explain why in earlier modeling studies

  14. A non-parametric, microdosimetric-based approach to the evaluation of the biological effects of low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Varma, M.N.; Zaider, M.

    1992-01-01

    A microdosimetric-based specific quality factor, q(y), is determined for eight sets of experimental data on cellular inactivation, mutation, chromosome aberration and neoplastic transformation. Bias-free Bayesian and maximum entropy approaches were used. A comparison of the curves q(y) thus determined reveals a surprising degree of uniformity. In our view this is prima facie evidence that the spatial pattern of microscopic energy deposition - rather than the specific end point or cellular system - is the quantity which determines the dependency of the cellular response to the quality of the ionizing radiation. For further applications of this approach to radiation protection experimental microdosimetric spectra are urgently needed. Further improvement in the quality of the q(y) functions could provide important clues on fundamental biophysical mechanisms. (author)

  15. Evaluation of a commercial biologically based IMRT treatment planning system

    International Nuclear Information System (INIS)

    Semenenko, Vladimir A.; Reitz, Bodo; Day, Ellen; Qi, X. Sharon; Miften, Moyed; Li, X. Allen

    2008-01-01

    A new inverse treatment planning system (TPS) for external beam radiation therapy with high energy photons is commercially available that utilizes both dose-volume-based cost functions and a selection of cost functions which are based on biological models. The purpose of this work is to evaluate quality of intensity-modulated radiation therapy (IMRT) plans resulting from the use of biological cost functions in comparison to plans designed using a traditional TPS employing dose-volume-based optimization. Treatment planning was performed independently at two institutions. For six cancer patients, including head and neck (one case from each institution), prostate, brain, liver, and rectal cases, segmental multileaf collimator IMRT plans were designed using biological cost functions and compared with clinically used dose-based plans for the same patients. Dose-volume histograms and dosimetric indices, such as minimum, maximum, and mean dose, were extracted and compared between the two types of treatment plans. Comparisons of the generalized equivalent uniform dose (EUD), a previously proposed plan quality index (fEUD), target conformity and heterogeneity indices, and the number of segments and monitor units were also performed. The most prominent feature of the biologically based plans was better sparing of organs at risk (OARs). When all plans from both institutions were combined, the biologically based plans resulted in smaller EUD values for 26 out of 33 OARs by an average of 5.6 Gy (range 0.24 to 15 Gy). Owing to more efficient beam segmentation and leaf sequencing tools implemented in the biologically based TPS compared to the dose-based TPS, an estimated treatment delivery time was shorter in most (five out of six) cases with some plans showing up to 50% reduction. The biologically based plans were generally characterized by a smaller conformity index, but greater heterogeneity index compared to the dose-based plans. Overall, compared to plans based on dose

  16. Dose estimate of exposure to radioisotopes in molecular and cellular biology

    International Nuclear Information System (INIS)

    Onado, C.; Faretta, M.; Ubezio, P.

    1999-01-01

    A method for prospectively evaluating the annual equivalent doses and effective dose to biomedical researchers working with unsealed radioisotopes, and their classification, is presented here. Simplified formulae relate occupational data to a reasonable overestimate of the annual effective dose, and the equivalent doses to the hands and to the skin. The procedure, up to the classification of personnel and laboratories, can be made fully automatic, using a common spreadsheet on a personal computer. The method is based on occupational data, accounting for the amounts of each radioisotope used by a researcher, the time of exposure and the overall amounts employed in the laboratories where experiments are performed. The former data serve to forecast a contribution to the dose arising from a researcher's own work, the latter to a forecast of an 'environmental' contribution deriving simply from the presence in a laboratory where other people are working with radioisotopes. The estimates of the doses due to one's own radioisotope handling and to 'environment' were corrected for accidental exposure, considered as a linear function of the manipulated activity or of the time spent in the laboratories respectively, and summed up to give the effective dose. The effective dose associated with some common experiments in molecular and cellular biology is pre-evaluated by this method. (author)

  17. The biological basis for dose limitation to the skin

    International Nuclear Information System (INIS)

    Fry, R.J.M.

    1992-01-01

    Ionizing radiation may cause deterministic effects and cancer. It has been the policy to base dose limits for radiation protection of the skin on the prevention of deterministic effects (1). In the case of cancer in general, dose limitation for radiation protection is based on limiting excess cancer mortality to low levels of radiation. Since skin cancers are seldom lethal, the general radiation protection standards will protect against an increase in excess mortality from skin cancer. However, with the dose limits selected to prevent deterministic effects, there is a significant probability of an excess incidence of skin cancer occurring as a result of exposure during a working lifetime. The induction of skin cancer by radiation is influenced significantly by subsequent exposure to ultraviolet radiation (UVR) from sunlight. This finding raises not only interesting questions about the mechanisms involved, but also about the differences in risk of skin cancer in different populations. The amount and distribution of melanin in the skin determines the degree of the effect of UVR. This paper discusses the mechanisms of the induction of both deterministic and stochastic effects in skin exposed to radiation in relation to radiation protection. (author)

  18. Biological dose estimation in a radiation accident involving low-dose ...

    African Journals Online (AJOL)

    Blood specimens were collected from 8 people 18 days after they had been accidentally exposed to a 947,2 GBq iridium192 source during industrial application. The equivalent whole-body dose received at day 0 was estimated using a model based on quantitative and qualitative chromosome aberration analysis in ...

  19. Biological clearance and committed dose equivalent in pulmonary region from inhaled radioaerosols for lung scanning

    Energy Technology Data Exchange (ETDEWEB)

    Soni, P.S.; Sharma, S.M.; Raghunath, B.; Somasundaram, S.

    1987-01-01

    Biological clearance half-lives (Tsub(b)) of different /sup 99/Tcsup(m)-labelled compounds from each lung have been determined, after administering the radioaerosol to normal subjects using the BARC dry aerosol generation and inhalation system. Based on these experimental clearance half-lives, the committed dose equivalent to the lungs has been computed using both the ICRP lung model and MIRD-11 values.

  20. Biological clearance and committed dose equivalent in pulmonary region from inhaled radioaerosols for lung scanning

    International Nuclear Information System (INIS)

    Soni, P.S.; Sharma, S.M.; Raghunath, B.; Somasundaram, S.

    1987-01-01

    Biological clearance half-lives (Tsub(b)) of different 99 Tcsup(m)-labelled compounds from each lung have been determined, after administering the radioaerosol to normal subjects using the BARC dry aerosol generation and inhalation system. Based on these experimental clearance half-lives, the committed dose equivalent to the lungs has been computed using both the ICRP lung model and MIRD-11 values. (author)

  1. Evaluation of the risk of perchlorate exposure in a population of late-gestation pregnant women in the United States: Application of probabilistic biologically-based dose response modeling

    International Nuclear Information System (INIS)

    Lumen, A; George, N I

    2017-01-01

    The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure. The reduction in maternal fT4 levels reached statistical significance when an added contribution from drinking water (i.e., 15 μg/L, 20 μg/L, or 24.5 μg/L) was assumed in addition to the 90th percentile of food intake for pregnant women (0.198 μg/kg/day). We determined that a daily intake of 0.45 to 0.50 μg/kg/day of perchlorate was necessary to produce results that were significantly different than those obtained from no perchlorate exposure. Adjusting for this food intake dose, the relative source contribution of perchlorate from drinking water (or other non-dietary sources) was estimated to range from 0.25–0.3 μg/kg/day. Assuming a drinking water intake rate of 0.033 L/kg/day, the drinking water concentration allowance for perchlorate equates to 7.6–9.2 μg/L. In summary, we have demonstrated the utility of a probabilistic biologically-based dose-response model for perchlorate risk assessment in a sensitive life-stage at a population level; however, there is a need for continued monitoring in regions of the U.S. where perchlorate exposure may be higher. - Highlights: • Probabilistic risk assessment for perchlorate in U.S. pregnant women was conducted. • No significant change in maternal fT4 predicted due to perchlorate from food alone. • Drinking water concentration allowance for perchlorate estimated as 7.6–9.2 μg/L

  2. Evaluation of the risk of perchlorate exposure in a population of late-gestation pregnant women in the United States: Application of probabilistic biologically-based dose response modeling

    Energy Technology Data Exchange (ETDEWEB)

    Lumen, A, E-mail: Annie.Lumen@fda.hhs.gov [Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd, HFT-110, Jefferson, AR 72079 (United States); George, N I, E-mail: Nysia.George@fda.hhs.gov [Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, U.S. Food and Drug Administration, 3900 NCTR Rd, HFT-20, Jefferson, AR 72079 (United States)

    2017-05-01

    The risk of ubiquitous perchlorate exposure and the dose-response on thyroid hormone levels in pregnant women in the United States (U.S.) have yet to be characterized. In the current work, we integrated a previously developed perchlorate submodel into a recently developed population-based pregnancy model to predict reductions in maternal serum free thyroxine (fT4) levels for late-gestation pregnant women in the U.S. Our findings indicated no significant difference in geometric mean estimates of fT4 when perchlorate exposure from food only was compared to no perchlorate exposure. The reduction in maternal fT4 levels reached statistical significance when an added contribution from drinking water (i.e., 15 μg/L, 20 μg/L, or 24.5 μg/L) was assumed in addition to the 90th percentile of food intake for pregnant women (0.198 μg/kg/day). We determined that a daily intake of 0.45 to 0.50 μg/kg/day of perchlorate was necessary to produce results that were significantly different than those obtained from no perchlorate exposure. Adjusting for this food intake dose, the relative source contribution of perchlorate from drinking water (or other non-dietary sources) was estimated to range from 0.25–0.3 μg/kg/day. Assuming a drinking water intake rate of 0.033 L/kg/day, the drinking water concentration allowance for perchlorate equates to 7.6–9.2 μg/L. In summary, we have demonstrated the utility of a probabilistic biologically-based dose-response model for perchlorate risk assessment in a sensitive life-stage at a population level; however, there is a need for continued monitoring in regions of the U.S. where perchlorate exposure may be higher. - Highlights: • Probabilistic risk assessment for perchlorate in U.S. pregnant women was conducted. • No significant change in maternal fT4 predicted due to perchlorate from food alone. • Drinking water concentration allowance for perchlorate estimated as 7.6–9.2 μg/L.

  3. Biological UV-doses and the effect on an ozone layer depletion

    International Nuclear Information System (INIS)

    Dahlback, A.; Henriksen, T.

    1988-08-01

    Effective UV-doses were calculated based on the integrated product of the biological action spectrum and the solar radiation. The calculations included absorption and scattering of UV-radiation in the atmosphere, both for normal ozone conditions as well as for a depleted ozone layer. The effective annual UV-dose increases by approximately 4% per degree of latitude towards the equator. An ozone depletion of 1% increases the annual UV-dose by approximately 1% at 60 o N. A large depletion of 50% over Scandinavia (60 o N) would give this region an effective UV-dose similar to that obtained, with normal ozone conditions, at a latitude of 40 o N (California or the Mediterranean countries). The Antarctic ozone hole increases the annual UV-dose by 20 to 25% which is a similar increase as that attained by moving 5 to 6 degrees of latitude nearer the equator. The annual UV-dose on higher latitudes is mainly determined by the summer values of ozone. Both the ozone values and the effective UV-doses vary from one year to another (within ±4%). No positive or negative trend is observed for Scandinavia from 1978 to 1988

  4. Biologically based analysis of lung cancer incidence in a large Canadian occupational cohort with low-LET low-dose radiation exposure, and comparison with Japanese atomic bomb survivors

    International Nuclear Information System (INIS)

    Hazelton, W.D.; Curtis, S.B.; Moolgavkar, S.H.; Hutchinson, F.; Krewski, D.

    2003-01-01

    Lung cancer incidence is analyzed in a large Canadian National Dose Registry (CNDR) cohort with individual annual dosimetry for low-dose occupational exposure to gamma and tritium radiation using several types of multistage models. The primary analysis utilizes the two-stage clonal expansion model (TSCE), with sensitivity analyses using extensions of this model incorporating additional stages. Characteristic and distinct temporal patterns of risk are found for dose-response affecting early, middle, or late stages of carcinogenesis, e.g. initiation with one or more stages, clonal expansion, or malignant conversion. Fixed lag or lag distributions are used to model time from first malignant cell to incidence. Background rates are analyzed by gender, job classification and birth cohort. Lacking individual smoking data, surrogate doses based on US annual per capita cigarette consumption appear to account for much of the birth cohort effect. Males, with mean cumulative exposure for gamma and tritium of 11.5 mSv and 322 incident lung cancer cases have a significant dose-response with 33 cases attributable to radiation. Female dose-response, with mean cumulative exposure of 1.7 mSv and 78 incident cases, appears similar but is not statistically significant. Findings for males include an inverse-dose-rate effect (increased risk with protraction of a given dose) and dose-response effects on initiation, promotion and malignant conversion, although the effect on initiation is not statistically significant. The excess relative risk (ERR) and excess absolute risk (EAR) depend on age at exposure, duration, dose, and age at follow-up. The ERR increases with dose, tapering off at higher doses, making a plot of ERR against dose concave-downward, similar to apparent low-dose results seen below 1 Sv for solid tumor mortality of atomic bomb survivors. The concave-downward trend of ERR and the inverse-dose-rate effect are both counter to prevailing beliefs about effects of low

  5. Biological Bases for Radiation Adaptive Responses in the Lung

    Energy Technology Data Exchange (ETDEWEB)

    Scott, Bobby R. [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Lin, Yong [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Wilder, Julie [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States); Belinsky, Steven [Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States)

    2015-03-01

    Our main research objective was to determine the biological bases for low-dose, radiation-induced adaptive responses in the lung, and use the knowledge gained to produce an improved risk model for radiation-induced lung cancer that accounts for activated natural protection, genetic influences, and the role of epigenetic regulation (epiregulation). Currently, low-dose radiation risk assessment is based on the linear-no-threshold hypothesis, which now is known to be unsupported by a large volume of data.

  6. Clinical oncology based upon radiation biology

    International Nuclear Information System (INIS)

    Hirata, Hideki

    2016-01-01

    This paper discussed the biological effects of radiation as physical energy, especially those of X-ray as electromagnetic radiation, by associating the position of clinical oncology with classical radiation cell biology as well as recent molecular biology. First, it described the physical and biological effects of radiation, cell death due to radiation and recovery, radiation effects at tissue level, and location information and dosage information in the radiotherapy of cancer. It also described the territories unresolved through radiation biology, such as low-dose high-sensitivity, bystander effects, etc. (A.O.)

  7. TU-AB-BRC-09: Fast Dose-Averaged LET and Biological Dose Calculations for Proton Therapy Using Graphics Cards

    International Nuclear Information System (INIS)

    Wan, H; Tseung, Chan; Beltran, C

    2016-01-01

    Purpose: To demonstrate fast and accurate Monte Carlo (MC) calculations of proton dose-averaged linear energy transfer (LETd) and biological dose (BD) on a Graphics Processing Unit (GPU) card. Methods: A previously validated GPU-based MC simulation of proton transport was used to rapidly generate LETd distributions for proton treatment plans. Since this MC handles proton-nuclei interactions on an event-by-event using a Bertini intranuclear cascade-evaporation model, secondary protons were taken into account. The smaller contributions of secondary neutrons and recoil nuclei were ignored. Recent work has shown that LETd values are sensitive to the scoring method. The GPU-based LETd calculations were verified by comparing with a TOPAS custom scorer that uses tabulated stopping powers, following recommendations by other authors. Comparisons were made for prostate and head-and-neck patients. A python script is used to convert the MC-generated LETd distributions to BD using a variety of published linear quadratic models, and to export the BD in DICOM format for subsequent evaluation. Results: Very good agreement is obtained between TOPAS and our GPU MC. Given a complex head-and-neck plan with 1 mm voxel spacing, the physical dose, LETd and BD calculations for 10"8 proton histories can be completed in ∼5 minutes using a NVIDIA Titan X card. The rapid turnover means that MC feedback can be obtained on dosimetric plan accuracy as well as BD hotspot locations, particularly in regards to their proximity to critical structures. In our institution the GPU MC-generated dose, LETd and BD maps are used to assess plan quality for all patients undergoing treatment. Conclusion: Fast and accurate MC-based LETd calculations can be performed on the GPU. The resulting BD maps provide valuable feedback during treatment plan review. Partially funded by Varian Medical Systems.

  8. TU-AB-BRC-09: Fast Dose-Averaged LET and Biological Dose Calculations for Proton Therapy Using Graphics Cards

    Energy Technology Data Exchange (ETDEWEB)

    Wan, H; Tseung, Chan; Beltran, C [Mayo Clinic, Rochester, MN (United States)

    2016-06-15

    Purpose: To demonstrate fast and accurate Monte Carlo (MC) calculations of proton dose-averaged linear energy transfer (LETd) and biological dose (BD) on a Graphics Processing Unit (GPU) card. Methods: A previously validated GPU-based MC simulation of proton transport was used to rapidly generate LETd distributions for proton treatment plans. Since this MC handles proton-nuclei interactions on an event-by-event using a Bertini intranuclear cascade-evaporation model, secondary protons were taken into account. The smaller contributions of secondary neutrons and recoil nuclei were ignored. Recent work has shown that LETd values are sensitive to the scoring method. The GPU-based LETd calculations were verified by comparing with a TOPAS custom scorer that uses tabulated stopping powers, following recommendations by other authors. Comparisons were made for prostate and head-and-neck patients. A python script is used to convert the MC-generated LETd distributions to BD using a variety of published linear quadratic models, and to export the BD in DICOM format for subsequent evaluation. Results: Very good agreement is obtained between TOPAS and our GPU MC. Given a complex head-and-neck plan with 1 mm voxel spacing, the physical dose, LETd and BD calculations for 10{sup 8} proton histories can be completed in ∼5 minutes using a NVIDIA Titan X card. The rapid turnover means that MC feedback can be obtained on dosimetric plan accuracy as well as BD hotspot locations, particularly in regards to their proximity to critical structures. In our institution the GPU MC-generated dose, LETd and BD maps are used to assess plan quality for all patients undergoing treatment. Conclusion: Fast and accurate MC-based LETd calculations can be performed on the GPU. The resulting BD maps provide valuable feedback during treatment plan review. Partially funded by Varian Medical Systems.

  9. Biological dose estimation and comet analysis of the victims in a high dose 60Co radiation accident

    International Nuclear Information System (INIS)

    Chen Ying; Liu Xiulin; Luo Yisheng; Li You; Yao Bo

    2007-01-01

    Objective: To explore the methods of chromosome preparation in human peripheral blood and bone marrow after very high dose exposure and fit the dose-response curve of dicentrics and tings in the range of high doses over 6 Gy for estimating biological dose and detecting DNA damage in the victims of '10.21' accident. Methods: The samples of peripheral blood and bone marrow in 2 victims were collected to prepare chromosome mataphases and dicentrics (multicentrics) + rings were counted. The dose-response curve and equation of human blood irradiated between 6-22 Gy in vitro were established and applied to assess biological dose of 2 victims. In addition, their DNA damages were tested by alkaline single cell gel electrophoresis. Results: The dicentric + ring numbers of 4.47 per cell in victims B's peripheral blood lymphocytes and 9.15 per cell in victim A's bone marrow who had no mitosis in peripheral blood cell. The whole body average doses of victims B and A estimated by 6-22 Gy equation arrived at 9.4 Gy and 19.5 Gy, respectively. The serious DNA damages were expressed by small head and large tail comet figures. Conclusions: The biological doses of 2 victims estimated by 6-22 Gy dose-response curve have reached the levels of extreme grave bone marrow and intestinal ARS, respectively. (authors)

  10. Low doses of ionizing radiation: Relationship between biological benefit and damage induction. A synopsis

    International Nuclear Information System (INIS)

    Feinendegen, L.E.

    2005-01-01

    Absorption of ionizing radiation in biological tissue stochastically interacts with constituent atoms and molecules and always generates energy deposition (track) events accompanied by bursts of reactive oxygen species (ROS). These ROS are quite similar to those ROS that arise abundantly and constantly by normal oxidative metabolism. ROS effects from either source need attention when assessing radiation-induced alterations in biological structure and function. Endogenous ROS alone induce about 10 6 DNA oxyadducts per cell per day compared to about 5x10 -3 total DNA damage per average cell per day from background radiation exposure (1 mGy per year). At this background level, the corresponding ratio of probabilities of endogenous versus radiogenic DNA double strand breaks (DSBs) per cell per day is about 103 with some 25-40 % of low-LET caused radiogenic DNA-DSBs being of the multi-damage-site type. Radiogenic DNA damage increases in proportion to absorbed dose over a certain dose range. By evolution, tissues possess physiological mechanisms of protection against an array of potentially toxic agents, externally from the environment and endogenously from metabolism, mainly against the abundantly and constantly produced ROS. Ad hoc protection operates at a level that is genetically determined. Following small to moderate perturbation of cell-tissue homeostasis by a toxic impact, adaptive responses develop with a delay and may last from hours to weeks, even months, and aim at protecting the system against renewed insults. Protective responses encompass defense by scavenging mechanisms, DNA repair, damage removal largely by apoptosis and immune responses, as well as changes in cell proliferation. Acute low-dose irradiation below about 0.2 Gy can not only disturb cell-tissue homeostasis but also initiate adaptived protection that appears with a delay of hours and may last from less than a day to months. The balance between damage production and adaptive protection favors

  11. Definition of the dose(tempo)-distribution in the biological irradiation-facility of the RIVM

    International Nuclear Information System (INIS)

    Bader, F.J.M.

    1990-02-01

    The RIVM biological irradiation facility (BBF) for the irradiation of biological samples and small animals is a self shielded device and can be safely operated in an existing laboratory environment. There are two 137 Cs sources (15TBq) in a bilateral geometry to give maximum dose uniformity. The easily accessible irradiation chamber is housed in a rotating lead shielding. The dosimetry of BBF was performed by the Dosimetry Section of the RIVM. Experiments were made to determine the absorbed dose in plastic tubes filled with water and the dose distribution over the tube-holder. Separate experiments were made to determine the absorbed dose during the rotation of the irradiation chamber and to check the irradiation timer. For the experiments LiF:Mg,Ti (TLD-100) extruded ribbons were used. The TLDs were calibrated in a collimated beam of 137 Cs gamma rays. The determination of the absorbed dose in water was based on a users biological irradiation set up. The TLDs were individually sealed in thin plastic foil and put in plastic tubes filled for 1/3 with water. The tubes were vertically placed in the tube-holder and placed in the centre of the irradiation chamber. The results show that the absorbed dose in water (determined on January 1, 1990) is equal to 0.97 Gy/timer-unit, with a total uncertainty of 7 percent (1σ). During the rotation of the irradiation chamber the absorbed dose (determined on January 1, 1990) is equal to 0.38 Gy, with a total uncertainty of 15 percent (1σ). The variation of the dose distribution was determined at 15 different measurement points distributed over the tube-holder. The dosis in the measurement point in the centre of the tube-holder was taken as reference value. The maximum observed deviation over the other 14 measurement points amounts to -16 percent of it. The BBF-timer was checked against a special timer. The results indicate that within a range from 2-11 'timer-units' no differences are present. (author). 6 refs.; 6 figs.; 3 fotos

  12. Biologically based multistage modeling of radiation effects

    Energy Technology Data Exchange (ETDEWEB)

    William Hazelton; Suresh Moolgavkar; E. Georg Luebeck

    2005-08-30

    This past year we have made substantial progress in modeling the contribution of homeostatic regulation to low-dose radiation effects and carcinogenesis. We have worked to refine and apply our multistage carcinogenesis models to explicitly incorporate cell cycle states, simple and complex damage, checkpoint delay, slow and fast repair, differentiation, and apoptosis to study the effects of low-dose ionizing radiation in mouse intestinal crypts, as well as in other tissues. We have one paper accepted for publication in ''Advances in Space Research'', and another manuscript in preparation describing this work. I also wrote a chapter describing our combined cell-cycle and multistage carcinogenesis model that will be published in a book on stochastic carcinogenesis models edited by Wei-Yuan Tan. In addition, we organized and held a workshop on ''Biologically Based Modeling of Human Health Effects of Low dose Ionizing Radiation'', July 28-29, 2005 at Fred Hutchinson Cancer Research Center in Seattle, Washington. We had over 20 participants, including Mary Helen Barcellos-Hoff as keynote speaker, talks by most of the low-dose modelers in the DOE low-dose program, experimentalists including Les Redpath (and Mary Helen), Noelle Metting from DOE, and Tony Brooks. It appears that homeostatic regulation may be central to understanding low-dose radiation phenomena. The primary effects of ionizing radiation (IR) are cell killing, delayed cell cycling, and induction of mutations. However, homeostatic regulation causes cells that are killed or damaged by IR to eventually be replaced. Cells with an initiating mutation may have a replacement advantage, leading to clonal expansion of these initiated cells. Thus we have focused particularly on modeling effects that disturb homeostatic regulation as early steps in the carcinogenic process. There are two primary considerations that support our focus on homeostatic regulation. First, a number of

  13. Isoeffective dose: a concept for biological weighting of absorbed dose in proton and heavier-ion therapies

    CERN Document Server

    Wambersie, A; Menzel, H G; Gahbauer, R; DeLuca, P M; Hendry, J H; Jones, D T L

    2011-01-01

    When reporting radiation therapy procedures, International Commission on Radiation Units and Measurements (ICRU) recommends specifying absorbed dose at/in all clinically relevant points and/or volumes. In addition, treatment conditions should be reported as completely as possible in order to allow full understanding and interpretation of the treatment prescription. However, the clinical outcome does not only depend on absorbed dose but also on a number of other factors such as dose per fraction, overall treatment time and radiation quality radiation biology effectiveness (RBE). Therefore, weighting factors have to be applied when different types of treatments are to be compared or to be combined. This had led to the concept of `isoeffective absorbed dose', introduced by ICRU and International Atomic Energy Agency (IAEA). The isoeffective dose D(IsoE) is the dose of a treatment carried out under reference conditions producing the same clinical effects on the target volume as those of the actual treatment. It i...

  14. 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

  15. Dose estimation by biological methods; Estimacion de dosis por metodos biologicos

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero C, C; David C, L; Serment G, J; Brena V, M [Instituto Nacional de Investigaciones Nucleares, A.P. 18-1027, 11801 Mexico D.F. (Mexico)

    1997-07-01

    The human being is exposed to strong artificial radiation sources, mainly of two forms: the first is referred to the occupationally exposed personnel (POE) and the second, to the persons that require radiological treatment. A third form less common is by accidents. In all these conditions it is very important to estimate the absorbed dose. The classical biological dosimetry is based in the dicentric analysis. The present work is part of researches to the process to validate the In situ Fluorescent hybridation (FISH) technique which allows to analyse the aberrations on the chromosomes. (Author)

  16. Biological effects of low-dose ionizing radiation exposure; Biologische Wirkungen niedriger Dosen ionisierender Strahlung

    Energy Technology Data Exchange (ETDEWEB)

    Reinoehl-Kompa, Sabine; Baldauf, Daniela; Heller, Horst (comps.)

    2009-07-01

    The report on the meeting of the Strahlenschutzkommission 2007 concerning biological effects of low-dose ionizing radiation exposure includes the following contributions: Adaptive response. The importance of DNA damage mechanisms for the biological efficiency of low-energy photons. Radiation effects in mammography: the relative biological radiation effects of low-energy photons. Radiation-induced cataracts. Carcinomas following prenatal radiation exposure. Intercellular apoptosis induction and low-dose irradiation: possible consequences for the oncogenesis control. Mechanistic models for the carcinogenesis with radiation-induced cell inactivation: application to all solid tumors in the Japanese atomic bomb survivors. Microarrays at low radiation doses. Mouse models for the analysis of biological effects of low-dose ionizing radiation. The bystander effect: observations, mechanisms and implications. Lung carcinoma risk of Majak workers - modeling of carcinogenesis and the bystander effect. Microbeam studies in radiation biology - an overview. Carcinogenesis models with radiation-induced genomic instability. Application to two epidemiological cohorts.

  17. The Biological Bases of Conformity

    Science.gov (United States)

    Morgan, T. J. H.; Laland, K. N.

    2012-01-01

    Humans are characterized by an extreme dependence on culturally transmitted information and recent formal theory predicts that natural selection should favor adaptive learning strategies that facilitate effective copying and decision making. One strategy that has attracted particular attention is conformist transmission, defined as the disproportionately likely adoption of the most common variant. Conformity has historically been emphasized as significant in the social psychology literature, and recently there have also been reports of conformist behavior in non-human animals. However, mathematical analyses differ in how important and widespread they expect conformity to be, and relevant experimental work is scarce, and generates findings that are both mutually contradictory and inconsistent with the predictions of the models. We review the relevant literature considering the causation, function, history, and ontogeny of conformity, and describe a computer-based experiment on human subjects that we carried out in order to resolve ambiguities. We found that only when many demonstrators were available and subjects were uncertain was subject behavior conformist. A further analysis found that the underlying response to social information alone was generally conformist. Thus, our data are consistent with a conformist use of social information, but as subjects’ behavior is the result of both social and asocial influences, the resultant behavior may not be conformist. We end by relating these findings to an embryonic cognitive neuroscience literature that has recently begun to explore the neural bases of social learning. Here conformist transmission may be a particularly useful case study, not only because there are well-defined and tractable opportunities to characterize the biological underpinnings of this form of social learning, but also because early findings imply that humans may possess specific cognitive adaptations for effective social learning. PMID:22712006

  18. The Biological Bases of Conformity

    Directory of Open Access Journals (Sweden)

    Thomas Joshau Henry Morgan

    2012-06-01

    Full Text Available Humans are characterized by an extreme dependence on culturally transmitted information and recent formal theory predicts that natural selection should favour adaptive learning strategies that facilitate effective use of social information in decision making. One strategy that has attracted particular attention is conformist transmission, defined as the disproportionately likely adoption of the most common variant. Conformity has historically been emphasized as significant in the social psychology literature, and recently there have also been reports of conformist behaviour in nonhuman animals. However, mathematical analyses differ in how important and widespread they expect conformity to be, and relevant experimental work is scarce, and generates findings that are both mutually contradictory and inconsistent with the predictions of the models. We review the relevant literature considering the causation, function, history and ontogeny of conformity and describe a computer-based experiment on human subjects that we carried out in order to resolve ambiguities. We found that only when many demonstrators were available and subjects were uncertain was subject behaviour conformist. A further analysis found that the underlying response to social information alone was generally conformist. Thus, our data are consistent with a conformist use of social information, but as subject’s behaviour is the result of both social and asocial influences, the resultant behaviour may not be conformist. We end by relating these findings to an embryonic cognitive neuroscience literature that has recently begun to explore the neural bases of social learning. Here conformist transmission may be a particularly useful case study, not only because there are well-defined and tractable opportunities to characterize the biological underpinnings of this form of social learning, but also because early findings imply that humans may possess specific cognitive adaptations for

  19. Dose selection based on physiologically based pharmacokinetic (PBPK) approaches.

    Science.gov (United States)

    Jones, Hannah M; Mayawala, Kapil; Poulin, Patrick

    2013-04-01

    Physiologically based pharmacokinetic (PBPK) models are built using differential equations to describe the physiology/anatomy of different biological systems. Readily available in vitro and in vivo preclinical data can be incorporated into these models to not only estimate pharmacokinetic (PK) parameters and plasma concentration-time profiles, but also to gain mechanistic insight into compound properties. They provide a mechanistic framework to understand and extrapolate PK and dose across in vitro and in vivo systems and across different species, populations and disease states. Using small molecule and large molecule examples from the literature and our own company, we have shown how PBPK techniques can be utilised for human PK and dose prediction. Such approaches have the potential to increase efficiency, reduce the need for animal studies, replace clinical trials and increase PK understanding. Given the mechanistic nature of these models, the future use of PBPK modelling in drug discovery and development is promising, however some limitations need to be addressed to realise its application and utility more broadly.

  20. Biological influence from low dose and low-dose rate radiation

    International Nuclear Information System (INIS)

    Magae, Junji

    2007-01-01

    Although living organisms have defense mechanisms for radioadaptive response, the influence is considered to vary qualitatively and quantitatively for low dose and high dose, as well as for low-dose rate and high-dose rate. This article describes the bioresponse to low dose and low-dose rate. Among various biomolecules, DNA is the most sensitive to radiation, and accurate replication of DNA is an essential requirement for the survival of living organisms. Also, the influence of active enzymes resulted from the effect of radiation on enzymes in the body is larger than the direct influence of radiation on the body. After this, the article describes the carcinogenic risk by low-dose radiation, and then so-called Hormesis effect to create cancer inhibition effect by stimulating active physiology. (S.K.)

  1. Use of normalized total dose to represent the biological effect of fractionated radiotherapy

    International Nuclear Information System (INIS)

    Flickinger, J.C.; Kalend, A.

    1990-01-01

    There are currently a number of radiobiological models to account for the effects of dose fractionation and time. Normalized total dose (NTD) is not another new model but is a previously reported, clinically useful form in which to represent the biological effect, determined by any specific radiobiological dose-fractionation model, of a course of radiation using a single set of standardized, easily understood terminology. The generalized form of NTD reviewed in this paper describes the effect of a course of radiotherapy administered with nonstandard fractionation as the total dose of radiation in Gy that could be administered with a given reference fractionation such as 2 Gy per fraction, 5 fractions per week that would produce an equivalent biological effect (probability of complications or tumor control) as predicted by a given dose-fractionation formula. The use of normalized total dose with several different exponential and linear-quadratic dose-fraction formulas is presented. (author). 51 refs.; 1 fig.; 1 tab

  2. Use of normalized total dose to represent the biological effect of fractionated radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Flickinger, J C; Kalend, A [Pittsburgh University School of Medicine (USA). Department of Radiation Oncology Pittsburg Cancer Institute (USA)

    1990-03-01

    There are currently a number of radiobiological models to account for the effects of dose fractionation and time. Normalized total dose (NTD) is not another new model but is a previously reported, clinically useful form in which to represent the biological effect, determined by any specific radiobiological dose-fractionation model, of a course of radiation using a single set of standardized, easily understood terminology. The generalized form of NTD reviewed in this paper describes the effect of a course of radiotherapy administered with nonstandard fractionation as the total dose of radiation in Gy that could be administered with a given reference fractionation such as 2 Gy per fraction, 5 fractions per week that would produce an equivalent biological effect (probability of complications or tumor control) as predicted by a given dose-fractionation formula. The use of normalized total dose with several different exponential and linear-quadratic dose-fraction formulas is presented. (author). 51 refs.; 1 fig.; 1 tab.

  3. TLD estimation of absorbed dose for 131I on the surface of biological organs of REMCAL phantom

    International Nuclear Information System (INIS)

    Tandon, Pankaj; Gaur, P.K.; Bhatt, B.C.; Soni, P.S.

    2001-01-01

    In nuclear medicine, the accuracy of absorbed dose of an internally distributed radiopharmaceuticals estimated by the MIRD (medical internal radiation dose) method depends on the cumulated activity of the source organs and their mass. The usual method for obtaining the cumulated activities are: 1) direct measurements by a) positron emission tomography (PET) and b) single photon emission computed tomography (SPECT) 2) extrapolation from animal data and 3) calculations based on the mathematical biokinetic model. Among these methods, extrapolation of animal data to humans includes inevitable inaccuracy due to large interspecies metabolic differences with regard to the administered radiochemical. Biokinetic modeling requires adequate knowledge of various kinetic parameters, which is based on some biological assumptions. Direct measurements can provide cumulated distributions with fewer biological assumptions. But direct measurements of PET/SPECT are difficult to perform routinely. A method has been developed to obtain the surface dose of different biological organs by using TLDs. Here, a number of TLDs are placed just above the surface of the biological organs of the REMCAL Alderson human phantom filled with water. Firstly, investigation of the accuracy of this method by calibration studies using the said phantom, which is having the entire biological organ intact and simulate the organs as human body is done. These organs are filled with the known activity of the radioisotope. In the present study, estimation of radiation dose received by fifteen different target organs, when the known activity was filled in the three major organs of interest was carried out

  4. Biological effects of very low doses of ionizing radiation

    International Nuclear Information System (INIS)

    Evseev, V.S.

    1987-01-01

    The paper deals with a qualitative microdosimetric analysis of a new radiobiological phenomenon (physiological reaction of the cell as a whole to very low doses of ionizing radiations). The analysis is aimed at identifying the type of the primary interaction of radiation with the cell and finding its place in the cell

  5. Extension of the biological effective dose to the MIRD schema and possible implications in radionuclide therapy dosimetry

    International Nuclear Information System (INIS)

    Baechler, Sebastien; Hobbs, Robert F.; Prideaux, Andrew R.; Wahl, Richard L.; Sgouros, George

    2008-01-01

    In dosimetry-based treatment planning protocols, patients with rapid clearance of the radiopharmaceutical require a larger amount of initial activity than those with slow clearance to match the absorbed dose to the critical organ. As a result, the dose-rate to the critical organ is higher in patients with rapid clearance and may cause unexpected toxicity compared to patients with slow clearance. In order to account for the biological impact of different dose-rates, radiobiological modeling is beginning to be applied to the analysis of radionuclide therapy patient data. To date, the formalism used for these analyses is based on kinetics derived from activity in a single organ, the target. This does not include the influence of other source organs to the dose and dose-rate to the target organ. As a result, only self-dose irradiation in the target organ contributes to the dose-rate. In this work, the biological effective dose (BED) formalism has been extended to include the effect of multiple source organ contributions to the net dose-rate in a target organ. The generalized BED derivation has been based on the Medical Internal Radionuclide Dose Committee (MIRD) schema assuming multiple source organs following exponential effective clearance of the radionuclide. A BED-based approach to determine the largest safe dose to critical organs has also been developed. The extended BED formalism is applied to red marrow dosimetry, as well as kidney dosimetry considering the cortex and the medulla separately, since both those organs are commonly dose limiting in radionuclide therapy. The analysis shows that because the red marrow is an early responding tissue (high α/β), it is less susceptible to unexpected toxicity arising from rapid clearance of high levels of administered activity in the marrow or in the remainder of the body. In kidney dosimetry, the study demonstrates a complex interplay between clearance of activity in the cortex and the medulla, as well as the initial

  6. Evaluation of experimental animal biological state at exposure to low-dose ionizing radiation

    International Nuclear Information System (INIS)

    Rozanov, V.A.; Rejtarova, T.Je.; Chernyikov, G.B.; Timoshevs'ka, Je.V.; Kozozojeva, O.O.

    1997-01-01

    New approaches to quantitative evaluation of ionizing radiation absorbed dose within the low-dose range (up to 400 mGy) according to the degree of the organism biological response was developed. The purpose of the stage of the work published in Communication 1 is to evaluate the shifts in the animal behaviour and cellular composition of the blood at irradiation by the dose of 100,200 and 400 mGy. Distinct dose dependence of behaviour reactions and hematological indices within the dose range of 100-400 mGy was not noted

  7. Biological changes in experimental animals after irradiation with sublethal doses

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Dae Seong; Park, Yong Dae; Jin, Chang Hyun; Byun, Myung Woo; Jeong, Il Yun [Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup (Korea, Republic of)

    2008-05-15

    The objective of the present study was to investigate general clinical aspects such as weekly body weight and blood changes, and weekly food intake in gamma-irradiated C57BL/6j male mice fed AIN-76A purified rodent diet for 14 weeks. The mice were whole-body irradiated with 0, 2, 4 and 6 Gy of gamma-rays (Gammacell 40 Exactor, {sup 137}Cs, MDS Nordion) at a dose rate of 1.8 {sub c}Gy per second. The mean body weight change of 6 Gy-irradiated mice significantly decreased when compared to that of the non-irradiated control mice. Moreover, high dose of radiation resulted in decreased levels of AST, ALT, but in increased levels of total cholersterol, triglyceride, HDL-C in mice.

  8. Biological effects of low doses of ionising radiation

    International Nuclear Information System (INIS)

    Osmak, M.

    1998-01-01

    A study was performed with the aim to examine whether the progeny of cells that had been repeatedly irradiated with low doses of gamma rays will change their sensitivity to cytotoxic agents. Four mammalian cell lines were used in the experiment. It was found that the progeny of cells irradiated in this way do not change their sensitivity to gamma rays but would change their sensitivity to various cytostatics drugs. (A.K.)

  9. Biological effect of low-dose application beta-radiation on the gingival mucosa of dogs

    International Nuclear Information System (INIS)

    Ippolitov, Yu.A.; Kovtun, N.N.; Timofeev, L.V.

    1999-01-01

    Biological effect of low-dose application beta-radiation on the gingival mucosa of dogs is studied. Obtained data illustrate the interactions between tissues in local exposure of live tissue to beta-radiation and determine the threshold total dose as 400 sGy. Higher doses lead to secondary changes in the gingival mucosa after which the tissue barrier does not recover [ru

  10. Biological dose estimation of partial body exposures in cervix cancer patients

    International Nuclear Information System (INIS)

    Di Giorgio, Marina; Nasazzi, Nora B.; Taja, Maria R.; Roth, B.; Sardi, M.; Menendez, P.

    2000-01-01

    At present, unstable chromosome aberrations analysis in peripheral blood lymphocytes is the most sensitive method to provide a biological estimation of the dose in accidental radiation over exposures. The assessment of the dose is particularly reliable in cases of acute, uniform, whole-body exposures or after irradiation of large parts of the body. However, the scenarios of most radiation accidents result in partial-body exposures or non-uniform dose distribution, leading to a differential exposure of lymphocytes in the body. Inhomogeneity produces a yield of dicentrics, which does not conform to a Poisson distribution, but is generally over dispersed. This arises because those lymphocytes in tissues outside the radiation field will not be damaged. Most of the lymphocytes (80 %) belong to the 'redistributional pool' (lymphatic tissues and other organs) and made recirculate into peripheral blood producing a mixed irradiated and unirradiated population of lymphocytes. So-called over dispersion, with a variance greater than the mean, can be taken as an indication of non-uniform exposure. The main factors operating in vivo partial-body irradiation may be the location and size of the irradiation field and, at high doses, various cellular reactions such as reduced blast transformation, mitotic delay or interphase death may contribute. For partial-body exposures, mathematical-statistical analysis of chromosome aberration data can be performed to derive a dose estimate for the irradiated fraction of the body, been more realistic than to quote a mean equivalent uniform whole body dose. The 'Contaminated Poisson' method of Dolphin or the Qdr method of Sasaki, both based on similar principles, can achieve this. Contaminated Poisson considers the over dispersed distribution of dicentrics among all the cells scored. The observed distribution is considered to be the sum of a Poisson distribution, which represents the irradiated fraction of the body, and the remaining unexposed

  11. Activation of chemical biological defense mechanisms and remission of vital oxidative injury by low dose radiation

    International Nuclear Information System (INIS)

    Yamaoka, K.; Nomura, T.; Kojima, S.

    2000-01-01

    Excessive active oxygen produced in vivo by various causes is toxic. Accumulation of oxidation injuries due to excessive active causes cell and tissue injuries, inducing various pathologic conditions such as aging and carcinogenesis. On the other hand, there are chemical defense mechanisms in the body that eliminate active oxygen or repair damaged molecules, defending against resultant injury. It is interesting reports that appropriate oxidation stress activate the chemical biological defense mechanisms. In this study, to elucidate these phenomena and its mechanism by low dose radiation, we studied on the below subjects. Activation of chemical biological defense mechanisms by low dose radiation: (1) The effects radiation on lipid peroxide (LPO) levels in the organs, membrane fluidity and the superoxide dismutase (SOD) activity were examined in rats and rabbits. Rats were irradiated with low dose X-ray over their entire bodies, and rabbits inhaled vaporized radon spring water, which primarily emitted α-ray. The following results were obtained. Unlike high dose X-ray, low dose X-ray and radon inhalation both reduced LPO levels and made the state of the SH-group on membrane-bound proteins closer to that of juvenile animals, although the sensitivity to radioactivity varied depending on the age of the animals and among different organs and tissues. The SOD activity was elevated, suggesting that low dose X-ray and radon both activate the host defensive function. Those changes were particularly marked in the organs related to immune functions of the animals which received low dose X-ray, while they were particularly marked in the brain after radon inhalation. It was also found that those changes continued for longer periods after low dose X-irradiation. (2) Since SOD is an enzyme that mediates the dismutation of O 2 - to H 2 O 2 , the question as to whether the resultant H 2 O 2 is further detoxicated into H 2 O and O 2 or not must still be evaluated. Hence, we studied

  12. Radiation research contracts: Biological effects of small radiation doses

    International Nuclear Information System (INIS)

    Hug, O.

    1959-01-01

    According to its Statute the IAEA has to fulfil a dual function - to help individual countries in solving their specific problems and to undertake tasks in the common interest of all its Member States. With this latter aim in mind the Agency has placed a number of research contracts with national research institutes. The purpose and scope of two of them is described below by the scientists responsible for their execution. The Agency has contributed to this work by putting at the institutes' disposal scientists from its own staff apparatus and financial aid.IAEA placed a research contract concerning the effects of small radiation doses on cells, in particular on nervous cells, with the Pharmacological Institute of the University of Vienna. This Institute appeared well suited to deal with the problem owing to the type of its previous research work. The Director, Prof. Franz Bruecke, and his collaborator Dr. Otto Kraupp, have long been interested in the functioning of the nervous system and in the influence of different drugs upon it. It was particularly fortunate that the electrical properties and functions of cells had been measured by a method specially developed at this Institute. From the above mentioned observations one could expect that instantaneous reactions of cells to radiation would also lead to changes of the electrical status. Consequently, this method is now being applied to the research undertaken for IAEA. Different cells of plants and animals, ranging from algae to muscle fibres of mammals, were chosen as objects. So far changes of potentials-had been observed only during irradiation with very high doses. During these investigations another useful test for small radiation doses was developed, namely the measurement of the through-flow of an artificial blood solution through the blood vessels of an intestinal loop. It was observed that a few seconds after irradiation the flow rate diminishes, and returns to its normal level only when irradiation ends

  13. Radiation research contracts: Biological effects of small radiation doses

    Energy Technology Data Exchange (ETDEWEB)

    Hug, O

    1959-01-15

    According to its Statute the IAEA has to fulfil a dual function - to help individual countries in solving their specific problems and to undertake tasks in the common interest of all its Member States. With this latter aim in mind the Agency has placed a number of research contracts with national research institutes. The purpose and scope of two of them is described below by the scientists responsible for their execution. The Agency has contributed to this work by putting at the institutes' disposal scientists from its own staff apparatus and financial aid.IAEA placed a research contract concerning the effects of small radiation doses on cells, in particular on nervous cells, with the Pharmacological Institute of the University of Vienna. This Institute appeared well suited to deal with the problem owing to the type of its previous research work. The Director, Prof. Franz Bruecke, and his collaborator Dr. Otto Kraupp, have long been interested in the functioning of the nervous system and in the influence of different drugs upon it. It was particularly fortunate that the electrical properties and functions of cells had been measured by a method specially developed at this Institute. From the above mentioned observations one could expect that instantaneous reactions of cells to radiation would also lead to changes of the electrical status. Consequently, this method is now being applied to the research undertaken for IAEA. Different cells of plants and animals, ranging from algae to muscle fibres of mammals, were chosen as objects. So far changes of potentials-had been observed only during irradiation with very high doses. During these investigations another useful test for small radiation doses was developed, namely the measurement of the through-flow of an artificial blood solution through the blood vessels of an intestinal loop. It was observed that a few seconds after irradiation the flow rate diminishes, and returns to its normal level only when irradiation ends

  14. Clinical applicability of biologically effective dose calculation for spinal cord in fractionated spine stereotactic body radiation therapy

    International Nuclear Information System (INIS)

    Lee, Seung Heon; Lee, Kyu Chan; Choi, Jinho; Ahn, So Hyun; Lee, Seok Ho; Sung, Ki Hoon; Kil, Se Hee

    2015-01-01

    The aim of the study was to investigate whether biologically effective dose (BED) based on linear-quadratic model can be used to estimate spinal cord tolerance dose in spine stereotactic body radiation therapy (SBRT) delivered in 4 or more fractions. Sixty-three metastatic spinal lesions in 47 patients were retrospectively evaluated. The most frequently prescribed dose was 36 Gy in 4 fractions. In planning, we tried to limit the maximum dose to the spinal cord or cauda equina less than 50% of prescription or 45 Gy 2/2 . BED was calculated using maximum point dose of spinal cord. Maximum spinal cord dose per fraction ranged from 2.6 to 6.0 Gy (median 4.3 Gy). Except 4 patients with 52.7, 56.4, 62.4, and 67.9 Gy 2/2 , equivalent total dose in 2-Gy fraction of the patients was not more than 50 Gy 2/2 (12.1–67.9, median 32.0). The ratio of maximum spinal cord dose to prescription dose increased up to 82.2% of prescription dose as epidural spinal cord compression grade increased. No patient developed grade 2 or higher radiation-induced spinal cord toxicity during follow-up period of 0.5 to 53.9 months. In fractionated spine SBRT, BED can be used to estimate spinal cord tolerance dose, provided that the dose per fraction to the spinal cord is moderate, e.g. < 6.0 Gy. It appears that a maximum dose of up to 45–50 Gy 2/2 to the spinal cord is tolerable in 4 or more fractionation regimen

  15. Physics must join with biology in better assessing risk from low-dose irradiation

    International Nuclear Information System (INIS)

    Feinendegen, L. E.; Neumann, R. D.

    2005-01-01

    This review summarises the complex response of mammalian cells and tissues to low doses of ionising radiation. This thesis encompasses induction of DNA damage, and adaptive protection against both renewed damage and against propagation of damage from the basic level of biological organisation to the clinical expression of detriment. The induction of DNA damage at low radiation doses apparently is proportional to absorbed dose at the physical/chemical level. However, any propagation of such damage to higher levels of biological organisation inherently follows a sigmoid function. Moreover, low-dose-induced inhibition of damage propagation is not linear, but instead follows a dose-effect function typical for adaptive protection, after an initial rapid rise it disappears at doses higher than ∼0.1-0.2 Gy to cells. The particular biological response duality at low radiation doses precludes the validity of the linear-no-threshold hypothesis in the attempt to relate absorbed dose to cancer. In fact, theory and observation support not only a lower cancer incidence than expected from the linear-no-threshold hypothesis, but also a reduction of spontaneously occurring cancer, a hormetic response, in the healthy individual. (authors)

  16. Biological radiation dose estimation by chromosomal aberrations analysis in human peripheral blood (dose- effect curve)

    International Nuclear Information System (INIS)

    Al Achkar, W.

    2002-01-01

    In order to draw a dose-effect curve, blood from eight healthy people were studied. Samples were irradiated in tubes with 0.15-2.5 gray of gamma ray.Irradiated and control samples were incubated for cell cultures. Chromosomal aberrations from 67888 metaphases were scored. Curves from the total number of dicentrics, dicentrics+ rings and total numbers of breaks were drawn. The yield of chromosome aberrations is related to the dose used. These curves give a quick useful estimation of the accidentally radiation exposure. (author)

  17. The biologically equivalent dose BED - Is the approach for calculation of this factor really a reliable basis?

    International Nuclear Information System (INIS)

    Jensen, J.M.; Zimmermann, J.

    2000-01-01

    To predict the effect on tumours in radiotherapy, especially relating to irreversible effects, but also to realize the retrospective assessment the so called L-Q-model is relied on at present. Internal specific organ parameters, such as α, β, γ, T p , T k , and ρ, as well as external parameters, so as D, d, n, V, and V ref , were used for determination of the biologically equivalent dose BED. While the external parameters are determinable with small deviations, the internal parameters depend on biological varieties and dispersons: In some cases the lowest value is assumed to be Δ=±25%. This margin of error goes on to the biologically equivalent dose by means of the principle of superposition of errors. In some selected cases (lung, kidney, skin, rectum) these margins of error were calculated exemplarily. The input errors especially of the internal parameters cause a mean error Δ on the biologically equivalent dose and a dispersion of the single fraction dose d dependent on the organ taking into consideration, of approximately 8-30%. Hence it follows only a very critical and cautious application of those L-Q-algorithms in expert proceedings, and in radiotherapy more experienced based decisions are recommended, instead of acting only upon simple two-dimensional mechanistic ideas. (orig.) [de

  18. Low doses of ionizing radiation: Biological effects and regulatory control. Invited papers and discussions. Proceedings of an international conference

    International Nuclear Information System (INIS)

    1998-01-01

    The levels and biological effects resulting from exposure to ionizing radiation are continuously reviewed by the United Nations Committee on the Effects of Atomic Radiation (UNSCEAR). Since its creation in 1928, the International Commission on Radiological Protection (ICRP) has issued recommendations on protection against ionizing radiation. The UNSCEAR estimates and the ICRP recommendations have served as the basis for national and international safety standards on radiation safety, including those developed by the International Atomic Energy Agency (IAEA) and the World Health Organization (WHO). Concerning health effects of low doses of ionizing radiation, the international standards are based on the plausible assumption that, above the unavoidable background radiation dose, the probability of effects increases linearly with dose, i.e. on a 'linear, no threshold' (LNT) assumption. However, in recent years the biological estimates of health effects of low doses of ionizing radiation and the regulatory approach to the control of low level radiation exposure have been much debated. To foster information exchange on the relevant issues, an International Conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, jointly sponsored by the IAEA and WHO in co-operation with UNSCEAR, was held from 17-21 November 1997 at Seville, Spain. These Proceedings contain the invited special reports, keynote papers, summaries of discussions, session summaries and addresses presented at the opening and closing of the Conference

  19. Biological radiation dose estimation by chromosomal aberrations analysis in human peripheral blood (dose-effect curve)

    International Nuclear Information System (INIS)

    Al-Achkar, W.

    2001-09-01

    In order to draw a dose-effect curve, experimentally gamma ray induced chromosomal aberrations in human peripheral lymphocytes from eight healthy people were studied. Samples from 4 males and 4 females were irradiated in tubes with 0.15, 0.25, 0.5, 1, 1.5, 2, 2.5 gray of gamma ray (Co 60 at dose rate 0.3 Gy/min). Irradiated and control samples were incubated in 37 centigrade for 48 hours cell cultures. Cell cultures then were stopped and metaphases spread, Giemsa stained to score the induced chromosomal aberrations. Chromosomal aberrations from 67888 metaphases were scored. Curves from the total number of dicentrics, dicentrics + rings and total numbers of breaks in cell for each individual or for all people were drawn. An increase of all chromosomal aberrations types with the elevation of the doses was observed. The yield of chromosome aberrations is related to the dose used. These curves give a quick useful estimation of the accidentally radiation exposure. (author)

  20. Major cost savings associated with biologic dose reduction in patients with inflammatory arthritis.

    LENUS (Irish Health Repository)

    Murphy, C L

    2015-01-01

    The purpose of this study was to explore whether patients with Inflammatory Arthritis (IA) (Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) or Ankylosing Spondylitis (AS)) would remain in remission following a reduction in biologic dosing frequency and to calculate the cost savings associated with dose reduction. This prospective non-blinded non-randomised study commenced in 2010. Patients with Inflammatory Arthritis being treated with a biologic agent were screened for disease activity. A cohort of those in remission according to standardized disease activity indices (DAS28 < 2.6, BASDAI < 4) was offered a reduction in dosing frequency of two commonly used biologic therapies (etanercept 50 mg once per fortnight instead of weekly, adalimumab 40 mg once per month instead of fortnightly). Patients were assessed for disease activity at 3, 6, 12, 18 and 24 months following reduction in dosing frequency. Cost saving was calculated. 79 patients with inflammatory arthritis in remission were recruited. 57% had rheumatoid arthritis (n = 45), 13% psoriatic arthritis (n = 10) and 30% ankylosing spondylitis (n = 24). 57% (n = 45) were taking etanercept and 43% (n = 34) adalimumab. The percentage of patients in remission at 24 months was 56% (n = 44). This resulted in an actual saving to the state of approximately 600,000 euro over two years. This study demonstrates the reduction in biologic dosing frequency is feasible in Inflammatory Arthritis. There was a considerable cost saving at two years. The potential for major cost savings in biologic usage should be pursued further.

  1. Dose painting based on tumor uptake of Cu-ATSM and FDG

    DEFF Research Database (Denmark)

    Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael

    2014-01-01

    definitions based on FDG, 64Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64Cu-ATSM at two different time-points and FDG provide different biological information that has to be taken into account when using the dose painting...

  2. Validation of GPU based TomoTherapy dose calculation engine.

    Science.gov (United States)

    Chen, Quan; Lu, Weiguo; Chen, Yu; Chen, Mingli; Henderson, Douglas; Sterpin, Edmond

    2012-04-01

    The graphic processing unit (GPU) based TomoTherapy convolution/superposition(C/S) dose engine (GPU dose engine) achieves a dramatic performance improvement over the traditional CPU-cluster based TomoTherapy dose engine (CPU dose engine). Besides the architecture difference between the GPU and CPU, there are several algorithm changes from the CPU dose engine to the GPU dose engine. These changes made the GPU dose slightly different from the CPU-cluster dose. In order for the commercial release of the GPU dose engine, its accuracy has to be validated. Thirty eight TomoTherapy phantom plans and 19 patient plans were calculated with both dose engines to evaluate the equivalency between the two dose engines. Gamma indices (Γ) were used for the equivalency evaluation. The GPU dose was further verified with the absolute point dose measurement with ion chamber and film measurements for phantom plans. Monte Carlo calculation was used as a reference for both dose engines in the accuracy evaluation in heterogeneous phantom and actual patients. The GPU dose engine showed excellent agreement with the current CPU dose engine. The majority of cases had over 99.99% of voxels with Γ(1%, 1 mm) engine also showed similar degree of accuracy in heterogeneous media as the current TomoTherapy dose engine. It is verified and validated that the ultrafast TomoTherapy GPU dose engine can safely replace the existing TomoTherapy cluster based dose engine without degradation in dose accuracy.

  3. Radiobiological impact of dose calculation algorithms on biologically optimized IMRT lung stereotactic body radiation therapy plans

    International Nuclear Information System (INIS)

    Liang, X.; Penagaricano, J.; Zheng, D.; Morrill, S.; Zhang, X.; Corry, P.; Griffin, R. J.; Han, E. Y.; Hardee, M.; Ratanatharathom, V.

    2016-01-01

    The aim of this study is to evaluate the radiobiological impact of Acuros XB (AXB) vs. Anisotropic Analytic Algorithm (AAA) dose calculation algorithms in combined dose-volume and biological optimized IMRT plans of SBRT treatments for non-small-cell lung cancer (NSCLC) patients. Twenty eight patients with NSCLC previously treated SBRT were re-planned using Varian Eclipse (V11) with combined dose-volume and biological optimization IMRT sliding window technique. The total dose prescribed to the PTV was 60 Gy with 12 Gy per fraction. The plans were initially optimized using AAA algorithm, and then were recomputed using AXB using the same MUs and MLC files to compare with the dose distribution of the original plans and assess the radiobiological as well as dosimetric impact of the two different dose algorithms. The Poisson Linear-Quadatric (PLQ) and Lyman-Kutcher-Burman (LKB) models were used for estimating the tumor control probability (TCP) and normal tissue complication probability (NTCP), respectively. The influence of the model parameter uncertainties on the TCP differences and the NTCP differences between AAA and AXB plans were studied by applying different sets of published model parameters. Patients were grouped into peripheral and centrally-located tumors to evaluate the impact of tumor location. PTV dose was lower in the re-calculated AXB plans, as compared to AAA plans. The median differences of PTV(D 95% ) were 1.7 Gy (range: 0.3, 6.5 Gy) and 1.0 Gy (range: 0.6, 4.4 Gy) for peripheral tumors and centrally-located tumors, respectively. The median differences of PTV(mean) were 0.4 Gy (range: 0.0, 1.9 Gy) and 0.9 Gy (range: 0.0, 4.3 Gy) for peripheral tumors and centrally-located tumors, respectively. TCP was also found lower in AXB-recalculated plans compared with the AAA plans. The median (range) of the TCP differences for 30 month local control were 1.6 % (0.3 %, 5.8 %) for peripheral tumors and 1.3 % (0.5 %, 3.4 %) for centrally located tumors. The lower

  4. Biological dose estimation for charged-particle therapy using an improved PHITS code coupled with a microdosimetric kinetic model

    International Nuclear Information System (INIS)

    Sato, Tatsuhiko; Watanabe, Ritsuko; Kase, Yuki; Niita, Koji; Sihver, Lembit

    2009-01-01

    High-energy heavy ions (HZE particles) have become widely used for radiotherapy of tumors owing to their high biological effectiveness. In the treatment planning of such charged-particle therapy, it is necessary to estimate not only physical but also biological dose, which is the product of physical dose and relative biological effectiveness (RBE). In the Heavy-ion Medical Accelerator in Chiba (HIMAC), the biological dose is estimated by a method proposed by Kanai et al., which is based on the linear-quadratic (LQ) model with its parameters α and β determined by the dose distribution in terms of the unrestricted linear energy transfer (LET). Thus, RBE is simply expressed as a function of LET in their model. However, RBE of HZE particles cannot be uniquely determined from their LET because of their large cross sections for high-energy δ-ray production. Hence, development of a biological dose estimation model that can explicitly consider the track structure of δ-rays around the trajectory of HZE particles is urgently needed. Microdosimetric quantities such as lineal energy y are better indexes for representing RBE of HZE particles in comparison to LET, since they can express the decrease of ionization densities around their trajectories due to the production of δ-rays. The difference of the concept between LET and y is illustrated in Figure 1. However, the use of microdosimetric quantities in computational dosimetry was severely limited because of the difficulty in calculating their probability densities (PDs) in macroscopic matter. We therefore improved the 3-dimensional particle transport simulation code PHITS, providing it with the capability of estimating the microdosimetric PDs in a macroscopic framework by incorporating a mathematical function that can instantaneously calculate the PDs around the trajectory of HZE particles with precision equivalent to a microscopic track-structure simulation. A new method for estimating biological dose from charged

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

    International Nuclear Information System (INIS)

    Crawford-Brown, D.J.

    1989-01-01

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

  6. Developing point of care and high-throughput biological assays for determining absorbed radiation dose

    International Nuclear Information System (INIS)

    Joiner, Michael C.; Thomas, Robert A.; Grever, William E.; Smolinski, Joseph M.; Divine, George W.; Konski, Andre A.; Auner, Gregory W.; Tucker, James D.

    2011-01-01

    Background and purpose: Systems are being developed to assess radiation exposure based on leukocyte mRNA levels obtained by finger-stick sampling. The goal is to provide accurate detection of dose exposures up to 10 Gy for up to 1 week following exposure. We previously showed that specific mRNA sequences increase expression within an hour of exposure, and some genes continue to show elevated expression for at least 24 h. Full duration and dose-dependence of this persistence remain to be determined. In the present study, real-time quantitative PCR (qPCR) was used to determine changes in gene expression. qPCR can rapidly analyze small blood samples and could be adopted into a field-portable instrument that provides a radiation dose readout within 30 min. Materials and methods: From previous microarray analysis of 21,000 genes expressed in human lymphoblastoid cells 4 h post-irradiation (0–4 Gy), 118 genes were selected for evaluation by qPCR of gene expression in the leukocytes of human blood irradiated in vitro with doses of 0–10 Gy from a Co-60 gamma source at a dose rate of 30 cGy/min. Results: Blood from 20 normal healthy human donors yielded many mRNA sequences that could be used for radiation dosimetry. We observed four genes with large and persistent responses following exposure: ASTN2, CDKN1A, GADD45A, and GDF15. Five genes were identified as reliably non-responsive and were suitable for use as endogenous controls: DPM1, ITFG1, MAP4, PGK1, and SLC25A36; of these, ITFG1 was used for the analyses presented here. A significant dose-responsive increase in expression occurred for CDKN1A that was >16-fold at 10 Gy and 3-fold at 0.5 Gy compared to pre-irradiation values. Conclusions: These data show large, selective increases in mRNA transcript levels that persist for at least 48 h after single exposures between 0.5 and 10 Gy. Stable, non-responsive mRNA sequences for use as endogenous controls were also identified. These results indicate that following further

  7. Generation of Composite Dose and Biological Effective Dose (BED) Over Multiple Treatment Modalities and Multistage Planning Using Deformable Image Registration

    International Nuclear Information System (INIS)

    Zhang, Geoffrey; Huang, T-C; Feygelman, Vladimir; Stevens, Craig; Forster, Kenneth

    2010-01-01

    Currently there are no commercially available tools to generate composite plans across different treatment modalities and/or different planning image sets. Without a composite plan, it may be difficult to perform a meaningful dosimetric evaluation of the overall treatment course. In this paper, we introduce a method to generate composite biological effective dose (BED) plans over multiple radiotherapy treatment modalities and/or multistage plans, using deformable image registration. Two cases were used to demonstrate the method. Case I was prostate cancer treated with intensity-modulated radiation therapy (IMRT) and a permanent seed implant. Case II involved lung cancer treated with two treatment plans generated on two separate computed tomography image sets. Thin-plate spline or optical flow methods were used as appropriate to generate deformation matrices. The deformation matrices were then applied to the dose matrices and the resulting physical doses were converted to BED and added to yield the composite plan. Cell proliferation and sublethal repair were considered in the BED calculations. The difference in BED between normal tissues and tumor volumes was accounted for by using different BED models, α/β values, and cell potential doubling times. The method to generate composite BED plans presented in this paper provides information not available with the traditional simple dose summation or physical dose summation. With the understanding of limitations and uncertainties of the algorithms involved, it may be valuable for the overall treatment plan evaluation.

  8. Interpretation of proton relative biological effectiveness using lesion induction, lesion repair, and cellular dose distribution

    International Nuclear Information System (INIS)

    Paganetti, H.

    2005-01-01

    Phenomenological biophysical models have been successfully used to estimate the relative biological effectiveness (RBE) of ions. The predictive power of these models is limited because they require measured dose-response data that are not necessarily available for all clinically relevant end points. Furthermore, input parameters often lack mechanistic interpretation. In order to link RBE to more fundamental biological parameters we combine the concepts of two well-established biophysical models, i.e., the phenomenological 'track structure' model and the more mechanistic 'lethal lesion/potentially lethal lesion' (LPL) model. We parametrize a relation between RBE, dose homogeneity in the cell nucleus and induction rates for different lesion types. The macroscopic dose-response relationship is described in the LPL model and the microscopic, subcellular, relationship is determined by the local dose deposition pattern. The formalism provides a framework for a mechanistic interpretation of RBE values

  9. The radioinduced membranes injuries as biological dose indicators: mechanisms of studies and practical applications

    International Nuclear Information System (INIS)

    Vincent-Genod, Lucie

    2001-10-01

    After an accidental overexposure, the assessment of the received dose in biological dosimetry is performed by a method based on the effects of irradiation on the DNA molecule. But this technique shows some limitations; therefore we tried to find new bio-sensors of radiation exposure. We have pointed out that membrane is a critical target of ionising radiation after an in vitro and in vivo overexposure. In vitro, these modifications were involved in the radio-induced apoptotic pathway. The measure of membrane fluidity allowed us to obtain an overall view of cellular membrane. Moreover, in vivo, by changing the lipid nutritional status of animals, our results displayed the important role played by membrane lipid composition in radio-induced membrane alterations. Besides, membrane effects were adjusted by the extracellular physiological control, and in particular by the damages on membrane fatty acid pattern. Finally, we have tested the use of membrane fluidity index as a bio-sensor of radiation exposure on in vivo models and blood samples from medical total body irradiated patients. The results achieved on animal models suggested that the membrane fluidity index was a bio-sensor of radiation exposure. Nevertheless, the observations realised on patients highlight that the effect of the first dose fraction of the radiotherapy treatment had some difficulties to be noticed. Indeed, the combined treatment: chemotherapy and radiotherapy disturbed the membrane fluidity index measures. To conclude, whereas this parameter was not a bio-sensor of irradiation exposure usable in biological dosimetry, it may allow us to assess the radio-induced damages and their cellular but also tissue impacts. (author)

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

    Science.gov (United States)

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

    2010-02-01

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

  11. Relative biological effectiveness of alpha-particle emitters in vivo at low doses

    International Nuclear Information System (INIS)

    Howell, R.W.; Azure, M.T.; Narra, V.R.; Rao, D.V.

    1994-01-01

    The therapeutic potential of radionuclides that emit α particles, as well as their associated health hazards, have attracted considerable attention. The 224 Ra daughters 212 Pb and 212 Bi, by virtue of their radiation properties which involve emission of α and β particles in their decay to stable 208 Pb, have been proposed as candidates for radioimmunotherapy. Using mouse testes as the experimental model and testicular spermhead survival as the biological end point, the present work examines the radiotoxicity of 212 Pb and its daughters. When 212 Pb, in equilibrium with its daughters 212 Bi, 212 Po and 208 Tl, was administered directly into the testis, the dose required to achieve 37% survival (D 37 ) was 0.143 ± 0.014 Gy and the corresponding RBE of the mixed radiation field was 4.7 when compared to the D 37 for acute external 120 kVp X rays. This datum, in conjunction with our earlier results for 210 Po, was used to obtain an RBE-LET relationship for α particles emitted by tissue-incorporated radionuclides: RBE α = 4.8 - 6.1 x 10 -2 LET + 1.0 x 10 -3 LET 2 . Similarly, the dependence of RBE on α-particle energy E α was given by RBE α = 22 E α -0.73 . These relationships, based on in vivo experimental data, may be valuable in predicting biological effects of α-particle emitters. 46 refs., 6 figs

  12. Biological bases of human musicality.

    Science.gov (United States)

    Perrone-Capano, Carla; Volpicelli, Floriana; di Porzio, Umberto

    2017-04-01

    Music is a universal language, present in all human societies. It pervades the lives of most human beings and can recall memories and feelings of the past, can exert positive effects on our mood, can be strongly evocative and ignite intense emotions, and can establish or strengthen social bonds. In this review, we summarize the research and recent progress on the origins and neural substrates of human musicality as well as the changes in brain plasticity elicited by listening or performing music. Indeed, music improves performance in a number of cognitive tasks and may have beneficial effects on diseased brains. The emerging picture begins to unravel how and why particular brain circuits are affected by music. Numerous studies show that music affects emotions and mood, as it is strongly associated with the brain's reward system. We can therefore assume that an in-depth study of the relationship between music and the brain may help to shed light on how the mind works and how the emotions arise and may improve the methods of music-based rehabilitation for people with neurological disorders. However, many facets of the mind-music connection still remain to be explored and enlightened.

  13. Estimation of absorbed dose and its biological effects in subjects undergoing neuro interventional radiological procedures

    International Nuclear Information System (INIS)

    Basheerudeen, Safa Abdul Syed; Subramanian, Vinodhini; Venkatachalam, Perumal; Joseph, Santosh; Selvam, Paneer; Jose, M.T.; Annalakshmi, O.

    2016-01-01

    Radiological imaging has many applications due to its non-invasiveness, rapid diagnosis of life threatening diseases, and shorter hospital stay which benefit patients of all age groups. However, these procedures are complicated and time consuming, which use repeated imaging views and radiation, thereby increasing patient dose, and collective effective dose to the background at low doses. The effects of high dose radiation are well established. However, the effects of low dose exposure remain to be determined. Therefore, investigating the effect on medically exposed individuals is an alternative source to understand the low dose effects of radiation. The ESD (Entrance Surface Dose) was recorded using Lithium borate based TL dosimeters to measure the doses received by the head, neck and shoulder of the study subjects (n = 70) who underwent procedures like cerebral angiography, coiling, stenting and embolization

  14. Assay of micronuclei in peripheral blood lymphocytes as a biological indicator of radiation dose

    International Nuclear Information System (INIS)

    Sreedevi, B.; Rao, B.S.

    1994-01-01

    Chromosomal aberration analysis (CA) has regularly been used as a biological dosemeter to evaluate suspected overexposures to ionising radiations. Recently, the micronucleus (MN) assay has been suggested as an alternative method. An attempt has been made to explore the dose response parameters of MN assay in cytokinesis-blocked lymphocytes. Whole blood was irradiated with 60 Co gamma rays or 250 kV p X rays. A dose-dependent increase in micronuclei yield was observed. The dose response could be best described by a linear-quadratic relationship for both gamma rays and X rays. The α and β coefficients were found to be 1.9 x 10 -2 Gy -1 and 5.7 x 10 -2 Gy -2 for gamma rays and 6.3 x 10 -2 Gy -1 and 4.3 x 10 -2 Gy -2 for X rays, respectively. In the low dose region X rays were three times more efficient in inducing micronuclei. The background value derived for 25 samples from healthy individuals ranged from 6-18 micronuclei per 1000 cells, with a mean value of 12 ± 4 x 10 -3 . Biological dose estimates for individuals exposed in the range 0.1-1 Gy made by MN and CA methods yielded similar results for doses ≥ 0.5 Gy. Due to the uncertainties in the background incidence of MN, at present this technique cannot provide reliable estimates at low doses. (author)

  15. The integral biologically effective dose to predict brain stem toxicity of hypofractionated stereotactic radiotherapy

    International Nuclear Information System (INIS)

    Clark, Brenda G.; Souhami, Luis; Pla, Conrado; Al-Amro, Abdullah S.; Bahary, Jean-Paul; Villemure, Jean-Guy; Caron, Jean-Louis; Olivier, Andre; Podgorsak, Ervin B.

    1998-01-01

    Purpose: The aim of this work was to develop a parameter for use during fractionated stereotactic radiotherapy treatment planning to aid in the determination of the appropriate treatment volume and fractionation regimen that will minimize risk of late damage to normal tissue. Materials and Methods: We have used the linear quadratic model to assess the biologically effective dose at the periphery of stereotactic radiotherapy treatment volumes that impinge on the brain stem. This paper reports a retrospective study of 77 patients with malignant and benign intracranial lesions, treated between 1987 and 1995, with the dynamic rotation technique in 6 fractions over a period of 2 weeks, to a total dose of 42 Gy prescribed at the 90% isodose surface. From differential dose-volume histograms, we evaluated biologically effective dose-volume histograms and obtained an integral biologically-effective dose (IBED) in each case. Results: Of the 77 patients in the study, 36 had target volumes positioned so that the brain stem received more than 1% of the prescribed dose, and 4 of these, all treated for meningioma, developed serious late damage involving the brain stem. Other than type of lesion, the only significant variable was the volume of brain stem exposed. An analysis of the IBEDs received by these 36 patients shows evidence of a threshold value for late damage to the brain stem consistent with similar thresholds that have been determined for external beam radiotherapy. Conclusions: We have introduced a new parameter, the IBED, that may be used to represent the fractional effective dose to structures such as the brain stem that are partially irradiated with stereotactic dose distributions. The IBED is easily calculated prior to treatment and may be used to determine appropriate treatment volumes and fractionation regimens minimizing possible toxicity to normal tissue

  16. SU-E-T-500: Dose Escalation Strategy for Lung Cancer Patients Using a Biologically- Guided Target Definition

    International Nuclear Information System (INIS)

    Shusharina, N; Khan, F; Choi, N; Sharp, G

    2014-01-01

    Purpose: Dose escalation strategy for lung cancer patients can lead to late symptoms such as pneumonitis and cardiac injury. We propose a strategy to increase radiation dose for improving local tumor control while simultaneously striving to minimize the injury of organs at risk (OAR). Our strategy is based on defining a small, biologically-guided target volume for receiving additional radiation dose. Methods: 106 patients with lung cancer treated with radiotherapy were selected for patients diagnosed with stage II and III disease. Previous research has shown that 50% of the maximum SUV threshold in FDG-PET imaging is appropriate for delineation of the most aggressive part of a tumor. After PET- and CT-derived targets were contoured, an IMRT treatment plan was designed to deliver 60 Gy to the GTV as delineated on a 4D CT (Plan 1). A second plan was designed with additional dose of 18 Gy to the PET-derived volume (Plan 2). A composite plan was generated by the addition of Plan 1 and Plan 2. Results: Plan 1 was compared to the composite plan and increases in OAR dose were assessed. For seven patients on average, lung V5 was increased by 1.4% and V20 by 4.2% for ipsilateral lung and by 13.5% and 7% for contralateral lung. For total lung, V5 and V20 were increased by 4.5% and 4.8% respectively. Mean lung dose was increased by 9.7% for the total lung. The maximum dose to the spinal cord increased by 16% on average. For the heart, V20 increased by 4.2% and V40 by 5.2%. Conclusion: It seems feasible that an additional 18 Gy of radiation dose can be delivered to FDG PET-derived subvolume of the CT-based GTV of the primary tumor without significant increase in total dose to the critical organs such as lungs, spinal cord and heart

  17. SU-E-T-500: Dose Escalation Strategy for Lung Cancer Patients Using a Biologically- Guided Target Definition

    Energy Technology Data Exchange (ETDEWEB)

    Shusharina, N; Khan, F; Choi, N; Sharp, G [Massachusetts General Hospital, Boston, MA (United States)

    2014-06-01

    Purpose: Dose escalation strategy for lung cancer patients can lead to late symptoms such as pneumonitis and cardiac injury. We propose a strategy to increase radiation dose for improving local tumor control while simultaneously striving to minimize the injury of organs at risk (OAR). Our strategy is based on defining a small, biologically-guided target volume for receiving additional radiation dose. Methods: 106 patients with lung cancer treated with radiotherapy were selected for patients diagnosed with stage II and III disease. Previous research has shown that 50% of the maximum SUV threshold in FDG-PET imaging is appropriate for delineation of the most aggressive part of a tumor. After PET- and CT-derived targets were contoured, an IMRT treatment plan was designed to deliver 60 Gy to the GTV as delineated on a 4D CT (Plan 1). A second plan was designed with additional dose of 18 Gy to the PET-derived volume (Plan 2). A composite plan was generated by the addition of Plan 1 and Plan 2. Results: Plan 1 was compared to the composite plan and increases in OAR dose were assessed. For seven patients on average, lung V5 was increased by 1.4% and V20 by 4.2% for ipsilateral lung and by 13.5% and 7% for contralateral lung. For total lung, V5 and V20 were increased by 4.5% and 4.8% respectively. Mean lung dose was increased by 9.7% for the total lung. The maximum dose to the spinal cord increased by 16% on average. For the heart, V20 increased by 4.2% and V40 by 5.2%. Conclusion: It seems feasible that an additional 18 Gy of radiation dose can be delivered to FDG PET-derived subvolume of the CT-based GTV of the primary tumor without significant increase in total dose to the critical organs such as lungs, spinal cord and heart.

  18. Low doses of ionizing radiation: Biological effects and regulatory control. Contributed papers

    International Nuclear Information System (INIS)

    1997-11-01

    The International Atomic Energy Agency and the World Health Organization, in cooperation with the United Nations Scientific Committee on the Effects of Atomic Radiation, organized an international conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, held in seville, Spain, from 17 to 21 November 1997. This technical document contains concise papers submitted to the conference

  19. Low doses of ionizing radiation: Biological effects and regulatory control. Contributed papers

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-11-01

    The International Atomic Energy Agency and the World Health Organization, in cooperation with the United Nations Scientific Committee on the Effects of Atomic Radiation, organized an international conference on Low Doses of Ionizing Radiation: Biological Effects and Regulatory Control, held in seville, Spain, from 17 to 21 November 1997. This technical document contains concise papers submitted to the conference. Refs, figs, tabs.

  20. Limitations of high dose carrier based formulations.

    Science.gov (United States)

    Yeung, Stewart; Traini, Daniela; Tweedie, Alan; Lewis, David; Church, Tanya; Young, Paul M

    2018-06-10

    This study was performed to investigate how increasing the active pharmaceutical ingredient (API) content within a formulation affects the dispersion of particles and the aerosol performance efficiency of a carrier based dry powder inhalable (DPI) formulation, using a custom dry powder inhaler (DPI) development rig. Five formulations with varying concentrations of API beclomethasone dipropionate (BDP) between 1% and 30% (w/w) were formulated as a multi-component carrier system containing coarse lactose and fine lactose with magnesium stearate. The morphology of the formulation and each component were investigated using scanning electron micrographs while the particle size was measured by laser diffraction. The aerosol performance, in terms of aerodynamic diameter, was assessed using the British pharmacopeia Apparatus E cascade impactor (Next generation impactor). Chemical analysis of the API was observed by high performance liquid chromatography (HPLC). Increasing the concentration of BDP in the blend resulted in increasing numbers and size of individual agglomerates and densely packed BDP multi-layers on the surface of the lactose carrier. BDP present within the multi-layer did not disperse as individual primary particles but as dense agglomerates, which led to a decrease in aerosol performance and increased percentage of BDP deposition within the Apparatus E induction port and pre-separator. As the BDP concentration in the blends increases, aerosol performance of the formulation decreases, in an inversely proportional manner. Concurrently, the percentage of API deposition in the induction port and pre-separator could also be linked to the amount of micronized particles (BDP and Micronized composite carrier) present in the formulation. The effect of such dose increase on the behaviour of aerosol dispersion was investigated to gain greater insight in the development and optimisation of higher dosed carrier-based formulations. Copyright © 2018 Elsevier B.V. All

  1. Biological effects of low-dose radiation on human population living in high-background radiation areas of Kerala coast

    International Nuclear Information System (INIS)

    Das, Birajalaxmi

    2016-01-01

    High-level natural radiation areas (HLNRA) of Kerala coast is densely populated and known for its wide variation in background radiation dose levels due to uneven distribution of monazite in the beach sand. The background radiation dose varies from 1 to 45 mGv/y. The areas with >1.5mGy/y is considered as HLNRA. Human population inhabiting in this area are exposed to low-dose chronic radiation since generations. Hence, this population provides an ideal situation to study dose response and adaptive response, if any, due to natural chronic low-dose exposure. It has been investigated extensively to study the biological and health effects of long-term low-dose/low-dose radiation exposure. So far over 150, 000 newborns monitored from hospital-based study did not reveal any significant difference in the incidence of any of the malformations and stillbirth between HLNRA and adjacent control areas. A case-control study on cleft lip/palate and mental retardation did not show any association with background radiation dose. Cytogenetic investigation of over 27,000 newborns did not show any significant increase in the frequency of chromosome aberrations and karyotype anomalies. DNA damage endpoints, such as micronuclei, telomere length and DNA strand breaks, did not reveal any significant difference between control and exposed population. Studies on DNA damage and repair revealed efficient repair of DNA strand breaks in HLNRA individuals. Molecular studies using high throughput microarray analysis indicated a large number of genes involved in various molecular and cellular pathways. Indications of in vivo radioadaptive response due to natural chronic low-dose exposure in this population have important implications to human health. (author)

  2. Sample Based Unit Liter Dose Estimates

    International Nuclear Information System (INIS)

    JENSEN, L.

    2000-01-01

    The Tank Waste Characterization Program has taken many core samples, grab samples, and auger samples from the single-shell and double-shell tanks during the past 10 years. Consequently, the amount of sample data available has increased, both in terms of quantity of sample results and the number of tanks characterized. More and better data is available than when the current radiological and toxicological source terms used in the Basis for Interim Operation (BIO) (FDH 1999a) and the Final Safety Analysis Report (FSAR) (FDH 1999b) were developed. The Nuclear Safety and Licensing (NS and L) organization wants to use the new data to upgrade the radiological and toxicological source terms used in the BIO and FSAR. The NS and L organization requested assistance in producing a statistically based process for developing the source terms. This report describes the statistical techniques used and the assumptions made to support the development of a new radiological source term for liquid and solid wastes stored in single-shell and double-shell tanks. The results given in this report are a revision to similar results given in an earlier version of the document (Jensen and Wilmarth 1999). The main difference between the results in this document and the earlier version is that the dose conversion factors (DCF) for converting μCi/g or μCi/L to Sv/L (sieverts per liter) have changed. There are now two DCFs, one based on ICRP-68 and one based on ICW-71 (Brevick 2000)

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

    Science.gov (United States)

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

    2017-01-01

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

  4. Biological evidence of low ionizing radiation doses; Biologischer Nachweis niedriger Dosen ionisierender Strahlung

    Energy Technology Data Exchange (ETDEWEB)

    Mirsch, Johanna

    2017-03-17

    Throughout life, every person is constantly exposed to different types of ionising radiation, without even noticing the exposure. The mean radiation exposure for people living in Germany amounts to approximately 4 mSv per year and encompasses the exposure from natural and man-made sources. The risks associated with exposure to low doses of radiation are still the subject of intense and highly controversial discussions, emphasizing the social relevance of studies investigating the effects of low radiation doses. In this thesis, DNA double-strand breaks (DSBs) were analyzed within three projects covering different aspects. DSBs are among the most hazardous DNA lesions induced by ionizing radiation, because this type of damage can easily lead to the loss of genetic information. Consequently, the DSB presents a high risk for the genetic integrity of the cell. In the first project, extensive results uncovered the track structure of charged particles in a biological model tissue. This provided the first biological data that could be used for comparison with data that were measured or predicted using theoretical physical dosimetry methods and mathematical simulations. Charged particles contribute significantly to the natural radiation exposure and are used increasingly in cancer radiotherapy because they are more efficient in tumor cell killing than X- or γ-rays. The difference in the biological effects of high energy charged particles compared with X- or γ-rays is largely determined by the spatial distribution of their energy deposition and the track structure inducing a three-dimensional damage pattern in living cells. This damage pattern consists of cells directly hit by the particle receiving a high dose and neighboring cells not directly hit by primary particles but exposed to far-reaching secondary electrons (δ-electrons). These cells receive a much lower dose deposition in the order of a few mGy. The radial dose distribution of single particle tracks was

  5. Agent-based modelling in synthetic biology.

    Science.gov (United States)

    Gorochowski, Thomas E

    2016-11-30

    Biological systems exhibit complex behaviours that emerge at many different levels of organization. These span the regulation of gene expression within single cells to the use of quorum sensing to co-ordinate the action of entire bacterial colonies. Synthetic biology aims to make the engineering of biology easier, offering an opportunity to control natural systems and develop new synthetic systems with useful prescribed behaviours. However, in many cases, it is not understood how individual cells should be programmed to ensure the emergence of a required collective behaviour. Agent-based modelling aims to tackle this problem, offering a framework in which to simulate such systems and explore cellular design rules. In this article, I review the use of agent-based models in synthetic biology, outline the available computational tools, and provide details on recently engineered biological systems that are amenable to this approach. I further highlight the challenges facing this methodology and some of the potential future directions. © 2016 The Author(s).

  6. Center of cancer systems biology second annual workshop--tumor metronomics: timing and dose level dynamics.

    Science.gov (United States)

    Hahnfeldt, Philip; Hlatky, Lynn; Klement, Giannoula Lakka

    2013-05-15

    Metronomic chemotherapy, the delivery of doses in a low, regular manner so as to avoid toxic side effects, was introduced over 12 years ago in the face of substantial clinical and preclinical evidence supporting its tumor-suppressive capability. It constituted a marked departure from the classic maximum-tolerated dose (MTD) strategy, which, given its goal of rapid eradication, uses dosing sufficiently intense to require rest periods between cycles to limit toxicity. Even so, upfront tumor eradication is frequently not achieved with MTD, whereupon a de facto goal of longer-term tumor control is often pursued. As metronomic dosing has shown tumor control capability, even for cancers that have become resistant to the same drug delivered under MTD, the question arises whether it may be a preferable alternative dosing approach from the outset. To date, however, our knowledge of the coupled dynamics underlying metronomic dosing is neither sufficiently well developed nor widely enough disseminated to establish its actual potential. Meeting organizers thus felt the time was right, armed with new quantitative approaches, to call a workshop on "Tumor Metronomics: Timing and Dose Level Dynamics" to explore prospects for gaining a deeper, systems-level appreciation of the metronomics concept. The workshop proved to be a forum in which experts from the clinical, biologic, mathematical, and computational realms could work together to clarify the principles and underpinnings of metronomics. Among other things, the need for significant shifts in thinking regarding endpoints to be used as clinical standards of therapeutic progress was recognized. ©2013 AACR.

  7. Influence of variations in dose and dose rates on biological effects of inhaled beta-emitting radionuclides

    International Nuclear Information System (INIS)

    McClellan, R.O.; Benjamin, S.A.; Boecker, B.B.; Hahn, F.F.; Hobbs, C.H.; Jones, R.K.; Lundgren, D.L.

    1976-01-01

    The biological effects of inhaled β-emitting radionuclides, 90 Y, 91 Y, 144 Ce and 90 Sr, are being investigated in beagle dogs that received single acute exposures at 12 to 14 months of age. The aerosols studied have included 91 YC1 3 , 144 CeC1 3 , 90 SrC1 2 , and 90 Y, 91 Y, 144 Ce or 90 Sr in aluminosilicate particles. Thus, 91 YCl 3 , 144 CeCl 3 and the aluminosilicate containing radionuclide particles all resulted in significant exposures to lung; 91 YC1 3 , 144 CeC1 3 an 90 SrC1 2 resulted in significant exposures to bone; 91 YC1 3 and 144 CeC1 3 resulted in significant exposures to liver. The higher initial doserate exposures have been more effective than low dose-rate exposures on a per-rad basis in producing early effects. To date ( 144 CeO 2 , it was observed that, on a μCi initial lung burden per kilogram body weight basis, mice did not develop pulmonary tumours whereas beagle dogs did. To fid out the reason for this observation mice have been repeatedly exposed by inhalation to 144 CeO 2 to maintain lung burdens of 144 Ce that resulted in radiation dose rates similar to that observed in beagle dogs. Several of the repeatedly exposed mice developed malignant pulmonary tumours. Thus, with similar dose rates and cumulative doses to the lung, mice and dogs responded in a similar manner to chronic β radiation

  8. Testing the Capacity of the National Biological Dose Response Plan (NBDRP) EX40801

    Science.gov (United States)

    2009-11-01

    Blood Collection All donors were volunteers that willingly responded to an advertising call for participation in a research proposal approved by...Scorers from the same laboratory are shown in the same colour . In Figure 2, the dose estimates based on QuickScan are shown. Figure 3 shows the doses

  9. Gamma-irradiated onions as a biological indicator of radiation dose

    International Nuclear Information System (INIS)

    Vaijapurkar, S.G.; Agarwal, Deepshikha; Chaudhuri, S.K.; Ram Senwar, Kana; Bhatnagar, P.K.

    2001-01-01

    Post-irradiation identification and dose estimation are required to assess the radiation-induced effects on living things in any nuclear emergency. In this study, radiation-induced morphological/cytological changes i.e., number of root formation and its length, shooting length, reduction in mitotic index, micronuclei formation and chromosomal aberrations in the root tip cells of gamma-irradiated onions at lower doses (50-2000 cGy) are reported. The capabilities of this biological species to store the radiation-induced information are also studied

  10. Switching From Age-Based Stimulus Dosing to Dose Titration Protocols in Electroconvulsive Therapy: Empirical Evidence for Better Patient Outcomes With Lower Peak and Cumulative Energy Doses.

    Science.gov (United States)

    O'Neill-Kerr, Alex; Yassin, Anhar; Rogers, Stephen; Cornish, Janie

    2017-09-01

    The aim of this study was to test the proposition that adoption of a dose titration protocol may be associated with better patient outcomes, at lower treatment dose, and with comparable cumulative dose to that in patients treated using an age-based stimulus dosing protocol. This was an analysis of data assembled from archived records and based on cohorts of patients treated respectively on an age-based stimulus dosing protocol and on a dose titration protocol in the National Health Service in England. We demonstrated a significantly better response in the patient cohort treated with dose titration than with age-based stimulus dosing. Peak doses were less and the total cumulative dose was less in the dose titration group than in the age-based stimulus dosing group. Our findings are consistent with superior outcomes in patients treated using a dose titration protocol when compared with age-based stimulus dosing in a similar cohort of patients.

  11. Biologically effective dose (BED) for interstitial seed implants containing a mixture of radionuclides with different half-lives

    International Nuclear Information System (INIS)

    Chen Zhe; Nath, Ravinder

    2003-01-01

    Purpose: To develop a tool for evaluating interstitial seed implants that contain a mixture of radionuclides with different half-lives and to demonstrate its utility by examining the clinical implications of prescribing to an isodose surface for such an implant. Methods and Materials: A linear-quadratic model for continuous low dose rate irradiation was developed for permanent implants containing a mixture of radionuclides. Using a generalized equation for the biologically effective dose (BED), the effects of cell proliferation and sublethal damage repair were examined systematically for implants containing a mixture of radionuclides. A head-and-neck permanent seed implant that contained a mixture of 125 I and 103 Pd seeds was used to demonstrate the utility of the generalized BED. Results: An equation of BED for implants containing a mixture of radionuclides with different half-lives was obtained. In such an implant, the effective cell kill was shown to depend strongly on the relative dose contributions from each radionuclide type; dose delivered by radionuclides with shorter half-life always resulted in more cell kill for any given sublethal damage repair and cell proliferation rates. Application of the BED formula to an implant containing a mixture of 125 I and 103 Pd seeds demonstrates that the conventional dose prescription to an isodose surface is not unique for such an implant. When the prescription dose was based on existing clinical experience of using 125 I seeds alone, mixing 103 Pd seeds with 125 I seeds would increase the cell kill. On the other hand, if the prescription dose were based on existing clinical experience of using 103 Pd seeds alone, mixing 125 I seeds with 103 Pd seeds in the same implant would create radiobiologically 'cold' spots (i.e., an increase in cell survival) at locations where a major portion of the prescription dose is contributed by the 125 I seeds. For fast-growing tumors, these 'cold' spots can become significant

  12. The influence of low doses of ionizing radiation on biological systems

    International Nuclear Information System (INIS)

    Kwiecinska, T.

    1986-11-01

    Recent results concerning possible beneficial effects of low doses of ionizing radiation on biological systems are summarized. It is also pointed out on the basis of existing evidence that harmful effects on living organisms take place not only in the case of excess but also in the case of deficiency of ionizing radiation. Possibility of using radio-enhanced ultralow luminescence for studying hormesis phenomena is discussed. 24 refs., 4 figs. (author)

  13. Biological monitoring to determine worker dose in a butadiene processing plant

    Energy Technology Data Exchange (ETDEWEB)

    Bechtold, W.E.; Hayes, R.B. [National Cancer Inst., Bethesda, MD (United States)

    1995-12-01

    Butadiene (BD) is a reactive gas used extensively in the rubber industry and is also found in combustion products. Although BD is genotoxic and acts as an animal carcinogen, the evidence for carcinogenicity in humans is limited. Extrapolation from animal studies on BD carcinogenicity to risk in humans has been controversial because of uncertainties regarding relative biologic exposure and related effects in humans vs. experimental animals. To reduce this uncertainty, a study was designed to characterize exposure to BD at a polymer production facility and to relate this exposure to mutational and cytogenetic effects. Biological monitoring was used to better assess the internal dose of BD received by the workers. Measurement of 1,2-dihydroxy-4-(N-acetylcysteinyl) butane (M1) in urine served as the biomarker in this study. M1 has been shown to correlate with area monitoring in previous studies. Most studies that relate exposure to a toxic chemical with its biological effects rely on exposure concentration as the dose metric; however, exposure concentration may or may not reflect the actual internal dose of the chemical.

  14. Metabolomics identifies a biological response to chronic low-dose natural uranium contamination in urine samples.

    Science.gov (United States)

    Grison, Stéphane; Favé, Gaëlle; Maillot, Matthieu; Manens, Line; Delissen, Olivia; Blanchardon, Eric; Banzet, Nathalie; Defoort, Catherine; Bott, Romain; Dublineau, Isabelle; Aigueperse, Jocelyne; Gourmelon, Patrick; Martin, Jean-Charles; Souidi, Maâmar

    2013-01-01

    Because uranium is a natural element present in the earth's crust, the population may be chronically exposed to low doses of it through drinking water. Additionally, the military and civil uses of uranium can also lead to environmental dispersion that can result in high or low doses of acute or chronic exposure. Recent experimental data suggest this might lead to relatively innocuous biological reactions. The aim of this study was to assess the biological changes in rats caused by ingestion of natural uranium in drinking water with a mean daily intake of 2.7 mg/kg for 9 months and to identify potential biomarkers related to such a contamination. Subsequently, we observed no pathology and standard clinical tests were unable to distinguish between treated and untreated animals. Conversely, LC-MS metabolomics identified urine as an appropriate biofluid for discriminating the experimental groups. Of the 1,376 features detected in urine, the most discriminant were metabolites involved in tryptophan, nicotinate, and nicotinamide metabolic pathways. In particular, N -methylnicotinamide, which was found at a level seven times higher in untreated than in contaminated rats, had the greatest discriminating power. These novel results establish a proof of principle for using metabolomics to address chronic low-dose uranium contamination. They open interesting perspectives for understanding the underlying biological mechanisms and designing a diagnostic test of exposure.

  15. Environmental and biological monitoring in the estimation of absorbed doses of pesticides.

    Science.gov (United States)

    Aprea, Maria Cristina

    2012-04-25

    Exposure to pesticides affects most of the population, not only persons occupationally exposed. In a context of high variability of exposure, biological monitoring is important because of the various routes by which exposure can occur and because it assesses both occupational and non-occupational exposure. The main aim of this paper was to critically compare estimates of absorbed dose measured by environmental and biological monitoring in situations in which they could both be applied. The combination of exposure measurements and biological monitoring was found to provide extremely important information on the behaviour of employees, and on the proper use and effectiveness of personal protection equipment. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Contribution of the modulation of intensity and the optimization to deliver a dose adapted to the biological heterogeneities

    International Nuclear Information System (INIS)

    Kubs, F.

    2007-10-01

    The recent progress in functional imaging by Positron Emission Tomography (TEP) opens new perspectives in the delineation of target volumes in radiotherapy. The functional data is major; we can intend to adapt the irradiation doses on the tumor activity (TA) and to perform a dose escalation. Our objectives were (i) to characterize the TEP threshold, by quantifying the uncertainties of the target volume contour according to the lesion size and the threshold contour level, (ii) to set up the geometry suited to perform a high-precision irradiation based on the TA, (iii) to estimate the dosimetric impact of this new protocol and (iv) to verify that dosimetry is perfectly distributed. Three original phantoms were specially created to satisfy the constraints met, as well as two virtual phantoms containing 3 dose levels (dose level 3 = TA). Our results showed the importance of the effect threshold-volume on the planning in radiotherapy. To use this irradiation method, the diameter of 1 cm for the third level was able to be reached. A dose escalation of 20 Gy was possible between the second (70 Gy) and the third level (90 Gy). The dosimetric impact estimated on two real cases was suitable - increase of COIN (conformal index) from 0.6 to 0.8 and decrease of NTCP (normal tissue complication probability) of a factor 5 -. In absolute and relative dosimetry, the clinical tolerances were respected. So all the treatment process, going from the diagnosis with the TEP to reveal the TA, to the patient treatment made beforehand on phantom, and going through the ballistic and the dose calculation, was estimated and validated according to our objective to adapt the irradiation to the biological heterogeneities. However such high doses should be carefully estimated before being prescribed clinically and progress is also expected in imaging, because the minimal size which we can irradiate is on the limit of the resolution TEP. (author)

  17. The biological effect of 125I seed continuous low dose rate irradiation in CL187 cells

    Directory of Open Access Journals (Sweden)

    Zhuang Hong-Qing

    2009-01-01

    Full Text Available Abstract Background To investigate the effectiveness and mechanism of 125I seed continuous low-dose-rate irradiation on colonic cell line CL187 in vitro. Methods The CL187 cell line was exposed to radiation of 60Coγ ray at high dose rate of 2 Gy/min and 125I seed at low dose rate of 2.77 cGy/h. Radiation responses to different doses and dose rates were evaluated by colony-forming assay. Under 125I seed low dose rate irradiation, a total of 12 culture dishes were randomly divided into 4 groups: Control group, and 2, 5, and 10 Gy irradiation groups. At 48 h after irradiation, apoptosis was detected by Annexin and Propidium iodide (PI staining. Cell cycle arrests were detected by PI staining. In order to investigate the influence of low dose rate irradiation on the MAPK signal transduction, the expression changes of epidermal growth factor receptor (EGFR and Raf under continuous low dose rate irradiation (CLDR and/or EGFR monoclonal antibodies were determined by indirect immunofluorescence. Results The relative biological effect (RBE for 125I seeds compared with 60Co γ ray was 1.41. Apoptosis rates of CL187 cancer cells were 13.74% ± 1.63%, 32.58% ± 3.61%, and 46.27% ± 3.82% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 1.67% ± 0.19%. G2/M cell cycle arrests of CL187 cancer cells were 42.59% ± 3.21%, 59.84% ± 4.96%, and 34.61% ± 2.79% after 2 Gy, 5 Gy, and 10 Gy irradiation, respectively; however, the control group apoptosis rate was 26.44% ± 2.53%. P 2/M cell cycle arrest. After low dose rate irradiation, EGFR and Raf expression increased, but when EGFR was blocked by a monoclonal antibody, EGFR and Raf expression did not change. Conclusion 125I seeds resulted in more effective inhibition than 60Co γ ray high dose rate irradiation in CL187 cells. Apoptosis following G2/M cell cycle arrest was the main mechanism of cell-killing effects under low dose rate irradiation. CLDR could

  18. Relative biological effectiveness of 125I seeds for low-dose-rate irradiation of PANC-1

    International Nuclear Information System (INIS)

    Wang Jidong; Wang Junjie; Zhuang Hongqing; Liao Anyan; Zhao Yong

    2008-01-01

    Objective: To investigate the relative biological effectiveness(RBE) of National Model 6711 125 I seeds and the response patterns of PANC-1 exposed to 125 I seeds irradiation. Methods: PANC-1 cells in exponential growth were irradiated at initial dose rate of 2.59 cGy/h in vitro and exposed to 1, 2, 4, 6, 8 and 10 Gy. Meanwhile, the other part of cells were exposed to the same doses by 60 Co at dose rate of 2.21 Gy/min. After irradiation, the cells were stained by trypan blue to measure the cellular mortality rate and to compare the changes along with plating times of 12, 24, 48 and 72 h after 4 Gy. The colonies were counted to obtain the plating efficiencies by colony-forming assay and the cell surviving faction was calculated to plot cell survival curves, and RBE of 125 I seeds relative to 60 Co was determined. Results: The cell death rate for continuous low- dose-rate (LDR) irradiation by 125 I seeds was greater than 60 Co at the same doses above or equal to 4 Gy. After 4 Gy irradiation, the cellular mortality rates were increased with times. The difference was significant between 125 I seeds and 60 Co. The survival fractions of 125 I were lower than those of 60 Co, and the RBE of 125 I relative to 60 Co was determined to be 1.45. Conclusion: The cell-killing effects for continuous low-dose-rate (LDR) irradiation by 125 I seeds are greater than acute high-dose-rate of 60 Co. (authors)

  19. EUD-based biological optimization for carbon ion therapy

    International Nuclear Information System (INIS)

    Brüningk, Sarah C.; Kamp, Florian; Wilkens, Jan J.

    2015-01-01

    Purpose: Treatment planning for carbon ion therapy requires an accurate modeling of the biological response of each tissue to estimate the clinical outcome of a treatment. The relative biological effectiveness (RBE) accounts for this biological response on a cellular level but does not refer to the actual impact on the organ as a whole. For photon therapy, the concept of equivalent uniform dose (EUD) represents a simple model to take the organ response into account, yet so far no formulation of EUD has been reported that is suitable to carbon ion therapy. The authors introduce the concept of an equivalent uniform effect (EUE) that is directly applicable to both ion and photon therapies and exemplarily implemented it as a basis for biological treatment plan optimization for carbon ion therapy. Methods: In addition to a classical EUD concept, which calculates a generalized mean over the RBE-weighted dose distribution, the authors propose the EUE to simplify the optimization process of carbon ion therapy plans. The EUE is defined as the biologically equivalent uniform effect that yields the same probability of injury as the inhomogeneous effect distribution in an organ. Its mathematical formulation is based on the generalized mean effect using an effect-volume parameter to account for different organ architectures and is thus independent of a reference radiation. For both EUD concepts, quadratic and logistic objective functions are implemented into a research treatment planning system. A flexible implementation allows choosing for each structure between biological effect constraints per voxel and EUD constraints per structure. Exemplary treatment plans are calculated for a head-and-neck patient for multiple combinations of objective functions and optimization parameters. Results: Treatment plans optimized using an EUE-based objective function were comparable to those optimized with an RBE-weighted EUD-based approach. In agreement with previous results from photon

  20. Biological dosimetry of ionizing radiation: Evaluation of the dose with cytogenetic methodologies by the construction of calibration curves

    Science.gov (United States)

    Zafiropoulos, Demetre; Facco, E.; Sarchiapone, Lucia

    2016-09-01

    In case of a radiation accident, it is well known that in the absence of physical dosimetry biological dosimetry based on cytogenetic methods is a unique tool to estimate individual absorbed dose. Moreover, even when physical dosimetry indicates an overexposure, scoring chromosome aberrations (dicentrics and rings) in human peripheral blood lymphocytes (PBLs) at metaphase is presently the most widely used method to confirm dose assessment. The analysis of dicentrics and rings in PBLs after Giemsa staining of metaphase cells is considered the most valid assay for radiation injury. This work shows that applying the fluorescence in situ hybridization (FISH) technique, using telomeric/centromeric peptide nucleic acid (PNA) probes in metaphase chromosomes for radiation dosimetry, could become a fast scoring, reliable and precise method for biological dosimetry after accidental radiation exposures. In both in vitro methods described above, lymphocyte stimulation is needed, and this limits the application in radiation emergency medicine where speed is considered to be a high priority. Using premature chromosome condensation (PCC), irradiated human PBLs (non-stimulated) were fused with mitotic CHO cells, and the yield of excess PCC fragments in Giemsa stained cells was scored. To score dicentrics and rings under PCC conditions, the necessary centromere and telomere detection of the chromosomes was obtained using FISH and specific PNA probes. Of course, a prerequisite for dose assessment in all cases is a dose-effect calibration curve. This work illustrates the various methods used; dose response calibration curves, with 95% confidence limits used to estimate dose uncertainties, have been constructed for conventional metaphase analysis and FISH. We also compare the dose-response curve constructed after scoring of dicentrics and rings using PCC combined with FISH and PNA probes. Also reported are dose response curves showing scored dicentrics and rings per cell, combining

  1. Development of Software for dose Records Data Base Access

    International Nuclear Information System (INIS)

    Amaro, M.

    1990-01-01

    The CIEMAT personal dose records are computerized in a Dosimetric Data Base whose primary purpose was the individual dose follow-up control and the data handling for epidemiological studies. Within the Data Base management scheme, software development to allow searching of individual dose records by external authorised users was undertaken. The report describes the software developed to allow authorised persons to visualize on screen a summary of the individual dose records from workers included in the Data Base. The report includes the User Guide for the authorised list of users and listings of codes and subroutines developed. (Author) 2 refs

  2. The choice of a biological model in assessing internal dose equivalent

    International Nuclear Information System (INIS)

    Parodo, A.; Erre, N.

    1977-01-01

    Many are the biological models related to kinetic behavior of radioactive materials within the organism, or in an organ. This is true particularly for the metabolic kinetics of bone-seekers radionuclides described differently by various authors: as a consequence, different forms of the retention function have been used in calculating internal dose equivalent. In our opinion, the retention functions expressed as linear combinations of exponential terms with negative exponents are preferable. In fact, they can be obtained by coherent compartmental analysis and allow a mathematical formalism fairly well definite and easily adaptable to computers. Moreover, it is possible to make use of graphs and monograms already published. The role of the biological model in internal dosimetry, referred to the reliability of the quantitative informations on the kinetic behavior of the radionuclides in the organism and, therefrom, to the accuracy of the doses calculated, is discussed. By comparing the results obtained with different biological models, one finds that the choice of a model is less important than the choice of the value of the appropriate parameters

  3. The use of biologically based cancer risk models in radiation epidemiology

    International Nuclear Information System (INIS)

    Krewski, D.; Zielinski, J.M.; Hazelton, W.D.; Garner, M.J.; Moolgavkar, S.H.

    2003-01-01

    Biologically based risk projection models for radiation carcinogenesis seek to describe the fundamental biological processes involved in neoplastic transformation of somatic cells into malignant cancer cells. A validated biologically based model, whose parameters have a direct biological interpretation, can also be used to extrapolate cancer risks to different exposure conditions with some confidence. In this article, biologically based models for radiation carcinogenesis, including the two-stage clonal expansion (TSCE) model and its extensions, are reviewed. The biological and mathematical bases for such models are described, and the implications of key model parameters for cancer risk assessment examined. Specific applications of versions of the TSCE model to important epidemiologic datasets are discussed, including the Colorado uranium miners' cohort; a cohort of Chinese tin miners; the lifespan cohort of atomic bomb survivors in Hiroshima and Nagasaki; and a cohort of over 200,000 workers included in the National Dose Registry (NDR) of Canada. (author)

  4. Considerations on absorbed dose estimates based on different β-dose point kernels in internal dosimetry

    International Nuclear Information System (INIS)

    Uchida, Isao; Yamada, Yasuhiko; Yamashita, Takashi; Okigaki, Shigeyasu; Oyamada, Hiyoshimaru; Ito, Akira.

    1995-01-01

    In radiotherapy with radiopharmaceuticals, more accurate estimates of the three-dimensional (3-D) distribution of absorbed dose is important in specifying the activity to be administered to patients to deliver a prescribed absorbed dose to target volumes without exceeding the toxicity limit of normal tissues in the body. A calculation algorithm for the purpose has already been developed by the authors. An accurate 3-D distribution of absorbed dose based on the algorithm is given by convolution of the 3-D dose matrix for a unit cubic voxel containing unit cumulated activity, which is obtained by transforming a dose point kernel into a 3-D cubic dose matrix, with the 3-D cumulated activity distribution given by the same voxel size. However, beta-dose point kernels affecting accurate estimates of the 3-D absorbed dose distribution have been different among the investigators. The purpose of this study is to elucidate how different beta-dose point kernels in water influence on the estimates of the absorbed dose distribution due to the dose point kernel convolution method by the authors. Computer simulations were performed using the MIRD thyroid and lung phantoms under assumption of uniform activity distribution of 32 P. Using beta-dose point kernels derived from Monte Carlo simulations (EGS-4 or ACCEPT computer code), the differences among their point kernels gave little differences for the mean and maximum absorbed dose estimates for the MIRD phantoms used. In the estimates of mean and maximum absorbed doses calculated using different cubic voxel sizes (4x4x4 mm and 8x8x8 mm) for the MIRD thyroid phantom, the maximum absorbed doses for the 4x4x4 mm-voxel were estimated approximately 7% greater than the cases of the 8x8x8 mm-voxel. They were found in every beta-dose point kernel used in this study. On the other hand, the percentage difference of the mean absorbed doses in the both voxel sizes for each beta-dose point kernel was less than approximately 0.6%. (author)

  5. Biologically effective dose for permanent prostate brachytherapy taking into account postimplant edema

    International Nuclear Information System (INIS)

    Gellekom, Marion P.R. van; Moerland, Marinus A.; Kal, Henk B.; Battermann, Jan J.

    2002-01-01

    Purpose: To study the influence of radiobiologic and physical parameters and parameters related to edema on the biologically effective dose (BED) for permanent prostate implants and to determine the optimal timing of seed reconstruction for BED calculation. Methods and Materials: On the basis of the linear-quadratic model, an expression for the BED was derived, including the edema parameters. A set of parameter values was defined, and these parameter values were varied one at a time to examine the effect on the BED and the theoretically effective treatment time (t eff ). A ratio ε was defined to investigate the optimal timing of seed reconstruction. Results: The maximal BED decreases when the extent of lethal damage is smaller, the potential tumor doubling time is smaller, the half-life time of the seeds is shorter, and the magnitude of prostate volume increase is larger. For 125 I, the optimal timing of seed reconstruction is 25 days after implantation. Seed reconstruction 1 day after the implantation results in an underestimation of the BED of at most 43%, depending on the magnitude and half-life of edema. An overestimation of the BED of at most 22% is calculated when seed reconstruction took place at the effective treatment time. Conclusion: The maximal BED depends strongly on the value of α, the potential tumor doubling time, and the choice of isotope. If prostate volume increase due to edema is not taken into account, the BED will be underestimated shortly after the implantation and overestimated if the calculations are based on images taken several months after implantation. The optimal timing of BED evaluation for 125 I seed implants and typical prostate edema values is 25 days after implantation

  6. Nicotine dose-concentration relationship and pregnancy outcomes in rat: Biologic plausibility and implications for future research

    International Nuclear Information System (INIS)

    Hussein, Jabeen; Farkas, Svetlana; MacKinnon, Yolanda; Ariano, Robert E.; Sitar, Daniel S.; Hasan, Shabih U.

    2007-01-01

    Cigarette smoke (CS) exposure during pregnancy can lead to profound adverse effects on fetal development. Although CS contains several thousand chemicals, nicotine has been widely used as its surrogate as well as in its own right as a neuroteratogen. The justification for the route and dose of nicotine administration is largely based on inferential data suggesting that nicotine 6 mg/kg/day infused continuously via osmotic mini pumps (OMP) would mimic maternal CS exposure. We provide evidence that 6 mg/kg/day nicotine dose as commonly administered to pregnant rats leads to plasma nicotine concentrations that are 3-10-fold higher than those observed in moderate to heavy smokers and pregnant mothers, respectively. Furthermore, the cumulative daily nicotine dose exceeds by several hundred fold the amount consumed by human heavy smokers. Our study does not support the widely accepted notion that regardless of the nicotine dose, a linear nicotine dose-concentration relationship exists in a steady-state OMP model. We also show that total nicotine clearance increases with advancing pregnancy but no significant change is observed between the 2nd and 3rd trimester. Furthermore, nicotine infusion even at this extremely high dose has little effect on a number of maternal and fetal biologic variables and pregnancy outcome suggesting that CS constituents other than nicotine mediate the fetal growth restriction in infants born to smoking mothers. Our current study has major implications for translational research in developmental toxicology and pharmacotherapy using nicotine replacement treatment as an aid to cessation of cigarette smoking in pregnant mothers

  7. 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

  8. 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)

  9. 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

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

    International Nuclear Information System (INIS)

    Silva, Marcia Augusta da

    1997-01-01

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

  11. Radiation dose and biological effects to mouse testis from sodium 32P-phosphate

    International Nuclear Information System (INIS)

    Mian, T.A.; Glenn, H.J.; Haynie, T.P.; Meistrich, M.L.

    1982-01-01

    Radiation dose to mouse testis was estimated to be about 1.65 rad per μCi of intravenously injected 32 P. This high dose to the organ was due to the incorporation of this isotope into the macromolecules of the testis. Up to 30% of the total testis activity was in DNA molecules. Biologic effects on mouse testis from 32 P were determined by testis weight loss and the decrease in the number of sperm heads in the testis. Number of sperm heads reached a minimum of 1.3% of control 36 days after injection of 3.5 μCi/g body weight of 32 P. Significant decreases in sperm head counts were observed after as little as 0.2 μCi/g body weight of 32 P. (author)

  12. Biologically-equivalent dose and long-term survival time in radiation treatments

    International Nuclear Information System (INIS)

    Zaider, Marco; Hanin, Leonid

    2007-01-01

    Within the linear-quadratic model the biologically-effective dose (BED)-taken to represent treatments with an equal tumor control probability (TCP)-is commonly (and plausibly) calculated according to BED(D) = -log[S(D)]/α. We ask whether in the presence of cellular proliferation this claim is justified and examine, as a related question, the extent to which BED approximates an isoeffective dose (IED) defined, more sensibly, in terms of an equal long-term survival probability, rather than TCP. We derive, under the assumption that cellular birth and death rates are time homogeneous, exact equations for the isoeffective dose, IED. As well, we give a rigorous definition of effective long-term survival time, T eff . By using several sets of radiobiological parameters, we illustrate potential differences between BED and IED on the one hand and, on the other, between T eff calculated as suggested here or by an earlier recipe. In summary: (a) the equations currently in use for calculating the effective treatment time may underestimate the isoeffective dose and should be avoided. The same is the case for the tumor control probability (TCP), only more so; (b) for permanent implants BED may be a poor substitute for IED; (c) for a fractionated treatment schedule, interpreting the observed probability of cure in terms of a TCP formalism that refers to the end of the treatment (rather than T eff ) may result in a miscalculation (underestimation) of the initial number of clonogens

  13. Dose painting based on tumor uptake of Cu-ATSM and FDG: a comparative study

    International Nuclear Information System (INIS)

    Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael; Hollensen, Christian; Pommer, Tobias; Munck af Rosenschöld, Per; Kristensen, Annemarie Thuri; Kjær, Andreas; McEvoy, Fintan J; Engelholm, Svend Aage

    2014-01-01

    Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The purpose of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[ 18 F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis(N 4 )-methylsemithiocarbazone (Cu-ATSM) using spontaneous clinical canine tumor models. Positron emission tomography/computed tomography scans of five spontaneous canine sarcomas and carcinomas were obtained; FDG on day 1 and 64 Cu-ATSM on day 2 and 3 (approx. 3 and 24 hours pi.). Sub-volumes for dose escalation were defined by a threshold-based method for both tracers and five dose escalation levels were formed in each sub-volume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions for each scan for a total of three dose plans for each dog. The prescription dose for the GTV was 45 Gy (100%) and it was linearly escalated to a maximum of 150%. The correlations between dose painting plans were analyzed with construction of dose distribution density maps and quality volume histograms (QVH). Correlation between high-dose regions was investigated with Dice correlation coefficients. Comparison of dose plans revealed varying degree of correlation between cases. Some cases displayed a separation of high-dose regions in the comparison of FDG vs. 64 Cu-ATSM dose plans at both time points. Among the Dice correlation coefficients, the high dose regions showed the lowest degree of agreement, indicating potential benefit of using multiple tracers for dose painting. QVH analysis revealed that FDG-based dose painting plans adequately covered approximately 50% of the hypoxic regions. Radiotherapy plans optimized with the current approach for cut-off values and dose region definitions based on FDG, 64 Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64 Cu-ATSM at two

  14. UNCERTAINTY ON RADIATION DOSES ESTIMATED BY BIOLOGICAL AND RETROSPECTIVE PHYSICAL METHODS.

    Science.gov (United States)

    Ainsbury, Elizabeth A; Samaga, Daniel; Della Monaca, Sara; Marrale, Maurizio; Bassinet, Celine; Burbidge, Christopher I; Correcher, Virgilio; Discher, Michael; Eakins, Jon; Fattibene, Paola; Güçlü, Inci; Higueras, Manuel; Lund, Eva; Maltar-Strmecki, Nadica; McKeever, Stephen; Rääf, Christopher L; Sholom, Sergey; Veronese, Ivan; Wieser, Albrecht; Woda, Clemens; Trompier, Francois

    2018-03-01

    Biological and physical retrospective dosimetry are recognised as key techniques to provide individual estimates of dose following unplanned exposures to ionising radiation. Whilst there has been a relatively large amount of recent development in the biological and physical procedures, development of statistical analysis techniques has failed to keep pace. The aim of this paper is to review the current state of the art in uncertainty analysis techniques across the 'EURADOS Working Group 10-Retrospective dosimetry' members, to give concrete examples of implementation of the techniques recommended in the international standards, and to further promote the use of Monte Carlo techniques to support characterisation of uncertainties. It is concluded that sufficient techniques are available and in use by most laboratories for acute, whole body exposures to highly penetrating radiation, but further work will be required to ensure that statistical analysis is always wholly sufficient for the more complex exposure scenarios.

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

    International Nuclear Information System (INIS)

    Cristakou, H.D.

    1983-01-01

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

  16. Modification of the biologic dose to normal tissue by daily fraction

    Energy Technology Data Exchange (ETDEWEB)

    Wollin, M; Kagan, A R [Southern California Permanente Medical Group, Los Angeles Calif. (USA). Dep. of Radiation Therapy

    1976-12-01

    A method to predict normal tissue injury is proposed that includes high daily doses and unusual times successfully by calculating a new value called BIR (Biologic Index of Reaction). BIR and NSD were calculated for various normal tissue reactions. With the aid of statistical correlation techniques it is found that the BIR model is better than the NSD model in predicting radiation myelopathy and vocal edema and as good as NSD IN PREDICTING RIB FRACTURE/ Neither model predicts pericardial effusion. In no case were the results of BIR inferior to those of NSD.

  17. 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

  18. A meta-analysis of the abscopal effect in preclinical models: Is the biologically effective dose a relevant physical trigger?

    Directory of Open Access Journals (Sweden)

    Raffaella Marconi

    Full Text Available Preclinical in vivo studies using small animals are considered crucial in translational cancer research and clinical implementation of novel treatments. This is of paramount relevance in radiobiology, especially for any technological developments permitted to deliver high doses in single or oligo-fractionated regimens, such as stereotactic ablative radiotherapy (SABR. In this context, clinical success in cancer treatment needs to be guaranteed, sparing normal tissue and preventing the potential spread of disease or local recurrence. In this work we introduce a new dose-response relationship based on relevant publications concerning preclinical models with regard to delivered dose, fractionation schedule and occurrence of biological effects on non-irradiated tissue, abscopal effects.We reviewed relevant publications on murine models and the abscopal effect in radiation cancer research following PRISMA methodology. In particular, through a log-likelihood method, we evaluated whether the occurrence of abscopal effects may be related to the biologically effective dose (BED. To this aim, studies accomplished with different tumor histotypes were considered in our analysis including breast, colon, lung, fibrosarcoma, pancreas, melanoma and head and neck cancer. For all the tumors, the α / β ratio was assumed to be 10 Gy, as generally adopted for neoplastic cells.Our results support the hypothesis that the occurrence rate of abscopal effects in preclinical models increases with BED. In particular, the probability of revealing abscopal effects is 50% when a BED of 60 Gy is generated.Our study provides evidence that SABR treatments associated with high BEDs could be considered an effective strategy in triggering the abscopal effect, thus shedding light on the promising outcomes revealed in clinical practice.

  19. Long-term biological effects induced by ionizing radiation--implications for dose mediated risk.

    Science.gov (United States)

    Miron, S D; Astărăstoae, V

    2014-01-01

    Ionizing radiations are considered to be risk agents that are responsible for the effects on interaction with living matter. The occurring biological effects are due to various factors such as: dose, type of radiation, exposure time, type of biological tissue, health condition and the age of the person exposed. The mechanisms involved in the direct modifications of nuclear DNA and mitochondrial DNA are reviewed. Classical target theory of energy deposition in the nucleus that causes DNA damages, in particular DNA double-strand breaks and that explanation of the biological consequences of ionizing radiation exposure is a paradigm in radiobiology. Recent experimental evidences have demonstrated the existence of a molecular mechanism that explains the non-targeted effects of ionizing radiation exposure. Among these novel data, genomic instability and a variety of bystander effects are discussed here. Those bystander effects of ionizing radiation are fulfilled by cellular communication systems that give rise to non-targeted effects in the neighboring non irradiated cells. This paper provides also a commentary on the synergistic effects induced by the co-exposures to ionizing radiation and various physical agents such as electromagnetic fields and the co-exposures to ionizing radiation and chemical environmental contaminants such as metals. The biological effects of multiple stressors on genomic instability and bystander effects are also discussed. Moreover, a brief presentation of the methods used to characterize cyto- and genotoxic damages is offered.

  20. Establishment of a semi-biological phantom model for the study of the effect of dose reducing measures on radiation-induced DNA double strand breaks in CT using the example of risk organ based tube current modulation; Etablierung eines semibiologischen Phantommodells zur Untersuchung des Effekts dosisreduzierender Massnahmen auf strahleninduzierte DNA-Doppelstrangbrueche in der CT am Beispiel der risikoorganbasierten Roehrenstrommodulation

    Energy Technology Data Exchange (ETDEWEB)

    Sommer, Matthias

    2013-12-12

    The number of computed tomography (CT) examinations has been rising during the last decades. Therefore techniques for dose reduction receive increasing attention. Risk organ-based tube current modulation (RCM) in CT is a new approach and works by lowering the tube current, while the tube is in front of the patient's body. Therefore it should lead to a dose reduction for radiosensitive organs like the female breast, the eye lenses and the thyroid gland. Biological radiation effects cannot be estimated by physical-based dose measurements. γ-H2AX is a sensitive marker for the determination of x-ray induced DNA double-strand breaks (DSB). Hence the aim of this study was to establish a biological phantom model based on the γ-H2AX immunofluorescence microscopy method and to investigate the effect of RCM on radiation induced DNA damages. The γ-H2AX method is based on the phosphorylation of the histone variant H2AX. The phosphorylated histone γ-H2AX can be visualised using antibodies and is specific for radiation induced DSB. Blood lymphocytes from healthy volunteers, skin fibroblasts (LN) and mammary epithelial cells (HMEpC-p) were placed in different positions of an Alderson-phantom and exposed to x-rays using a 128-slice dual-source CT scanner. Standard head, neck and chest-CT scan protocols either with or without risk-organ based tube current modulation were used. RCM reduces the tube current to 20 percent at an angle of 130 degree anterior to the body, whereas tube current is increased at an angle of 230 degree posterior to the body. Afterwards cells were isolated, fixed on slides und stained with specific primary γ-H2AX antibodies and fluorescent secondary antibodies. Tiny green dots (named foci) can be detected and quantified with a fluorescence microscope and represent distinct DSB. Non-irradiated samples served as controls and CT-induced DSB were calculated by subtraction of pre- from post-exposure values. In this study a semibiological phantom model

  1. 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

  2. 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

  3. A perspective on dose limits and biological effects of radiation on the foetus

    International Nuclear Information System (INIS)

    Myers, D.K.; Gordon, K.

    1992-01-01

    The potential biological effects of radiation doses to pregnant workers consistent with Canadian regulations and ICRP recommendations are reviewed. These hazards are in general very small compared to the normal hazards associated with human development. Potential carcinogenic effects may well be the major biological problem associated with foetal exposures. Radiation hazards to the embryo are essentially zero for exposures occurring during the first four weeks after conception. The new ICRP recommendations on exposures of pregnant women suggest a number of problems to be solved. These include (a) improvements in current methods of measuring both external radiation doses and intakes of certain radionuclides in Canada, (b) further research on the metabolism of radionuclides in pregnant women, including concentrations of certain radionuclides in foetal/embryonic tissues and also in adjacent tissues of the mother; and (c) socio-economic problems that may be involved in the implementation of the recommendations on exposures of pregnant workers, particularly in small facilities such as nuclear medicine departments in hospitals. (Author) 3 tabs., 21 refs

  4. Usefulness and limits of biological dosimetry based on cytogenetic methods

    International Nuclear Information System (INIS)

    Leonard, A.; Rueff, J.; Gerber, G. B.; Leonard, E. D.

    2005-01-01

    Damage from occupational or accidental exposure to ionising radiation is often assessed by monitoring chromosome aberrations in peripheral blood lymphocytes, and these procedures have, in several cases, assisted physicians in the management of irradiated persons. Thereby, circulating lymphocytes, which are in the G0 stage of the cell cycle are stimulated with a mitogenic agent, usually phytohaemagglutinin, to replicate in vitro their DNA and enter cell division, and are then observed for abnormalities. Comparison with dose response relationships obtained in vitro allows an estimate of exposure based on scoring: - Unstable aberrations by the conventional, well-established analysis of metaphases for chromosome abnormalities or for micronuclei; - So-called stable aberrations by the classical G-banding (Giemsa-Stain-banding) technique or by the more recently developed fluorescent in situ hybridisation (FISH) method using fluorescent-labelled probes for centromeres and chromosomes. Three factors need to be considered in applying such biological dosimetry: (1) Radiation doses in the body are often inhomogeneous. A comparison of the distribution of the observed aberrations among with that expected from a normal poisson distribution can allow conclusions to be made with regard to the inhomogeneity of exposure by means of the so-called contaminated poisson distribution method; however, its application requires a sufficiently large number of aberrations, i.e. an exposure to a rather large dose at a high dose rate. (2) Exposure can occur at a low dose rate (e.g. from spread or lost radioactive sources) rendering a comparison with in vitro exposure hazardous. Dose-effect relationships of most aberrations that were scored, such as translocations, follow a square law. Repair intervening during exposure reduces the quadratic component with decreasing dose rate as exposure is spread over a longer period of time. No valid solution for this problem has yet been developed, although

  5. The biological effects of high dose total body irradiation in beagle dogs

    International Nuclear Information System (INIS)

    Luo Qingliang; Liu Xiaolan; Hao Jing; Xiong Guolin; Dong Bo; Zhao Zhenhu; Xia Zhengbiao; Qiu Liling; Mao Bingzhi

    2002-01-01

    Objective: To evaluate the biological effects of Beagle dogs irradiated by γ-rays at different doses. Methods: All Beagle dogs were divided into six groups and were subjected respectively to total-body irradiation (TBI) with a single dose of 6.5, 5.5, 5.0, 4.5, 3, 5 and 2.5 Gy γ-rays delivered by 60 Co sources at 7.224 x 10 -2 C/kg per minute. The general condition, blood cell counts and bone marrow cell CFC assays were observed. Results: Vomiting occurred at 0.5 to 2 hours after TBI in all groups. In 6.5 Gy group 3/5 dogs had blood-watery stool and 1/5 in 5.5 Gy group had watery stool. Diarrhea occurred in all other animals. Only one dog in 2.5 Gy group survived, all of others died. in order of decreasing irradiation dosage, the average survival time was 5.0, 8.0, 9.3, 9.5, 10.5 and 14.1 days, respectively. Conclusions: According to the clinical symptoms, leukocyte count and survival time of the dogs, the irradiation dose which will induce very severe hematopoietic radiation syndrome in Beagle dogs is 4.5 to 5.0 Gy

  6. Biologically effective dose in total-body irradiation and hematopoietic stem cell transplantation

    International Nuclear Information System (INIS)

    Kal, H.B.; Kempen-Harteveld, M.L. van; Heijenbrok-Kal, M.H.; Struikmans, H.

    2006-01-01

    Background and Purpose: Total-body irradiation (TBI) is an important part of the conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with hematologic malignancies. The results after treatment with various TBI regimes were compared, and dose-effect relationships for the endpoints relapse incidence, disease-free survival, treatment-related mortality, and overall survival were derived. The aim was to define requirements for an optimal treatment schedule with respect to leukemic cell kill and late normal-tissue morbidity. Material and Methods: A literature search was performed. Three randomized studies, four studies comparing results of two or three TBI regimens, and nine reports with results of one specific TBI regimen were identified. Biologically effective doses (BEDs) were calculated. The results of the randomized studies and the studies comparing results of two or three TBI regimens were pooled, and the pooled relative risk (RR) was calculated for the treatments with high BED values versus treatments with a low BED. BED-effect relationships were obtained. Results: RRs for the high BED treatments were significantly lower for relapse incidence, not significantly different for disease-free survival and treatment-related mortality, and significantly higher for overall survival. BED-effect relationships indicate a decrease in relapse incidence and treatment-related mortality and an increase in disease-free and overall survival with higher BED values. Conclusion: 'More dose is better', provided that a TBI setting is used limiting the BEDs of lungs, kidneys, and eye lenses. (orig.)

  7. KERMA-based radiation dose management system for real-time patient dose measurement

    Science.gov (United States)

    Kim, Kyo-Tae; Heo, Ye-Ji; Oh, Kyung-Min; Nam, Sang-Hee; Kang, Sang-Sik; Park, Ji-Koon; Song, Yong-Keun; Park, Sung-Kwang

    2016-07-01

    Because systems that reduce radiation exposure during diagnostic procedures must be developed, significant time and financial resources have been invested in constructing radiation dose management systems. In the present study, the characteristics of an existing ionization-based system were compared to those of a system based on the kinetic energy released per unit mass (KERMA). Furthermore, the feasibility of using the KERMA-based system for patient radiation dose management was verified. The ionization-based system corrected the effects resulting from radiation parameter perturbations in general radiography whereas the KERMA-based system did not. Because of this difference, the KERMA-based radiation dose management system might overestimate the patient's radiation dose due to changes in the radiation conditions. Therefore, if a correction factor describing the correlation between the systems is applied to resolve this issue, then a radiation dose management system can be developed that will enable real-time measurement of the patient's radiation exposure and acquisition of diagnostic images.

  8. Ozone dosing alters the biological potential and therapeutic outcomes of plasma rich in growth factors.

    Science.gov (United States)

    Anitua, E; Zalduendo, M M; Troya, M; Orive, G

    2015-04-01

    Until now, ozone has been used in a rather empirical way. This in-vitro study investigates, for the first time, whether different ozone treatments of plasma rich in growth factors (PRGF) alter the biological properties and outcomes of this autologous platelet-rich plasma. Human plasma rich in growth factors was treated with ozone using one of the following protocols: a continuous-flow method; or a syringe method in which constant volumes of ozone and PRGF were mixed. In both cases, ozone was added before, during and after the addition of calcium chloride. Three ozone concentrations, of the therapeutic range 20, 40 and 80 μg/mL, were tested. Fibrin clot properties, growth factor content and the proliferative effect on primary osteoblasts and gingival fibroblasts were evaluated. Ozone treatment of PRGF using the continuous flow protocol impaired formation of the fibrin scaffold, drastically reduced the levels of growth factors and significantly decreased the proliferative potential of PRGF on primary osteoblasts and gingival fibroblasts. In contrast, treatment of PRGF with ozone using the syringe method, before, during and after the coagulation process, did not alter the biological outcomes of the autologous therapy. These findings suggest that ozone dose and the way that ozone combines with PRGF may alter the biological potential and therapeutic outcomes of PRGF. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Choline PET based dose-painting in prostate cancer - Modelling of dose effects

    International Nuclear Information System (INIS)

    Niyazi, Maximilian; Bartenstein, Peter; Belka, Claus; Ganswindt, Ute

    2010-01-01

    Several randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed. Based on different assumptions for α/β, γ50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed. Using schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high γ50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition). Although a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the

  10. Somatic cell genetics of uranium miners and plutonium workers. A biological dose-response indicator

    International Nuclear Information System (INIS)

    Brandom, W.F.; Bloom, A.D.; Bistline, R.W.; Saccomanno, G.

    1978-01-01

    Two populations of underground uranium miners and plutonium workers work in the state of Colorado, United States of America. We have explored the prevalence of structural chromosome aberrations in peripheral blood lymphocytes as a possible biological indicator of absorbed radiation late-effects in these populations. The uranium miners are divided into four exposure groups expressed in Working Level Months (WLM), the plutonium workers into six groups with estimated 239 Pu burdens expressed in nCi. Comparison of chromosome aberration frequency data between controls, miners, and plutonium workers demonstrate: (1) a cytogenetic response to occupational ionizing radiation at low estimated doses; and (2) an increasing monotonic dose-response in the prevalence of complex (all exchange) or total aberrations in all exposure groups in these populations. We also compared trends in the prevalence of aberrations per exposure unit (WLM and nCi) in each exposure subgroup for each population. In the uranium miners, the effects per WLM seem to decrease monotonically with increasing dose, whereas in the Pu workers the change per nCi appears abrupt, with all exposure groups over 1.3 nCi (minimum detectable level) having essentially similar rates. The calculations of aberrations per respective current maximum permissible dose (120 WLM and 40 nCi) for the two populations yield 4.8 X 10 -2 /100 cells for uranium miners and 90.6 X 10 -2 /100 cells for Pu workers. Factors which may have influenced this apparent 20-fold increase in the effectiveness of plutonium in the production of complex aberrations (9-fold increase in total aberrations) are discussed. (author)

  11. Low dose effects of ionizing radiations in in vitro and in vivo biological systems: a multi-scale approach study

    International Nuclear Information System (INIS)

    Antoccia, A.; Berardinelli, F.; Argazzi, E.; Balata, M.; Bedogni, R.

    2011-01-01

    Long-term biological effects of low-dose radiation are little known nowadays and its carcinogenic risk is estimated on the assumption that risk remains linearly proportional to the radiation dose down to low-dose levels. However in the last 20 years this hypothesis has gradually begun to seem in contrast with a huge collection of experimental evidences, which has shown the presence of plethora of non-linear phenomena (including hypersensitivity and induced radioresistance, adaptive response, and non-targeted phenomena like bystander effect and genomic instability) occurring after low-dose irradiation. These phenomena might imply a non-linear behaviour of cancer risk curves in the low-dose region and question the validity of the Linear No-Threshold (LNT) model currently used for cancer risk assessment through extrapolation from existing high-dose data. Moreover only few information is available regarding the effects induced on cryo preserved cells by multi-year background radiation exposure, which might induce a radiation-damage accumulation, due to the inhibition of cellular repair mechanisms. In this framework, the multi-year Excalibur (Exposure effects at low doses of ionizing radiation in biological culture) experiment, funded by INFN-CNS5, has undertaken a multi-scale approach investigation on the biological effects induced in in vitro and in vivo biological systems, in culture and cryo preserved conditions, as a function of radiation quality (X/γ-rays, protons, He-4 ions of various energies) and dose, with particular emphasis on the low-dose region and non-linear phenomena, in terms of different biological endpoints.

  12. Absorbed doses behind bones with MR image-based dose calculations for radiotherapy treatment planning.

    Science.gov (United States)

    Korhonen, Juha; Kapanen, Mika; Keyrilainen, Jani; Seppala, Tiina; Tuomikoski, Laura; Tenhunen, Mikko

    2013-01-01

    Magnetic resonance (MR) images are used increasingly in external radiotherapy target delineation because of their superior soft tissue contrast compared to computed tomography (CT) images. Nevertheless, radiotherapy treatment planning has traditionally been based on the use of CT images, due to the restrictive features of MR images such as lack of electron density information. This research aimed to measure absorbed radiation doses in material behind different bone parts, and to evaluate dose calculation errors in two pseudo-CT images; first, by assuming a single electron density value for the bones, and second, by converting the electron density values inside bones from T(1)∕T(2)∗-weighted MR image intensity values. A dedicated phantom was constructed using fresh deer bones and gelatine. The effect of different bone parts to the absorbed dose behind them was investigated with a single open field at 6 and 15 MV, and measuring clinically detectable dose deviations by an ionization chamber matrix. Dose calculation deviations in a conversion-based pseudo-CT image and in a bulk density pseudo-CT image, where the relative electron density to water for the bones was set as 1.3, were quantified by comparing the calculation results with those obtained in a standard CT image by superposition and Monte Carlo algorithms. The calculations revealed that the applied bulk density pseudo-CT image causes deviations up to 2.7% (6 MV) and 2.0% (15 MV) to the dose behind the examined bones. The corresponding values in the conversion-based pseudo-CT image were 1.3% (6 MV) and 1.0% (15 MV). The examinations illustrated that the representation of the heterogeneous femoral bone (cortex denser compared to core) by using a bulk density for the whole bone causes dose deviations up to 2% both behind the bone edge and the middle part of the bone (diameter bones). This study indicates that the decrease in absorbed dose is not dependent on the bone diameter with all types of bones. Thus

  13. Off-label biologic regimens in psoriasis: a systematic review of efficacy and safety of dose escalation, reduction, and interrupted biologic therapy.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Brezinski

    Full Text Available OBJECTIVES: While off-label dosing of biologic treatments may be necessary in selected psoriasis patients, no systematic review exists to date that synthesizes the efficacy and safety of these off-label dosing regimens. The aim of this systematic review is to evaluate efficacy and safety of off-label dosing regimens (dose escalation, dose reduction, and interrupted treatment with etanercept, adalimumab, infliximab, ustekinumab, and alefacept for psoriasis treatment. DATA SOURCES AND STUDY SELECTION: We searched OVID Medline from January 1, 1990 through August 1, 2011 for prospective clinical trials that studied biologic therapy for psoriasis treatment in adults. Individual articles were screened for studies that examined escalated, reduced, or interrupted therapy with etanercept, adalimumab, infliximab, ustekinumab, or alefacept. DATA SYNTHESIS: A total of 23 articles with 12,617 patients matched the inclusion and exclusion criteria for the systematic review. Data were examined for primary and secondary efficacy outcomes and adverse events including infections, malignancies, cardiovascular events, and anti-drug antibodies. The preponderance of data suggests that continuous treatment with anti-TNF agents and anti-IL12/23 agent was necessary for maintenance of disease control. Among non-responders, dose escalation with etanercept, adalimumab, ustekinumab, and alefacept typically resulted in greater efficacy than standard dosing. Dose reduction with etanercept and alefacept resulted in reduced efficacy. Withdrawal of the examined biologics led to an increase in disease activity; efficacy from retreatment did not result in equivalent initial response rates for most biologics. Safety data on off-label dosing regimens are limited. CONCLUSION: Dose escalation in non-responders generally resulted in increased efficacy in the examined biologics used to treat moderate-to-severe psoriasis. Continuous treatment with anti-TNF agents and anti-IL12/23 agent

  14. Brillouin Spectroscopy Data Base for Biological Threats

    National Research Council Canada - National Science Library

    Rubel, Glenn

    2003-01-01

    .... Brillouin scattering from DNA, ovalbumen, the Bacillus spores globigii and thuringiensis were measured to determine the feasibility of biological material discrimination using Brillouin scattering...

  15. Donor-specific cell-based assays in studying sensitivity to low-dose radiation: a population-based perspective

    Directory of Open Access Journals (Sweden)

    Dora eIl'yasova

    2014-11-01

    Full Text Available Currently, a linear no-threshold model is used to estimate health risks associated with exposure to low-dose radiation, a prevalent exposure in the general population, because the direct estimation from epidemiological studies suffers from uncertainty. This model has been criticized based on unique biology of low-dose radiation. Whether the departure from linearity is toward increased or decreased risk is intensely debated. We present an approach based on individual radiosensitivity testing and discuss how individual radiosensitivity can be assessed with the goal to develop a quantifiable measure of cellular response that can be conducted via high-throughput population testing.

  16. Embracing model-based designs for dose-finding trials.

    Science.gov (United States)

    Love, Sharon B; Brown, Sarah; Weir, Christopher J; Harbron, Chris; Yap, Christina; Gaschler-Markefski, Birgit; Matcham, James; Caffrey, Louise; McKevitt, Christopher; Clive, Sally; Craddock, Charlie; Spicer, James; Cornelius, Victoria

    2017-07-25

    Dose-finding trials are essential to drug development as they establish recommended doses for later-phase testing. We aim to motivate wider use of model-based designs for dose finding, such as the continual reassessment method (CRM). We carried out a literature review of dose-finding designs and conducted a survey to identify perceived barriers to their implementation. We describe the benefits of model-based designs (flexibility, superior operating characteristics, extended scope), their current uptake, and existing resources. The most prominent barriers to implementation of a model-based design were lack of suitable training, chief investigators' preference for algorithm-based designs (e.g., 3+3), and limited resources for study design before funding. We use a real-world example to illustrate how these barriers can be overcome. There is overwhelming evidence for the benefits of CRM. Many leading pharmaceutical companies routinely implement model-based designs. Our analysis identified barriers for academic statisticians and clinical academics in mirroring the progress industry has made in trial design. Unified support from funders, regulators, and journal editors could result in more accurate doses for later-phase testing, and increase the efficiency and success of clinical drug development. We give recommendations for increasing the uptake of model-based designs for dose-finding trials in academia.

  17. Single-dose relative biological effectiveness and toxicity studies under conditions of hypothermia and hyperbaric oxygen

    International Nuclear Information System (INIS)

    Hering, E.R.; Blekkenhorst, G.; Harrison, G.G.; Morrell, D.; Korrubel, J.; Gregory, A.; Phillips, J.; Manca, V.; Sealy, R.; Cape Town Univ.

    1986-01-01

    An approach to using hyperbaric oxygen with radiation in a clinical situation has been described in the preceding paper in this issue. To ascertain whether there might be a change in the relative biological effectiveness of radiation on normal mammalian tissue treated under conditions of hypothermia and hyperbaric oxygen, the acute reaction to radiation of pig skin was studied. A single dose enhancement ratio at the erythema reaction level of 1.4+-0.08 was obtained when compared with irradiation at normal body temperature in air. The authors studied also a series of antioxidant enzymes in rat liver and lung after exposure to hypothermia and hyperbaric oxygen. Enzyme changes were such as to combat oxygen toxicity which might develop as a result of the pre-treatment. (author)

  18. Model predictions and analysis of enhanced biological effectiveness at low dose rates

    International Nuclear Information System (INIS)

    Watt, D.E.; Sykes, C.E.; Younis, A.-R.S.

    1988-01-01

    A severe challenge to all models purporting to describe the biological effects of ionizing radiation has arisen with the discovery of two phenomena: the anomalous trend with dose rate of the frequency of neoplastic transformation of mammalian cells and the apparent excessive damaging power of electron-capture radionuclides when incorporated into cell nuclei. A new model is proposed which predicts and enables interpretation of these phenomena. Radiation effectiveness is found to be expressible absolutely in terms of the geometrical cross-sectional area of the radiosensitive sites. The duration of the irradiation, the mean free path for ionization, the influence of particles in the slowing-down spectrum perrtaining in the medium and two collective time factors determining the mean repair rate and the mean lifetime of unidentified reactive chemical species [pt

  19. OEDIPE, a software for personalized Monte Carlo dosimetry and treatment planning optimization in nuclear medicine: absorbed dose and biologically effective dose considerations

    International Nuclear Information System (INIS)

    Petitguillaume, A.; Broggio, D.; Franck, D.; Desbree, A.; Bernardini, M.; Labriolle Vaylet, C. de

    2014-01-01

    For targeted radionuclide therapies, treatment planning usually consists of the administration of standard activities without accounting for the patient-specific activity distribution, pharmacokinetics and dosimetry to organs at risk. The OEDIPE software is a user-friendly interface which has an automation level suitable for performing personalized Monte Carlo 3D dosimetry for diagnostic and therapeutic radionuclide administrations. Mean absorbed doses to regions of interest (ROIs), isodose curves superimposed on a personalized anatomical model of the patient and dose-volume histograms can be extracted from the absorbed dose 3D distribution. Moreover, to account for the differences in radiosensitivity between tumoral and healthy tissues, additional functionalities have been implemented to calculate the 3D distribution of the biologically effective dose (BED), mean BEDs to ROIs, isoBED curves and BED-volume histograms along with the Equivalent Uniform Biologically Effective Dose (EUD) to ROIs. Finally, optimization tools are available for treatment planning optimization using either the absorbed dose or BED distributions. These tools enable one to calculate the maximal injectable activity which meets tolerance criteria to organs at risk for a chosen fractionation protocol. This paper describes the functionalities available in the latest version of the OEDIPE software to perform personalized Monte Carlo dosimetry and treatment planning optimization in targeted radionuclide therapies. (authors)

  20. Fetal dose from radiotherapy photon beams: Physical basis, techniques to estimate radiation dose outside of the treatment field, biological effects and professional considerations

    International Nuclear Information System (INIS)

    Stovell, Marilyn; Blackwell, C. Robert

    1997-01-01

    Purpose/Objective: The presentation will review: 1. The physical basis of radiation dose outside of the treatment field. 2. Techniques to estimate and reduce fetal dose. 3. Clinical examples of fetal dose estimation and reduction. 4. Biological effects of fetal irradiation. 5. Professional considerations. Approximately 4000 women per year in the United States require radiotherapy during pregnancy. This report presents data and techniques that allow the medical physicist to estimate the radiation dose the fetus will receive and to reduce this dose with appropriate shielding. Out-of-beam data are presented for a variety of photon beams, including cobalt-60 gamma rays and x rays from 4 to 18 MV. Designs for simple and inexpensive to more complex and expensive types of shielding equipment are described. Clinical examples show that proper shielding can reduce the radiation dose to the fetus by 50%. In addition, a review of the biological aspects of irradiation enables estimates of the risks of lethality, growth retardation, mental retardation, malformation, sterility, cancer induction, and genetic defects to the fetus. A summary of professional considerations/recommendations is also provided as a guide for the radiation oncologist and medical physicist

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

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

    International Nuclear Information System (INIS)

    Niemierko, Andrzej; Terahara, Atsuro; Goitein, Michael

    1997-01-01

    Objective: To extract dose-response characteristics from dose-volume histograms and corresponding actuarial survival statistics for 115 patients with skull base chordomas. Materials and Methods: We analyzed data for 115 patients with skull base chordoma treated with combined photon and proton conformal radiotherapy to doses in the range 66.6Gy - 79.2Gy. Data set for each patient included gender, histology, age, tumor volume, prescribed dose, overall treatment time, time to recurrence or time to last observation, target dose-volume histogram, and several dosimetric parameters (minimum/mean/median/maximum target dose, percent of the target volume receiving the prescribed dose, dose to 90% of the target volume, and the Equivalent Uniform Dose (EUD). Data were analyzed using the Kaplan-Meier survivor function estimate, the proportional hazards (Cox) model, and parametric modeling of the actuarial probability of recurrence. Parameters of dose-response characteristics were obtained using the maximum likelihood method. Results: Local failure developed in 42 (36%) of patients, with actuarial local control rates at 5 years of 59.2%. The proportional hazards model revealed significant dependence of gender on the probability of recurrence, with female patients having significantly poorer prognosis (hazard ratio of 2.3 with the p value of 0.008). The Wilcoxon and the log-rank tests of the corresponding Kaplan-Meier recurrence-free survival curves confirmed statistical significance of this effect. The Cox model with stratification by gender showed significance of tumor volume (p=0.01), the minimum target dose (p=0.02), and the EUD (p=0.02). Other parameters were not significant at the α level of significance of 0.05, including the prescribed dose (p=0.21). Parametric analysis using a combined model of tumor control probability (to account for non-uniformity of target dose distribution) and the Weibull failure time model (to account for censoring) allowed us to estimate

  3. Analysis of Relative Biological Effectiveness of Proton Beams and Isoeffective Dose Profiles Using Geant4

    Directory of Open Access Journals (Sweden)

    Hosseini M. A.

    2017-06-01

    Full Text Available Background: The assessment of RBE quantity in the treatment of cancer tumors with proton beams in treatment planning systems (TPS is of high significance. Given the significance of the issue and the studies conducted in the literature, this quantity is fixed and is taken as equal to 1.1. Objective: The main objective of this study was to assess RBE quantity of proton beams and their variations in different depths of the tumor. This dependency makes RBE values used in TPS no longer be fixed as they depend on the depth of the tumor and therefore this dependency causes some changes in the physical dose profile. Materials and Methods: The energy spectrum of protons was measured at various depths of the tumor using proton beam simulations and well as the complete simulation of a cell to a pair of DNA bases through Monte Carlo GEANT4. The resulting energy spectrum was used to estimate the number of double-strand breaks generated in cells. Finally, RBE values were calculated in terms of the penetration depth in the tumor. Results and Conclusion: The simulation results show that the RBE value not fixed terms of the depth of the tumor and it differs from the clinical value of 1.1 at the end of the dose profile and this will lead to a non-uniform absorbed dose profile. Therefore, to create a uniform impact dose area, deep-finishing systems need to be designed by taking into account deep RBE values.

  4. Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

    Science.gov (United States)

    Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

    2010-09-01

    A low-energy electronic brachytherapy source (EBS), the model S700 Axxent™ x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95

  5. Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

    Energy Technology Data Exchange (ETDEWEB)

    Shi Chengyu; Guo Bingqi; Eng, Tony; Papanikolaou, Nikos [Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, TX 78229 (United States); Cheng, Chih-Yao, E-mail: shic@uthscsa.ed [Radiation Oncology Department, Oklahoma University Health Science Center, Oklahoma, OK 73104 (United States)

    2010-09-21

    A low-energy electronic brachytherapy source (EBS), the model S700 Axxent(TM) x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V{sub 100} reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as

  6. Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

    International Nuclear Information System (INIS)

    Shi Chengyu; Guo Bingqi; Eng, Tony; Papanikolaou, Nikos; Cheng, Chih-Yao

    2010-01-01

    A low-energy electronic brachytherapy source (EBS), the model S700 Axxent(TM) x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V 100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95

  7. 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

  8. The metabolomic approach identifies a biological signature of low-dose chronic exposure to Cesium 137

    International Nuclear Information System (INIS)

    Grison, S.; Grandcolas, L.; Martin, J.C.

    2012-01-01

    Reports have described apparent biological effects of 137 Cs (the most persistent dispersed radionuclide) irradiation in people living in Chernobyl-contaminated territory. The sensitive analytical technology described here should now help assess the relation of this contamination to the observed effects. A rat model chronically exposed to 137 Cs through drinking water was developed to identify biomarkers of radiation-induced metabolic disorders, and the biological impact was evaluated by a metabolomic approach that allowed us to detect several hundred metabolites in biofluids and assess their association with disease states. After collection of plasma and urine from contaminated and non-contaminated rats at the end of the 9-months contamination period, analysis with a liquid chromatography coupled to mass spectrometry (LC-MS) system detected 742 features in urine and 1309 in plasma. Biostatistical discriminant analysis extracted a subset of 26 metabolite signals (2 urinary, 4 plasma non-polar, and 19 plasma polar metabolites) that in combination were able to predict from 68 up to 94% of the contaminated rats, depending on the prediction method used, with a misclassification rate as low as 5.3%. The difference in this metabolic score between the contaminated and non-contaminated rats was highly significant (P=0.019 after ANOVA cross-validation). In conclusion, our proof-of-principle study demonstrated for the first time the usefulness of a metabolomic approach for addressing biological effects of chronic low-dose contamination. We can conclude that a metabolomic signature discriminated 137 Cs-contaminated from control animals in our model. Further validation is nevertheless required together with full annotation of the metabolic indicators. (author)

  9. Sample Based Unit Liter Dose Estimates

    International Nuclear Information System (INIS)

    JENSEN, L.

    1999-01-01

    The Tank Waste Characterization Program has taken many core samples, grab samples, and auger samples from the single-shell and double-shell tanks during the past 10 years. Consequently, the amount of sample data available has increased, both in terms of quantity of sample results and the number of tanks characterized. More and better data is available than when the current radiological and toxicological source terms used in the Basis for Interim Operation (BIO) (FDH 1999) and the Final Safety Analysis Report (FSAR) (FDH 1999) were developed. The Nuclear Safety and Licensing (NS and L) organization wants to use the new data to upgrade the radiological and toxicological source terms used in the BIO and FSAR. The NS and L organization requested assistance in developing a statistically based process for developing the source terms. This report describes the statistical techniques used and the assumptions made to support the development of a new radiological source term for liquid and solid wastes stored in single-shell and double-shell tanks

  10. Reconstruction of absorbed dose by methods biological dosimetry inhabitans living in Semipalatinsk Nuclear Test Site

    International Nuclear Information System (INIS)

    Abildinova, G.

    2010-01-01

    As a result perennial overland and atmospheric test the nucleus weapon on Semipalatinsk nucler test site (NTS) about 1,2 ml person were subjected to frequentative sharp and chronic irradiation in different range of doses. Besides a significant number of battle radioactive matters tests with radionuclei dispersion on soil surface and an atmosphere was realized also. All this activity has caused the significant radioactive contamination and damage to an environment, and the local population has received extra exposure to radiation. These circumstances have essentially complicated the economy development of the given region. Aim: Reconstruction of absorbed dose by modern methods biological dosimetry beside inhabitants living in region of influence Semipalatinsk NTS. The cytogenetically examination of population Semipalatinsk region, living in different zones radiation risk: s. Dolon, s. Sarzhal, s. Mostik. Installed that total frequency of chromosome aberrations forms 4,8/100; 2,1/100; 2,5/100 cells, accordingly. High level of chromosome aberrations is conditioned to account radiations markers - acentric fragments (2,1/100 cells in s. Dolon; 1,09/100 cells in s. Sarzhal; 0,79/100 cells in s. Mostik); dysenteric and ring chromosomes (0,6; 0,2; 0,11) and stable type chromosome aberrations (1,02; 0,3; 1,0, accordingly). Frequency and spectrum of chromosome aberrations are indicative of significant mutation action ionizing radiations on chromosome device of somatic cells. Studied dependency an cytogenetically of effects from dose of irradiation within before 0,5 Gr in vitro for calibrated curve standard when undertaking reconstruction efficient dose at the time of irradiations examined group of population. Dependency is described the model a*cos(x) 1 + sin (x), where x - correlation a dysenteric and ring chromosomes to acentric fragments. Dependence of cytogenetic parameters upon ESR-doses had been studied. Had been received dependences: for the total frequency of

  11. Biological dosimetry - a Bayesian approach in the presentation of the uncertainty of the estimated dose in cases of exposure to low dose radiation

    International Nuclear Information System (INIS)

    Di Giorgio, Marina; Zaretzky, A.

    2010-01-01

    Biodosimetry laboratory experience has shown that there are limitations in the existing statistical methodology. Statistical difficulties generally occur due to the low number of aberrations leading to large uncertainties for dose estimation. Some problems derived from limitations of the classical statistical methodology, which requires that chromosome aberration yields be considered as something fixed and consequently provides a deterministic dose estimation and associated confidence limits. On the other hand, recipients of biological dosimetry reports, including medical doctors, regulators and the patients themselves may have a limited comprehension of statistics and of informed reports. Thus, the objective of the present paper is to use a Bayesian approach to present the uncertainty on the estimated dose to which a person could be exposed, in the case of low dose (occupational doses) radiation exposure. Such methodology will allow the biodosimetrists to adopt a probabilistic approach for the cytogenetic data analysis. At present, classical statistics allows to produce a confidence interval to report such dose, with a lower limit that could not detach from zero. In this situation it becomes difficult to make decisions as they could impact on the labor activities of the worker if an exposure exceeding the occupational dose limits is inferred. The proposed Bayesian approach is applied to occupational exposure scenario to contribute to take the appropriate radiation protection measures. (authors) [es

  12. Optimum dose of 2-hydroxyethyl methacrylate based bonding material on pulp cells toxicity

    OpenAIRE

    Saraswati, Widya

    2010-01-01

    Background: 2-hydroxyethyl methacrylate (HEMA), one type of resins commonly used as bonding base material, is commonly used due to its advantageous chemical characteristics. Several preliminary studies indicated that resin is a material capable to induce damage in dentin-pulp complex. It is necessary to perform further investigation related with its biological safety for hard and soft tissues in oral cavity. Purpose: The author performed an in vitro test to find optimum dose of HEMA resin mon...

  13. Comparison in the determination of absorbed dose by biological and physical methods to patients in treatment of cardiac intervention

    International Nuclear Information System (INIS)

    Guerrero C, C.; Arceo M, C.

    2014-10-01

    The use of less invasive procedures, lower risk and quick recovery as cardiac intervention have proven to be an efficient alternative to reestablish the correct bloodstream of the patient. In this case the patient is subjected to values of absorbed dose above to which is subjected in a study with X-rays for medical diagnosis, and this can cause radiation injuries to the skin. The target organ, in this case can be exposed to doses of 2 Gy above. Different methods to estimate the dose were use, physical by Radiochromic film, as biological by dicentric analysis. Both methods provided additional information demonstrating thus the risk in the target organ and the patient. The most reliable biological indicator of exposure to ionizing radiation is the study of chromosomal aberrations, specifically dicentric in human lymphocytes. This test allowed establishing the exposure dose depending of the damage. (Author)

  14. Biological effects in lymphocytes irradiated with 99mTc: determination of the curve dose-response

    International Nuclear Information System (INIS)

    Oliveira, Romero Marcilio Barros Matias de

    2002-08-01

    Biological dosimetry estimates the absorbed dose taking into account changes in biological parameters. The most used biological indicator of an exposition to ionizing radiation is the quantification of chromosomal aberrations of lymphocytes from irradiated individuals. The curves of dose versus induced biological effects, obtained through bionalyses, are used in used in retrospective evaluations of the dose, mainly in the case of accidents. In this research, a simple model for electrons and photons transports was idealized to simulate the irradiation of lymphocytes with 99m Tc, representing a system used for irradiation of blood cells. The objective of the work was to establish a curve of dose versus frequencies of chromosomal aberrations in lymphocytes of human blood. For the irradiation of blood samples micro spheres of human serum of albumin (HSAM) market with 99m Tc were used, allowing the irradiation of blood with different administered activities of 99m Tc, making possible the study the cytogenetical effects as a function of such activities. The conditions of irradiation in vivo using HSAM spheres marked with 99m Tc were simulated with MCNP 4C (Monte Carlo N-Particle) code to obtain the dose-response curve. Soft tissue composition was employed to simulate blood tissue and the analyses of the curve of dose versus biological effect showed a linear quadratic response of the unstable chromosomal aberrations. As a result, the response of dose versus chromosomal aberrations of blood irradiation with 99m Tc was best fitted by the curve Y=(8,99 ±2,06) x 1- -4 + (1,24 ±0,62) x 10 -2 D + (5,67 ± 0,64) x 10 -2 D 2 . (author)

  15. 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)

  16. Electron dose map inversion based on several algorithms

    International Nuclear Information System (INIS)

    Li Gui; Zheng Huaqing; Wu Yican; Fds Team

    2010-01-01

    The reconstruction to the electron dose map in radiation therapy was investigated by constructing the inversion model of electron dose map with different algorithms. The inversion model of electron dose map based on nonlinear programming was used, and this model was applied the penetration dose map to invert the total space one. The realization of this inversion model was by several inversion algorithms. The test results with seven samples show that except the NMinimize algorithm, which worked for just one sample, with great error,though,all the inversion algorithms could be realized to our inversion model rapidly and accurately. The Levenberg-Marquardt algorithm, having the greatest accuracy and speed, could be considered as the first choice in electron dose map inversion.Further tests show that more error would be created when the data close to the electron range was used (tail error). The tail error might be caused by the approximation of mean energy spectra, and this should be considered to improve the method. The time-saving and accurate algorithms could be used to achieve real-time dose map inversion. By selecting the best inversion algorithm, the clinical need in real-time dose verification can be satisfied. (authors)

  17. 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.

  18. Fully automated treatment planning for head and neck radiotherapy using a voxel-based dose prediction and dose mimicking method

    Science.gov (United States)

    McIntosh, Chris; Welch, Mattea; McNiven, Andrea; Jaffray, David A.; Purdie, Thomas G.

    2017-08-01

    Recent works in automated radiotherapy treatment planning have used machine learning based on historical treatment plans to infer the spatial dose distribution for a novel patient directly from the planning image. We present a probabilistic, atlas-based approach which predicts the dose for novel patients using a set of automatically selected most similar patients (atlases). The output is a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces the need to specify and tune dose-volume objectives. Voxel-based dose mimicking optimization then converts the predicted dose distribution to a complete treatment plan with dose calculation using a collapsed cone convolution dose engine. In this study, we investigated automated planning for right-sided oropharaynx head and neck patients treated with IMRT and VMAT. We compare four versions of our dose prediction pipeline using a database of 54 training and 12 independent testing patients by evaluating 14 clinical dose evaluation criteria. Our preliminary results are promising and demonstrate that automated methods can generate comparable dose distributions to clinical. Overall, automated plans achieved an average of 0.6% higher dose for target coverage evaluation criteria, and 2.4% lower dose at the organs at risk criteria levels evaluated compared with clinical. There was no statistically significant difference detected in high-dose conformity between automated and clinical plans as measured by the conformation number. Automated plans achieved nine more unique criteria than clinical across the 12 patients tested and automated plans scored a significantly higher dose at the evaluation limit for two high-risk target coverage criteria and a significantly lower dose in one critical organ maximum dose. The novel dose prediction method with dose mimicking can generate complete treatment plans in 12-13 min without user interaction. It is a promising approach for fully automated treatment

  19. Updating biological bases of social behavior.

    Science.gov (United States)

    O'Connor, Thomas G

    2014-09-01

    This month's collation of papers deals with social behaviors that operationalize key constructs in fields covered by the journal, including attachment theory and parenting; emotional regulation; psychopathology of several forms; general and specific cognitive abilities. Notably, many examples are offered of how these social behaviors link with biology. That is an obvious and important direction for clinical research insofar as it helps to erase a perceptual chasm and artificial duality between 'behavior' and 'biology'. But, although it must be the case that social behavior has biological connections of one sort or other, identifying reliable connections with practical application has proved to be a non-trivial challenge. In particular, the challenge seems to be in measuring social behavior meaningfully enough that it could be expected to have a biological pulse, and in measuring biological markers systematically enough that emergent-downstream effects would surface. Associations are not especially uncommon, but it has been a frustrating task in constructing a practically broad model from a bricolage of scattered and disconnected parts and findings in the literature. Several reports in this issue offer contrasts that may help move along this line of study. © 2014 Association for Child and Adolescent Mental Health.

  20. Track structure and dose: Alternative conceptual bases for nuclear therapy

    International Nuclear Information System (INIS)

    Katz, R.

    1987-01-01

    As one departs from the island of radiation quality encompassing photons and electrons of initial energy from about 100 keV to about 10 MeV toward increasingly higher LET particle irradiations, and from relatively uniform to inherently non-uniform radiation fields, dose and LET become less useful indices of radiation effect. Isodose profiles are not isoeffect profiles. RBEs vary with end point, with the state of oxygenation, with cell line, with tissue identity and with dose, and are multiple valued functions of LET. Dose, microdose and LET lack the descrimination needed to predict biological end points. RBE calculations made from cellular radiosensitivity parameters are consistent with RBEs measured both in vitro and in vivo. For such calculations, we must know the spectrum of particles and particle energies making up a high LET radiation field. To sharpen the calculations and make them directly relevant to therapy, we need to evaluate radiosensitivity parameters for human tissues. Both physical and biological data are needed for radiobiology and radiotherapy. For the question of hazard evaluation, we need to know the relation between transformations in vitro and cancer production in vivo. Using the same model as was used earlier for cellular inactivations, we have fitted tentative radiosensitivity parameters to recent data for cell transformations. The model is consistent with both gamma ray and fission neutron measurements. But a wider range of irradiations is needed to test these results. Delta rays play an important role in heavy ion radiobiology, but we do not now know either the cross-sections for delta ray production or the radial deposition of their energy with sufficient precision or generality. But it is this, the radial dose deposition, which is the physical basis for the calculation of action cross-sections. Studies for radiobiology and radiotherapy should also include the response of different physical detectors to a range of radiations, especially

  1. Reconstruction of biological networks based on life science data integration

    Directory of Open Access Journals (Sweden)

    Kormeier Benjamin

    2010-06-01

    Full Text Available For the implementation of the virtual cell, the fundamental question is how to model and simulate complex biological networks. Therefore, based on relevant molecular database and information systems, biological data integration is an essential step in constructing biological networks. In this paper, we will motivate the applications BioDWH - an integration toolkit for building life science data warehouses, CardioVINEdb - a information system for biological data in cardiovascular-disease and VANESA- a network editor for modeling and simulation of biological networks. Based on this integration process, the system supports the generation of biological network models. A case study of a cardiovascular-disease related gene-regulated biological network is also presented.

  2. Reconstruction of biological networks based on life science data integration.

    Science.gov (United States)

    Kormeier, Benjamin; Hippe, Klaus; Arrigo, Patrizio; Töpel, Thoralf; Janowski, Sebastian; Hofestädt, Ralf

    2010-10-27

    For the implementation of the virtual cell, the fundamental question is how to model and simulate complex biological networks. Therefore, based on relevant molecular database and information systems, biological data integration is an essential step in constructing biological networks. In this paper, we will motivate the applications BioDWH--an integration toolkit for building life science data warehouses, CardioVINEdb--a information system for biological data in cardiovascular-disease and VANESA--a network editor for modeling and simulation of biological networks. Based on this integration process, the system supports the generation of biological network models. A case study of a cardiovascular-disease related gene-regulated biological network is also presented.

  3. Function-Based Algorithms for Biological Sequences

    Science.gov (United States)

    Mohanty, Pragyan Sheela P.

    2015-01-01

    Two problems at two different abstraction levels of computational biology are studied. At the molecular level, efficient pattern matching algorithms in DNA sequences are presented. For gene order data, an efficient data structure is presented capable of storing all gene re-orderings in a systematic manner. A common characteristic of presented…

  4. Data base on nuclear power plant dose reduction research projects

    Energy Technology Data Exchange (ETDEWEB)

    Khan, T.A.; Baum, J.W.

    1986-10-01

    Staff at the ALARA Center of Brookhaven National Laboratory have established a data base of information about current research that is likely to result in lower radiation doses to workers. The data base, concerned primarily with nuclear power generation, is part of a project that the ALARA Center is carrying out for the Nuclear Regulatory Commission. This report describes its current status. A substantial amount of research on reducing occupational exposure is being done in the US and abroad. This research is beginning to have an impact on the collective dose expenditures at nuclear power plants. The collective radiation doses in Europe, Japan, and North America all show downward trends. A large part of the research in the US is either sponsored by the nuclear industry through joint industry organizations such as EPRI and ESEERCO or is done by individual corporations. There is also significant participation by smaller companies. The main emphasis of the research on dose reduction is on engineering approaches aimed at reducing radiation fields or keeping people out of high-exposure areas by using robotics. Effective ALARA programs are also underway at a large number of nuclear plants. Additional attention should be given to non-engineering approaches to dose reduction, which are potentially very useful and cost effective but require quantitative study and analysis based on data from nuclear power plants. 9 refs., 1 fig.

  5. Biologically Based Restorative Management of Tooth Wear

    Directory of Open Access Journals (Sweden)

    Martin G. D. Kelleher

    2012-01-01

    Full Text Available The prevalence and severity of tooth wear is increasing in industrialised nations. Yet, there is no high-level evidence to support or refute any therapeutic intervention. In the absence of such evidence, many currently prevailing management strategies for tooth wear may be failing in their duty of care to first and foremost improve the oral health of patients with this disease. This paper promotes biologically sound approaches to the management of tooth wear on the basis of current best evidence of the aetiology and clinical features of this disease. The relative risks and benefits of the varying approaches to managing tooth wear are discussed with reference to long-term follow-up studies. Using reference to ethical standards such as “The Daughter Test”, this paper presents case reports of patients with moderate-to-severe levels of tooth wear managed in line with these biologically sound principles.

  6. Statistical analysis of MRI-only based dose planning

    DEFF Research Database (Denmark)

    Korsholm, M. E.; Waring, L. W.; Paulsen, Rasmus Reinhold

    2012-01-01

    . MRIonly based RT eliminates these errors and reduce the time and costs of a CT scan. The aim of this study is to investigate the dosimetric differences of a treatment plan when the dose calculation is based on MRI as compared to CT. Materials and Methods: Four diagnostic groups are investigated; 12...... as a clinically approved treatment plan. The treatment planning software is Eclipse v.10.0 (Varian Medical Systems). The dose calculation based on MRI data is evaluated in two different ways; a homogeneous density assigned MRI (MRI unit), where the entire body is assigned an HU equal to water and a heterogeneous...... density assigned MRI (MRI bulk) where in addition the CT segmented bone is transferred to the MRI and assigned an age dependent HU based on ICRU report 46. The CT based clinical treatment plan and structure set are registered to the corresponding MRI unit and MRI bulk. The body is outlined on both the MRI...

  7. Impact of respiratory motion on variable relative biological effectiveness in 4D-dose distributions of proton therapy.

    Science.gov (United States)

    Ulrich, Silke; Wieser, Hans-Peter; Cao, Wenhua; Mohan, Radhe; Bangert, Mark

    2017-11-01

    Organ motion during radiation therapy with scanned protons leads to deviations between the planned and the delivered physical dose. Using a constant relative biological effectiveness (RBE) of 1.1 linearly maps these deviations into RBE-weighted dose. However, a constant value cannot account for potential nonlinear variations in RBE suggested by variable RBE models. Here, we study the impact of motion on recalculations of RBE-weighted dose distributions using a phenomenological variable RBE model. 4D-dose calculation including variable RBE was implemented in the open source treatment planning toolkit matRad. Four scenarios were compared for one field and two field proton treatments for a liver cancer patient assuming (α∕β) x  = 2 Gy and (α∕β) x  = 10 Gy: (A) the optimized static dose distribution with constant RBE, (B) a static recalculation with variable RBE, (C) a 4D-dose recalculation with constant RBE and (D) a 4D-dose recalculation with variable RBE. For (B) and (D), the variable RBE was calculated by the model proposed by McNamara. For (C), the physical dose was accumulated with direct dose mapping; for (D), dose-weighted radio-sensitivity parameters of the linear quadratic model were accumulated to model synergistic irradiation effects on RBE. Dose recalculation with variable RBE led to an elevated biological dose at the end of the proton field, while 4D-dose recalculation exhibited random deviations everywhere in the radiation field depending on the interplay of beam delivery and organ motion. For a single beam treatment assuming (α∕β) x  = 2 Gy, D 95 % was 1.98 Gy (RBE) (A), 2.15 Gy (RBE) (B), 1.81 Gy (RBE) (C) and 1.98 Gy (RBE) (D). The homogeneity index was 1.04 (A), 1.08 (B), 1.23 (C) and 1.25 (D). For the studied liver case, intrafractional motion did not reduce the modulation of the RBE-weighted dose postulated by variable RBE models for proton treatments.

  8. PENERAPAN BLENDED-PROBLEM BASED LEARNING DALAM PEMBELAJARAN BIOLOGI

    Directory of Open Access Journals (Sweden)

    Samuel Agus Triyanto

    2016-07-01

    Biologi abad 21 merupakan integrasi dan mengintegrasikan kembali sub disiplin ilmu biologi, serta integrasi biologi dengan disiplin ilmu lain untuk mengatasi permasalahan sosial. Penelitian ini bertujuan untuk mengetahui penerapan Blended-Problem Based Learning, aktivitas belajar, dan respon siswa dalam pembelajaran biologi. Penelitian ini merupakan penelitian survei dengan pendekatan deskriptif kualitatif. Data hasil penelitian menunjukkan bahwa aktivitas positif siswa dalam pembelajaran memuaskan, sedangkan respon siswa baik terhadap pembelajaran. Berdasarkan hasil penelitian, disimpulkan bahwa Blended-Problem Based Learning dapat diterapkan dan diterima sebagai model dalam pembelajaran.

  9. Radiosensitivity of Nicotiana protoplasts. Action on cell; cycle effects of low dose and fractionated irradiations; biological repair

    International Nuclear Information System (INIS)

    Magnien, E.

    1981-10-01

    Leaf protoplasts of Nicotiana plumbaginifolia and Nicotiana sylvestris demonstrate five main qualities: they can be maintained as haploid lines; they constitute starting populations with a remarkable cytological homogeneity; they show a transient initial lag-phase; they yield very high plating efficiencies and retain permanently a complete differentiation capacity; being derived of a cell wall, they appear well adapted for fusion experiments or enzymatic dosages. The resumption of mitotic activity was followed by cytophotometric measurements, labelling experiments, nuclear sizing and enzymatic assays. The action of 5 Gy gamma-ray irradiations delayed entrance in the S-phase, provoked an otherwise not verified dependency between transcription, translation and protein synthesis, increased nuclear volumes in the G2-phase, and slightly stimulated the activity of a repair enzyme. The plating efficiency was a sensitive end-point which allowed the evaluation of the biological effectiveness of low to medium radiation-doses after gamma-ray and fast neutron irradiations. The neutron dose-RBE relationship increased from 3 to 25 when the dose decreased from 5 Gy to 5 mGy. When fractionated into low single doses only, a neutron dose of 300 mGy markedly increased its biological effectiveness: this phenomenon could not be explained by cell progression, and necessitated additional hypotheses involving other mechanisms in the specific action of low radiation doses. Radiation-induced UDS was measured in presence of aphidicolin. A beta-like DNA-polymerase was shown to be definitely involved in nuclear repair synthesis [fr

  10. Data base for terrestrial food pathways dose commitment calculations

    International Nuclear Information System (INIS)

    Bailey, C.E.

    1979-01-01

    A computer program is under development to allow calculation of the dose-to-man in Georgia and South Carolina from ingestion of radionuclides in terrestrial foods resulting from deposition of airborne radionuclides. This program is based on models described in Regulatory Guide 1.109 (USNRC, 1977). The data base describes the movement of radionuclides through the terrestrial food chain, growth and consumption factors for a variety of radionuclides

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

    Directory of Open Access Journals (Sweden)

    Paul D. Loprinzi

    2013-08-01

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

  12. Gamma regularization based reconstruction for low dose CT

    International Nuclear Information System (INIS)

    Zhang, Junfeng; Chen, Yang; Hu, Yining; Luo, Limin; Shu, Huazhong; Li, Bicao; Liu, Jin; Coatrieux, Jean-Louis

    2015-01-01

    Reducing the radiation in computerized tomography is today a major concern in radiology. Low dose computerized tomography (LDCT) offers a sound way to deal with this problem. However, more severe noise in the reconstructed CT images is observed under low dose scan protocols (e.g. lowered tube current or voltage values). In this paper we propose a Gamma regularization based algorithm for LDCT image reconstruction. This solution is flexible and provides a good balance between the regularizations based on l 0 -norm and l 1 -norm. We evaluate the proposed approach using the projection data from simulated phantoms and scanned Catphan phantoms. Qualitative and quantitative results show that the Gamma regularization based reconstruction can perform better in both edge-preserving and noise suppression when compared with other norms. (paper)

  13. Analysis of the relationship between tumor dose inhomogeneity and local control in patients with skull base chordoma

    International Nuclear Information System (INIS)

    Terahara, Atsuro; Niemierko, Andrzej; Goitein, Michael; Finkelstein, Dianne; Hug, Eugen; Liebsch, Norbert; O'Farrell, Desmond; Lyons, Sue; Munzenrider, John

    1999-01-01

    models including gender and EUD, or gender and the target volume, or gender and the minimum target dose were significant. The more biologically meaningful of these models is that of gender and EUD. Conclusion: This study suggests that the probability of recurrence of skull base chordomas depends on gender, target volume, and the level of target dose inhomogeneity. EUD was shown to be a useful parameter to evaluate dose distribution for the target volume

  14. Biological in situ Dose Painting for Image-Guided Radiation Therapy Using Drug-Loaded Implantable Devices

    International Nuclear Information System (INIS)

    Cormack, Robert A.; Sridhar, Srinivas; Suh, W. Warren; D'Amico, Anthony V.; Makrigiorgos, G. Mike

    2010-01-01

    Purpose: Implantable devices routinely used for increasing spatial accuracy in modern image-guided radiation treatments (IGRT), such as fiducials or brachytherapy spacers, encompass the potential for in situ release of biologically active drugs, providing an opportunity to enhance the therapeutic ratio. We model this new approach for two types of treatment. Methods and Materials: Radiopaque fiducials used in IGRT, or prostate brachytherapy spacers ('eluters'), were assumed to be loaded with radiosensitizer for in situ drug slow release. An analytic function describing the concentration of radiosensitizer versus distance from eluters, depending on diffusion-elimination properties of the drug in tissue, was developed. Tumor coverage by the drug was modeled for tumors typical of lung stereotactic body radiation therapy treatments for various eluter dimensions and drug properties. Six prostate 125 I brachytherapy cases were analyzed by assuming implantation of drug-loaded spacers. Radiosensitizer-induced subvolume boost was simulated from which biologically effective doses for typical radiosensitizers were calculated in one example. Results: Drug distributions from three-dimensional arrangements of drug eluters versus eluter size and drug properties were tabulated. Four radiosensitizer-loaded fiducials provide adequate radiosensitization for ∼4-cm-diameter lung tumors, thus potentially boosting biologically equivalent doses in centrally located stereotactic body treated lesions. Similarly, multiple drug-loaded spacers provide prostate brachytherapy with flexible shaping of 'biologically equivalent doses' to fit requirements difficult to meet by using radiation alone, e.g., boosting a high-risk region juxtaposed to the urethra while respecting normal tissue tolerance of both the urethra and the rectum. Conclusions: Drug loading of implantable devices routinely used in IGRT provides new opportunities for therapy modulation via biological in situ dose painting.

  15. Measurement of radiation dose with a PC-based instrument

    International Nuclear Information System (INIS)

    Jangland, L.; Neubeck, R.

    1994-01-01

    The purpose of this study was to investigate in what way the introduction of Digital Subtraction Angiography has influenced absorbed doses to the patient and personnel. Calculation of the energy imparted to the patient, ε, was based on measurements of the dose-area product, tube potential and tube current which were registered with a PC-based instrument. The absorbed doses to the personnel were measured with TLD. The measurements on the personnel were made only at the digital system. The results indicate large variations in ε between different types of angiographic examinations of the same type. The total ε were similar on both systems, although the relative contribution from image acquisition and fluoroscopy were different. At the conventional system fluoroscopy and image acquisition contributed almost equally to the total ε. At the digital system 25% of the total ε was due to fluoroscopy and 75% to image acquisition. The differences were due to longer fluoroscopic times on the conventional system, mainly due to lack of image memory and road mapping, and lower ε/image, due to lower dose settings to the film changer compared to the image intensifier on the digital system. 11 refs., 8 figs., 9 tabs

  16. Optimizing CT radiation dose based on patient size and image quality: the size-specific dose estimate method

    Energy Technology Data Exchange (ETDEWEB)

    Larson, David B. [Stanford University School of Medicine, Department of Radiology, Stanford, CA (United States)

    2014-10-15

    The principle of ALARA (dose as low as reasonably achievable) calls for dose optimization rather than dose reduction, per se. Optimization of CT radiation dose is accomplished by producing images of acceptable diagnostic image quality using the lowest dose method available. Because it is image quality that constrains the dose, CT dose optimization is primarily a problem of image quality rather than radiation dose. Therefore, the primary focus in CT radiation dose optimization should be on image quality. However, no reliable direct measure of image quality has been developed for routine clinical practice. Until such measures become available, size-specific dose estimates (SSDE) can be used as a reasonable image-quality estimate. The SSDE method of radiation dose optimization for CT abdomen and pelvis consists of plotting SSDE for a sample of examinations as a function of patient size, establishing an SSDE threshold curve based on radiologists' assessment of image quality, and modifying protocols to consistently produce doses that are slightly above the threshold SSDE curve. Challenges in operationalizing CT radiation dose optimization include data gathering and monitoring, managing the complexities of the numerous protocols, scanners and operators, and understanding the relationship of the automated tube current modulation (ATCM) parameters to image quality. Because CT manufacturers currently maintain their ATCM algorithms as secret for proprietary reasons, prospective modeling of SSDE for patient populations is not possible without reverse engineering the ATCM algorithm and, hence, optimization by this method requires a trial-and-error approach. (orig.)

  17. Optimization of total arc degree for stereotactic radiotherapy by using integral biologically effective dose and irradiated volume

    International Nuclear Information System (INIS)

    Lim, Do Hoon; Kim, Dae Yong; Lee, Myung Za; Chun, Ha Chung

    2001-01-01

    To find the optimal values of total arc degree to protect the normal brain tissue from high dose radiation in stereotactic radiotherapy planning. With Xknife-3 planning system and 4 MV linear accelerator, the authors planned under various values of parameters. One isocenter, 12, 20, 30, 40, 50, and 60 mm of collimator diameters, 100 deg, 200 deg, 300 deg, 400 deg, 500 deg, 600 deg, of total arc degrees, and 30 deg or 45 deg of arc intervals were used. After the completion of planning, the plans were compared each other using V 50 (the volume of normal brain that is delivered high dose radiation) and integral biologically effective dose. At 30 deg of arc interval, the values of V 50 had the decreased pattern with the increase of total arc degree in any collimator diameter. At 45 deg arc interval, up to 400 deg of total arc degree, the values of V 50 decreased with the increase of total arc degree, but at 500 deg and 600 deg of total arc degrees, the values increased. At 30 deg of arc interval, integral biologically effective dose showed the decreased pattern with the increase of total arc degree in any collimator diameter. At 45 deg arc interval with less than 40 mm collimator diameter, the integral biologically effective dose decreased with the increase of total arc degree, but with 50 and 60 mm of collimator diameters, up to 400 deg of total arc degree, integral biologically effective dose decreased with the increase of total arc degree, but at 500 deg and 600 deg of total arc degrees, the values increased. In the stereotactic radiotherapy planning for brain lesions, planning with 400 deg of total arc degree is optimal. Especially, when the larger collimator more than 50 mm diameter should be used, the uses of 500 deg and 600 deg of total arc degrees make the increase of V 50 and integral biologically effective dose, Therefore stereotactic radiotherapy planning using 400 deg of total arc degree can increase the therapeutic ratio and produce the effective outcome

  18. A Web-Based System for Bayesian Benchmark Dose Estimation.

    Science.gov (United States)

    Shao, Kan; Shapiro, Andrew J

    2018-01-11

    Benchmark dose (BMD) modeling is an important step in human health risk assessment and is used as the default approach to identify the point of departure for risk assessment. A probabilistic framework for dose-response assessment has been proposed and advocated by various institutions and organizations; therefore, a reliable tool is needed to provide distributional estimates for BMD and other important quantities in dose-response assessment. We developed an online system for Bayesian BMD (BBMD) estimation and compared results from this software with U.S. Environmental Protection Agency's (EPA's) Benchmark Dose Software (BMDS). The system is built on a Bayesian framework featuring the application of Markov chain Monte Carlo (MCMC) sampling for model parameter estimation and BMD calculation, which makes the BBMD system fundamentally different from the currently prevailing BMD software packages. In addition to estimating the traditional BMDs for dichotomous and continuous data, the developed system is also capable of computing model-averaged BMD estimates. A total of 518 dichotomous and 108 continuous data sets extracted from the U.S. EPA's Integrated Risk Information System (IRIS) database (and similar databases) were used as testing data to compare the estimates from the BBMD and BMDS programs. The results suggest that the BBMD system may outperform the BMDS program in a number of aspects, including fewer failed BMD and BMDL calculations and estimates. The BBMD system is a useful alternative tool for estimating BMD with additional functionalities for BMD analysis based on most recent research. Most importantly, the BBMD has the potential to incorporate prior information to make dose-response modeling more reliable and can provide distributional estimates for important quantities in dose-response assessment, which greatly facilitates the current trend for probabilistic risk assessment. https://doi.org/10.1289/EHP1289.

  19. BEDVH--A method for evaluating biologically effective dose volume histograms: Application to eye plaque brachytherapy implants

    International Nuclear Information System (INIS)

    Gagne, Nolan L.; Leonard, Kara L.; Huber, Kathryn E.; Mignano, John E.; Duker, Jay S.; Laver, Nora V.; Rivard, Mark J.

    2012-01-01

    Purpose: A method is introduced to examine the influence of implant duration T, radionuclide, and radiobiological parameters on the biologically effective dose (BED) throughout the entire volume of regions of interest for episcleral brachytherapy using available radionuclides. This method is employed to evaluate a particular eye plaque brachytherapy implant in a radiobiological context. Methods: A reference eye geometry and 16 mm COMS eye plaque loaded with 103 Pd, 125 I, or 131 Cs sources were examined with dose distributions accounting for plaque heterogeneities. For a standardized 7 day implant, doses to 90% of the tumor volume ( TUMOR D 90 ) and 10% of the organ at risk volumes ( OAR D 10 ) were calculated. The BED equation from Dale and Jones and published α/β and μ parameters were incorporated with dose volume histograms (DVHs) for various T values such as T = 7 days (i.e., TUMOR 7 BED 10 and OAR 7 BED 10 ). By calculating BED throughout the volumes, biologically effective dose volume histograms (BEDVHs) were developed for tumor and OARs. Influence of T, radionuclide choice, and radiobiological parameters on TUMOR BEDVH and OAR BEDVH were examined. The nominal dose was scaled for shorter implants to achieve biological equivalence. Results: TUMOR D 90 values were 102, 112, and 110 Gy for 103 Pd, 125 I, and 131 Cs, respectively. Corresponding TUMOR 7 BED 10 values were 124, 140, and 138 Gy, respectively. As T decreased from 7 to 0.01 days, the isobiologically effective prescription dose decreased by a factor of three. As expected, TUMOR 7 BEDVH did not significantly change as a function of radionuclide half-life but varied by 10% due to radionuclide dose distribution. Variations in reported radiobiological parameters caused TUMOR 7 BED 10 to deviate by up to 46%. Over the range of OAR α/β values, OAR 7 BED 10 varied by up to 41%, 3.1%, and 1.4% for the lens, optic nerve, and lacrimal gland, respectively. Conclusions: BEDVH permits evaluation of the

  20. Radiation-induced temporary partial epilation in the pig: a biological indicator of radiation dose and dose distribution to the skin

    International Nuclear Information System (INIS)

    Sieber, V.K.; Hopewell, J.W.

    1990-01-01

    Radiation damage to the matrix cells of actively growing hairs can result in transient epilation in the pig, the severity of which can be assessed using a visual scoring system. The extent of hair loss was found to be dose-dependent for single doses in the range 6 - 14 Gy for 250 kV X rays. The ED 50 for detectable hair loss was 9.83 ± 0.58 Gy whilst that for the loss of > 50% of hairs was 13.78 ± 0.90 Gy. The system is simple, non-invasive and would appear to have considerable potential for use in biological dosimetry for high exposures that are likely to require local treatment. (author)

  1. Application of biological effective dose (BED) to estimate the duration of symptomatic relief and repopulation dose equivalent in palliative radiotherapy and chemotherapy

    International Nuclear Information System (INIS)

    Jones, Bleddyn; Cominos, Matilda; Dale, Roger G.

    2003-01-01

    Purpose: To investigate the potential for mathematic modeling in the assessment of symptom relief in palliative radiotherapy and cytotoxic chemotherapy. Methods: The linear quadratic model of radiation effect with the overall treatment time and the daily dose equivalent of repopulation is modified to include the regrowth time after completion of therapy. Results: The predicted times to restore the original tumor volumes after treatment are dependent on the biological effective dose (BED) delivered and the repopulation parameter (K); it is also possible to estimate K values from analysis of palliative treatment response durations. Hypofractionated radiotherapy given at a low total dose may produce long symptom relief in slow-growing tumors because of their low α/β ratios (which confer high fraction sensitivity) and their slow regrowth rates. Cancers that have high α/β ratios (which confer low fraction sensitivity), and that are expected to repopulate rapidly during therapy, are predicted to have short durations of symptom control. The BED concept can be used to estimate the equivalent dose of radiotherapy that will achieve the same duration of symptom relief as palliative chemotherapy. Conclusion: Relatively simple radiobiologic modeling can be used to guide decision-making regarding the choice of the most appropriate palliative schedules and has important implications in the design of radiotherapy or chemotherapy clinical trials. The methods described provide a rationalization for treatment selection in a wide variety of tumors

  2. Biological-based optimization and volumetric modulated arc therapy delivery for stereotactic body radiation therapy

    International Nuclear Information System (INIS)

    Diot, Quentin; Kavanagh, Brian; Timmerman, Robert; Miften, Moyed

    2012-01-01

    Purpose: To describe biological-based optimization and Monte Carlo (MC) dose calculation-based treatment planning for volumetric modulated arc therapy (VMAT) delivery of stereotactic body radiation therapy (SBRT) in lung, liver, and prostate patients. Methods: Optimization strategies and VMAT planning parameters using a biological-based optimization MC planning system were analyzed for 24 SBRT patients. Patients received a median dose of 45 Gy [range, 34-54 Gy] for lung tumors in 1-5 fxs and a median dose of 52 Gy [range, 48-60 Gy] for liver tumors in 3-6 fxs. Prostate patients received a fractional dose of 10 Gy in 5 fxs. Biological-cost functions were used for plan optimization, and its dosimetric quality was evaluated using the conformity index (CI), the conformation number (CN), the ratio of the volume receiving 50% of the prescription dose over the planning target volume (Rx/PTV50). The quality and efficiency of the delivery were assessed according to measured quality assurance (QA) passing rates and delivery times. For each disease site, one patient was replanned using physical cost function and compared to the corresponding biological plan. Results: Median CI, CN, and Rx/PTV50 for all 24 patients were 1.13 (1.02-1.28), 0.79 (0.70-0.88), and 5.3 (3.1-10.8), respectively. The median delivery rate for all patients was 410 MU/min with a maximum possible rate of 480 MU/min (85%). Median QA passing rate was 96.7%, and it did not significantly vary with the tumor site. Conclusions: VMAT delivery of SBRT plans optimized using biological-motivated cost-functions result in highly conformal dose distributions. Plans offer shorter treatment-time benefits and provide efficient dose delivery without compromising the plan conformity for tumors in the prostate, lung, and liver, thereby improving patient comfort and clinical throughput. The short delivery times minimize the risk of patient setup and intrafraction motion errors often associated with long SBRT treatment

  3. The usefulness of metal markers for CTV-based dose prescription in high-dose-rate interstitial brachytherapy

    International Nuclear Information System (INIS)

    Yoshida, Ken; Mitomo, Masanori; Nose, Takayuki; Koizumi, Masahiko; Nishiyama, Kinji; Yoshida, Mineo

    2002-01-01

    We employ a clinical target volume (CTV)-based dose prescription for high-dose-rate (HDR) interstitial brachytherapy. However, it is not easy to define CTV and organs at risk (OAR) from X-ray film or CT scanning. To solve this problem, we have utilized metal markers since October 1999. Moreover, metal markers can help modify dose prescription. By regulating the doses to the metal markers, refining the dose prescription can easily be achieved. In this research, we investigated the usefulness of the metal markers. Between October 1999 and May 2001, 51 patients were implanted with metal markers at Osaka Medical Center for Cancer and Cardiovascular Diseases (OMCC), Osaka National Hospital (ONH) and Sanda City Hospital (SCH). Forty-nine patients (head and neck: 32; pelvis: 11; soft tissue: 3; breast: 3) using metal markers were analyzed. During operation, we implanted 179 metal markers (49 patients) to CTV and 151 markers (26 patients) to OAR. At treatment planning, CTV was reconstructed judging from the metal markers, applicator position and operation records. Generally, we prescribed the tumoricidal dose to an isodose surface that covers CTV. We also planned to limit the doses to OAR lower than certain levels. The maximum normal tissue doses were decided 80%, 150%, 100%, 50% and 200% of the prescribed doses for the rectum, the urethra, the mandible, the skin and the large vessel, respectively. The doses to the metal markers using CTV-based dose prescription were generated. These were compared with the doses theoretically calculated with the Paris system. Treatment results were also investigated. The doses to the 158 metal markers (42 patients) for CTV were higher than ''tumoricidal dose''. In 7 patients, as a result of compromised dose prescription, 9 markers were lower than the tumoricidal dose. The other 12 markers (7%) were excluded from dose evaluation because they were judged as miss-implanted. The doses to the 142 metal markers (24 patients) for OAR were lower

  4. The biological response of plucked human hair to low-dose radiation: a measure of individual radiosensitivity and a technique for biological dosimetry

    International Nuclear Information System (INIS)

    Swain, D.

    1997-01-01

    It is often assumed that the effects of radiation are linear with dose and that high dose effects can be extrapolated to low dose levels. However, there are a variety of mechanisms which can alter the response at low doses. The most important of these relate to induced sensitivity or induced repair mechanisms. It is therefore important that this area is studied in more depth by looking at the molecular effects and damage to cells at low doses. It is well known that there are certain rare genetic syndromes which predispose individuals to cancer, e.g. ataxia telangiectasia. It is also probable that there is a large range of sensitivity in the natural variation of individuals to the risk of radiation-induced cancer. It is proposed that radiosensitivity is studied using stimulated lymphocytes from whole blood and the technique extended to look at the effects in cell cultures established from human hair. Radiation treatment of cell cultures established from plucked human hair has been previously advocated as a non-invasive technique for non-uniform biological dosimetry and it is proposed that these techniques are adapted to the use of hair to estimate individual radiosensitivity. The aim is to establish and optimize these techniques for culturing keratinocytes from plucked human hair follicles with a view to study biological markers for the subsequent assessment of radiosensitivity. Preliminary results are promising and suggest that the technique for culturing keratinocytes from hair presents a feasible approach. Results from this primary cell culture technique and results from the comparison of the micronuclei data obtained from the cell cultures and stimulated lymphocytes will be presented. (author)

  5. Development of microcontroller based instrumentation for low dose implantation

    International Nuclear Information System (INIS)

    Suresh, K.; Saravanan, K.; Panigrahi, B.K.; Nair, K.G.M.

    2011-01-01

    In experiments like ion implantation based ion track formations, the sample is implanted to low doses of the order of 10 10 ions/cm 2 , limiting the ion beam currents to be less than 1-5 x 10 -12 A. However the standard current integrators available are not sensitive to very low currents, causing an unacceptable high level of error in dose measurement. Hence a low dose implantation measurement system has been developed. It consists of a very sensitive low current preamplifier with full scale input 1nA/100pA, a standard current integrator, a microcontroller based interface circuit, which are connected to a personal computer(PC) through USB. Two types of the software are developed for the system: the microcontroller firmware using C and windows based virtual instrument programs using LabVIEW 7.0. Necessary precautions associated with pA level measurement like rigidly fastened good quality cables, low ripple DC power supply, shielding, close mounting of the preamplifier to the sample are adopted. After necessary calibrations with an ECIL make low current source, the system has been put into regular use. Design and development details, salient features are discussed in this paper. (author)

  6. Contribution of the modulation of intensity and the optimization to deliver a dose adapted to the biological heterogeneities; Apport de la modulation d'intensite et de l'optimisation pour delivrer une dose adaptee aux heterogeneites biologiques

    Energy Technology Data Exchange (ETDEWEB)

    Kubs, F

    2007-10-15

    The recent progress in functional imaging by Positron Emission Tomography (TEP) opens new perspectives in the delineation of target volumes in radiotherapy. The functional data is major; we can intend to adapt the irradiation doses on the tumor activity (TA) and to perform a dose escalation. Our objectives were (i) to characterize the TEP threshold, by quantifying the uncertainties of the target volume contour according to the lesion size and the threshold contour level, (ii) to set up the geometry suited to perform a high-precision irradiation based on the TA, (iii) to estimate the dosimetric impact of this new protocol and (iv) to verify that dosimetry is perfectly distributed. Three original phantoms were specially created to satisfy the constraints met, as well as two virtual phantoms containing 3 dose levels (dose level 3 = TA). Our results showed the importance of the effect threshold-volume on the planning in radiotherapy. To use this irradiation method, the diameter of 1 cm for the third level was able to be reached. A dose escalation of 20 Gy was possible between the second (70 Gy) and the third level (90 Gy). The dosimetric impact estimated on two real cases was suitable - increase of COIN (conformal index) from 0.6 to 0.8 and decrease of NTCP (normal tissue complication probability) of a factor 5 -. In absolute and relative dosimetry, the clinical tolerances were respected. So all the treatment process, going from the diagnosis with the TEP to reveal the TA, to the patient treatment made beforehand on phantom, and going through the ballistic and the dose calculation, was estimated and validated according to our objective to adapt the irradiation to the biological heterogeneities. However such high doses should be carefully estimated before being prescribed clinically and progress is also expected in imaging, because the minimal size which we can irradiate is on the limit of the resolution TEP. (author)

  7. Biological Treatment of Solvent-Based Paint

    Science.gov (United States)

    2011-01-01

    yeast extract, bone meal, and 80 gallons of water. The acid and base containers should also be filled with sulfuric acid and sodium hydroxide...strength brewery wastewater using a membrane-aeration bioreactor. Water Environ. Res. 71:1197-1204. 19 Cicek, N., J. P. Franco, M. T. Suidan, V

  8. Image noise-based dose adaptation in dynamic volume CT of the heart: dose and image quality optimisation in comparison with BMI-based dose adaptation

    Energy Technology Data Exchange (ETDEWEB)

    Odedra, Devang [Queen' s University, School of Medicine, Kingston, ON (Canada); Blobel, Joerg [Toshiba Medical Systems Europe BV, Zoetermeer (Netherlands); University of Toronto, Division of Cardiothoracic Imaging, Department of Medical Imaging, Toronto General Hospital, Toronto, ON (Canada); AlHumayyd, Saad; Durand, Miranda; Jimenez-Juan, Laura; Paul, Narinder [University of Toronto, Division of Cardiothoracic Imaging, Department of Medical Imaging, Toronto General Hospital, Toronto, ON (Canada)

    2014-01-15

    To compare the image quality and radiation dose using image-noise (IN)-based determination of X-ray tube settings compared with a body mass index (BMI)-based protocol during CT coronary angiography (CTCA). Two hundred consecutive patients referred for CTCA to our institution were divided into two groups: BMI-based, 100 patients had CTCA with the X-ray tube current adjusted to the patient's BMI while maintaining a fixed tube potential of 120 kV; IN-based, 100 patients underwent imaging with the X-ray tube current and voltage adjusted to the IN measured within the mid-left ventricle on a pre-acquisition trans-axial image. Two independent cardiac radiologists performed blinded image quality assessment with quantification of the IN and signal-to-noise ratio (SNR) from the mid-LV and qualitative assessment using a three-point score. Radiation dose (CTDI and DLP) was recorded from the console. Results showed: IN (HU): BMI-based, 30.1 ± 9.9; IN-based, 33.1 ± 6.7; 32 % variation reduction (P = 0.001); SNR: BMI-based, 18.6 ± 7.1; IN-based, 15.4 ± 3.7; 48 % variation reduction (P < 0.0001). Visual scores: BMI-based, 2.3 ± 0.6; IN-based, 2.2 ± 0.5 (P = 0.54). Radiation dose: CTDI (mGy), BMI-based, 22.68 ± 8.9; IN-based, 17.16 ± 7.6; 24.3 % reduction (P < 0.001); DLP (mGy.cm), BMI-based, 309.3 ± 127.5; IN-based, 230.6 ± 105.5; 25.4 % reduction (P < 0.001). Image-noise-based stratification of X-ray tube parameters for CTCA results in 32 % improvement in image quality and 25 % reduction in radiation dose compared with a BMI-based protocol. (orig.)

  9. The relative biological effectiveness of fractionated doses of fast neutrons (42 MeVd→Be) for normal tissues. Pt. 3

    International Nuclear Information System (INIS)

    Rezvani, M.; Hopewell, J.W.; Robbins, M.E.C.; Hamlet, R.; Barnes, D.W.H.; Sansom, J.M.; Adams, P.J.V.

    1990-01-01

    The effect of single and fractionated doses of fast neutrons (42 MeV d→Bc ) on the early and late radiation responses of the pig lung have been assessed by the measurement of changes in lung function using a 133 Xe washout technique. The results obtained for irradiation schedules with fast neutrons have been compared with those after photon irradiation. There was no statistically significant difference between the values for the relative biological effectiveness (RBE) for the early and late radiation response of the lung. The RBE of the neutron beam increased with decreasing size of dose/fraction with an upper limit value of 4.39 ± 0.94 for infinitely small X-ray doses per fraction. (author)

  10. Environmental dose measurement with microprocessor based portable TLD reader

    International Nuclear Information System (INIS)

    Deme, S.; Apathy, I.; Feher, I.

    1996-01-01

    Application of TL method for environmental gamma-radiation dosimetry involves uncertainty caused by the dose collected during the transport from the point of annealing to the place of exposure and back to the place of evaluation. Should an accident occur read out is delayed due to the need to transport to a laboratory equipped with a TLD reader. A portable reader capable of reading out the TL dosemeter at the place of exposure ('in situ TLD reader') eliminates the above mentioned disadvantages. We have developed a microprocessor based portable TLD reader for monitoring environmental gamma-radiation doses and for on board reading out of doses on space stations. The first version of our portable, battery operated reader (named Pille - 'butterfly') was made at the beginning of the 80s. These devices used CaSO 4 bulb dosemeters and the evaluation technique was based on analogue timing circuits and analogue to digital conversion of the photomultiplier current with a read out precision of 1 μGy and a measuring range up to 10 Gy. The measured values were displayed and manually recorded. The version with an external power supply was used for space dosimetry as an onboard TLD reader

  11. Brachytherapy optimization using radiobiological-based planning for high dose rate and permanent implants for prostate cancer treatment

    Science.gov (United States)

    Seeley, Kaelyn; Cunha, J. Adam; Hong, Tae Min

    2017-01-01

    We discuss an improvement in brachytherapy--a prostate cancer treatment method that directly places radioactive seeds inside target cancerous regions--by optimizing the current standard for delivering dose. Currently, the seeds' spatiotemporal placement is determined by optimizing the dose based on a set of physical, user-defined constraints. One particular approach is the ``inverse planning'' algorithms that allow for tightly fit isodose lines around the target volumes in order to reduce dose to the patient's organs at risk. However, these dose distributions are typically computed assuming the same biological response to radiation for different types of tissues. In our work, we consider radiobiological parameters to account for the differences in the individual sensitivities and responses to radiation for tissues surrounding the target. Among the benefits are a more accurate toxicity rate and more coverage to target regions for planning high-dose-rate treatments as well as permanent implants.

  12. Report of task group on the biological basis for dose limitation in the skin

    International Nuclear Information System (INIS)

    1989-08-01

    Researchers have drawn attention to what they consider inconsistencies in the manner in which ICRP have considered skin in relation to the effective dose equivalent. They urge that the dose to the skin should be considered routinely for inclusion in the effective dose equivalent in the context of protection of individuals and population groups. They note that even with a weighting factor of only 0.01 that the dose to the skin can be a significant contributor to the effective dose equivalent including skin for practical exposure conditions. In the case of many exposures the risk to the skin can be ignored but exposure in an uniformly contaminated cloud that might occur with 85 Kr the dose to the skin could contribute 60% of the stochastic risk if included in the effective dose equivalent with a W T of 0.01. Through the years and even today the same questions about radiation effects in the skin and dosimetry keep being asked. This report collates the available data and current understanding of radiation effects on the skin, and may make it possible to estimate risks more accurately and to improve the approach to characterizing skin irradiations. 294 refs., 29 figs

  13. 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.

  14. Dose banding as an alternative to body surface area-based dosing of chemotherapeutic agents

    NARCIS (Netherlands)

    E. Chatelut (Etienne); M.L. White-Koning (M.); A.H.J. Mathijssen (Ron); F. Puisset (F.); S.D. Baker (Sharyn); A. Sparreboom (Alex)

    2012-01-01

    textabstractBackground: Dose banding is a recently suggested dosing method that uses predefined ranges (bands) of body surface area (BSA) to calculate each patients dose by using a single BSA-value per band. Thus, drugs with sufficient long-term stability can be prepared in advance. The main

  15. Temporal Lobe Reactions After Carbon Ion Radiation Therapy: Comparison of Relative Biological Effectiveness–Weighted Tolerance Doses Predicted by Local Effect Models I and IV

    Energy Technology Data Exchange (ETDEWEB)

    Gillmann, Clarissa, E-mail: clarissa.gillmann@med.uni-heidelberg.de [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Jäkel, Oliver [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Heidelberg Ion Beam Therapy Center (HIT), Heidelberg (Germany); Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany); Schlampp, Ingmar [Department of Radiation Oncology and Radiation Therapy, Heidelberg University Hospital, Heidelberg (Germany); Karger, Christian P. [Department of Medical Physics in Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg (Germany)

    2014-04-01

    Purpose: To compare the relative biological effectiveness (RBE)–weighted tolerance doses for temporal lobe reactions after carbon ion radiation therapy using 2 different versions of the local effect model (LEM I vs LEM IV) for the same patient collective under identical conditions. Methods and Materials: In a previous study, 59 patients were investigated, of whom 10 experienced temporal lobe reactions (TLR) after carbon ion radiation therapy for low-grade skull-base chordoma and chondrosarcoma at Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt, Germany in 2002 and 2003. TLR were detected as visible contrast enhancements on T1-weighted MRI images within a median follow-up time of 2.5 years. Although the derived RBE-weighted temporal lobe doses were based on the clinically applied LEM I, we have now recalculated the RBE-weighted dose distributions using LEM IV and derived dose-response curves with Dmax,V-1 cm³ (the RBE-weighted maximum dose in the remaining temporal lobe volume, excluding the volume of 1 cm³ with the highest dose) as an independent dosimetric variable. The resulting RBE-weighted tolerance doses were compared with those of the previous study to assess the clinical impact of LEM IV relative to LEM I. Results: The dose-response curve of LEM IV is shifted toward higher values compared to that of LEM I. The RBE-weighted tolerance dose for a 5% complication probability (TD{sub 5}) increases from 68.8 ± 3.3 to 78.3 ± 4.3 Gy (RBE) for LEM IV as compared to LEM I. Conclusions: LEM IV predicts a clinically significant increase of the RBE-weighted tolerance doses for the temporal lobe as compared to the currently applied LEM I. The limited available photon data do not allow a final conclusion as to whether RBE predictions of LEM I or LEM IV better fit better clinical experience in photon therapy. The decision about a future clinical application of LEM IV therefore requires additional analysis of temporal lobe reactions in a

  16. Knowledge base and functionality of concepts of some Filipino biology teachers in five biology topics

    Science.gov (United States)

    Barquilla, Manuel B.

    2018-01-01

    This mixed research, is a snapshot of some Filipino Biology teachers' knowledge structure and how their concepts of the five topics in Biology (Photosynthesis, Cellular Respiration, human reproductive system, Mendelian genetics and NonMendelian genetics) functions and develops inside a biology classroom. The study focuses on the six biology teachers and a total of 222 students in their respective classes. Of the Six (6) teachers, three (3) are under the Science curriculum and the other three (3) are under regular curriculum in both public and private schools in Iligan city and Lanao del Norte, Philippines. The study utilized classroom discourses, concept maps, interpretative case-study method, bracketing method, and concept analysis for qualitative part; the quantitative part uses a nonparametric statistical tool, Kendall's tau Coefficient for determining relationship and congruency while measures of central tendencies and dispersion (mean, and standard deviation) for concept maps scores interpretation. Knowledge Base of Biology teachers were evaluated by experts in field of specialization having a doctorate program (e.g. PhD in Genetics) and PhD Biology candidates. The data collection entailed seven (7) months immersion: one (1) month for preliminary phase for the researcher to gain teachers' and students' confidence and the succeeding six (6) months for main observation and data collection. The evaluation of teachers' knowledge base by experts indicated that teachers' knowledge of (65%) is lower than the minimum (75%) recommended by ABD-el-Khalick and Boujaoude (1997). Thus, the experts believe that content knowledge of the teachers is hardly adequate for their teaching assignment. Moreover, the teachers in this study do not systematically use reallife situation to apply the concepts they teach. They can identify concepts too abstract for their student; however, they seldom use innovative ways to bring the discussion to their students' level of readiness and

  17. Segment-based dose optimization using a genetic algorithm

    International Nuclear Information System (INIS)

    Cotrutz, Cristian; Xing Lei

    2003-01-01

    Intensity modulated radiation therapy (IMRT) inverse planning is conventionally done in two steps. Firstly, the intensity maps of the treatment beams are optimized using a dose optimization algorithm. Each of them is then decomposed into a number of segments using a leaf-sequencing algorithm for delivery. An alternative approach is to pre-assign a fixed number of field apertures and optimize directly the shapes and weights of the apertures. While the latter approach has the advantage of eliminating the leaf-sequencing step, the optimization of aperture shapes is less straightforward than that of beamlet-based optimization because of the complex dependence of the dose on the field shapes, and their weights. In this work we report a genetic algorithm for segment-based optimization. Different from a gradient iterative approach or simulated annealing, the algorithm finds the optimum solution from a population of candidate plans. In this technique, each solution is encoded using three chromosomes: one for the position of the left-bank leaves of each segment, the second for the position of the right-bank and the third for the weights of the segments defined by the first two chromosomes. The convergence towards the optimum is realized by crossover and mutation operators that ensure proper exchange of information between the three chromosomes of all the solutions in the population. The algorithm is applied to a phantom and a prostate case and the results are compared with those obtained using beamlet-based optimization. The main conclusion drawn from this study is that the genetic optimization of segment shapes and weights can produce highly conformal dose distribution. In addition, our study also confirms previous findings that fewer segments are generally needed to generate plans that are comparable with the plans obtained using beamlet-based optimization. Thus the technique may have useful applications in facilitating IMRT treatment planning

  18. A Dose-Volume Analysis of Magnetic Resonance Imaging-Aided High-Dose-Rate Image-Based Interstitial Brachytherapy for Uterine Cervical Cancer

    International Nuclear Information System (INIS)

    Yoshida, Ken; Yamazaki, Hideya; Takenaka, Tadashi; Kotsuma, Tadayuki; Yoshida, Mineo; Furuya, Seiichi; Tanaka, Eiichi; Uegaki, Tadaaki; Kuriyama, Keiko; Matsumoto, Hisanobu; Yamada, Shigetoshi; Ban, Chiaki

    2010-01-01

    Purpose: To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). Methods and Materials: Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD 2 ). Results: The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D 2cc of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). Conclusions: Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results.

  19. A dose-volume analysis of magnetic resonance imaging-aided high-dose-rate image-based interstitial brachytherapy for uterine cervical cancer.

    Science.gov (United States)

    Yoshida, Ken; Yamazaki, Hideya; Takenaka, Tadashi; Kotsuma, Tadayuki; Yoshida, Mineo; Furuya, Seiichi; Tanaka, Eiichi; Uegaki, Tadaaki; Kuriyama, Keiko; Matsumoto, Hisanobu; Yamada, Shigetoshi; Ban, Chiaki

    2010-07-01

    To investigate the feasibility of our novel image-based high-dose-rate interstitial brachytherapy (HDR-ISBT) for uterine cervical cancer, we evaluated the dose-volume histogram (DVH) according to the recommendations of the Gynecological GEC-ESTRO Working Group for image-based intracavitary brachytherapy (ICBT). Between June 2005 and June 2007, 18 previously untreated cervical cancer patients were enrolled. We implanted magnetic resonance imaging (MRI)-available plastic applicators by our unique ambulatory technique. Total treatment doses were 30-36 Gy (6 Gy per fraction) combined with external beam radiotherapy (EBRT). Treatment plans were created based on planning computed tomography with MRI as a reference. DVHs of the high-risk clinical target volume (HR CTV), intermediate-risk CTV (IR CTV), and the bladder and rectum were calculated. Dose values were biologically normalized to equivalent doses in 2-Gy fractions (EQD(2)). The median D90 (HR CTV) and D90 (IR CTV) per fraction were 6.8 Gy (range, 5.5-7.5) and 5.4 Gy (range, 4.2-6.3), respectively. The median V100 (HR CTV) and V100 (IR CTV) were 98.4% (range, 83-100) and 81.8% (range, 64-93.8), respectively. When the dose of EBRT was added, the median D90 and D100 of HR CTV were 80.6 Gy (range, 65.5-96.6) and 62.4 Gy (range, 49-83.2). The D(2cc) of the bladder was 62 Gy (range, 51.4-89) and of the rectum was 65.9 Gy (range, 48.9-76). Although the targets were advanced and difficult to treat effectively by ICBT, MRI-aided image-based ISBT showed favorable results for CTV and organs at risk compared with previously reported image-based ICBT results. (c) 2010 Elsevier Inc. All rights reserved.

  20. Effect of substerilization doses of radiation on the biology of diamondback moth

    International Nuclear Information System (INIS)

    Omar, D.; Mansor, M.

    1993-01-01

    The pupae of the diamondback moth, Plutella xylostella, were exposed to four substerilizing doses (100, 150, 200 and 250 Gy) of gamma radiation. The fecundity, sterility and progeny development of parental crosses and certain F 1 backcrosses (progeny of irradiated males) were studied in the laboratory. All doses caused sterility in the parental crosses and F 1 backcrosses. Doses above 20 Gy greatly affected the development of larvae in parental crosses of irradiated females with normal males and of irradiated males with irradiated females, as no pupation was observed. The study indicated that a dose between 150 and 200 Gy would be suitable for inherited sterility of the diamondback moth. However, the backcross of progeny from irradiated males showed no significant increase in inheritance of deleterious effects. (author). 10 refs, 7 tabs

  1. Heme-based sensors in biological systems.

    Science.gov (United States)

    Rodgers, K R

    1999-04-01

    The past several years have been witness to a staggering rate of advancement in the understanding of how organisms respond to changes in the availability of diatomic molecules that are toxic and/or crucial to survival. Heme-based sensors presently constitute the majority of the proteins known to sense NO, O2 and CO and to initiate the chemistry required to adapt to changes in their availabilities. Knowledge of the three characterized members of this class, soluble guanylate cyclase, FixL and CooA, has grown substantially during the past year. The major advances have resulted from a broad range of approaches to elucidation of both function and mechanism. They include growth in the understanding of the interplay between the heme and protein in soluble guanylate cyclase, as well as alternate means for its stimulation. Insight into the O2-induced structural changes in FixL has been supplied by the single crystal structure of the heme domain of Bradyrhizobium japonicum. Finally, the ligation environment and ligand interchange that facilitates CO sensing by CooA has been established by spectroscopic and mutagenesis techniques.

  2. Biological dose assessment by cytogenetic dosimetry in the Goianian radiation accident

    International Nuclear Information System (INIS)

    Ramalho, A.T.; Nascimento, A.C.H.; Bellido, P.

    1989-01-01

    During the recent Goianian radiation accident, 112 exposed or potentially exposed individuals were analyzed for the frequencies of chromosomal aberrations (dicentrics and rings) in their lymphocytes, for estimation of the absorbed radiation dose. Of these, 29 subjects had dose estimates exceeding 0.5 Gy, 21 exceeded 1.0 Gy and eight exceeded 4.0 Gy. None of the estimates exceeded 7.0 Gy. (author)

  3. Radiation dose response of normal lung assessed by Cone Beam CT - A potential tool for biologically adaptive radiation therapy

    International Nuclear Information System (INIS)

    Bertelsen, Anders; Schytte, Tine; Bentzen, Soren M.; Hansen, Olfred; Nielsen, Morten; Brink, Carsten

    2011-01-01

    Background: Density changes of healthy lung tissue during radiotherapy as observed by Cone Beam CT (CBCT) might be an early indicator of patient specific lung toxicity. This study investigates the time course of CBCT density changes and tests for a possible correlation with locally delivered dose. Methods: A total of 665 CBCTs in 65 lung cancer patients treated with IMRT/VMAT to 60 or 66 Gy in 2 Gy fractions were analyzed. For each patient, CBCT lung density changes during the treatment course were related to the locally delivered dose. Results: A dose response is observed for the patient population at the end of the treatment course. However, the observed dose response is highly variable among patients. Density changes at 10th and 20th fraction are clearly correlated to those observed at the end of the treatment course. Conclusions: CBCT density changes in healthy lung tissue during radiotherapy correlate with the locally delivered dose and can be detected relatively early during the treatment. If these density changes are correlated to subsequent clinical toxicity this assay could form the basis for biological adaptive radiotherapy.

  4. Mechanism of action for anti-radiation vaccine in reducing the biological impact of high-dose gamma irradiation

    Science.gov (United States)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after high-dose gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naïve animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which they mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  5. Dose rate considerations in brachytherapy: biological equivalence of LDR and HDR

    International Nuclear Information System (INIS)

    Orton, C.G.

    1994-01-01

    The linear-quadratic model for cell survival and bioeffect doses is discussed and equations for low dose rate (LDR), high dose rate (HDR) and intermediate situations are presented. The model, when used to define LDR and single fractions of HDR, shows, that these correspond to irradiations lasting longer than about 14 hours or shorter than about 0.7 hours, respectively. It is shown that, for HDR to be as safe and effective as LDR, the dose-rate effect of LDR has to be replaced by the fractionation-effect of HDR. This is necessary in order to take advantage of the differential repair characteristics between late-reacting normal tissue and tumor cells at low doses and low dose rates. Using the linear-quadratic model to simulate repair mathematically, it is shown that the number of fractions required is highly dependent upon what parameters are assumed for normal tissues and tumor, as well as whether or not there is any physical advantage gained by conversion from LDR to HDR. (author). 20 refs., 7 figs

  6. Small-scale laser based electron accelerators for biology and medicine: a comparative study of the biological effectiveness

    Science.gov (United States)

    Labate, Luca; Andreassi, Maria Grazia; Baffigi, Federica; Basta, Giuseppina; Bizzarri, Ranieri; Borghini, Andrea; Candiano, Giuliana C.; Casarino, Carlo; Cresci, Monica; Di Martino, Fabio; Fulgentini, Lorenzo; Ghetti, Francesco; Gilardi, Maria Carla; Giulietti, Antonio; Köster, Petra; Lenci, Francesco; Levato, Tadzio; Oishi, Yuji; Russo, Giorgio; Sgarbossa, Antonella; Traino, Claudio; Gizzi, Leonida A.

    2013-05-01

    Laser-driven electron accelerators based on the Laser Wakefield Acceleration process has entered a mature phase to be considered as alternative devices to conventional radiofrequency linear accelerators used in medical applications. Before entering the medical practice, however, deep studies of the radiobiological effects of such short bunches as the ones produced by laser-driven accelerators have to be performed. Here we report on the setup, characterization and first test of a small-scale laser accelerator for radiobiology experiments. A brief description of the experimental setup will be given at first, followed by an overview of the electron bunch characterization, in particular in terms of dose delivered to the samples. Finally, the first results from the irradiation of biological samples will be briefly discussed.

  7. Biological information systems: Evolution as cognition-based information management.

    Science.gov (United States)

    Miller, William B

    2018-05-01

    An alternative biological synthesis is presented that conceptualizes evolutionary biology as an epiphenomenon of integrated self-referential information management. Since all biological information has inherent ambiguity, the systematic assessment of information is required by living organisms to maintain self-identity and homeostatic equipoise in confrontation with environmental challenges. Through their self-referential attachment to information space, cells are the cornerstone of biological action. That individualized assessment of information space permits self-referential, self-organizing niche construction. That deployment of information and its subsequent selection enacted the dominant stable unicellular informational architectures whose biological expressions are the prokaryotic, archaeal, and eukaryotic unicellular forms. Multicellularity represents the collective appraisal of equivocal environmental information through a shared information space. This concerted action can be viewed as systematized information management to improve information quality for the maintenance of preferred homeostatic boundaries among the varied participants. When reiterated in successive scales, this same collaborative exchange of information yields macroscopic organisms as obligatory multicellular holobionts. Cognition-Based Evolution (CBE) upholds that assessment of information precedes biological action, and the deployment of information through integrative self-referential niche construction and natural cellular engineering antecedes selection. Therefore, evolutionary biology can be framed as a complex reciprocating interactome that consists of the assessment, communication, deployment and management of information by self-referential organisms at multiple scales in continuous confrontation with environmental stresses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Biological effective dose evaluation in gynaecological brachytherapy: LDR and HDR treatments, dependence on radiobiological parameters, and treatment optimisation.

    Science.gov (United States)

    Bianchi, C; Botta, F; Conte, L; Vanoli, P; Cerizza, L

    2008-10-01

    This study was undertaken to compare the biological efficacy of different high-dose-rate (HDR) and low-dose-rate (LDR) treatments of gynaecological lesions, to identify the causes of possible nonuniformity and to optimise treatment through customised calculation. The study considered 110 patients treated between 2001 and 2006 with external beam radiation therapy and/or brachytherapy with either LDR (afterloader Selectron, (137)Cs) or HDR (afterloader microSelectron Classic, (192)Ir). The treatments were compared in terms of biologically effective dose (BED) to the tumour and to the rectum (linear-quadratic model) by using statistical tests for comparisons between independent samples. The difference between the two treatments was statistically significant in one case only. However, within each technique, we identified considerable nonuniformity in therapeutic efficacy due to differences in fractionation schemes and overall treatment time. To solve this problem, we created a Microsoft Excel spreadsheet allowing calculation of the optimal treatment for each patient: best efficacy (BED(tumour)) without exceeding toxicity threshold (BED(rectum)). The efficacy of a treatment may vary as a result of several factors. Customised radiobiological evaluation is a useful adjunct to clinical evaluation in planning equivalent treatments that satisfy all dosimetric constraints.

  9. Histological image classification using biologically interpretable shape-based features

    International Nuclear Information System (INIS)

    Kothari, Sonal; Phan, John H; Young, Andrew N; Wang, May D

    2013-01-01

    Automatic cancer diagnostic systems based on histological image classification are important for improving therapeutic decisions. Previous studies propose textural and morphological features for such systems. These features capture patterns in histological images that are useful for both cancer grading and subtyping. However, because many of these features lack a clear biological interpretation, pathologists may be reluctant to adopt these features for clinical diagnosis. We examine the utility of biologically interpretable shape-based features for classification of histological renal tumor images. Using Fourier shape descriptors, we extract shape-based features that capture the distribution of stain-enhanced cellular and tissue structures in each image and evaluate these features using a multi-class prediction model. We compare the predictive performance of the shape-based diagnostic model to that of traditional models, i.e., using textural, morphological and topological features. The shape-based model, with an average accuracy of 77%, outperforms or complements traditional models. We identify the most informative shapes for each renal tumor subtype from the top-selected features. Results suggest that these shapes are not only accurate diagnostic features, but also correlate with known biological characteristics of renal tumors. Shape-based analysis of histological renal tumor images accurately classifies disease subtypes and reveals biologically insightful discriminatory features. This method for shape-based analysis can be extended to other histological datasets to aid pathologists in diagnostic and therapeutic decisions

  10. Improved normal tissue sparing in head and neck radiotherapy using biological cost function based-IMRT.

    Science.gov (United States)

    Anderson, N; Lawford, C; Khoo, V; Rolfo, M; Joon, D L; Wada, M

    2011-12-01

    Intensity-modulated radiotherapy (IMRT) has reduced the impact of acute and late toxicities associated with head and neck radiotherapy. Treatment planning system (TPS) advances in biological cost function based optimization (BBO) and improved segmentation techniques have increased organ at risk (OAR) sparing compared to conventional dose-based optimization (DBO). A planning study was undertaken to compare OAR avoidance in DBO and BBO treatment planning. Simultaneous integrated boost treatment plans were produced for 10 head and neck patients using both planning systems. Plans were compared for tar get coverage and OAR avoidance. Comparisons were made using the BBO TPS Monte Carlo dose engine to eliminate differences due to inherent algorithms. Target coverage (V95%) was maintained for both solutions. BBO produced lower OAR doses, with statistically significant improvement to left (12.3%, p = 0.005) and right parotid mean dose (16.9%, p = 0.004), larynx V50_Gy (71.0%, p = 0.005), spinal cord (21.9%, p < 0.001) and brain stem dose maximums (31.5%, p = 0.002). This study observed improved OAR avoidance with BBO planning. Further investigations will be undertaken to review any clinical benefit of this improved planned dosimetry.

  11. Background study of absorbed dose in biological experiments at the Modane Underground Laboratory

    Directory of Open Access Journals (Sweden)

    Lampe Nathanael

    2016-01-01

    Full Text Available Aiming to explore how biological systems respond to ultra-low background environ-ments, we report here our background studies for biological experiments in the Modane Under-ground Laboratory. We find that the minimum radioactive background for biology experiments is limited by the potassium content of the biological sample itself, coming from its nutritive me-dium, which we find in our experimental set-up to be 26 nGy hr-1. Compared to our reference radiation environment in Clermont-Ferrand, biological experiments can be conducted in the Modane laboratory with a radiation background 8.2 times lower than the reference above-ground level. As the radiation background may be further reduced by using different nutritive media, we also provide measurements of the potassium concentration by gamma spectroscopy of yeast extract (63.3±1.2 mg g-1 and tryptone (2.5±0.2 mg g-1 in order to guide media selection in future experiments.

  12. Comparison of two dose and three dose human papillomavirus vaccine schedules: cost effectiveness analysis based on transmission model.

    Science.gov (United States)

    Jit, Mark; Brisson, Marc; Laprise, Jean-François; Choi, Yoon Hong

    2015-01-06

    To investigate the incremental cost effectiveness of two dose human papillomavirus vaccination and of additionally giving a third dose. Cost effectiveness study based on a transmission dynamic model of human papillomavirus vaccination. Two dose schedules for bivalent or quadrivalent human papillomavirus vaccines were assumed to provide 10, 20, or 30 years' vaccine type protection and cross protection or lifelong vaccine type protection without cross protection. Three dose schedules were assumed to give lifelong vaccine type and cross protection. United Kingdom. Males and females aged 12-74 years. No, two, or three doses of human papillomavirus vaccine given routinely to 12 year old girls, with an initial catch-up campaign to 18 years. Costs (from the healthcare provider's perspective), health related utilities, and incremental cost effectiveness ratios. Giving at least two doses of vaccine seems to be highly cost effective across the entire range of scenarios considered at the quadrivalent vaccine list price of £86.50 (€109.23; $136.00) per dose. If two doses give only 10 years' protection but adding a third dose extends this to lifetime protection, then the third dose also seems to be cost effective at £86.50 per dose (median incremental cost effectiveness ratio £17,000, interquartile range £11,700-£25,800). If two doses protect for more than 20 years, then the third dose will have to be priced substantially lower (median threshold price £31, interquartile range £28-£35) to be cost effective. Results are similar for a bivalent vaccine priced at £80.50 per dose and when the same scenarios are explored by parameterising a Canadian model (HPV-ADVISE) with economic data from the United Kingdom. Two dose human papillomavirus vaccine schedules are likely to be the most cost effective option provided protection lasts for at least 20 years. As the precise duration of two dose schedules may not be known for decades, cohorts given two doses should be closely

  13. Data base on nuclear power plant dose reduction research projects

    Energy Technology Data Exchange (ETDEWEB)

    Khan, T.A.; Dionne, B.J.; Baum, J.W.

    1985-12-01

    This report contains project information on the research and development activities of the nuclear power industry in the area of dose reduction. It is based on a data base of information set up at the ALARA Center of Brookhaven National Laboratory. One purpose of this report is to draw attention to work in progress and to enable researchers and subscribers to obtain further information from the investigators and project managers. Information is provided on 180 projects, divided according to whether they are oriented to Engineering Research or to Health Physics Technology. The report contains indices on main category, project manager, principal investigator, sponsoring organization, contracting organization, and subject. This is an initial report. It is intended that periodic updates be issued whenever sufficient material has been accumulated.

  14. Data base on nuclear power plant dose reduction research projects

    International Nuclear Information System (INIS)

    Khan, T.A.; Dionne, B.J.; Baum, J.W.

    1985-12-01

    This report contains project information on the research and development activities of the nuclear power industry in the area of dose reduction. It is based on a data base of information set up at the ALARA Center of Brookhaven National Laboratory. One purpose of this report is to draw attention to work in progress and to enable researchers and subscribers to obtain further information from the investigators and project managers. Information is provided on 180 projects, divided according to whether they are oriented to Engineering Research or to Health Physics Technology. The report contains indices on main category, project manager, principal investigator, sponsoring organization, contracting organization, and subject. This is an initial report. It is intended that periodic updates be issued whenever sufficient material has been accumulated

  15. PET/CT Based Dose Planning in Radiotherapy

    DEFF Research Database (Denmark)

    Berthelsen, Anne Kiil; Jakobsen, Annika Loft; Sapru, Wendy

    2011-01-01

    radiotherapy planning with PET/CT prior to the treatment. The PET/CT, including the radiotherapy planning process as well as the radiotherapy process, is outlined in detail. The demanding collaboration between mould technicians, nuclear medicine physicians and technologists, radiologists and radiology......This mini-review describes how to perform PET/CT based radiotherapy dose planning and the advantages and possibilities obtained with the technique for radiation therapy. Our own experience since 2002 is briefly summarized from more than 2,500 patients with various malignant diseases undergoing...... technologists, radiation oncologists, physicists, and dosimetrists is emphasized. We strongly believe that PET/CT based radiotherapy planning will improve the therapeutic output in terms of target definition and non-target avoidance and will play an important role in future therapeutic interventions in many...

  16. Non-Linear Dose-Response Relationships in Biology, Toxicology and Medicine - An International Conference

    Energy Technology Data Exchange (ETDEWEB)

    Calabrese, Edward J.; Kostecki, Paul T.

    2002-05-28

    Conference abstract book contains seven sections: Plenary-4 abstracts; Chemical-9 abstracts; Radiation-7 abstracts; Ultra Low Doses and Medicine-6 abstracts; Biomedical-11 abstracts; Risk Assessment-5 abstracts and Poster Sessions-25 abstracts. Each abstract was provided by the author/presenter participating in the conference.

  17. Quantification of radiation-induced epilation in the pig: a biological indicator of radiation dose to the skin

    International Nuclear Information System (INIS)

    Sieber, V.K.; Wilkinson, J.; Aluri, G.R.; Bywaters, T.

    1993-01-01

    Epilation in the pig has been quantified following single exposures of X-rays in the range 1.0-25.0Gy. Hair loss was dose-dependent for exposures between 1.0 and 15.0 Gy and this response was linearly related to dose. No further increase in hair loss was observed for doses ≥ 15.0 Gy as 20-30% of the hairs remained. It was assumed that these hairs were not actively growing at the time of irradiation and did, therefore, not express damage. The ED 50 for the loss of ≥ 30% of hairs was 3.8 Gy whilst that for the loss of ≥ 50% of hairs was 6.8 Gy and for the loss of ≥ 67% of hairs was 12.5 Gy. There was ± 7% hair loss per Gy exposure for doses between 0.0 and 15.0 Gy. Quantification of hair loss provided a more sensitive assay than the use of visual scoring systems. Hair loss was detectable within 4 weeks of irradiation. The system is simple, non-invasive and appears to have considerable potential for use as a biological dosemeter. (Author)

  18. The induction of a tumor suppressor gene (p53) expression by low-dose radiation and its biological meaning

    International Nuclear Information System (INIS)

    Ohnishi, Takeo

    1997-01-01

    I report the induced accumulation of wild-type p53 protein of a tumor suppressor gene within 12 h in various organs of rats exposed to X-ray irradiation at low doses (10-50 cGy). The levels of p53 in some organs of irradiated rats were increased about 2- to 3-fold in comparison with the basal p53 levels in non-irradiated rats. Differences in the levels of p53 induction after low-dose X-ray irradiation were observed among the small intestine, bone marrow, brain, liver, adrenal gland, spleen, hypophysis and skin. In contrast, there was no obvious accumulation of p53 protein in the testis and ovary. Thus, the induction of cellular p.53 accumulation by low-dose X-ray irradiation in rats seems to be organ-specific. I consider that cell type, and interactions with other signal transduction pathways of the hormone system, immune system and nervous system may contribute to the variable induction of p53 by low-dose X-ray irradiation. I discussed the induction of p53 by radiation and its biological meaning from an aspect of the defense system for radiation-induced cancer. (author)

  19. Mechanism of Action for Anti-radiation Vaccine in Reducing the Biological Impact of High-dose Gamma Irradiation

    Science.gov (United States)

    Maliev, Vladislav; Popov, Dmitri; Jones, Jeffrey A.; Casey, Rachael C.

    2007-01-01

    Ionizing radiation is a major health risk of long-term space travel, the biological consequences of which include genetic and oxidative damage. In this study, we propose an original mechanism by which high doses of ionizing radiation induce acute toxicity. We identified biological components that appear in the lymphatic vessels shortly after gamma irradiation. These radiation-induced toxins, which we have named specific radiation determinants (SRD), were generated in the irradiated tissues and then collected and circulated throughout the body via the lymph circulation and bloodstream. Depending on the type of SRD elicited, different syndromes of acute radiation sickness (ARS) were expressed. The SRDs were developed into a vaccine used to confer active immunity against acute radiation toxicity in immunologically naive animals. Animals that were pretreated with SRDs exhibited resistance to lethal doses of gamma radiation, as measured by increased survival times and survival rates. In comparison, untreated animals that were exposed to similar large doses of gamma radiation developed acute radiation sickness and died within days. This phenomenon was observed in a number of mammalian species. Initial analysis of the biochemical characteristics indicated that the SRDs were large molecular weight (200-250 kDa) molecules that were comprised of a mixture of protein, lipid, carbohydrate, and mineral. Further analysis is required to further identify the SRD molecules and the biological mechanism by which the mediate the toxicity associated with acute radiation sickness. By doing so, we may develop an effective specific immunoprophylaxis as a countermeasure against the acute effects of ionizing radiation.

  20. Cancer and non-cancer risk at low doses of radiation: biological basis of radiation-environment interplay

    International Nuclear Information System (INIS)

    Sasaki, Masao S.

    2013-01-01

    Cancer and non-cancer risk at low doses of ionizing radiation remains poorly defined due to ambiguity at low doses caused by limitations in statistical power and information available on interplay with environment. To deal with these problems, a novel non-parametric statistics was developed based on artificial neural networks theorem and applied to cancer and non-cancer risk in A-bomb survivors. The analysis revealed several unique features at low doses that could not be accounted for by nominal radiation dose alone. They include (1) threshold that varies with organ, gender and age, including cardiovascular diseases, (2) prevalence of infectious diseases, and (3) suppression of pathogenesis of HTLV1. The threshold is unique as it is manifested as negative excess relative risk, a reduction of spontaneous rate at low doses. The response is consistent with currently emerging laboratory data on DNA double-strand break (DSB) repair pathway choice and its sustainability as epigenetic memory in accordance with histone code theory. In response to DSB, of radiation or DNA replication arrest origin, distinct and competitively operating repair pathways are instigated. Activation by low doses of restitution-directed canonical non-homologous end-joining (C-NHEJ) suppresses both error-prone alternative end-joining (Alt-NHEJ) and homologous recombination (HR). The latter two present major pathways to mutagenesis at stalled replication folk associated with endogenous and exogenous genotoxin such as tobacco smoke metabolites and AID-associated somatic hypermutation and class switch recombination in Ig gene. Suppression of these error-prone pathways by low doses of low LET radiation is consistent with the reduction of cancer occurrence by environmental genotoxin, immunodiversity and stable integration of retrovirus DNA, providing a significant modulator of dose linearity at low doses. Whole picture may bring about a new landscape of cancer and non-cancer molecular epidemiology which

  1. A trial of radiation dose prescription based on dose-cell survival formula

    International Nuclear Information System (INIS)

    Allen, E.P.

    1984-01-01

    Radiation treatment has been prescribed for 379 basal cell carcinomata on the basis of a selected equivalent single dose derived from the standard multi-target dose-cell survival formula using values of m = 2 and Do = 130 rads for orthovoltage x-rays. The results suggest that the approach provides a flexible and acceptable alternative to prescription by total dose or by Nominal Standard Dose. It is submitted that Total Dose is an inadequate expression of radiobiological effects: that the NSD and related systems are valuable measures of the ability of normal tissues to recover from radiation damage: and that a parallel measure of the degree of tumour depopulation has become necessary to allow further progress in alternative fractionation schedules

  2. Biological effects of low doses of ionizing radiation: Conflict between assumptions and observations

    International Nuclear Information System (INIS)

    Kesavan, P.C.; Devasagayam, T.P.A.

    1997-01-01

    Recent epidemiological data on cancer incidence among the A-bomb survivors and more importantly experimental studies in cell and molecular radiobiology do not lend unequivocal support to the ''linear, no threshold'' (LNT) hypothesis; in fact, the discernible evidence that low and high doses of ionizing radiations induce qualitatively different/opposite effects cannot be summarily rejected. A time has come to examine the mechanistic aspects of ''radiation hormesis'' and ''radioadaptive response'' seriously rather than proclaiming one's profound disbelief about these phenomena. To put the discussion in a serious scientific mode, we briefly catalogue here reports in the literature on gene expression differentially influenced by low and high doses. These are not explicable in terms of the current radiation paradigm. (author)

  3. A Project-Based Biologically-Inspired Robotics Module

    Science.gov (United States)

    Crowder, R. M.; Zauner, K.-P.

    2013-01-01

    The design of any robotic system requires input from engineers from a variety of technical fields. This paper describes a project-based module, "Biologically-Inspired Robotics," that is offered to Electronics and Computer Science students at the University of Southampton, U.K. The overall objective of the module is for student groups to…

  4. Biological Impact of Music and Software-Based Auditory Training

    Science.gov (United States)

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals--both young and old--encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in…

  5. The biological effects of low doses of ionizing radiation on adaptive possibilities of the organism

    International Nuclear Information System (INIS)

    Bulbuc, G.

    1997-01-01

    The study of adaptive possibilities and cancer risk in animals exposed at low doses of ionizing radiation was the object of the present work. The action of immunostimulating treatment on these processes was studied as well. In previously irradiated animals the diminution of adaptive possibilities and of the antitumoral resistance of the organism was observed. The stimulating action of Bufostimulin on these processes in irradiated animals was less pronounced than in unirradiated ones. (author)

  6. Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization.

    Directory of Open Access Journals (Sweden)

    Devaraj Jayachandran

    Full Text Available 6-Mercaptopurine (6-MP is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN through enzymatic reaction involving thiopurine methyltransferase (TPMT. Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP's widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient's ability to metabolize the drug instead of the traditional standard-dose-for-all approach.

  7. Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization

    Science.gov (United States)

    Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami

    2015-01-01

    6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP’s widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient’s ability to metabolize the drug instead of the traditional standard-dose-for-all approach. PMID:26226448

  8. Method of predicting the mean lung dose based on a patient's anatomy and dose-volume histograms

    Energy Technology Data Exchange (ETDEWEB)

    Zawadzka, Anna, E-mail: a.zawadzka@zfm.coi.pl [Medical Physics Department, Centre of Oncology, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw (Poland); Nesteruk, Marta [Faculty of Physics, University of Warsaw, Warsaw (Poland); Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich (Switzerland); Brzozowska, Beata [Faculty of Physics, University of Warsaw, Warsaw (Poland); Kukołowicz, Paweł F. [Medical Physics Department, Centre of Oncology, Maria Sklodowska-Curie Memorial Cancer Center, Warsaw (Poland)

    2017-04-01

    The aim of this study was to propose a method to predict the minimum achievable mean lung dose (MLD) and corresponding dosimetric parameters for organs-at-risk (OAR) based on individual patient anatomy. For each patient, the dose for 36 equidistant individual multileaf collimator shaped fields in the treatment planning system (TPS) was calculated. Based on these dose matrices, the MLD for each patient was predicted by the homemade DosePredictor software in which the solution of linear equations was implemented. The software prediction results were validated based on 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) plans previously prepared for 16 patients with stage III non–small-cell lung cancer (NSCLC). For each patient, dosimetric parameters derived from plans and the results calculated by DosePredictor were compared. The MLD, the maximum dose to the spinal cord (D{sub max} {sub cord}) and the mean esophageal dose (MED) were analyzed. There was a strong correlation between the MLD calculated by the DosePredictor and those obtained in treatment plans regardless of the technique used. The correlation coefficient was 0.96 for both 3D-CRT and VMAT techniques. In a similar manner, MED correlations of 0.98 and 0.96 were obtained for 3D-CRT and VMAT plans, respectively. The maximum dose to the spinal cord was not predicted very well. The correlation coefficient was 0.30 and 0.61 for 3D-CRT and VMAT, respectively. The presented method allows us to predict the minimum MLD and corresponding dosimetric parameters to OARs without the necessity of plan preparation. The method can serve as a guide during the treatment planning process, for example, as initial constraints in VMAT optimization. It allows the probability of lung pneumonitis to be predicted.

  9. Relative Biological Effectiveness of HZE Fe Ions for Induction ofMicro-Nuclei at Low Doses

    Energy Technology Data Exchange (ETDEWEB)

    Groesser, Torsten; Chun, Eugene; Rydberg, Bjorn

    2007-01-16

    Dose-response curves for induction of micro-nuclei (MN) was measured in Chinese hamster V79 and xrs6 (Ku80-) cells and in human mammary epithelial MCF10A cells in the dose range of 0.05-1 Gy. The Chinese Hamster cells were exposed to 1 GeV/u Fe ions, 600 MeV/u Fe ions, and 300 MeV/u Fe ions (LETs of 151, 176 and 235 keV/{micro}m respectively) as well as with 320 kVp X-rays as reference. Second-order polynomials were fitted to the induction curves and the initial slopes (the alpha values) were used to calculate RBE. For the repair proficient V79 cells the RBE at these low doses increased with LET. The values obtained were 3.1 (LET=151 keV/{micro}m), 4.3 (LET = 176 keV/{micro}m) and 5.7 (LET = 235 keV/{micro}m), while the RBE was close to 1 for the repair deficient xrs6 cells regardless of LET. For the MCF10A cells the RBE was determined for 1 GeV/u Fe ions and found to be 5.4, slightly higher than for V79 cells. To test the effect of shielding, the 1 GeV/u Fe ion beam was intercepted by various thickness of high-density polyethylene plastic absorbers, which resulted in energy loss and fragmentation. It was found that the MN yield for V79 cells placed behind the absorbers decreased in proportion to the decrease in dose both before and after the Fe ion Bragg peak (excluding the area around the Fe-ion Bragg peak itself), indicating that RBE did not change significantly due to shielding. At the Bragg peak the effectiveness for MN formation per unit dose was decreased, indicating an 'overkill' effect by low-energy very high-LET Fe ions.

  10. The internal radiation dose calculations based on Chinese mathematical phantom

    International Nuclear Information System (INIS)

    Wang Haiyan; Li Junli; Cheng Jianping; Fan Jiajin

    2006-01-01

    The internal radiation dose calculations built on Chinese facts become more and more important according to the development of nuclear medicine. the MIRD method developed and consummated by the society of Nuclear Medicine (America) is based on the European and American mathematical phantom and can't fit Chinese well. The transport of γ-ray in the Chinese mathematical phantom was simulated with Monte Carlo method in programs as MCNP4C. the specific absorbed fraction (Φ) of Chinese were calculated and the Chinese Φ database was created. The results were compared with the recommended values by ORNL. the method was proved correct by the coherence when the target organ was the same with the source organ. Else, the difference was due to the different phantom and the choice of different physical model. (authors)

  11. Synthetic biology for microbial production of lipid-based biofuels.

    Science.gov (United States)

    d'Espaux, Leo; Mendez-Perez, Daniel; Li, Rachel; Keasling, Jay D

    2015-12-01

    The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. We further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing. Published by Elsevier Ltd.

  12. Mobile-based biology edutainment application for secondary schools

    Science.gov (United States)

    AL-Modwahi, Ashraf Abbas M.; Kaisara, Onalenna; Parkizkar, Behrang; Habibi Lashkari, Arash

    2013-03-01

    The high increase of mobile technology is leading to mobilized learning environment, thus making traditional learning to diminish slowly and become inactive and unproductive. Learners worldwide are being attracted to mobile environment more so that it promotes anytime, anywhere learning. Biology as a secondary school subject will be applicable for mobile learning for such a time and generation as this. This paper is therefore an attempt to mobile based biology edutainment system for the students who normally range from the ages of thirteen to sixteen.

  13. Construction of a Linux based chemical and biological information system.

    Science.gov (United States)

    Molnár, László; Vágó, István; Fehér, András

    2003-01-01

    A chemical and biological information system with a Web-based easy-to-use interface and corresponding databases has been developed. The constructed system incorporates all chemical, numerical and textual data related to the chemical compounds, including numerical biological screen results. Users can search the database by traditional textual/numerical and/or substructure or similarity queries through the web interface. To build our chemical database management system, we utilized existing IT components such as ORACLE or Tripos SYBYL for database management and Zope application server for the web interface. We chose Linux as the main platform, however, almost every component can be used under various operating systems.

  14. Synthetic biology for microbial production of lipid-based biofuels

    Energy Technology Data Exchange (ETDEWEB)

    d' Espaux, L; Mendez-Perez, D; Li, R; Keasling, JD

    2015-10-23

    The risks of maintaining current CO2 emission trends have led to interest in producing biofuels using engineered microbes. Microbial biofuels reduce emissions because CO2 produced by fuel combustion is offset by CO2 captured by growing biomass, which is later used as feedstock for biofuel fermentation. Hydrocarbons found in petroleum fuels share striking similarity with biological lipids. Here in this paper we review synthetic metabolic pathways based on fatty acid and isoprenoid metabolism to produce alkanes and other molecules suitable as biofuels. Lastly, we further discuss engineering strategies to optimize engineered biosynthetic routes, as well as the potential of synthetic biology for sustainable manufacturing.

  15. Biological impact of music and software-based auditory training

    OpenAIRE

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals – both young and old – encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in noisy environments and reading, pointing to an intersection between hearing and cognition. Musical experience, amplification, and software-based ...

  16. Simulation of computed tomography dose based on voxel phantom

    Science.gov (United States)

    Liu, Chunyu; Lv, Xiangbo; Li, Zhaojun

    2017-01-01

    Computed Tomography (CT) is one of the preferred and the most valuable imaging tool used in diagnostic radiology, which provides a high-quality cross-sectional image of the body. It still causes higher doses of radiation to patients comparing to the other radiological procedures. The Monte-Carlo method is appropriate for estimation of the radiation dose during the CT examinations. The simulation of the Computed Tomography Dose Index (CTDI) phantom was developed in this paper. Under a similar conditions used in physical measurements, dose profiles were calculated and compared against the measured values that were reported. The results demonstrate a good agreement between the calculated and the measured doses. From different CT exam simulations using the voxel phantom, the highest absorbed dose was recorded for the lung, the brain, the bone surface. A comparison between the different scan type shows that the effective dose for a chest scan is the highest one, whereas the effective dose values during abdomen and pelvis scan are very close, respectively. The lowest effective dose resulted from the head scan. Although, the dose in CT is related to various parameters, such as the tube current, exposure time, beam energy, slice thickness and patient size, this study demonstrates that the MC simulation is a useful tool to accurately estimate the dose delivered to any specific organs for patients undergoing the CT exams and can be also a valuable technique for the design and the optimization of the CT x-ray source.

  17. Intravascular ultrasound based dose assessment in endovascular brachytherapy

    International Nuclear Information System (INIS)

    Catalano, Gianpiero; Tamburini, Vittorio; Colombo, Antonio; Nishida, Takahiro; Parisi, Giovanni; Mazzetta, Chiara; Orecchia, Roberto

    2003-01-01

    Background: the role of endovascular brachytherapy in restenosis prevention is well documented. Dose is usually prescribed at a fixed distance from the source axis by angiographic quantification of vessel diameter. Recently, intravascular ultrasound (IVUS) was introduced in dose prescription, allowing a better evaluation of the vessel anatomy. This study retrospectively explores the difference between prescription following angiographic vessel sizing and delivered dose calculated with IVUS. Methods and results: Seventeen lesions were studied with IVUS, identifying on irradiated segment, three sections on which measuring minimal and maximal distance from the centre of IVUS catheter to the adventitia; using dedicated software, corresponding doses were calculated. The dose ranged widely, with maximal and minimal values of 71.6 and 4.9 Gy; furthermore, heterogeneity in dose among different sections was observed. In the central section, the maximal dose was 206% of the one prescribed with the QCA model at 2 mm from the source axis, while the minimal dose was 96%. In proximal and distal sections, respective values were 182, 45, 243, and 122%. Conclusions: Our analysis confirmed the dose inhomogeneity delivered with an angiographic fixed-dose prescription strategy. A dose variation was found along the irradiated segment due to the differences in vessel thickness. IVUS emerged as an important tool in endovascular brachytherapy, especially for irregular-shaped vessels

  18. Analysis of CT radiation dose based on radiation-dose-structured reports

    International Nuclear Information System (INIS)

    Wang Weipeng; Zhang Yi; Zhang Menglong; Zhang Dapeng; Song Shaojuan

    2014-01-01

    Objective: To analyse the CT radiation dose statistically using the standardized radiation-dose-structured report (RDSR) of digital imaging and communications in medicine (DICOM). Methods: Using the self-designed software, 1230 RDSR files about CT examination were obtained searching on the picture archiving and communication system (PACS). The patient dose database was established by combination of the extracted relevant information with the scanned sites. The patients were divided into adult group (over 10 years) and child groups (0-1 year, 1-5 years, 5-10 years) according to the age. The average volume CT dose index (CTDI vol ) and dose length product (DLP) of all scans were recorded respectively, and then the effective dose (E) was estimated. The DLP value at 75% quantile was calculated and compared with the diagnostic reference level (DRL). Results: In adult group, CTDI vol and DLP values were moderately and positively correlated (r = 0.41), the highest E was observed in upper abdominal enhanced scan, and the DLP value at 75% quantile was 60% higher than DRL. In child group, their CTDI vol in group of 5-10 years was greater than that in groups of 0-1 and 1-5 years (t = 2.42, 2.04, P < 0.05); the DLP value was slightly and positively correlated with the age (r = 0.16), while E was moderately and negatively correlated with the age (r = -0.48). Conclusions: It is a simple and efficient method to use RDSR to obtain the radiation doses of patients. With the popularization of the new equipment and the application of regionalized medical platform, RDSR would become the main tool for the dosimetric level surveying and individual dose recording. (authors)

  19. Comparison of the predictions of the LQ and CRE models for normal tissue damage due to biologically targeted radiotherapy with exponentially decaying dose rates

    International Nuclear Information System (INIS)

    O'Donoghue, J.A.; West of Schotland Health Boards, Glasgow

    1989-01-01

    For biologically targeted radiotherapy organ dose rates may be complex functions of time, related to the biodistribution kinetics of the delivery vehicle and radiolabel. The simples situation is where dose rates are exponentially decaying functions of time. Two normal tissue isoeffect models enable the effects of exponentially decaying dose rates to be addressed. These are the extension of the linear-quadratic model and the cumulative radiation effect model. This communication will compare the predictions of these models. (author). 14 refs.; 1 fig

  20. Should repository release criteria be based on collective dose, release limits, or individual doses?

    International Nuclear Information System (INIS)

    Channell, J.K.; Neill, R.H.

    1999-01-01

    The advantages and disadvantages of using each of 3 alternative methods (collective dose, release limits, and individual dose) as release criteria for determining long-term high level or transuranic waste repository performance of naturally occurring releases or man-made intrusions are evaluated. Each of the alternative approaches have positive aspects and each has uncertainties that require some arbitrary assumptions. A comparison of the numerical results from evaluating the three alternatives at WIPP leads to the conclusion that a collective dose is preferable because it is more site specific and allows consideration of the full effects of human intrusion. The main objection to release limits is they do not use site specific criteria to determine the radiological effect on local and regional populations. Individual dose criteria used and recommended in the United States have ignored doses to drillers and the public from wastes brought to the surface by human intrusion because these doses can be greater than acceptable limits. Also, there is disagreement about defining the location and lifestyle of the individual

  1. The potential of standards-based agriculture biology as an alternative to traditional biology in California

    Science.gov (United States)

    Sellu, George Sahr

    schools. Thoron & Meyer (2011) suggested that research into the contribution of integrated science courses toward higher test scores yielded mixed results. This finding may have been due in part to the fact that integrated science courses only incorporate select topics into agriculture education courses. In California, however, agriculture educators have developed standards-based courses such as Agriculture Biology (AgBio) that cover the same content standards as core traditional courses such as traditional biology. Students in both AgBio and traditional biology take the same standardized biology test. This is the first time there has been an opportunity for a fair comparison and a uniform metric for an agriscience course such as AgBio to be directly compared to traditional biology. This study will examine whether there are differences between AgBio and traditional biology with regard to standardized test scores in biology. Furthermore, the study examines differences in perception between teachers and students regarding teaching and learning activities associated with higher achievement in science. The findings of the study could provide a basis for presenting AgBio as a potential alternative to traditional biology. The findings of this study suggest that there are no differences between AgBio and traditional biology students with regard to standardized biology test scores. Additionally, the findings indicate that co-curricular activities in AgBio could contribute higher student achievement in biology. However, further research is required to identify specific activities in AgBio that contribute to higher achievement in science.

  2. Prototype Biology-Based Radiation Risk Module Project

    Science.gov (United States)

    Terrier, Douglas; Clayton, Ronald G.; Patel, Zarana; Hu, Shaowen; Huff, Janice

    2015-01-01

    Biological effects of space radiation and risk mitigation are strategic knowledge gaps for the Evolvable Mars Campaign. The current epidemiology-based NASA Space Cancer Risk (NSCR) model contains large uncertainties (HAT #6.5a) due to lack of information on the radiobiology of galactic cosmic rays (GCR) and lack of human data. The use of experimental models that most accurately replicate the response of human tissues is critical for precision in risk projections. Our proposed study will compare DNA damage, histological, and cell kinetic parameters after irradiation in normal 2D human cells versus 3D tissue models, and it will use a multi-scale computational model (CHASTE) to investigate various biological processes that may contribute to carcinogenesis, including radiation-induced cellular signaling pathways. This cross-disciplinary work, with biological validation of an evolvable mathematical computational model, will help reduce uncertainties within NSCR and aid risk mitigation for radiation-induced carcinogenesis.

  3. Design of synthetic biological logic circuits based on evolutionary algorithm.

    Science.gov (United States)

    Chuang, Chia-Hua; Lin, Chun-Liang; Chang, Yen-Chang; Jennawasin, Tanagorn; Chen, Po-Kuei

    2013-08-01

    The construction of an artificial biological logic circuit using systematic strategy is recognised as one of the most important topics for the development of synthetic biology. In this study, a real-structured genetic algorithm (RSGA), which combines general advantages of the traditional real genetic algorithm with those of the structured genetic algorithm, is proposed to deal with the biological logic circuit design problem. A general model with the cis-regulatory input function and appropriate promoter activity functions is proposed to synthesise a wide variety of fundamental logic gates such as NOT, Buffer, AND, OR, NAND, NOR and XOR. The results obtained can be extended to synthesise advanced combinational and sequential logic circuits by topologically distinct connections. The resulting optimal design of these logic gates and circuits are established via the RSGA. The in silico computer-based modelling technology has been verified showing its great advantages in the purpose.

  4. The effects of periphyton, fish and fertilizer dose on biological processes affecting water quality in earthen fish ponds.

    NARCIS (Netherlands)

    Milstein, A.; Azim, M.E.; Wahab, M.A.; Verdegem, M.C.J.

    2003-01-01

    The potential of periphyton-based aquaculture in South Asia is under investigation in an extensive research program. This paper is a further analysis of data from four experiments carried out in that framework, to explore periphyton, fish and fertilizer dose effects on water quality. Factor analysis

  5. Soft x-ray-controlled dose deposition in yeast cells: techniques, model, and biological assessment

    Science.gov (United States)

    Milani, Marziale; Batani, Dimitri; Conti, Aldo; Masini, Alessandra; Costato, Michele; Pozzi, Achille; Turcu, I. C. Edmond

    1996-12-01

    A procedure is presented to release soft x-rays onto yeast cell membrane allegedly damaging the resident enzymatic processes connected with fermentation. The damage is expected to be restricted to regulating fermentation processes without interference with respiration. By this technique fermentation is followed leading to CO2 production, and respiration resulting in global pressure measurements. A solid state pressure sensor system has been developed linked to a data acquisition system. Yeast cells cultures have been investigated at different concentrations and with different nutrients. A non-monotone response in CO2 production as a function of the delivered x-ray dose is observed.

  6. Mathematical biology modules based on modern molecular biology and modern discrete mathematics.

    Science.gov (United States)

    Robeva, Raina; Davies, Robin; Hodge, Terrell; Enyedi, Alexander

    2010-01-01

    We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network.

  7. Mathematical Biology Modules Based on Modern Molecular Biology and Modern Discrete Mathematics

    Science.gov (United States)

    Davies, Robin; Hodge, Terrell; Enyedi, Alexander

    2010-01-01

    We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to introduce students to mathematical methods beyond the interface of biology with calculus. Based on ongoing research, and designed to use the project-based-learning approach, the modules highlight applications of modern discrete mathematics and algebraic statistics to pressing problems in molecular biology. For the majority of projects, calculus is not a required prerequisite and, due to the modest amount of mathematical background needed for some of the modules, the materials can be used for an early introduction to mathematical modeling. At the same time, most modules are connected with topics in linear and abstract algebra, algebraic geometry, and probability, and they can be used as meaningful applied introductions into the relevant advanced-level mathematics courses. Open-source software is used to facilitate the relevant computations. As a detailed example, we outline a module that focuses on Boolean models of the lac operon network. PMID:20810955

  8. ARAC: a computer-based emergency dose-assessment service

    International Nuclear Information System (INIS)

    Sullivan, T.J.

    1990-01-01

    Over the past 15 years, the Lawrence Livermore National Laboratory's Atmospheric Release Advisory Capability (ARAC) has developed and evolved a computer-based, real-time, radiological-dose-assessment service for the United States Departments of Energy and Defense. This service is built on the integrated components of real-time computer-acquired meteorological data, extensive computer databases, numerical atmospheric-dispersion models, graphical displays, and operational-assessment-staff expertise. The focus of ARAC is the off-site problem where regional meteorology and topography are dominant influences on transport and dispersion. Through application to numerous radiological accidents/releases on scales from small accidental ventings to the Chernobyl reactor disaster, ARAC has developed methods to provide emergency dose assessments from the local to the hemispheric scale. As the power of computers has evolved inversely with respect to cost and size, ARAC has expanded its service and reduced the response time from hours to minutes for an accident within the United States. Concurrently the quality of the assessments has improved as more advanced models have been developed and incorporated into the ARAC system. Over the past six years, the number of directly connected facilities has increased from 6 to 73. All major U.S. Federal agencies now have access to ARAC via the Department of Energy. This assures a level of consistency as well as experience. ARAC maintains its real-time skills by participation in approximately 150 exercises per year; ARAC also continuously validates its modeling systems by application to all available tracer experiments and data sets

  9. A phantom based method for deriving typical patient doses from measurements of dose-area product on populations of patients

    International Nuclear Information System (INIS)

    Chapple, C.-L.; Broadhead, D.A.

    1995-01-01

    One of the chief sources of uncertainty in the comparison of patient dosimetry data is the influence of patient size on dose. Dose has been shown to relate closely to the equivalent diameter of the patient. This concept has been used to derive a prospective, phantom based method for determining size correction factors for measurements of dose-area product. The derivation of the size correction factor has been demonstrated mathematically, and the appropriate factor determined for a number of different X-ray sets. The use of phantom measurements enables the effect of patient size to be isolated from other factors influencing patient dose. The derived factors agree well with those determined retrospectively from patient dose survey data. Size correction factors have been applied to the results of a large scale patient dose survey, and this approach has been compared with the method of selecting patients according to their weight. For large samples of data, mean dose-area product values are independent of the analysis method used. The chief advantage of using size correction factors is that it allows all patient data to be included in a survey, whereas patient selection has been shown to exclude approximately half of all patients. (author)

  10. Repeated dose titration versus age-based method in electroconvulsive therapy: a pilot study

    NARCIS (Netherlands)

    Aten, J.J.; Oudega, M.L.; van Exel, E.; Stek, M.L.; van Waarde, J.A.

    2015-01-01

    In electroconvulsive therapy (ECT), a dose titration method (DTM) was suggested to be more individualized and therefore more accurate than formula-based dosing methods. A repeated DTM (every sixth session and dose adjustment accordingly) was compared to an age-based method (ABM) regarding treatment

  11. In situ biological dose mapping estimates the radiation burden delivered to 'spared' tissue between synchrotron X-ray microbeam radiotherapy tracks.

    Directory of Open Access Journals (Sweden)

    Kai Rothkamm

    Full Text Available Microbeam radiation therapy (MRT using high doses of synchrotron X-rays can destroy tumours in animal models whilst causing little damage to normal tissues. Determining the spatial distribution of radiation doses delivered during MRT at a microscopic scale is a major challenge. Film and semiconductor dosimetry as well as Monte Carlo methods struggle to provide accurate estimates of dose profiles and peak-to-valley dose ratios at the position of the targeted and traversed tissues whose biological responses determine treatment outcome. The purpose of this study was to utilise γ-H2AX immunostaining as a biodosimetric tool that enables in situ biological dose mapping within an irradiated tissue to provide direct biological evidence for the scale of the radiation burden to 'spared' tissue regions between MRT tracks. Γ-H2AX analysis allowed microbeams to be traced and DNA damage foci to be quantified in valleys between beams following MRT treatment of fibroblast cultures and murine skin where foci yields per unit dose were approximately five-fold lower than in fibroblast cultures. Foci levels in cells located in valleys were compared with calibration curves using known broadbeam synchrotron X-ray doses to generate spatial dose profiles and calculate peak-to-valley dose ratios of 30-40 for cell cultures and approximately 60 for murine skin, consistent with the range obtained with conventional dosimetry methods. This biological dose mapping approach could find several applications both in optimising MRT or other radiotherapeutic treatments and in estimating localised doses following accidental radiation exposure using skin punch biopsies.

  12. Estimated neutron-activation data for TFTR. Part II. Biological dose rate from sample-materials activation

    International Nuclear Information System (INIS)

    Ku, L.; Kolibal, J.G.

    1982-06-01

    The neutron induced material activation dose rate data are summarized for the TFTR operation. This report marks the completion of the second phase of the systematic study of the activation problem on the TFTR. The estimations of the neutron induced activation dose rates were made for spherical and slab objects, based on a point kernel method, for a wide range of materials. The dose rates as a function of cooling time for standard samples are presented for a number of typical neutron spectrum expected during TFTR DD and DT operations. The factors which account for the variations of the pulsing history, the characteristic size of the object and the distance of observation relative to the standard samples are also presented

  13. Development of dose equivalent meters based on microdosimetric principles

    International Nuclear Information System (INIS)

    Booz, J.

    1984-01-01

    In this paper, the employment of microdosimetric dose-equivalent meters in radiation protection is described considering the advantages of introducing microdosimetric methods into radiation protection, the technical suitability of such instruments for measuring dose equivalent, and finally technical requirements, constraints and solutions together with some examples of instruments and experimental results. The advantage of microdosimetric methods in radiation protection is illustrated with the evaluation of dose-mean quality factors in radiation fields of unknown composition and with the methods of evaluating neutron- and gamma-dose fractions. - It is shown that there is good correlation between dose-mean lineal energy, anti ysub(anti D), and the ICRP quality factor. - Neutron- and gamma-dose fractions of unknown radiation fields can be evaluated with microdosimetric proportional counters without recurrence to other instruments and methods. The problems of separation are discussed. The technical suitability of microdosimetric instruments for measuring dose equivalent is discussed considering the energy response to neutrons and photons and the sensitivity in terms of dose-equivalent rate. Then, considering technical requirements, constraints, and solutions, the problem of the large dynamic range in LET, the large dynamic range in pulse rate, geometry of sensitive volume and electrodes, evaluation of dose-mean quality factors, calibration methods, and uncertainties are discussed. (orig.)

  14. Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Linda X.; Garg, Madhur; Lasala, Patrick; Kim, Mimi; Mah, Dennis; Chen, Chin-Cheng; Yaparpalvi, Ravindra; Mynampati, Dinesh; Kuo, Hsiang-Chi; Guha, Chandan; Kalnicki, Shalom [Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Neurosurgery, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Epidemiology and Population Health, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Department of Radiation Oncology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, New York 10461 (United States)

    2011-03-15

    Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems, Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group

  15. TU-F-CAMPUS-T-05: Dose Escalation to Biological Tumor Volumes of Prostate Cancer Patients Using Gold Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Jermoumi, M; Ngwa, W [Department of Physics and Applied Physics, Medical Physics Program, University of Massachusetts Lowell (United States); Department of Radiation Oncology, Dana Farber Cancer Insitute, Brigham and Women’s Hospital, Harvard Medical, Boston, MA (United States); Sajo, E [Department of Physics and Applied Physics, Medical Physics Program, University of Massachusetts Lowell (United States); Houari, K [Department of Radiation Oncology, Dana Farber Cancer Insitute, Brigham and Women’s Hospital, Harvard Medical, Boston, MA (United States)

    2015-06-15

    Purpose: Studies have shown that radiation boosting could help reduce prostate cancer (PCa) recurrence. Biological tumor volumes (BTV) are a high priority for such radiation boosting. The purpose of this study is to investigate the potential of radiation boosting of real patient BTVs using gold nanoparticles (GNP) released from gold-loaded brachytherapy spacers (GBS) during brachytherapy. Methods: The BTVs of 12 patients having prostate adenocarcinoma identified with positron emission tomography (PET) and CT scanner using C-11 labeled tracer [11C]acetate were investigated. The initial GNP concentration and time to achieve a dose enhancement effect (DEF) of 2 was simulated using the freely downloadable software RAID APP. The investigations were carried out for low dose rate (LDR) brachytherapy sources (BTS) described in AAPM Task Group report 43: Cs-131, I-125, and Pd-103. In first case, we used 7 mg/g and 18 mg/g of GNP initial concentrations to estimate the time needed for released GNP to achieve a DEF of 2 for the different BTS, and compare with clinically relevant treatment times. In second case, we calculated the initial concentration of GNPs needed to achieve a DEF of 2 during the time the BTS would typically deliver 50%, 70% and 90% of the total dose. Results: For an initial concentration of 18 mg/g, when using Cs-131, and Pd-103, a DEF of 2 could only be achieved for BTV of 3.3 cm3 and 1 cm3 respectively. Meanwhile a DEF of 2 could be achieved for all 12 BTVs when using I-125. To achieve a DEF of 2 for all patients using Cs-131 and Pd-103, much higher initial concentrations would have to be used than have been typically employed in pre-clinical studies. Conclusion: The I-125 is the most viable BTS that can be employed with GBS to guide dose painting treatment planning for localized PCa.

  16. High biologically effective dose radiation therapy using brachytherapy in combination with external beam radiotherapy for high-risk prostate cancer

    Directory of Open Access Journals (Sweden)

    Keisei Okamoto

    2017-02-01

    Full Text Available Purpose : To evaluate the outcomes of high-risk prostate cancer patients treated with biologically effective dose (BED ≥ 220 Gy of high-dose radiotherapy, using low-dose-rate (LDR brachytherapy in combination with external beam radiotherapy (EBRT and short-term androgen deprivation therapy (ADT. Material and methods : From 2005 to 2013, a total of 143 patients with high-risk prostate cancer were treated by radiotherapy of BED ≥ 220 Gy with a combination of LDR brachytherapy, EBRT, and androgen deprivation therapy (ADT. The high-risk patients in the present study included both high-risk and very high-risk prostate cancer. The number of high-risk features were: 60 patients with 1 high-risk factor (42%, 61 patients with 2 high-risk factors (43%, and 22 patients with 3 high-risk factors (15% including five N1 disease. External beam radiotherapy fields included prostate and seminal vesicles only or whole pelvis depending on the extension of the disease. Biochemical failure was defined by the Phoenix definition. Results : Six patients developed biochemical failure, thus providing a 5-year actual biochemical failure-free survival (BFFS rate of 95.2%. Biochemical failure was observed exclusively in cases with distant metastasis in the present study. All six patients with biochemical relapse had clinical failure due to bone metastasis, thus yielding a 5-year freedom from clinical failure (FFCF rate of 93.0%. None of the cases with N1 disease experienced biochemical failure. We observed four deaths, including one death from prostate cancer, therefore yielding a cause-specific survival (CSS rate of 97.2%, and an overall survival (OS rate of 95.5%. Conclusions : High-dose (BED ≥ 220 Gy radiotherapy by LDR in combination with EBRT has shown an excellent outcome on BFFS in high-risk and very high-risk cancer, although causal relationship between BED and BFFS remain to be explained further.

  17. What is infidelity? Perceptions based on biological sex and personality

    OpenAIRE

    Thornton, Victoria; Nagurney, Alexander

    2011-01-01

    Victoria Thornton, Alexander NagurneyTexas State University – San Marcos, San Marcos, Texas, USAAbstract: The study examines perceptions of infidelity, paying particular attention to how these perceptions differ based on biological sex and personality traits, specifically agency and communion and their unmitigated counterparts. The study utilizes a sample of 125 male and 233 female college students. In addition to the personality measures, participants completed a 19-item checklist ...

  18. Low dose/low fluence ionizing radiation-induced biological effects: The role of intercellular communication and oxidative metabolism

    Science.gov (United States)

    Azzam, Edouard

    Mechanistic investigations have been considered critical to understanding the health risks of exposure to ionizing radiation. To gain greater insight in the biological effects of exposure to low dose/low fluence space radiations with different linear energy transfer (LET) properties, we examined short and long-term biological responses to energetic protons and high charge (Z) and high energy (E) ions (HZE particles) in human cells maintained in culture and in targeted and non-targeted tissues of irradiated rodents. Particular focus of the studies has been on mod-ulation of gene expression, proliferative capacity, induction of DNA damage and perturbations in oxidative metabolism. Exposure to mean doses of 1000 MeV/nucleon iron ions, by which a small to moderate proportion of cells in an exposed population is targeted through the nucleus by an HZE particle, induced stressful effects in the irradiated and non-irradiated cells in the population. Direct intercellular communication via gap-junctions was a primary mediator of the propagation of stressful effects from irradiated to non-irradiated cells. Compromised prolif-erative capacity, elevated level of DNA damage and oxidative stress evaluated by measurements of protein carbonylation, lipid peroxidation and activity of metabolic enzymes persisted in the progeny of irradiated and non-irradiated cells. In contrast, progeny of cells exposed to high or low doses from 150-1000 MeV protons retained the ability to form colonies and harbored similar levels of micronuclei, a surrogate form of DNA damage, as control, which correlated with normal reactive oxygen species (ROS) levels. Importantly, a significant increase in the spontaneous neoplastic transformation frequency was observed in progeny of bystander mouse embryo fibroblasts (MEFs) co-cultured with MEFs irradiated with energetic iron ions but not protons. Of particular significance, stressful effects were detected in non-targeted tissues of rats that received partial

  19. A Biologically Based Chemo-Sensing UAV for Humanitarian Demining

    Directory of Open Access Journals (Sweden)

    Paul F.M.J. Verschure

    2008-11-01

    Full Text Available Antipersonnel mines, weapons of cheap manufacture but lethal effect, have a high impact on the population even decades after the conflicts have finished. Here we investigate the use of a chemo-sensing Unmanned Aerial Vehicle (cUAV for demining tasks. We developed a blimp based UAV that is equipped with a broadly tuned metal-thin oxide chemo-sensor. A number of chemical mapping strategies were investigated including two biologically based localization strategies derived from the moth chemical search that can optimize the efficiency of the detection and localization of explosives and therefore be used in the demining process. Additionally, we developed a control layer that allows for both fully autonomous and manual controlled flight, as well as for the scheduling of a fleet of cUAVs. Our results confirm the feasibility of this technology for demining in real-world scenarios and give further support to a biologically based approach where the understanding of biological systems is used to solve difficult engineering problems.

  20. A Biologically Based Chemo-Sensing UAV for Humanitarian Demining

    Directory of Open Access Journals (Sweden)

    Sergi Bermúdez i Badia

    2007-06-01

    Full Text Available Antipersonnel mines, weapons of cheap manufacture but lethal effect, have a high impact on the population even decades after the conflicts have finished. Here we investigate the use of a chemo-sensing Unmanned Aerial Vehicle (cUAV for demining tasks. We developed a blimp based UAV that is equipped with a broadly tuned metal-thin oxide chemo-sensor. A number of chemical mapping strategies were investigated including two biologically based localization strategies derived from the moth chemical search that can optimize the efficiency of the detection and localization of explosives and therefore be used in the demining process. Additionally, we developed a control layer that allows for both fully autonomous and manual controlled flight, as well as for the scheduling of a fleet of cUAVs. Our results confirm the feasibility of this technology for demining in real-world scenarios and give further support to a biologically based approach where the understanding of biological systems is used to solve difficult engineering problems.

  1. Systems Biology Model of Interactions between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFβ and ATM Signaling

    International Nuclear Information System (INIS)

    Cucinotta, Francis A

    2016-01-01

    The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently, the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses, and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low-dose responses and cross-talk between the ATM and TGFβ pathways initiated by low- and high-LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to crosstalk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental

  2. Systems Biology Model of Interactions Between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFbeta and ATM Signaling

    Energy Technology Data Exchange (ETDEWEB)

    O' Neill, Peter [University of Oxford; Anderson, Jennifer [University of Oxford

    2014-10-02

    The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low dose responses and cross-talk between the ATM and TGFβ pathways initiated by low and high LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to cross- talk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental

  3. Systems Biology Model of Interactions between Tissue Growth Factors and DNA Damage Pathways: Low Dose Response and Cross-Talk in TGFβ and ATM Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Cucinotta, Francis A [Univ. of Nevada, Las Vegas, NV (United States)

    2016-09-01

    The etiology of radiation carcinogenesis has been described in terms of aberrant changes that span several levels of biological organization. Growth factors regulate many important cellular and tissue functions including apoptosis, differentiation and proliferation. A variety of genetic and epigenetic changes of growth factors have been shown to contribute to cancer initiation and progression. It is known that cellular and tissue damage to ionizing radiation is in part initiated by the production of reactive oxygen species, which can activate cytokine signaling, and the DNA damage response pathways, most notably the ATM signaling pathway. Recently, the transforming growth factor β (TGFβ) pathway has been shown to regulate or directly interact with the ATM pathway in the response to radiation. The relevance of this interaction with the ATM pathway is not known although p53 becomes phosphorylated and DNA damage responses are involved. However, growth factor interactions with DNA damage responses have not been elucidated particularly at low doses, and further characterization of their relationship to cancer processes is warranted. Our goal will be to use a systems biology approach to mathematically and experimentally describe the low-dose responses and cross-talk between the ATM and TGFβ pathways initiated by low- and high-LET radiation. We will characterize ATM and TGFβ signaling in epithelial and fibroblast cells using 2D models and ultimately extending to 3D organotypic cell culture models to begin to elucidate possible differences that may occur for different cell types and/or inter-cellular communication. We will investigate the roles of the Smad and Activating transcription factor 2 (ATF2) proteins as the potential major contributors to crosstalk between the TGFβ and ATM pathways, and links to cell cycle control and/or the DNA damage response, and potential differences in their responses at low and high doses. We have developed various experimental

  4. Optimisation of antimicrobial dosing based on pharmacokinetic and pharmacodynamic principles

    Directory of Open Access Journals (Sweden)

    Grace Si Ru Hoo

    2017-01-01

    Full Text Available While suboptimal dosing of antimicrobials has been attributed to poorer clinical outcomes, clinical cure and mortality advantages have been demonstrated when target pharmacokinetic (PK and pharmacodynamic (PD indices for various classes of antimicrobials were achieved to maximise antibiotic activity. Dosing optimisation requires a good knowledge of PK/PD principles. This review serves to provide a foundation in PK/PD principles for the commonly prescribed antibiotics (β-lactams, vancomycin, fluoroquinolones and aminoglycosides, as well as dosing considerations in special populations (critically ill and obese patients. PK principles determine whether an appropriate dose of antimicrobial reaches the intended pathogen(s. It involves the fundamental processes of absorption, distribution, metabolism and elimination, and is affected by the antimicrobial's physicochemical properties. Antimicrobial pharmacodynamics define the relationship between the drug concentration and its observed effect on the pathogen. The major indicator of the effect of the antibiotics is the minimum inhibitory concentration. The quantitative relationship between a PK and microbiological parameter is known as a PK/PD index, which describes the relationship between dose administered and the rate and extent of bacterial killing. Improvements in clinical outcomes have been observed when antimicrobial agents are dosed optimally to achieve their respective PK/PD targets. With the rising rates of antimicrobial resistance and a limited drug development pipeline, PK/PD concepts can foster more rational and individualised dosing regimens, improving outcomes while simultaneously limiting the toxicity of antimicrobials.

  5. Development of internal dose calculation model and the data base updated IDES (Internal Dose Estimation System)

    International Nuclear Information System (INIS)

    Hongo, Shozo; Yamaguchi, Hiroshi; Takeshita, Hiroshi; Iwai, Satoshi.

    1994-01-01

    A computer program named IDES is developed by BASIC language for a personal computer and translated to C language of engineering work station. The IDES carries out internal dose calculations described in ICRP Publication 30 and it installs the program of transformation method which is an empirical method to estimate absorbed fractions of different physiques from ICRP Referenceman. The program consists of three tasks: productions of SAF for Japanese including children, productions of SEE, Specific Effective Energy, and calculation of effective dose equivalents. Each task and corresponding data file appear as a module so as to meet future requirement for revisions of the related data. Usefulness of IDES is discussed by exemplifying the case that 5 age groups of Japanese intake orally Co-60 or Mn-54. (author)

  6. Biological effects in lymphocytes irradiated with {sup 99m}Tc: determination of the curve dose-response; Efeitos biologicos em linfocitos irradiados com {sup 99m}Tc: determinacao da curva dose-resposta

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Romero Marcilio Barros Matias de

    2002-08-01

    Biological dosimetry estimates the absorbed dose taking into account changes in biological parameters. The most used biological indicator of an exposition to ionizing radiation is the quantification of chromosomal aberrations of lymphocytes from irradiated individuals. The curves of dose versus induced biological effects, obtained through bionalyses, are used in used in retrospective evaluations of the dose, mainly in the case of accidents. In this research, a simple model for electrons and photons transports was idealized to simulate the irradiation of lymphocytes with {sup 99m} Tc, representing a system used for irradiation of blood cells. The objective of the work was to establish a curve of dose versus frequencies of chromosomal aberrations in lymphocytes of human blood. For the irradiation of blood samples micro spheres of human serum of albumin (HSAM) market with {sup 99m} Tc were used, allowing the irradiation of blood with different administered activities of {sup 99m} Tc, making possible the study the cytogenetical effects as a function of such activities. The conditions of irradiation in vivo using HSAM spheres marked with {sup 99m} Tc were simulated with MCNP 4C (Monte Carlo N-Particle) code to obtain the dose-response curve. Soft tissue composition was employed to simulate blood tissue and the analyses of the curve of dose versus biological effect showed a linear quadratic response of the unstable chromosomal aberrations. As a result, the response of dose versus chromosomal aberrations of blood irradiation with {sup 99m} Tc was best fitted by the curve Y=(8,99 {+-}2,06) x 1-{sup -4} + (1,24 {+-}0,62) x 10{sup -2} D + (5,67 {+-} 0,64) x 10{sup -2} D{sup 2}. (author)

  7. Biological impact of music and software-based auditory training

    Science.gov (United States)

    Kraus, Nina

    2012-01-01

    Auditory-based communication skills are developed at a young age and are maintained throughout our lives. However, some individuals – both young and old – encounter difficulties in achieving or maintaining communication proficiency. Biological signals arising from hearing sounds relate to real-life communication skills such as listening to speech in noisy environments and reading, pointing to an intersection between hearing and cognition. Musical experience, amplification, and software-based training can improve these biological signals. These findings of biological plasticity, in a variety of subject populations, relate to attention and auditory memory, and represent an integrated auditory system influenced by both sensation and cognition. Learning outcomes The reader will (1) understand that the auditory system is malleable to experience and training, (2) learn the ingredients necessary for auditory learning to successfully be applied to communication, (3) learn that the auditory brainstem response to complex sounds (cABR) is a window into the integrated auditory system, and (4) see examples of how cABR can be used to track the outcome of experience and training. PMID:22789822

  8. Small bowel toxicity after high dose spot scanning-based proton beam therapy for paraspinal/retroperitoneal neoplasms

    Energy Technology Data Exchange (ETDEWEB)

    Schneider, R.A.; Albertini, F.; Koch, T.; Ares, C.; Lomax, A.; Goitein, G. [Paul Scherrer Institute PSI, Villigen (Switzerland). Center for Proton Therapy; Vitolo, V. [Fondazione CNAO, Pavia (Italy); Hug, E.B. [Paul Scherrer Institute PSI, Villigen (Switzerland). Center for Proton Therapy; ProCure Proton Therapy Centers, New York, NY (United States)

    2013-12-15

    Purpose: Mesenchymal tumours require high-dose radiation therapy (RT). Small bowel (SB) dose constraints have historically limited dose delivery to paraspinal and retroperitoneal targets. This retrospective study correlated SB dose-volume histograms with side-effects after proton radiation therapy (PT). Patients and methods: Between 1997 and 2008, 31 patients (mean age 52.1 years) underwent spot scanning-based PT for paraspinal/retroperitoneal chordomas (81 %), sarcomas (16 %) and meningiom (3 %). Mean total prescribed dose was 72.3 Gy (relative biologic effectiveness, RBE) delivered in 1.8-2 Gy (RBE) fractions. Mean follow-up was 3.8 years. Based on the pretreatment planning CT, SB dose distributions were reanalysed. Results: Planning target volume (PTV) was defined as gross tumour volume (GTV) plus 5-7 mm margins. Mean PTV was 560.22 cm{sup 3}. A mean of 93.2 % of the PTV was covered by at least 90 % of the prescribed dose. SB volumes (cm{sup 3}) receiving doses of 5, 20, 30, 40, 50, 60, 70, 75 and 80 Gy (RBE) were calculated to give V5, V20, V30, V40, V50, V60, V70, V75 and V80 respectively. In 7/31 patients, PT was accomplished without any significant SB irradiation (V5 = 0). In 24/31 patients, mean maximum dose (Dmax) to SB was 64.1 Gy (RBE). Despite target doses of > 70 Gy (RBE), SB received > 50 and > 60 Gy (RBE) in only 61 and 54 % of patients, respectively. Mean SB volumes (cm{sup 3}) covered by different dose levels (Gy, RBE) were: V20 (n = 24): 45.1, V50 (n = 19): 17.7, V60 (n = 17): 7.6 and V70 (n = 12): 2.4. No acute toxicity {>=} grade 2 or late SB sequelae were observed. Conclusion: Small noncircumferential volumes of SB tolerated doses in excess of 60 Gy (RBE) without any clinically-significant late adverse effects. This small retrospective study has limited statistical power but encourages further efforts with higher patient numbers to define and establish high-dose threshold models for SB toxicity in modern radiation oncology. (orig.)

  9. Feasibility of TCP-based dose painting by numbers applied to a prostate case with 18F-choline PET imaging

    International Nuclear Information System (INIS)

    Dirscherl, Thomas; Bogner, Ludwig; Rickhey, Mark

    2012-01-01

    Introduction: A biologically adaptive radiation treatment method to maximize the TCP is shown. Functional imaging is used to acquire a heterogeneous dose prescription in terms of Dose Painting by Numbers and to create a patient-specific IMRT plan. Method and Materials: Adapted from a method for selective dose escalation under the guidance of spatial biology distribution, a model, which translates heterogeneously distributed radiobiological parameters into voxelwise dose prescriptions, was developed. At the example of a prostate case with 18 F-choline PET imaging, different sets of reported values for the parameters were examined concerning their resulting range of dose values. Furthermore, the influence of each parameter of the linear-quadratic model was investigated. A correlation between PET signal and proliferation as well as cell density was assumed. Using our in-house treatment planning software Direct Monte Carlo Optimization (DMCO), a treatment plan based on the obtained dose prescription was generated. Gafchromic EBT films were irradiated for evaluation. Results: When a TCP of 95% was aimed at, the maximal dose in a voxel of the prescription exceeded 100 Gy for most considered parameter sets. One of the parameter sets resulted in a dose range of 87.1 Gy to 99.3 Gy, yielding a TCP of 94.7%, and was investigated more closely. The TCP of the plan decreased to 73.5% after optimization based on that prescription. The dose difference histogram of optimized and prescribed dose revealed a mean of -1.64 Gy and a standard deviation of 4.02 Gy. Film verification showed a reasonable agreement of planned and delivered dose. Conclusion: If the distribution of radiobiological parameters within a tumor is known, this model can be used to create a dose-painting by numbers plan which maximizes the TCP. It could be shown, that such a heterogeneous dose distribution is technically feasible. (orig.)

  10. Biology-based combined-modality radiotherapy: workshop report

    International Nuclear Information System (INIS)

    Mason, Kathryn A.; Komaki, Ritsuko; Cox, James D.; Milas, Luka

    2001-01-01

    Purpose: The purpose of this workshop summary is to provide an overview of preclinical and clinical data on combined-modality radiotherapy. Methods and Materials: The 8th Annual Radiation Workshop at Round Top was held April 13-16, 2000 at the International Festival Institute (Round Top, TX). Results: Presentations by 30 speakers (from Germany, Netherlands, Australia, England, and France along with U.S. participants and M. D. Anderson Cancer Center faculty) formed the framework for discussions on the current status and future perspectives of biology-based combined-modality radiotherapy. Conclusion: Cellular and molecular pathways available for radiation modification by chemical and biologic agents are numerous, providing new opportunities for translational research in radiation oncology and for more effective combined-modality treatment of cancer

  11. Agent-Based Modeling in Molecular Systems Biology.

    Science.gov (United States)

    Soheilypour, Mohammad; Mofrad, Mohammad R K

    2018-06-08

    Molecular systems orchestrating the biology of the cell typically involve a complex web of interactions among various components and span a vast range of spatial and temporal scales. Computational methods have advanced our understanding of the behavior of molecular systems by enabling us to test assumptions and hypotheses, explore the effect of different parameters on the outcome, and eventually guide experiments. While several different mathematical and computational methods are developed to study molecular systems at different spatiotemporal scales, there is still a need for methods that bridge the gap between spatially-detailed and computationally-efficient approaches. In this review, we summarize the capabilities of agent-based modeling (ABM) as an emerging molecular systems biology technique that provides researchers with a new tool in exploring the dynamics of molecular systems/pathways in health and disease. © 2018 WILEY Periodicals, Inc.

  12. Computer Based Dose Control System on Linear Accelerator

    International Nuclear Information System (INIS)

    Taxwim; Djoko-SP; Widi-Setiawan; Agus-Budi Wiyatna

    2000-01-01

    The accelerator technology has been used for radio therapy. DokterKaryadi Hospital in Semarang use electron or X-ray linear accelerator (Linac)for cancer therapy. One of the control parameter of linear accelerator isdose rate. It is particle current or amount of photon rate to the target. Thecontrol of dose rate in linac have been done by adjusting repetition rate ofanode pulse train of electron source. Presently the control is stillproportional control. To enhance the quality of the control result (minimalstationer error, velocity and stability), the dose control system has beendesigned by using the PID (Proportional Integral Differential) controlalgorithm and the derivation of transfer function of control object.Implementation of PID algorithm control system is done by giving an input ofdose error (the different between output dose and dose rate set point). Theoutput of control system is used for correction of repetition rate set pointfrom pulse train of electron source anode. (author)

  13. Compressed sensing electron tomography of needle-shaped biological specimens – Potential for improved reconstruction fidelity with reduced dose

    Energy Technology Data Exchange (ETDEWEB)

    Saghi, Zineb, E-mail: saghizineb@gmail.com [Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS (United Kingdom); Divitini, Giorgio [Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS (United Kingdom); Winter, Benjamin [Center for Nanoanalysis and Electron Microscopy (CENEM), Friedrich-Alexander-Universität Erlangen-Nürnberg, Cauerstraße 6, 91058 Erlangen (Germany); Leary, Rowan [Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS (United Kingdom); Spiecker, Erdmann [Center for Nanoanalysis and Electron Microscopy (CENEM), Friedrich-Alexander-Universität Erlangen-Nürnberg, Cauerstraße 6, 91058 Erlangen (Germany); Ducati, Caterina [Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS (United Kingdom); Midgley, Paul A., E-mail: pam33@cam.ac.uk [Department of Materials Science and Metallurgy, University of Cambridge, 27 Charles Babbage Road, Cambridge CB3 0FS (United Kingdom)

    2016-01-15

    Electron tomography is an invaluable method for 3D cellular imaging. The technique is, however, limited by the specimen geometry, with a loss of resolution due to a restricted tilt range, an increase in specimen thickness with tilt, and a resultant need for subjective and time-consuming manual segmentation. Here we show that 3D reconstructions of needle-shaped biological samples exhibit isotropic resolution, facilitating improved automated segmentation and feature detection. By using scanning transmission electron tomography, with small probe convergence angles, high spatial resolution is maintained over large depths of field and across the tilt range. Moreover, the application of compressed sensing methods to the needle data demonstrates how high fidelity reconstructions may be achieved with far fewer images (and thus greatly reduced dose) than needed by conventional methods. These findings open the door to high fidelity electron tomography over critically relevant length-scales, filling an important gap between existing 3D cellular imaging techniques. - Highlights: • On-axis electron tomography of a needle-shaped biological sample is presented. • A reconstruction with isotropic resolution is achieved. • Compressed sensing methods are compared to conventional reconstruction algorithms. • High fidelity reconstructions are achieved with greatly undersampled datasets.

  14. Compressed sensing electron tomography of needle-shaped biological specimens – Potential for improved reconstruction fidelity with reduced dose

    International Nuclear Information System (INIS)

    Saghi, Zineb; Divitini, Giorgio; Winter, Benjamin; Leary, Rowan; Spiecker, Erdmann; Ducati, Caterina; Midgley, Paul A.

    2016-01-01

    Electron tomography is an invaluable method for 3D cellular imaging. The technique is, however, limited by the specimen geometry, with a loss of resolution due to a restricted tilt range, an increase in specimen thickness with tilt, and a resultant need for subjective and time-consuming manual segmentation. Here we show that 3D reconstructions of needle-shaped biological samples exhibit isotropic resolution, facilitating improved automated segmentation and feature detection. By using scanning transmission electron tomography, with small probe convergence angles, high spatial resolution is maintained over large depths of field and across the tilt range. Moreover, the application of compressed sensing methods to the needle data demonstrates how high fidelity reconstructions may be achieved with far fewer images (and thus greatly reduced dose) than needed by conventional methods. These findings open the door to high fidelity electron tomography over critically relevant length-scales, filling an important gap between existing 3D cellular imaging techniques. - Highlights: • On-axis electron tomography of a needle-shaped biological sample is presented. • A reconstruction with isotropic resolution is achieved. • Compressed sensing methods are compared to conventional reconstruction algorithms. • High fidelity reconstructions are achieved with greatly undersampled datasets.

  15. Dose estimation of heavy ion beam by microdosimetry. Examination of the method to estimate biological effect from physical measurement of radiation quality

    International Nuclear Information System (INIS)

    Kase, Yuki; Sakama, Makoto; Tsuzuki, Daigo; Abe, Kyoko; Saotome, Naoya; Matsufuji, Naruhiro; Kanai, Tatsuaki; Matsumoto, Kouki; Furusawa, Yoshiya

    2007-01-01

    The absorbed dose (AD) of heavy ion (HI) beam (here, carbon beam) in HI therapy (unit, EGy) (D st ) to exert the actual clinical effect is for the irradiation of tumors deep in the body and is thus estimated by AD corrected with the relative biological effectiveness (RBE) of clinical endpoint: i.e., the relation is expressed by the equation RBE=D st /D rad | same-effect (D rad is AD of the reference X-ray to yield the same effect as the HI used for the intended clinical endpoint). This paper describes the process of the estimation in the title with consideration of depth dependences of AD of HI in accordance to Bragg curve, and of biological AD as determined by colony assay of human salivary gland tumor cells: in NIRS, the desired AD in HI therapy is calculated by multiplying 1.5 to physically measured AD of HI at RBE 10% (10% survival of the cells). This factor has been obtained by microdosimetry of Heavy Ion Medical Accelerator in Chiba (HIMAC) ions in NIRS with a small spherical proportional counter (LET-1/2, Far West Technology) of the diameter 1.27 cm having the tissue equivalent plastic wall and chamber filled with 4.4 kPa of propane-based gas to make the tissue-equivalence size 1.0 μm diameter. The measuring principle is based on the microdosimetric kinetic model reported previously. The calculated dose is found to agree with AD in HI therapeutic planning within 10% fluctuation. (R.T.)

  16. The radioinduced membranes injuries as biological dose indicators: mechanisms of studies and practical applications; Les dommages membranaires radio-induits comme bio-indicateurs de dose: etudes des mecanismes et applications pratiques

    Energy Technology Data Exchange (ETDEWEB)

    Vincent-Genod, Lucie

    2001-10-15

    After an accidental overexposure, the assessment of the received dose in biological dosimetry is performed by a method based on the effects of irradiation on the DNA molecule. But this technique shows some limitations; therefore we tried to find new bio-sensors of radiation exposure. We have pointed out that membrane is a critical target of ionising radiation after an in vitro and in vivo overexposure. In vitro, these modifications were involved in the radio-induced apoptotic pathway. The measure of membrane fluidity allowed us to obtain an overall view of cellular membrane. Moreover, in vivo, by changing the lipid nutritional status of animals, our results displayed the important role played by membrane lipid composition in radio-induced membrane alterations. Besides, membrane effects were adjusted by the extracellular physiological control, and in particular by the damages on membrane fatty acid pattern. Finally, we have tested the use of membrane fluidity index as a bio-sensor of radiation exposure on in vivo models and blood samples from medical total body irradiated patients. The results achieved on animal models suggested that the membrane fluidity index was a bio-sensor of radiation exposure. Nevertheless, the observations realised on patients highlight that the effect of the first dose fraction of the radiotherapy treatment had some difficulties to be noticed. Indeed, the combined treatment: chemotherapy and radiotherapy disturbed the membrane fluidity index measures. To conclude, whereas this parameter was not a bio-sensor of irradiation exposure usable in biological dosimetry, it may allow us to assess the radio-induced damages and their cellular but also tissue impacts. (author)

  17. Optimization of dose distribution for the system of linear accelerator-based stereotactic radiosurgery

    International Nuclear Information System (INIS)

    Suh Taesuk.

    1990-01-01

    This work addresses a method for obtaining an optimal dose distribution of stereotactic radiosurgery. Since stereotactic radiosurgery utilizes multiple noncoplanar arcs and a three-dimensional dose evaluation technique, many beam parameters and complex optimization criteria are included in the dose optimization. Consequently, a lengthy computation time is required to optimize even the simplest case by a trial and error method. The basic approach presented here is to use both an analytical and an experimental optimization to minimize the dose to critical organs while maintaining a dose shaped to the target. The experimental approach is based on shaping the target volumes using multiple isocenters from dose experience, or on field shaping using a beam's eye view technique. The analytical approach is to adapt computer-aided design optimization to find optimum parameters automatically. Three-dimensional approximate dose models are developed to simulate the exact dose model using a spherical or cylindrical coordinate system. Optimum parameters are found much faster with the use of computer-aided design optimization techniques. The implementation of computer-aided design algorithms with the approximate dose model and the application of the algorithms to several cases are discussed. It is shown that the approximate dose model gives dose distributions similar to those of the exact dose model, which makes the approximate dose model an attractive alternative to the exact dose model, and much more efficient in terms of computer-aided design and visual optimization

  18. Effect of low dose radiation (LDR) on biological activity of NK cell

    International Nuclear Information System (INIS)

    Yang Liyun; Lin Meixiong; Luo Min; Ran Min; Liang Xuefei

    2006-01-01

    Objective: To study the in vitro and in vivo effect of LDR on the proliferation and killing activity of mouse NK cells with exploitation of the related mechanism of signal transduction. The effect of infused NK cells on inhibiton of oncogenesis and tumor burden regression was also studied. Methods: Mononuclear cells extracted from mouse spleen were treated with immunomagnetic bead for the isolation of CD3 - /CD16 + , CD56 + cells. After verified with flowcytometry, these NK cells were cultured with mice splenic cells (irradiated with 20Gy 60 Co gamma ray) as feeder cells and rhIL-2 as induction factor for 3 rounds (5 days each round). Specimens of cultured NK cells were treated with different doses of radiation (25mGy, 75mGy, 200mGy, 500mGy), the proliferation index (PI) with tumoreidal activity on K562 cells (with 3 H-TdR) incorporation was examined at 4h, 24h, 48h, 72h after irradiation respectively. The role of P38MAPK signal pathway in the LDR effect was examined with adding either inhibitor (SB203580) or activator (P79350) of P38MAPK into the culture and measuring the PI, Killing activity (as expression of the related factors IFN-gamma, FasL, perforin) of NK cells thereafter. The in vivo test involved exposing mice to whole body 25mGy irradiation, harvesting splenic NK cells at 4h, 24h, 48h, 72h later respectively and performing the above-described in vitro procedures. Inhibition of oncogenesis was examined in vivo with infusion of cultured NK cells (LDR treated vs LDR non-treated) 10 days after infusion of K562 cells into mice and examination of hepatic/splenic CD 13+ , S-stage cells and peripheral blood tumor cells in the sacrificed animal another 10 days later. Also, K562 cells were innoculated subcutaneously into mice. After tumor nodule formation (2.0 x 2.0 mm), NK cells (LDR treated vs non-treated) were infused and regression of the tumor nodule with the weight of hepatic tumor mass was noticed in sacrificed animals on d 8 and the survival rate on d 40

  19. SU-F-T-335: Piecewise Uniform Dose Prescription and Optimization Based On PET/CT Images

    Energy Technology Data Exchange (ETDEWEB)

    Liu, G; Liu, J [Hunan University, Changsha, Hunan (China)

    2016-06-15

    Purpose: In intensity modulated radiation therapy (IMRT), the tumor target volume is given a uniform dose prescription, which does not consider the heterogeneous characteristics of tumor such as hypoxia, clonogen density, radiosensitivity, tumor proliferation rate and so on. Our goal is to develop a nonuniform target dose prescription method which can spare organs at risk (OARs) better and does not decrease the tumor control probability (TCP). Methods: We propose a piecewise uniform dose prescription (PUDP) based on PET/CT images of tumor. First, we propose to delineate biological target volumes (BTV) and sub-biological target volumes (sub-BTVs) by our Hierarchical Mumford-Shah Vector Model based on PET/CT images of tumor. Then, in order to spare OARs better, we make the BTV mean dose minimized while restrict the TCP to a constant. So, we can get a general formula for determining an optimal dose prescription based on a linearquadratic model (LQ). However, this dose prescription is high heterogeneous, it is very difficult to deliver by IMRT. Therefore we propose to use the equivalent uniform dose (EUD) in each sub-BTV as its final dose prescription, which makes a PUDP for the BTV. Results: We have evaluated the IMRT planning of a patient with nasopharyngeal carcinoma respectively using PUDP and UDP. The results show that the highest and mean doses inside brain stem are 48.425Gy and 19.151Gy respectively when the PUDP is used for IMRT planning, while they are 52.975Gy and 20.0776Gy respectively when the UDP is used. Both of the resulting TCPs(0.9245, 0.9674) are higher than the theoretical TCP(0.8739), when 70Gy is delivered to the BTV. Conclusion: Comparing with the UDP, the PUDP can spare the OARs better while the resulting TCP by PUDP is not significantly lower than by UDP. This work was supported in part by National Natural Science Foundation of China undergrant no.61271382 and by the foundation for construction of scientific project platform forthe cancer

  20. SU-F-T-335: Piecewise Uniform Dose Prescription and Optimization Based On PET/CT Images

    International Nuclear Information System (INIS)

    Liu, G; Liu, J

    2016-01-01

    Purpose: In intensity modulated radiation therapy (IMRT), the tumor target volume is given a uniform dose prescription, which does not consider the heterogeneous characteristics of tumor such as hypoxia, clonogen density, radiosensitivity, tumor proliferation rate and so on. Our goal is to develop a nonuniform target dose prescription method which can spare organs at risk (OARs) better and does not decrease the tumor control probability (TCP). Methods: We propose a piecewise uniform dose prescription (PUDP) based on PET/CT images of tumor. First, we propose to delineate biological target volumes (BTV) and sub-biological target volumes (sub-BTVs) by our Hierarchical Mumford-Shah Vector Model based on PET/CT images of tumor. Then, in order to spare OARs better, we make the BTV mean dose minimized while restrict the TCP to a constant. So, we can get a general formula for determining an optimal dose prescription based on a linearquadratic model (LQ). However, this dose prescription is high heterogeneous, it is very difficult to deliver by IMRT. Therefore we propose to use the equivalent uniform dose (EUD) in each sub-BTV as its final dose prescription, which makes a PUDP for the BTV. Results: We have evaluated the IMRT planning of a patient with nasopharyngeal carcinoma respectively using PUDP and UDP. The results show that the highest and mean doses inside brain stem are 48.425Gy and 19.151Gy respectively when the PUDP is used for IMRT planning, while they are 52.975Gy and 20.0776Gy respectively when the UDP is used. Both of the resulting TCPs(0.9245, 0.9674) are higher than the theoretical TCP(0.8739), when 70Gy is delivered to the BTV. Conclusion: Comparing with the UDP, the PUDP can spare the OARs better while the resulting TCP by PUDP is not significantly lower than by UDP. This work was supported in part by National Natural Science Foundation of China undergrant no.61271382 and by the foundation for construction of scientific project platform forthe cancer

  1. A hybrid evolutionary algorithm for multi-objective anatomy-based dose optimization in high-dose-rate brachytherapy

    International Nuclear Information System (INIS)

    Lahanas, M; Baltas, D; Zamboglou, N

    2003-01-01

    Multiple objectives must be considered in anatomy-based dose optimization for high-dose-rate brachytherapy and a large number of parameters must be optimized to satisfy often competing objectives. For objectives expressed solely in terms of dose variances, deterministic gradient-based algorithms can be applied and a weighted sum approach is able to produce a representative set of non-dominated solutions. As the number of objectives increases, or non-convex objectives are used, local minima can be present and deterministic or stochastic algorithms such as simulated annealing either cannot be used or are not efficient. In this case we employ a modified hybrid version of the multi-objective optimization algorithm NSGA-II. This, in combination with the deterministic optimization algorithm, produces a representative sample of the Pareto set. This algorithm can be used with any kind of objectives, including non-convex, and does not require artificial importance factors. A representation of the trade-off surface can be obtained with more than 1000 non-dominated solutions in 2-5 min. An analysis of the solutions provides information on the possibilities available using these objectives. Simple decision making tools allow the selection of a solution that provides a best fit for the clinical goals. We show an example with a prostate implant and compare results obtained by variance and dose-volume histogram (DVH) based objectives

  2. Biologically based neural network for mobile robot navigation

    Science.gov (United States)

    Torres Muniz, Raul E.

    1999-01-01

    The new tendency in mobile robots is to crete non-Cartesian system based on reactions to their environment. This emerging technology is known as Evolutionary Robotics, which is combined with the Biorobotic field. This new approach brings cost-effective solutions, flexibility, robustness, and dynamism into the design of mobile robots. It also provides fast reactions to the sensory inputs, and new interpretation of the environment or surroundings of the mobile robot. The Subsumption Architecture (SA) and the action selection dynamics developed by Brooks and Maes, respectively, have successfully obtained autonomous mobile robots initiating this new trend of the Evolutionary Robotics. Their design keeps the mobile robot control simple. This work present a biologically inspired modification of these schemes. The hippocampal-CA3-based neural network developed by Williams Levy is used to implement the SA, while the action selection dynamics emerge from iterations of the levels of competence implemented with the HCA3. This replacement by the HCA3 results in a closer biological model than the SA, combining the Behavior-based intelligence theory with neuroscience. The design is kept simple, and it is implemented in the Khepera Miniature Mobile Robot. The used control scheme obtains an autonomous mobile robot that can be used to execute a mail delivery system and surveillance task inside a building floor.

  3. Biological and chemical sensors based on graphene materials.

    Science.gov (United States)

    Liu, Yuxin; Dong, Xiaochen; Chen, Peng

    2012-03-21

    Owing to their extraordinary electrical, chemical, optical, mechanical and structural properties, graphene and its derivatives have stimulated exploding interests in their sensor applications ever since the first isolation of free-standing graphene sheets in year 2004. This article critically and comprehensively reviews the emerging graphene-based electrochemical sensors, electronic sensors, optical sensors, and nanopore sensors for biological or chemical detection. We emphasize on the underlying detection (or signal transduction) mechanisms, the unique roles and advantages of the used graphene materials. Properties and preparations of different graphene materials, their functionalizations are also comparatively discussed in view of sensor development. Finally, the perspective and current challenges of graphene sensors are outlined (312 references).

  4. Learning Cell Biology as a Team: A Project-Based Approach to Upper-Division Cell Biology

    Science.gov (United States)

    Wright, Robin; Boggs, James

    2002-01-01

    To help students develop successful strategies for learning how to learn and communicate complex information in cell biology, we developed a quarter-long cell biology class based on team projects. Each team researches a particular human disease and presents information about the cellular structure or process affected by the disease, the cellular…

  5. Monte Carlo-based dose reconstruction in a rat model for scattered ionizing radiation investigations.

    Science.gov (United States)

    Kirkby, Charles; Ghasroddashti, Esmaeel; Kovalchuk, Anna; Kolb, Bryan; Kovalchuk, Olga

    2013-09-01

    In radiation biology, rats are often irradiated, but the precise dose distributions are often lacking, particularly in areas that receive scatter radiation. We used a non-dedicated set of resources to calculate detailed dose distributions, including doses to peripheral organs well outside of the primary field, in common rat exposure settings. We conducted a detailed dose reconstruction in a rat through an analog to the conventional human treatment planning process. The process consisted of: (i) Characterizing source properties of an X-ray irradiator system, (ii) acquiring a computed tomography (CT) scan of a rat model, and (iii) using a Monte Carlo (MC) dose calculation engine to generate the dose distribution within the rat model. We considered cranial and liver irradiation scenarios where the rest of the body was protected by a lead shield. Organs of interest were the brain, liver and gonads. The study also included paired scenarios where the dose to adjacent, shielded rats was determined as a potential control for analysis of bystander effects. We established the precise doses and dose distributions delivered to the peripheral organs in single and paired rats. Mean doses to non-targeted organs in irradiated rats ranged from 0.03-0.1% of the reference platform dose. Mean doses to the adjacent rat peripheral organs were consistent to within 10% those of the directly irradiated rat. This work provided details of dose distributions in rat models under common irradiation conditions and established an effective scenario for delivering only scattered radiation consistent with that in a directly irradiated rat.

  6. Quantification of dose uncertainties for the bladder in prostate cancer radiotherapy based on dominant eigenmodes

    Science.gov (United States)

    Rios, Richard; Acosta, Oscar; Lafond, Caroline; Espinosa, Jairo; de Crevoisier, Renaud

    2017-11-01

    In radiotherapy for prostate cancer the dose at the treatment planning for the bladder may be a bad surrogate of the actual delivered dose as the bladder presents the largest inter-fraction shape variations during treatment. This paper presents PCA models as a virtual tool to estimate dosimetric uncertainties for the bladder produced by motion and deformation between fractions. Our goal is to propose a methodology to determine the minimum number of modes required to quantify dose uncertainties of the bladder for motion/deformation models based on PCA. We trained individual PCA models using the bladder contours available from three patients with a planning computed tomography (CT) and on-treatment cone-beam CTs (CBCTs). Based on the above models and via deformable image registration (DIR), we estimated two accumulated doses: firstly, an accumulated dose obtained by integrating the planning dose over the Gaussian probability distribution of the PCA model; and secondly, an accumulated dose obtained by simulating treatment courses via a Monte Carlo approach. We also computed a reference accumulated dose for each patient using his available images via DIR. Finally, we compared the planning dose with the three accumulated doses, and we calculated local dose variability and dose-volume histogram uncertainties.

  7. PTTL Dose Re-estimation Applied to Quality Control in TLD-100 Based Personal Dosimetry

    International Nuclear Information System (INIS)

    Muniz, J.L.; Correcher, V.; Delgado, A.

    1999-01-01

    A new method for quality control of dose performance in Personal Dosimetry using TLD-100 is presented. This method consists of the application of dose reassessment techniques based on phototransferred thermoluminescence (PTTL). Reassessment is achieved through a second TL readout of the dosemeters worn by the controlled workers, after a reproducible UV exposure. Recent refinements in the PTTL technique developed in our laboratory allow reassessing doses as low as 0.2 mSv, thus extending the reassessment capability to the entire dose range that must be monitored in personal dosimetry. After a one month exposure, even purely environmental doses can be reassessed. This method can be applied for either re-estimation of single doses or of the total dose accumulated after a number of exposures and dose measurements. Several tests to reconfirm low doses in normal working conditions for personal dosimetry have been performed. Each test consisted of several cycles of exposure and TL evaluations and a final PTTL re-estimation of the total accumulated dose in those cycles. The results obtained always showed very good agreement between the sum of the partial doses and the total reassessed dose. The simplicity of the method and the possibility of re-evaluating the doses assessed to the workers employing their own dosemeters are advantageous features to be considered in designing systems for the determination of real performance in personal dosimetry. (author)

  8. Application of Biologically-Based Lumping To Investigate the ...

    Science.gov (United States)

    People are often exposed to complex mixtures of environmental chemicals such as gasoline, tobacco smoke, water contaminants, or food additives. However, investigators have often considered complex mixtures as one lumped entity. Valuable information can be obtained from these experiments, though this simplification provides little insight into the impact of a mixture's chemical composition on toxicologically-relevant metabolic interactions that may occur among its constituents. We developed an approach that applies chemical lumping methods to complex mixtures, in this case gasoline, based on biologically relevant parameters used in physiologically-based pharmacokinetic (PBPK) modeling. Inhalation exposures were performed with rats to evaluate performance of our PBPK model. There were 109 chemicals identified and quantified in the vapor in the chamber. The time-course kinetic profiles of 10 target chemicals were also determined from blood samples collected during and following the in vivo experiments. A general PBPK model was used to compare the experimental data to the simulated values of blood concentration for the 10 target chemicals with various numbers of lumps, iteratively increasing from 0 to 99. Large reductions in simulation error were gained by incorporating enzymatic chemical interactions, in comparison to simulating the individual chemicals separately. The error was further reduced by lumping the 99 non-target chemicals. Application of this biologic

  9. Clinical significance of cumulative biological effective dose and overall treatment time in the treatment of carcinoma cervix

    Directory of Open Access Journals (Sweden)

    Mandal Abhijit

    2007-01-01

    Full Text Available The purpose of this retrospective study is to report the radiotherapy treatment response of, and complications in, patients with cervical cancer on the basis of cumulative biologic effective dose (BED and overall treatment time (OTT. Sixty-four (stage II - 35/64; stage III - 29/64 patients of cervical cancer were treated with combination of external beam radiotherapy (EBRT and low dose rate intracavitary brachytherapy (ICBT. The cumulative BED was calculated at Point A (BED 10 ; and bladder, rectal reference points (BED 2.5 using the linear-quadratic BED equations. The local control (LC rate and 5-year disease-free survival (DFS rate in patients of stage II were comparable for BED 10 < 84.5 and BED 10 > 84.5 but were much higher for BED 10 > 84.5 than BED 10 < 84.5 ( P < 0.01 in stage III patients. In the stage II patients, The LC rate and 5-year DFS rate were comparable for OTT < 50 days and for OTT> 50 days but were much higher in stage III patients with OTT < 50 than OTT> 50 days ( P < 0.001. It was also observed that patients who received BED 2.5 < 105 had lesser rectal ( P < 0.001 and bladder complications than BED 2.5 > 105. Higher rectal complication-free survival (CFS R rate, bladder complication-free survival (CFS B rate and all-type late complication-free survival rate were observed in patients who received BED 2.5 < 105 than BED 2.5 > 105. A balanced, optimal and justified radiotherapy treatment schedule to deliver higher BED 10 (>84.5 and lower BED 2.5 (< 105 in lesser OTT (< 50 days is essential in carcinoma cervix to expect a better treatment outcome in all respects.

  10. The Biological Responses to Magnesium-Based Biodegradable Medical Devices

    Directory of Open Access Journals (Sweden)

    Lumei Liu

    2017-11-01

    Full Text Available The biocompatibility of Magnesium-based materials (MBMs is critical to the safety of biodegradable medical devices. As a promising metallic biomaterial for medical devices, the issue of greatest concern is devices’ safety as degrading products are possibly interacting with local tissue during complete degradation. The aim of this review is to summarize the biological responses to MBMs at the cellular/molecular level, including cell adhesion, transportation signaling, immune response, and tissue growth during the complex degradation process. We review the influence of MBMs on gene/protein biosynthesis and expression at the site of implantation, as well as throughout the body. This paper provides a systematic review of the cellular/molecular behavior of local tissue on the response to Mg degradation, which may facilitate a better prediction of long-term degradation and the safe use of magnesium-based implants through metal innovation.

  11. WORKSHOP ON APPLICATION OF STATISTICAL METHODS TO BIOLOGICALLY-BASED PHARMACOKINETIC MODELING FOR RISK ASSESSMENT

    Science.gov (United States)

    Biologically-based pharmacokinetic models are being increasingly used in the risk assessment of environmental chemicals. These models are based on biological, mathematical, statistical and engineering principles. Their potential uses in risk assessment include extrapolation betwe...

  12. Determination of the dose of gamma radiation sterilization for assessment of biological parameters of male Ceratitis capitada (Diptera: Tephritidae), tsl - Vienna 8 strain

    International Nuclear Information System (INIS)

    Rocha, Aline Cristina Pereira da

    2011-01-01

    The Vienna-8, tsl (temperature sensitive lethal) strain of Ceratitis capitata, by presenting mutations that facilitate the mass rearing and release only of sterile males in the field, has been used in (Sterile Insect Technique) programmes. The objective of this study was to determine the radiation dose that provides the highest level of sterility for Vienna-8, tsl males assessing their biological parameters that indicate the quality of sterile males to be released. Brown pupae (males) of the tsl strain were obtained from the mass rearing of the Food Irradiation and Radio entomology laboratory of CENA/USP, and they were irradiated (with gamma radiation - 60 Co) 24 hours before the emergence at rates of 0, 30, 60, 90 and 120 Gy. The determination of the sterilizing dose was based on fertility of sexually mature females of the bisexual strain and not irradiated, mated with males of different treatments. Eggs were collected daily during 6 days, were counted and it was possible to estimate fecundity, and assess the hatching rate. The emergence and flight ability were determined by following the protocol of quality control manual for FAO/IAEA/USDA (2003). To assess the longevity under nutritional stress, the insects were kept a period of 48 h after emergence in the absence of water and food, and after this period, mortality was recorded. The size of the testes (left and right) was obtained by dissecting irradiated and non-irradiated males at the eighth day of life, and measure the testes in an ocular micrometer, considering the maximum length and width of each sample. To determine the sperm number was necessary to dissect the males and break their testicles. No difference was observed in emergence rate, flight ability and longevity of irradiated and non-irradiated males, nor in the fecundity of females mated with males of different treatments. The sterilizing dose that resulted in lower fertility of females was 120 Gy, with 1.5% hatching. Considering the parameters of

  13. Data base of dose coefficients called ecrin-V1-internet reference handbook; Base de donnees de coefficients de dose ecrin-V1-internet manuel de reference

    Energy Technology Data Exchange (ETDEWEB)

    Perrin, M.L

    2003-07-01

    The objective of this data base is to dispose on a only computer medium the values of radiation doses allowing to guarantee the tracing and the coherence of radiation doses received by man. These data are usable to evaluate the risks in the frame of studies or expertise. They include the doses coming from external irradiations, internal contamination by inhalation or ingestion and receive by workers or public. The definitions and reference values come from international publications (the list is given). (N.C.)

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

    DEFF Research Database (Denmark)

    Christiansen, E; Goldney, R D; Beautrai, A L

    2011-01-01

    BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk for suic......BACKGROUND: There is a lack of specific knowledge about the dose-response effect of multiple parental risk factors for suicide attempts among children and adolescents. The aim of this study was to determine the dose-response effect of multiple parental risk factors on an offspring's risk...... for suicide attempt.MethodWe designed a population-based two-generation nested case-control study and used Danish register data. A population of 403 431 individuals born between 1983 and 1989 was sampled. Among these, 3465 (0.8%) were registered as having had a suicide attempt. Twenty controls were matched...... to each case and a link to the offspring's biological parents was established. RESULTS: There was a dose-response relationship between the number of exposures and the risk of suicide attempts, with the increased risk seeming to be a multiplicative effect. Parental suicide, suicide attempt, psychiatric...

  15. Assessment of beta-emitter radionuclides in biological samples using liquid scintillation counting. Application to the study of internal doses in molecular and cellular biology techniques

    International Nuclear Information System (INIS)

    Sierra, I.; Delgado, A.; Navarro, T.; Macias, M. T.

    2007-01-01

    The radioisotopic techniques used in Molecular and Cellular Biology involve external and internal irradiation risk. It is necessary to control the possible internal contamination associated to the development of these techniques. The internal contamination risk can be due to physical and chemical properties of the labelled compounds, aerosols generated during the performance technique. The aim of this work was to estimate the possible intake of specific beta emitters during the technique development and to propose the required criterions to perform Individual Monitoring. The most representative radioisotopic techniques were selected attending their potential risk of internal contamination. Techniques were analysed applying IAEA methodology according to the used activity in each technique. It was necessary to identify the worker groups that would require individual monitoring on the base of their specific risk. Different measurement procedures were applied to study the possible intake in group risk and more than 160 persons were measured by in vitro bioassay. (Author) 96 refs

  16. Value-Based Medicine and Integration of Tumor Biology.

    Science.gov (United States)

    Brooks, Gabriel A; Bosserman, Linda D; Mambetsariev, Isa; Salgia, Ravi

    2017-01-01

    Clinical oncology is in the midst of a genomic revolution, as molecular insights redefine our understanding of cancer biology. Greater awareness of the distinct aberrations that drive carcinogenesis is also contributing to a growing armamentarium of genomically targeted therapies. Although much work remains to better understand how to combine and sequence these therapies, improved outcomes for patients are becoming manifest. As we welcome this genomic revolution in cancer care, oncologists also must grapple with a number of practical problems. Costs of cancer care continue to grow, with targeted therapies responsible for an increasing proportion of spending. Rising costs are bringing the concept of value into sharper focus and challenging the oncology community with implementation of value-based cancer care. This article explores the ways that the genomic revolution is transforming cancer care, describes various frameworks for considering the value of genomically targeted therapies, and outlines key challenges for delivering on the promise of personalized cancer care. It highlights practical solutions for the implementation of value-based care, including investment in biomarker development and clinical trials to improve the efficacy of targeted therapy, the use of evidence-based clinical pathways, team-based care, computerized clinical decision support, and value-based payment approaches.

  17. Sensors of absorbed dose of ionizing radiation based on mosfet

    Directory of Open Access Journals (Sweden)

    Perevertaylo V. L.

    2010-10-01

    Full Text Available The requirements to technology and design of p-channel and n-channel MOS transistors with a thick oxide layer designed for use in the capacity of integral dosimeters of absorbed dose of ionizing radiation are defined. The technology of radiation-sensitive MOS transistors with a thick oxide in the p-channel and n-channel version is created.

  18. A systems biology-based classifier for hepatocellular carcinoma diagnosis.

    Directory of Open Access Journals (Sweden)

    Yanqiong Zhang

    Full Text Available AIM: The diagnosis of hepatocellular carcinoma (HCC in the early stage is crucial to the application of curative treatments which are the only hope for increasing the life expectancy of patients. Recently, several large-scale studies have shed light on this problem through analysis of gene expression profiles to identify markers correlated with HCC progression. However, those marker sets shared few genes in common and were poorly validated using independent data. Therefore, we developed a systems biology based classifier by combining the differential gene expression with topological features of human protein interaction networks to enhance the ability of HCC diagnosis. METHODS AND RESULTS: In the Oncomine platform, genes differentially expressed in HCC tissues relative to their corresponding normal tissues were filtered by a corrected Q value cut-off and Concept filters. The identified genes that are common to different microarray datasets were chosen as the candidate markers. Then, their networks were analyzed by GeneGO Meta-Core software and the hub genes were chosen. After that, an HCC diagnostic classifier was constructed by Partial Least Squares modeling based on the microarray gene expression data of the hub genes. Validations of diagnostic performance showed that this classifier had high predictive accuracy (85.88∼92.71% and area under ROC curve (approximating 1.0, and that the network topological features integrated into this classifier contribute greatly to improving the predictive performance. Furthermore, it has been demonstrated that this modeling strategy is not only applicable to HCC, but also to other cancers. CONCLUSION: Our analysis suggests that the systems biology-based classifier that combines the differential gene expression and topological features of human protein interaction network may enhance the diagnostic performance of HCC classifier.

  19. SU-F-J-194: Development of Dose-Based Image Guided Proton Therapy Workflow

    Energy Technology Data Exchange (ETDEWEB)

    Pham, R; Sun, B; Zhao, T; Li, H; Yang, D; Grantham, K; Goddu, S; Santanam, L; Bradley, J; Mutic, S; Kandlakunta, P; Zhang, T [Washington University School of Medicine, Saint Louis, MO (United States)

    2016-06-15

    Purpose: To implement image-guided proton therapy (IGPT) based on daily proton dose distribution. Methods: Unlike x-ray therapy, simple alignment based on anatomy cannot ensure proper dose coverage in proton therapy. Anatomy changes along the beam path may lead to underdosing the target, or overdosing the organ-at-risk (OAR). With an in-room mobile computed tomography (CT) system, we are developing a dose-based IGPT software tool that allows patient positioning and treatment adaption based on daily dose distributions. During an IGPT treatment, daily CT images are acquired in treatment position. After initial positioning based on rigid image registration, proton dose distribution is calculated on daily CT images. The target and OARs are automatically delineated via deformable image registration. Dose distributions are evaluated to decide if repositioning or plan adaptation is necessary in order to achieve proper coverage of the target and sparing of OARs. Besides online dose-based image guidance, the software tool can also map daily treatment doses to the treatment planning CT images for offline adaptive treatment. Results: An in-room helical CT system is commissioned for IGPT purposes. It produces accurate CT numbers that allow proton dose calculation. GPU-based deformable image registration algorithms are developed and evaluated for automatic ROI-delineation and dose mapping. The online and offline IGPT functionalities are evaluated with daily CT images of the proton patients. Conclusion: The online and offline IGPT software tool may improve the safety and quality of proton treatment by allowing dose-based IGPT and adaptive proton treatments. Research is partially supported by Mevion Medical Systems.

  20. Absence of hydrocortisone from cytoplasmic hormone-protein complexes formed in vivo after administration of biologically active doses of [3H] hydrocortisone

    International Nuclear Information System (INIS)

    Voigt, J.; Grote, H.; Sekeris, C.E.

    1981-01-01

    After administration of [ 3 H] hydrocortisone to adrenalectomized rats, hormone-protein complexes were isolated from liver cytosol by DEAE-cellulose chromatography. After application of biologically active and inactive doses of hydrocortisone five binding components were detected eluting at the same salt concentrations as the hormone-protein complexes observed after incubation of cytosol with [ 3 H] hydrocortisone in vitro. The isolated hormone-protein fractions were acidified and extracted with ethylacetate and the steroids were analyzed by thin-layer chromatography. No significant amount of hydrocortisone could be detected in any of the complexes formed in vivo 5-60 min after administration of biologically active doses of hydrocortisone. 3xi,11β,17α,20xi, 21-Pentahydroxypregnane, steroidal carboxy acids, glucuronides and a very polar conjugate of hydrocortisone were found in the different fractions. After an in vivo dose of hydrocortisone of about 1/5000th of the minimal dose required for enzyme induction, hydrocortisone could be found in all the cytoplasmic hormone-protein complexes formed. In contrast to the cytoplasmic hormone-protein complexes, hydrocortisone could be readily demonstrated in nuclei isolated after the administration of biologically active doses of hormone, although acid metabolites were found to represent the main part of the radioactive compounds present in the nuclei. These acid metabolites were located in the nuclear envelope. (orig.)

  1. The Fukushima nuclear accident and the pale grass blue butterfly: evaluating biological effects of long-term low-dose exposures.

    Science.gov (United States)

    Hiyama, Atsuki; Nohara, Chiyo; Taira, Wataru; Kinjo, Seira; Iwata, Masaki; Otaki, Joji M

    2013-08-12

    resistant to short-term high-dose irradiation. This discrepancy is reconcilable based on the differences in the experimental conditions. We are just beginning to understand the biological effects of long-term low-dose exposures in animals. Further research is necessary to accurately assess the possible biological effects of the accident.

  2. 4D cone beam CT-based dose assessment for SBRT lung cancer treatment

    International Nuclear Information System (INIS)

    Cai, Weixing; Dhou, Salam; Cifter, Fulya; Myronakis, Marios; Hurwitz, Martina H; Williams, Christopher L; Berbeco, Ross I; Seco, Joao; Lewis, John H

    2016-01-01

    The purpose of this research is to develop a 4DCBCT-based dose assessment method for calculating actual delivered dose for patients with significant respiratory motion or anatomical changes during the course of SBRT. To address the limitation of 4DCT-based dose assessment, we propose to calculate the delivered dose using time-varying (‘fluoroscopic’) 3D patient images generated from a 4DCBCT-based motion model. The method includes four steps: (1) before each treatment, 4DCBCT data is acquired with the patient in treatment position, based on which a patient-specific motion model is created using a principal components analysis algorithm. (2) During treatment, 2D time-varying kV projection images are continuously acquired, from which time-varying ‘fluoroscopic’ 3D images of the patient are reconstructed using the motion model. (3) Lateral truncation artifacts are corrected using planning 4DCT images. (4) The 3D dose distribution is computed for each timepoint in the set of 3D fluoroscopic images, from which the total effective 3D delivered dose is calculated by accumulating deformed dose distributions. This approach is validated using six modified XCAT phantoms with lung tumors and different respiratory motions derived from patient data. The estimated doses are compared to that calculated using ground-truth XCAT phantoms. For each XCAT phantom, the calculated delivered tumor dose values generally follow the same trend as that of the ground truth and at most timepoints the difference is less than 5%. For the overall delivered dose, the normalized error of calculated 3D dose distribution is generally less than 3% and the tumor D95 error is less than 1.5%. XCAT phantom studies indicate the potential of the proposed method to accurately estimate 3D tumor dose distributions for SBRT lung treatment based on 4DCBCT imaging and motion modeling. Further research is necessary to investigate its performance for clinical patient data. (paper)

  3. Therapeutic treatment plan optimization with probability density-based dose prescription

    International Nuclear Information System (INIS)

    Lian Jun; Cotrutz, Cristian; Xing Lei

    2003-01-01

    The dose optimization in inverse planning is realized under the guidance of an objective function. The prescription doses in a conventional approach are usually rigid values, defining in most instances an ill-conditioned optimization problem. In this work, we propose a more general dose optimization scheme based on a statistical formalism [Xing et al., Med. Phys. 21, 2348-2358 (1999)]. Instead of a rigid dose, the prescription to a structure is specified by a preference function, which describes the user's preference over other doses in case the most desired dose is not attainable. The variation range of the prescription dose and the shape of the preference function are predesigned by the user based on prior clinical experience. Consequently, during the iterative optimization process, the prescription dose is allowed to deviate, with a certain preference level, from the most desired dose. By not restricting the prescription dose to a fixed value, the optimization problem becomes less ill-defined. The conventional inverse planning algorithm represents a special case of the new formalism. An iterative dose optimization algorithm is used to optimize the system. The performance of the proposed technique is systematically studied using a hypothetical C-shaped tumor with an abutting circular critical structure and a prostate case. It is shown that the final dose distribution can be manipulated flexibly by tuning the shape of the preference function and that using a preference function can lead to optimized dose distributions in accordance with the planner's specification. The proposed framework offers an effective mechanism to formalize the planner's priorities over different possible clinical scenarios and incorporate them into dose optimization. The enhanced control over the final plan may greatly facilitate the IMRT treatment planning process

  4. Convolution-based estimation of organ dose in tube current modulated CT

    Science.gov (United States)

    Tian, Xiaoyu; Segars, W. Paul; Dixon, Robert L.; Samei, Ehsan

    2016-05-01

    Estimating organ dose for clinical patients requires accurate modeling of the patient anatomy and the dose field of the CT exam. The modeling of patient anatomy can be achieved using a library of representative computational phantoms (Samei et al 2014 Pediatr. Radiol. 44 460-7). The modeling of the dose field can be challenging for CT exams performed with a tube current modulation (TCM) technique. The purpose of this work was to effectively model the dose field for TCM exams using a convolution-based method. A framework was further proposed for prospective and retrospective organ dose estimation in clinical practice. The study included 60 adult patients (age range: 18-70 years, weight range: 60-180 kg). Patient-specific computational phantoms were generated based on patient CT image datasets. A previously validated Monte Carlo simulation program was used to model a clinical CT scanner (SOMATOM Definition Flash, Siemens Healthcare, Forchheim, Germany). A practical strategy was developed to achieve real-time organ dose estimation for a given clinical patient. CTDIvol-normalized organ dose coefficients ({{h}\\text{Organ}} ) under constant tube current were estimated and modeled as a function of patient size. Each clinical patient in the library was optimally matched to another computational phantom to obtain a representation of organ location/distribution. The patient organ distribution was convolved with a dose distribution profile to generate {{≤ft(\\text{CTD}{{\\text{I}}\\text{vol}}\\right)}\\text{organ, \\text{convolution}}} values that quantified the regional dose field for each organ. The organ dose was estimated by multiplying {{≤ft(\\text{CTD}{{\\text{I}}\\text{vol}}\\right)}\\text{organ, \\text{convolution}}} with the organ dose coefficients ({{h}\\text{Organ}} ). To validate the accuracy of this dose estimation technique, the organ dose of the original clinical patient was estimated using Monte Carlo program with TCM profiles explicitly modeled. The

  5. Incidence of late rectal bleeding in high-dose conformal radiotherapy of prostate cancer using equivalent uniform dose-based and dose-volume-based normal tissue complication probability models

    International Nuclear Information System (INIS)

    Soehn, Matthias; Yan Di; Liang Jian; Meldolesi, Elisa; Vargas, Carlos; Alber, Markus

    2007-01-01

    Purpose: Accurate modeling of rectal complications based on dose-volume histogram (DVH) data are necessary to allow safe dose escalation in radiotherapy of prostate cancer. We applied different equivalent uniform dose (EUD)-based and dose-volume-based normal tissue complication probability (NTCP) models to rectal wall DVHs and follow-up data for 319 prostate cancer patients to identify the dosimetric factors most predictive for Grade ≥ 2 rectal bleeding. Methods and Materials: Data for 319 patients treated at the William Beaumont Hospital with three-dimensional conformal radiotherapy (3D-CRT) under an adaptive radiotherapy protocol were used for this study. The following models were considered: (1) Lyman model and (2) logit-formula with DVH reduced to generalized EUD (3) serial reconstruction unit (RU) model (4) Poisson-EUD model, and (5) mean dose- and (6) cutoff dose-logistic regression model. The parameters and their confidence intervals were determined using maximum likelihood estimation. Results: Of the patients, 51 (16.0%) showed Grade 2 or higher bleeding. As assessed qualitatively and quantitatively, the Lyman- and Logit-EUD, serial RU, and Poisson-EUD model fitted the data very well. Rectal wall mean dose did not correlate to Grade 2 or higher bleeding. For the cutoff dose model, the volume receiving > 73.7 Gy showed most significant correlation to bleeding. However, this model fitted the data more poorly than the EUD-based models. Conclusions: Our study clearly confirms a volume effect for late rectal bleeding. This can be described very well by the EUD-like models, of which the serial RU- and Poisson-EUD model can describe the data with only two parameters. Dose-volume-based cutoff-dose models performed worse

  6. What is infidelity? Perceptions based on biological sex and personality

    Science.gov (United States)

    Thornton, Victoria; Nagurney, Alexander

    2011-01-01

    The study examines perceptions of infidelity, paying particular attention to how these perceptions differ based on biological sex and personality traits, specifically agency and communion and their unmitigated counterparts. The study utilizes a sample of 125 male and 233 female college students. In addition to the personality measures, participants completed a 19-item checklist that assessed their perceptions of specific items that could potentially be construed as infidelity. It was hypothesized that females would construe more items as infidelity than would males. It was also predicted that unmitigated communion and communion would be positively correlated with these perceptions and that unmitigated agency would be negatively correlated with these perceptions. No correlation was predicted between agency and infidelity. All hypotheses were supported. Implications and suggestions for future research are discussed. PMID:22114535

  7. What is infidelity? Perceptions based on biological sex and personality

    Directory of Open Access Journals (Sweden)

    Thornton V

    2011-05-01

    Full Text Available Victoria Thornton, Alexander NagurneyTexas State University – San Marcos, San Marcos, Texas, USAAbstract: The study examines perceptions of infidelity, paying particular attention to how these perceptions differ based on biological sex and personality traits, specifically agency and communion and their unmitigated counterparts. The study utilizes a sample of 125 male and 233 female college students. In addition to the personality measures, participants completed a 19-item checklist that assessed their perceptions of specific items that could potentially be construed as infidelity. It was hypothesized that females would construe more items as infidelity than would males. It was also predicted that unmitigated communion and communion would be positively correlated with these perceptions and that unmitigated agency would be negatively correlated with these perceptions. No correlation was predicted between agency and infidelity. All hypotheses were supported. Implications and suggestions for future research are discussed.Keywords: infidelity, communion, agency, questionnaire, relationship

  8. Synthetic biology in cell-based cancer immunotherapy.

    Science.gov (United States)

    Chakravarti, Deboki; Wong, Wilson W

    2015-08-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. We first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Independent Monte-Carlo dose calculation for MLC based CyberKnife radiotherapy

    Science.gov (United States)

    Mackeprang, P.-H.; Vuong, D.; Volken, W.; Henzen, D.; Schmidhalter, D.; Malthaner, M.; Mueller, S.; Frei, D.; Stampanoni, M. F. M.; Dal Pra, A.; Aebersold, D. M.; Fix, M. K.; Manser, P.

    2018-01-01

    This work aims to develop, implement and validate a Monte Carlo (MC)-based independent dose calculation (IDC) framework to perform patient-specific quality assurance (QA) for multi-leaf collimator (MLC)-based CyberKnife® (Accuray Inc., Sunnyvale, CA) treatment plans. The IDC framework uses an XML-format treatment plan as exported from the treatment planning system (TPS) and DICOM format patient CT data, an MC beam model using phase spaces, CyberKnife MLC beam modifier transport using the EGS++ class library, a beam sampling and coordinate transformation engine and dose scoring using DOSXYZnrc. The framework is validated against dose profiles and depth dose curves of single beams with varying field sizes in a water tank in units of cGy/Monitor Unit and against a 2D dose distribution of a full prostate treatment plan measured with Gafchromic EBT3 (Ashland Advanced Materials, Bridgewater, NJ) film in a homogeneous water-equivalent slab phantom. The film measurement is compared to IDC results by gamma analysis using 2% (global)/2 mm criteria. Further, the dose distribution of the clinical treatment plan in the patient CT is compared to TPS calculation by gamma analysis using the same criteria. Dose profiles from IDC calculation in a homogeneous water phantom agree within 2.3% of the global max dose or 1 mm distance to agreement to measurements for all except the smallest field size. Comparing the film measurement to calculated dose, 99.9% of all voxels pass gamma analysis, comparing dose calculated by the IDC framework to TPS calculated dose for the clinical prostate plan shows 99.0% passing rate. IDC calculated dose is found to be up to 5.6% lower than dose calculated by the TPS in this case near metal fiducial markers. An MC-based modular IDC framework was successfully developed, implemented and validated against measurements and is now available to perform patient-specific QA by IDC.

  10. A biological-based model that links genomic instability, bystander effects, and adaptive response

    International Nuclear Information System (INIS)

    Scott, B.R.

    2004-01-01

    This paper links genomic instability, bystander effects, and adaptive response in mammalian cell communities via a novel biological-based, dose-response model called NEOTRANS 3 . The model is an extension of the NEOTRANS 2 model that addressed stochastic effects (genomic instability, mutations, and neoplastic transformation) associated with brief exposure to low radiation doses. With both models, ionizing radiation produces DNA damage in cells that can be associated with varying degrees of genomic instability. Cells with persistent problematic instability (PPI) are mutants that arise via misrepair of DNA damage. Progeny of PPI cells also have PPI and can undergo spontaneous neoplastic transformation. Unlike NEOTRANS 2 , with NEOTRANS 3 newly induced mutant PPI cells and their neoplastically transformed progeny can be suppressed via our previously introduced protective apoptosis-mediated (PAM) process, which can be activated by low linear energy transfer (LET) radiation. However, with NEOTRANS 3 (which like NEOTRANS 2 involves cross-talk between nongenomically compromised [e.g., nontransformed, nonmutants] and genomically compromised [e.g., mutants, transformants, etc.] cells), it is assumed that PAM is only activated over a relatively narrow, dose-rate-dependent interval (D PAM ,D off ); where D PAM is a small stochastic activation threshold, and D off is the stochastic dose above which PAM does not occur. PAM cooperates with activated normal DNA repair and with activated normal apoptosis in guarding against genomic instability. Normal repair involves both error-free repair and misrepair components. Normal apoptosis and the error-free component of normal repair protect mammals by preventing the occurrence of mutant cells. PAM selectively removes mutant cells arising via the misrepair component of normal repair, selectively removes existing neoplastically transformed cells, and probably selectively removes other genomically compromised cells when it is activated

  11. Biological Detection System Technologies Technology and Industrial Base Study. A Primer on Biological Detection Technologies

    National Research Council Canada - National Science Library

    2001-01-01

    .... and Canadian military personnel. In light of these concerns both defense departments have increased efforts to develop and field biological agent detection systems to help protect their military forces and fixed assets...

  12. SU-E-T-806: Very Fast GPU-Based IMPT Dose Computation

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, A; Brand, M [Mitsubishi Electric Research Lab, Cambridge, MA (United States)

    2015-06-15

    Purpose: Designing particle therapy treatment plans is a dosimetrist-in-the-loop optimization wherein the conflicting constraints of achieving a desired tumor dose distribution must be balanced against the need to minimize the dose to nearby OARs. IMPT introduces an additional, inner, numerical optimization step in which the dosimetrist’s current set of constraints are used to determine the weighting of beam spots. Very fast dose calculations are needed to enable the dosimetrist to perform many iterations of the outer optimization in a commercially reasonable time. Methods: We have developed a GPU-based convolution-type dose computation algorithm that more accurately handles heterogeneities than earlier algorithms by redistributing energy from dose computed in a water volume. The depth dependence of the beam size is handled by pre-processing Bragg curves using a weighted superposition of Gaussian bases. Additionally, scattering, the orientation of treatment ports, and the non-parallel propagation of beams are handled by large, but sparse, energy-redistribution matrices that implement affine transforms. Results: We tested our algorithm using a brain tumor dataset with 1 mm voxels and a single treatment port from the patient’s anterior through the sinuses. The resulting dose volume is 100 × 100 × 230 mm with 66,200 beam spots on a 3 × 3 × 2 mm grid. The dose computation takes <1 msec on a GeForce GTX Titan GPU with the Gamma passing rate for 2mm/2% criterion of 99.1% compared to dose calculated by an alternative dose algorithm based on pencil beams. We will present comparisons to Monte Carlo dose calculations. Conclusion: Our high-speed dose computation method enables the IMPT spot weights to be optimized in <1 second, resulting in a nearly instantaneous response to user changes to dose constraints. This permits the creation of higher quality plans by allowing the dosimetrist to evaluate more alternatives in a short period of time.

  13. Systematically biological prioritizing remediation sites based on datasets of biological investigations and heavy metals in soil

    Science.gov (United States)

    Lin, Wei-Chih; Lin, Yu-Pin; Anthony, Johnathen

    2015-04-01

    Heavy metal pollution has adverse effects on not only the focal invertebrate species of this study, such as reduction in pupa weight and increased larval mortality, but also on the higher trophic level organisms which feed on them, either directly or indirectly, through the process of biomagnification. Despite this, few studies regarding remediation prioritization take species distribution or biological conservation priorities into consideration. This study develops a novel approach for delineating sites which are both contaminated by any of 5 readily bioaccumulated heavy metal soil contaminants and are of high ecological importance for the highly mobile, low trophic level focal species. The conservation priority of each site was based on the projected distributions of 6 moth species simulated via the presence-only maximum entropy species distribution model followed by the subsequent application of a systematic conservation tool. In order to increase the number of available samples, we also integrated crowd-sourced data with professionally-collected data via a novel optimization procedure based on a simulated annealing algorithm. This integration procedure was important since while crowd-sourced data can drastically increase the number of data samples available to ecologists, still the quality or reliability of crowd-sourced data can be called into question, adding yet another source of uncertainty in projecting species distributions. The optimization method screens crowd-sourced data in terms of the environmental variables which correspond to professionally-collected data. The sample distribution data was derived from two different sources, including the EnjoyMoths project in Taiwan (crowd-sourced data) and the Global Biodiversity Information Facility (GBIF) ?eld data (professional data). The distributions of heavy metal concentrations were generated via 1000 iterations of a geostatistical co-simulation approach. The uncertainties in distributions of the heavy

  14. Warfarin: do we need genotype-based dose prediction?

    Directory of Open Access Journals (Sweden)

    Yenny Yenny

    2016-02-01

    Full Text Available For the treatment and prevention of thrombo-embolic disease, the most frequently used anticoagulant drug worldwide is warfarin, an oral coumarin derivative, with more than 30 million prescriptions written for this drug in the United States in 2004.(1 The drug has a narrow therapeutic index and its metabolism varies by as much as a factor of 10 among individual patients, making warfarin therapy difficult to manage. Hemorrhagic complication rates of warfarin are estimated to be 5-7.9% for major (life threatening hemorrhage and 14-36% for minor hemorrhage (e.g. nosebleeds, microscopic hematuria.(2 This condition makes it difficult to establish the appropriate dose of warfarin.

  15. GTV-based prescription in SBRT for lung lesions using advanced dose calculation algorithms

    International Nuclear Information System (INIS)

    Lacornerie, Thomas; Lisbona, Albert; Mirabel, Xavier; Lartigau, Eric; Reynaert, Nick

    2014-01-01

    The aim of current study was to investigate the way dose is prescribed to lung lesions during SBRT using advanced dose calculation algorithms that take into account electron transport (type B algorithms). As type A algorithms do not take into account secondary electron transport, they overestimate the dose to lung lesions. Type B algorithms are more accurate but still no consensus is reached regarding dose prescription. The positive clinical results obtained using type A algorithms should be used as a starting point. In current work a dose-calculation experiment is performed, presenting different prescription methods. Three cases with three different sizes of peripheral lung lesions were planned using three different treatment platforms. For each individual case 60 Gy to the PTV was prescribed using a type A algorithm and the dose distribution was recalculated using a type B algorithm in order to evaluate the impact of the secondary electron transport. Secondly, for each case a type B algorithm was used to prescribe 48 Gy to the PTV, and the resulting doses to the GTV were analyzed. Finally, prescriptions based on specific GTV dose volumes were evaluated. When using a type A algorithm to prescribe the same dose to the PTV, the differences regarding median GTV doses among platforms and cases were always less than 10% of the prescription dose. The prescription to the PTV based on type B algorithms, leads to a more important variability of the median GTV dose among cases and among platforms, (respectively 24%, and 28%). However, when 54 Gy was prescribed as median GTV dose, using a type B algorithm, the variability observed was minimal. Normalizing the prescription dose to the median GTV dose for lung lesions avoids variability among different cases and treatment platforms of SBRT when type B algorithms are used to calculate the dose. The combination of using a type A algorithm to optimize a homogeneous dose in the PTV and using a type B algorithm to prescribe the

  16. Accuracy of radiotherapy dose calculations based on cone-beam CT: comparison of deformable registration and image correction based methods

    Science.gov (United States)

    Marchant, T. E.; Joshi, K. D.; Moore, C. J.

    2018-03-01

    Radiotherapy dose calculations based on cone-beam CT (CBCT) images can be inaccurate due to unreliable Hounsfield units (HU) in the CBCT. Deformable image registration of planning CT images to CBCT, and direct correction of CBCT image values are two methods proposed to allow heterogeneity corrected dose calculations based on CBCT. In this paper we compare the accuracy and robustness of these two approaches. CBCT images for 44 patients were used including pelvis, lung and head & neck sites. CBCT HU were corrected using a ‘shading correction’ algorithm and via deformable registration of planning CT to CBCT using either Elastix or Niftyreg. Radiotherapy dose distributions were re-calculated with heterogeneity correction based on the corrected CBCT and several relevant dose metrics for target and OAR volumes were calculated. Accuracy of CBCT based dose metrics was determined using an ‘override ratio’ method where the ratio of the dose metric to that calculated on a bulk-density assigned version of the same image is assumed to be constant for each patient, allowing comparison to the patient’s planning CT as a gold standard. Similar performance is achieved by shading corrected CBCT and both deformable registration algorithms, with mean and standard deviation of dose metric error less than 1% for all sites studied. For lung images, use of deformed CT leads to slightly larger standard deviation of dose metric error than shading corrected CBCT with more dose metric errors greater than 2% observed (7% versus 1%).

  17. Individualized Hydrocodone Therapy Based on Phenotype, Pharmacogenetics, and Pharmacokinetic Dosing.

    Science.gov (United States)

    Linares, Oscar A; Fudin, Jeffrey; Daly, Annemarie L; Boston, Raymond C

    2015-12-01

    (1) To quantify hydrocodone (HC) and hydromorphone (HM) metabolite pharmacokinetics with pharmacogenetics in CYP2D6 ultra-rapid metabolizer (UM), extensive metabolizer (EM), and poor metabolizer (PM) metabolizer phenotypes. (2) To develop an HC phenotype-specific dosing strategy for HC that accounts for HM production using clinical pharmacokinetics integrated with pharmacogenetics for patient safety. In silico clinical trial simulation. Healthy white men and women without comorbidities or history of opioid, or any other drug or nutraceutical use, age 26.3±5.7 years (mean±SD; range, 19 to 36 y) and weight 71.9±16.8 kg (range, 50 to 108 kg). CYP2D6 phenotype-specific HC clinical pharmacokinetic parameter estimates and phenotype-specific percentages of HM formed from HC. PMs had lower indices of HC disposition compared with UMs and EMs. Clearance was reduced by nearly 60% and the t1/2 was increased by about 68% compared with EMs. The canonical order for HC clearance was UM>EM>PM. HC elimination mainly by the liver, represented by ke, was reduced about 70% in PM. However, HC's apparent Vd was not significantly different among UMs, EMs, and PM. The canonical order of predicted plasma HM concentrations was UM>EM>PM. For each of the CYP2D6 phenotypes, the mean predicted HM levels were within HM's therapeutic range, which indicates HC has significant phenotype-dependent pro-drug effects. Our results demonstrate that pharmacogenetics afford clinicians an opportunity to individualize HC dosing, while adding enhanced opportunity to account for its conversion to HM in the body.

  18. An inter-hospital comparison of patient dose based on clinical indications

    International Nuclear Information System (INIS)

    Teeuwisse, W.; Geleijns, J.; Veldkamp, W.

    2007-01-01

    Patient dose is usually estimated for a single radiographic projection or computed tomography (CT) series. In this study, patient dose was calculated for predefined clinical indications (24 radiography, 11 CT). Members of the radiology staff of each of 11 hospitals were trained in dose measurement and calculation techniques. Based on clinical indications participants decided on imaging protocols and calculated cumulative effective dose for a complete examination. Effective dose ranged from <1 μSv to 0.6 mSv for examinations with radiographs and from 0.2 to 12 mSv for CT scans. Differences in the imaging protocols contributedd to a substantial variation in patient dose. For mammography, average glandular dose (AGD) was estimated for 32-, 53- and 90-mm compressed breast thicknesses, with a median value of 0.74, 1.74 and 3.40 mGy, respectively. The results presented here demonstrate that a pragmatic choice of dosimetry methods enables local staff to estimate effective dose. The inclusion of imaging protocols in the dose surveys provided a broader view on the variations in patient dose between hospitals. (orig.)

  19. The Implementation of Research-based Learning on Biology Seminar Course in Biology Education Study Program of FKIP UMRAH

    Science.gov (United States)

    Amelia, T.

    2018-04-01

    Biology Seminar is a course in Biology Education Study Program of Faculty of Teacher Training and Education University of Maritim Raja Ali Haji (FKIP UMRAH) that requires students to have the ability to apply scientific attitudes, perform scientific writing and undertake scientific publications on a small scale. One of the learning strategies that can drive the achievement of learning outcomes in this course is Research-Based Learning. Research-Based Learning principles are considered in accordance with learning outcomes in Biology Seminar courses and generally in accordance with the purpose of higher education. On this basis, this article which is derived from a qualitative research aims at describing Research-based Learning on Biology Seminar course. Based on a case study research, it was known that Research-Based Learning on Biology Seminar courses is applied through: designing learning activities around contemporary research issues; teaching research methods, techniques and skills explicitly within program; drawing on personal research in designing and teaching courses; building small-scale research activities into undergraduate assignment; and infusing teaching with the values of researchers.

  20. Breast dose reduction for chest CT by modifying the scanning parameters based on the pre-scan size-specific dose estimate (SSDE)

    Energy Technology Data Exchange (ETDEWEB)

    Kidoh, Masafumi; Utsunomiya, Daisuke; Oda, Seitaro; Nakaura, Takeshi; Yuki, Hideaki; Hirata, Kenichiro; Namimoto, Tomohiro; Sakabe, Daisuke; Hatemura, Masahiro; Yamashita, Yasuyuki [Kumamoto University, Department of Diagnostic Radiology, Faculty of Life Sciences, Honjo, Kumamoto (Japan); Funama, Yoshinori [Kumamoto University, Department of Medical Physics, Faculty of Life Sciences, Honjo, Kumamoto (Japan)

    2017-06-15

    To investigate the usefulness of modifying scanning parameters based on the size-specific dose estimate (SSDE) for a breast-dose reduction for chest CT. We scanned 26 women with a fixed volume CT dose index (CTDI{sub vol}) (15 mGy) and another 26 with a fixed SSDE (15 mGy) protocol (protocol 1 and 2, respectively). In protocol 2, tube current was calculated based on the patient habitus obtained on scout images. We compared the mean breast dose and the inter-patient breast dose variability and performed linear regression analysis of the breast dose and the body mass index (BMI) of the two protocols. The mean breast dose was about 35 % lower under protocol 2 than protocol 1 (10.9 mGy vs. 16.8 mGy, p < 0.01). The inter-patient breast dose variability was significantly lower under protocol 2 than 1 (1.2 mGy vs. 2.5 mGy, p < 0.01). We observed a moderate negative correlation between the breast dose and the BMI under protocol 1 (r = 0.43, p < 0.01); there was no significant correlation (r = 0.06, p = 0.35) under protocol 2. The SSDE-based protocol achieved a reduction in breast dose and in inter-patient breast dose variability. (orig.)

  1. Reconstruction of the external dose of evacuees from the contaminated areas based on simulation modelling

    International Nuclear Information System (INIS)

    Meckbach, R.; Chumak, V.V.

    1996-01-01

    Model calculations are being performed for the reconstruction of individual external gamma doses of population evacuated during the Chernobyl accident from the city of Pripyat and other settlements of the 30-km zone. The models are based on sets of dose rate measurements performed during the accident, on individual behavior histories of more than 30000 evacuees obtained by questionnaire survey and on location factors determined for characteristic housing buildings. Location factors were calculated by Monte Carlo simulations of photon transport for a typical housing block and village houses. Stochastic models for individual external dose reconstruction are described. Using Monte Carlo methods, frequency distributions representing the uncertainty of doses are calculated from an assessment of the uncertainty of the data. The determination of dose rate distributions in Pripyat is discussed. Exemplary results for individual external doses are presented

  2. Limiting CT radiation dose in children with craniosynostosis: phantom study using model-based iterative reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Kaasalainen, Touko; Lampinen, Anniina [University of Helsinki and Helsinki University Hospital, HUS Medical Imaging Center, Radiology, POB 340, Helsinki (Finland); University of Helsinki, Department of Physics, Helsinki (Finland); Palmu, Kirsi [University of Helsinki and Helsinki University Hospital, HUS Medical Imaging Center, Radiology, POB 340, Helsinki (Finland); School of Science, Aalto University, Department of Biomedical Engineering and Computational Science, Helsinki (Finland); Reijonen, Vappu; Kortesniemi, Mika [University of Helsinki and Helsinki University Hospital, HUS Medical Imaging Center, Radiology, POB 340, Helsinki (Finland); Leikola, Junnu [University of Helsinki and Helsinki University Hospital, Department of Plastic Surgery, Helsinki (Finland); Kivisaari, Riku [University of Helsinki and Helsinki University Hospital, Department of Neurosurgery, Helsinki (Finland)

    2015-09-15

    Medical professionals need to exercise particular caution when developing CT scanning protocols for children who require multiple CT studies, such as those with craniosynostosis. To evaluate the utility of ultra-low-dose CT protocols with model-based iterative reconstruction techniques for craniosynostosis imaging. We scanned two pediatric anthropomorphic phantoms with a 64-slice CT scanner using different low-dose protocols for craniosynostosis. We measured organ doses in the head region with metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters. Numerical simulations served to estimate organ and effective doses. We objectively and subjectively evaluated the quality of images produced by adaptive statistical iterative reconstruction (ASiR) 30%, ASiR 50% and Veo (all by GE Healthcare, Waukesha, WI). Image noise and contrast were determined for different tissues. Mean organ dose with the newborn phantom was decreased up to 83% compared to the routine protocol when using ultra-low-dose scanning settings. Similarly, for the 5-year phantom the greatest radiation dose reduction was 88%. The numerical simulations supported the findings with MOSFET measurements. The image quality remained adequate with Veo reconstruction, even at the lowest dose level. Craniosynostosis CT with model-based iterative reconstruction could be performed with a 20-μSv effective dose, corresponding to the radiation exposure of plain skull radiography, without compromising required image quality. (orig.)

  3. Neutron relative biological effectiveness for solid cancer incidence in the Japanese A-bomb survivors: an analysis considering the degree of independent effects from γ-ray and neutron absorbed doses with hierarchical partitioning

    Energy Technology Data Exchange (ETDEWEB)

    Walsh, Linda [Federal Office for Radiation Protection, Department Radiation Protection and Health, Oberschleissheim (Germany); University of Manchester, The Faculty of Medical and Human Sciences, Manchester (United Kingdom)

    2013-03-15

    It has generally been assumed that the neutron and γ-ray absorbed doses in the data from the life span study (LSS) of the Japanese A-bomb survivors are too highly correlated for an independent separation of the all solid cancer risks due to neutrons and due to γ-rays. However, with the release of the most recent data for all solid cancer incidence and the increased statistical power over previous datasets, it is instructive to consider alternatives to the usual approaches. Simple excess relative risk (ERR) models for radiation-induced solid cancer incidence fitted to the LSS epidemiological data have been applied with neutron and γ-ray absorbed doses as separate explanatory covariables. A simple evaluation of the degree of independent effects from γ-ray and neutron absorbed doses on the all solid cancer risk with the hierarchical partitioning (HP) technique is presented here. The degree of multi-collinearity between the γ-ray and neutron absorbed doses has also been considered. The results show that, whereas the partial correlation between the neutron and γ-ray colon absorbed doses may be considered to be high at 0.74, this value is just below the level beyond which remedial action, such as adding the doses together, is usually recommended. The resulting variance inflation factor is 2.2. Applying HP indicates that just under half of the drop in deviance resulting from adding the γ-ray and neutron absorbed doses to the baseline risk model comes from the joint effects of the neutrons and γ-rays - leaving a substantial proportion of this deviance drop accounted for by individual effects of the neutrons and γ-rays. The average ERR/Gy γ-ray absorbed dose and the ERR/Gy neutron absorbed dose that have been obtained here directly for the first time, agree well with previous indirect estimates. The average relative biological effectiveness (RBE) of neutrons relative to γ-rays, calculated directly from fit parameters to the all solid cancer ERR model with both

  4. Monte Carlo MCNP-4B-based absorbed dose distribution estimates for patient-specific dosimetry.

    Science.gov (United States)

    Yoriyaz, H; Stabin, M G; dos Santos, A

    2001-04-01

    This study was intended to verify the capability of the Monte Carlo MCNP-4B code to evaluate spatial dose distribution based on information gathered from CT or SPECT. A new three-dimensional (3D) dose calculation approach for internal emitter use in radioimmunotherapy (RIT) was developed using the Monte Carlo MCNP-4B code as the photon and electron transport engine. It was shown that the MCNP-4B computer code can be used with voxel-based anatomic and physiologic data to provide 3D dose distributions. This study showed that the MCNP-4B code can be used to develop a treatment planning system that will provide such information in a time manner, if dose reporting is suitably optimized. If each organ is divided into small regions where the average energy deposition is calculated with a typical volume of 0.4 cm(3), regional dose distributions can be provided with reasonable central processing unit times (on the order of 12-24 h on a 200-MHz personal computer or modest workstation). Further efforts to provide semiautomated region identification (segmentation) and improvement of marrow dose calculations are needed to supply a complete system for RIT. It is envisioned that all such efforts will continue to develop and that internal dose calculations may soon be brought to a similar level of accuracy, detail, and robustness as is commonly expected in external dose treatment planning. For this study we developed a code with a user-friendly interface that works on several nuclear medicine imaging platforms and provides timely patient-specific dose information to the physician and medical physicist. Future therapy with internal emitters should use a 3D dose calculation approach, which represents a significant advance over dose information provided by the standard geometric phantoms used for more than 20 y (which permit reporting of only average organ doses for certain standardized individuals)

  5. 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.

  6. CT-based dose calculations and in vivo dosimetry for lung cancer treatment

    International Nuclear Information System (INIS)

    Essers, M.; Lanson, J.H.; Leunens, G.; Schnabel, T.; Mijnheer, B.J.

    1995-01-01

    Reliable CT-based dose calculations and dosimetric quality control are essential for the introduction of new conformal techniques for the treatment of lung cancer. The first aim of this study was therefore to check the accuracy of dose calculations based on CT-densities, using a simple inhomogeneity correction model, for lung cancer patients irradiated with an AP-PA treatment technique. Second, the use of diodes for absolute exit dose measurements and an Electronic Portal Imaging Device (EPID) for relative transmission dose verification was investigated for 22 and 12 patients, respectively. The measured dose values were compared with calculations performed using our 3-dimensional treatment planning system, using CT-densities or assuming the patient to be water-equivalent. Using water-equivalent calculations, the actual exit dose value under lung was, on average, underestimated by 30%, with an overall spread of 10% (1 SD). Using inhomogeneity corrections, the exit dose was, on average, overestimated by 4%, with an overall spread of 6% (1 SD). Only 2% of the average deviation was due to the inhomogeneity correction model. An uncertainty in exit dose calculation of 2.5% (1 SD) could be explained by organ motion, resulting from the ventilatory or cardiac cycle. The most important reason for the large overall spread was, however, the uncertainty involved in performing point measurements: about 4% (1 SD). This difference resulted from the systematic and random deviation in patient set-up and therefore in diode position with respect to patient anatomy. Transmission and exit dose values agreed with an average difference of 1.1%. Transmission dose profiles also showed good agreement with calculated exit dose profiles. Our study shows that, for this treatment technique, the dose in the thorax region is quite accurately predicted using CT-based dose calculations, even if a simple inhomogeneity correction model is used. Point detectors such as diodes are not suitable for exit

  7. Organization of a radioisotope based molecular biology laboratory

    International Nuclear Information System (INIS)

    2006-12-01

    Polymerase chain reaction (PCR) has revolutionized the application of molecular techniques to medicine. Together with other molecular biology techniques it is being increasingly applied to human health for identifying prognostic markers and drug resistant profiles, developing diagnostic tests and genotyping systems and for treatment follow-up of certain diseases in developed countries. Developing Member States have expressed their need to also benefit from the dissemination of molecular advances. The use of radioisotopes, as a step in the detection process or for increased sensitivity and specificity is well established, making it ideally suitable for technology transfer. Many molecular based projects using isotopes for detecting and studying micro organisms, hereditary and neoplastic diseases are received for approval every year. In keeping with the IAEA's programme, several training activities and seminars have been organized to enhance the capabilities of developing Member States to employ in vitro nuclear medicine technologies for managing their important health problems and for undertaking related basic and clinical research. The background material for this publication was collected at training activities and from feedback received from participants at research and coordination meetings. In addition, a consultants' meeting was held in June 2004 to compile the first draft of this report. Previous IAEA TECDOCS, namely IAEA-TECDOC-748 and IAEA-TECDOC-1001, focused on molecular techniques and their application to medicine while the present publication provides information on organization of the laboratory, quality assurance and radio-safety. The technology has specific requirements of the way the laboratory is organized (e.g. for avoiding contamination and false positives in PCR) and of quality assurance in order to provide accurate information to decision makers. In addition while users of the technology accept the scientific rationale of using radio

  8. Metoprolol Dose Equivalence in Adult Men and Women Based on Gender Differences: Pharmacokinetic Modeling and Simulations

    Directory of Open Access Journals (Sweden)

    Andy R. Eugene

    2016-11-01

    Full Text Available Recent meta-analyses and publications over the past 15 years have provided evidence showing there are considerable gender differences in the pharmacokinetics of metoprolol. Throughout this time, there have not been any research articles proposing a gender stratified dose-adjustment resulting in an equivalent total drug exposure. Metoprolol pharmacokinetic data was obtained from a previous publication. Data was modeled using nonlinear mixed effect modeling using the MONOLIX software package to quantify metoprolol concentration–time data. Gender-stratified dosing simulations were conducted to identify equivalent total drug exposure based on a 100 mg dose in adults. Based on the pharmacokinetic modeling and simulations, a 50 mg dose in adult women provides an approximately similar metoprolol drug exposure to a 100 mg dose in adult men.

  9. SimDoseCT: dose reporting software based on Monte Carlo simulation for a 320 detector-row cone-beam CT scanner and ICRP computational adult phantoms

    Science.gov (United States)

    Cros, Maria; Joemai, Raoul M. S.; Geleijns, Jacob; Molina, Diego; Salvadó, Marçal

    2017-08-01

    This study aims to develop and test software for assessing and reporting doses for standard patients undergoing computed tomography (CT) examinations in a 320 detector-row cone-beam scanner. The software, called SimDoseCT, is based on the Monte Carlo (MC) simulation code, which was developed to calculate organ doses and effective doses in ICRP anthropomorphic adult reference computational phantoms for acquisitions with the Aquilion ONE CT scanner (Toshiba). MC simulation was validated by comparing CTDI measurements within standard CT dose phantoms with results from simulation under the same conditions. SimDoseCT consists of a graphical user interface connected to a MySQL database, which contains the look-up-tables that were generated with MC simulations for volumetric acquisitions at different scan positions along the phantom using any tube voltage, bow tie filter, focal spot and nine different beam widths. Two different methods were developed to estimate organ doses and effective doses from acquisitions using other available beam widths in the scanner. A correction factor was used to estimate doses in helical acquisitions. Hence, the user can select any available protocol in the Aquilion ONE scanner for a standard adult male or female and obtain the dose results through the software interface. Agreement within 9% between CTDI measurements and simulations allowed the validation of the MC program. Additionally, the algorithm for dose reporting in SimDoseCT was validated by comparing dose results from this tool with those obtained from MC simulations for three volumetric acquisitions (head, thorax and abdomen). The comparison was repeated using eight different collimations and also for another collimation in a helical abdomen examination. The results showed differences of 0.1 mSv or less for absolute dose in most organs and also in the effective dose calculation. The software provides a suitable tool for dose assessment in standard adult patients undergoing CT

  10. The direct biologic effects of radioactive 125I seeds on pancreatic cancer cells PANC-1, at continuous low-dose rates.

    Science.gov (United States)

    Wang, Jidong; Wang, Junjie; Liao, Anyan; Zhuang, Hongqing; Zhao, Yong

    2009-08-01

    The relative biologic effectiveness of model 6711 125I seeds (Ningbo Junan Pharmaceutical Technology Company,Ningbo, China) and their effects on growth, cell cycle, and apoptosis in human pancreatic cancer cell line PANC-1 were examined in the present study. PANC-1 cells were exposed to the absorbed doses of 1, 2, 4, 6, 8, and 10 Gyeither with 125I seeds (initial dose rate, 2.59 cGy=h) or with 60Co g-ray irradiation (dose rate, 221 cGy=min),respectively. Significantly greater numbers of apoptotic PANC-1 cells were detected following the continuouslow-dose-rate (CLDR) irradiation of 125I seeds, compared with cells irradiated with identical doses of 60Co g-ray. The D(0) for 60Co g-ray and 125I seed irradiation were 2.30 and 1.66, respectively. The survival fraction after 125Iseed irradiation was significantly lower than that of 60Co g-ray, with a relative biologic effectiveness of 1.39.PANC-1 cells were dose dependently arrested in the S-phase by 60Co g-rays and in the G2=M phase by 125I seeds,24 hour after irradiation. CLDR irradiation by 125I seeds was more effective in inducing cell apoptosis in PANC-1cells than acute high-dose-rate 60Co g irradiation. Interestingly, CLDR irradiation by 125I seeds can cause PANC-1cell-cycle arrest at the G2=M phase and induce apoptosis, which may be an important mechanism underlying 125Iseed-induced PANC-1 cell inhibition.

  11. A Color-Opponency Based Biological Model for Color Constancy

    Directory of Open Access Journals (Sweden)

    Yongjie Li

    2011-05-01

    Full Text Available Color constancy is the ability of the human visual system to adaptively correct color-biased scenes under different illuminants. Most of the existing color constancy models are nonphysiologically plausible. Among the limited biological models, the great majority is Retinex and its variations, and only two or three models directly simulate the feature of color-opponency, but only of the very earliest stages of visual pathway, i.e., the single-opponent mechanisms involved at the levels of retinal ganglion cells and lateral geniculate nucleus (LGN neurons. Considering the extensive physiological evidences supporting that both the single-opponent cells in retina and LGN and the double-opponent neurons in primary visual cortex (V1 are the building blocks for color constancy, in this study we construct a color-opponency based color constancy model by simulating the opponent fashions of both the single-opponent and double-opponent cells in a forward manner. As for the spatial structure of the receptive fields (RF, both the classical RF (CRF center and the nonclassical RF (nCRF surround are taken into account for all the cells. The proposed model was tested on several typical image databases commonly used for performance evaluation of color constancy methods, and exciting results were achieved.

  12. Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer.

    Science.gov (United States)

    González, S J; Pozzi, E C C; Monti Hughes, A; Provenzano, L; Koivunoro, H; Carando, D G; Thorp, S I; Casal, M R; Bortolussi, S; Trivillin, V A; Garabalino, M A; Curotto, P; Heber, E M; Santa Cruz, G A; Kankaanranta, L; Joensuu, H; Schwint, A E

    2017-10-03

    Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson's correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed

  13. Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer

    Science.gov (United States)

    González, S. J.; Pozzi, E. C. C.; Monti Hughes, A.; Provenzano, L.; Koivunoro, H.; Carando, D. G.; Thorp, S. I.; Casal, M. R.; Bortolussi, S.; Trivillin, V. A.; Garabalino, M. A.; Curotto, P.; Heber, E. M.; Santa Cruz, G. A.; Kankaanranta, L.; Joensuu, H.; Schwint, A. E.

    2017-10-01

    Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson’s correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed

  14. Variability of Marker-Based Rectal Dose Evaluation in HDR Cervical Brachytherapy

    International Nuclear Information System (INIS)

    Wang Zhou; Jaggernauth, Wainwright; Malhotra, Harish K.; Podgorsak, Matthew B.

    2010-01-01

    In film-based intracavitary brachytherapy for cervical cancer, position of the rectal markers may not accurately represent the anterior rectal wall. This study was aimed at analyzing the variability of rectal dose estimation as a result of interfractional variation of marker placement. A cohort of five patients treated with multiple-fraction tandem and ovoid high-dose-rate (HDR) brachytherapy was studied. The cervical os point and the orientation of the applicators were matched among all fractional plans for each patient. Rectal points obtained from all fractions were then input into each clinical treated plan. New fractional rectal doses were obtained and a new cumulative rectal dose for each patient was calculated. The maximum interfractional variation of distances between rectal dose points and the closest source positions was 1.1 cm. The corresponding maximum variability of fractional rectal dose was 65.5%. The percentage difference in cumulative rectal dose estimation for each patient was 5.4%, 19.6%, 34.6%, 23.4%, and 13.9%, respectively. In conclusion, care should be taken when using rectal markers as reference points for estimating rectal dose in HDR cervical brachytherapy. The best estimate of true rectal dose for each fraction should be determined by the most anterior point among all fractions.

  15. Sustainable production of biologically active molecules of marine based origin.

    Science.gov (United States)

    Murray, Patrick M; Moane, Siobhan; Collins, Catherine; Beletskaya, Tanya; Thomas, Olivier P; Duarte, Alysson W F; Nobre, Fernando S; Owoyemi, Ifeloju O; Pagnocca, Fernando C; Sette, L D; McHugh, Edward; Causse, Eric; Pérez-López, Paula; Feijoo, Gumersindo; Moreira, Ma T; Rubiolo, Juan; Leirós, Marta; Botana, Luis M; Pinteus, Susete; Alves, Celso; Horta, André; Pedrosa, Rui; Jeffryes, Clayton; Agathos, Spiros N; Allewaert, Celine; Verween, Annick; Vyverman, Wim; Laptev, Ivan; Sineoky, Sergei; Bisio, Angela; Manconi, Renata; Ledda, Fabio; Marchi, Mario; Pronzato, Roberto; Walsh, Daniel J

    2013-09-25

    The marine environment offers both economic and scientific potential which are relatively untapped from a biotechnological point of view. These environments whilst harsh are ironically fragile and dependent on a harmonious life form balance. Exploitation of natural resources by exhaustive wild harvesting has obvious negative environmental consequences. From a European industry perspective marine organisms are a largely underutilised resource. This is not due to lack of interest but due to a lack of choice the industry faces for cost competitive, sustainable and environmentally conscientious product alternatives. Knowledge of the biotechnological potential of marine organisms together with the development of sustainable systems for their cultivation, processing and utilisation are essential. In 2010, the European Commission recognised this need and funded a collaborative RTD/SME project under the Framework 7-Knowledge Based Bio-Economy (KBBE) Theme 2 Programme 'Sustainable culture of marine microorganisms, algae and/or invertebrates for high value added products'. The scope of that project entitled 'Sustainable Production of Biologically Active Molecules of Marine Based Origin' (BAMMBO) is outlined. Although the Union is a global leader in many technologies, it faces increasing competition from traditional rivals and emerging economies alike and must therefore improve its innovation performance. For this reason innovation is placed at the heart of a European Horizon 2020 Strategy wherein the challenge is to connect economic performance to eco performance. This article provides a synopsis of the research activities of the BAMMBO project as they fit within the wider scope of sustainable environmentally conscientious marine resource exploitation for high-value biomolecules. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. SU-E-T-762: Toward Volume-Based Independent Dose Verification as Secondary Check

    International Nuclear Information System (INIS)

    Tachibana, H; Tachibana, R

    2015-01-01

    Purpose: Lung SBRT plan has been shifted to volume prescription technique. However, point dose agreement is still verified using independent dose verification at the secondary check. The volume dose verification is more affected by inhomogeneous correction rather than point dose verification currently used as the check. A feasibility study for volume dose verification was conducted in lung SBRT plan. Methods: Six SBRT plans were collected in our institute. Two dose distributions with / without inhomogeneous correction were generated using Adaptive Convolve (AC) in Pinnacle3. Simple MU Analysis (SMU, Triangle Product, Ishikawa, JP) was used as the independent dose verification software program, in which a modified Clarkson-based algorithm was implemented and radiological path length was computed using CT images independently to the treatment planning system. The agreement in point dose and mean dose between the AC with / without the correction and the SMU were assessed. Results: In the point dose evaluation for the center of the GTV, the difference shows the systematic shift (4.5% ± 1.9 %) in comparison of the AC with the inhomogeneous correction, on the other hands, there was good agreement of 0.2 ± 0.9% between the SMU and the AC without the correction. In the volume evaluation, there were significant differences in mean dose for not only PTV (14.2 ± 5.1 %) but also GTV (8.0 ± 5.1 %) compared to the AC with the correction. Without the correction, the SMU showed good agreement for GTV (1.5 ± 0.9%) as well as PTV (0.9% ± 1.0%). Conclusion: The volume evaluation for secondary check may be possible in homogenous region. However, the volume including the inhomogeneous media would make larger discrepancy. Dose calculation algorithm for independent verification needs to be modified to take into account the inhomogeneous correction

  17. Mathematical Biology Modules Based on Modern Molecular Biology and Modern Discrete Mathematics

    Science.gov (United States)

    Robeva, Raina; Davies, Robin; Hodge, Terrell; Enyedi, Alexander

    2010-01-01

    We describe an ongoing collaborative curriculum materials development project between Sweet Briar College and Western Michigan University, with support from the National Science Foundation. We present a collection of modules under development that can be used in existing mathematics and biology courses, and we address a critical national need to…

  18. A new method for dosing uranium in biological media; Nouvelle methode de dosage de l'uranium dans les milieux biologiques

    Energy Technology Data Exchange (ETDEWEB)

    Henry, Ph; Kobisch, Ch [Commissariat a l' Energie Atomique, Centre de Production de Plutonium, Marcoule (France). Centre d' Etudes Nucleaires

    1964-07-01

    This report describes a new method for dosing uranium in biological media based on measurement of alpha activity. After treatment of the sample with a mineral acid, the uranium is reduced to the valency four by trivalent titanium and is precipitated as phosphate in acid solution. The uranium is then separated from the titanium by precipitation as UF{sub 4} with lanthanum as carrier. A slight modification, unnecessary in the case of routine analyses, makes it possible to eliminate other possible alpha emitters (thorium and transuranic elements). (authors) [French] Ce rapport decrit une nouvelle methode de dosage de l'uranium dans les milieux biologiques par mesure de l'activite alpha. Apres mineralisation de l'echantillon, l'uranium est reduit a la valence IV par le titane trivalent et precipite en milieu acide sous forme de phosphate. L'uranium est ensuite separe du titane par precipitation a l'etat d'UF{sub 4} avec du lanthane entraineur. Une legere modification, inutile dans le cas d'analyses de routine, permet d'effectuer l'elimination d'autres emetteurs alpha eventuels (thorium et transuraniens). (auteurs)

  19. Model-based dose calculations for COMS eye plaque brachytherapy using an anatomically realistic eye phantom.

    Science.gov (United States)

    Lesperance, Marielle; Inglis-Whalen, M; Thomson, R M

    2014-02-01

    To investigate the effects of the composition and geometry of ocular media and tissues surrounding the eye on dose distributions for COMS eye plaque brachytherapy with(125)I, (103)Pd, or (131)Cs seeds, and to investigate doses to ocular structures. An anatomically and compositionally realistic voxelized eye model with a medial tumor is developed based on a literature review. Mass energy absorption and attenuation coefficients for ocular media are calculated. Radiation transport and dose deposition are simulated using the EGSnrc Monte Carlo user-code BrachyDose for a fully loaded COMS eye plaque within a water phantom and our full eye model for the three radionuclides. A TG-43 simulation with the same seed configuration in a water phantom neglecting the plaque and interseed effects is also performed. The impact on dose distributions of varying tumor position, as well as tumor and surrounding tissue media is investigated. Each simulation and radionuclide is compared using isodose contours, dose volume histograms for the lens and tumor, maximum, minimum, and average doses to structures of interest, and doses to voxels of interest within the eye. Mass energy absorption and attenuation coefficients of the ocular media differ from those of water by as much as 12% within the 20-30 keV photon energy range. For all radionuclides studied, average doses to the tumor and lens regions in the full eye model differ from those for the plaque in water by 8%-10% and 13%-14%, respectively; the average doses to the tumor and lens regions differ between the full eye model and the TG-43 simulation by 2%-17% and 29%-34%, respectively. Replacing the surrounding tissues in the eye model with water increases the maximum and average doses to the lens by 2% and 3%, respectively. Substituting the tumor medium in the eye model for water, soft tissue, or an alternate melanoma composition affects tumor dose compared to the default eye model simulation by up to 16%. In the full eye model

  20. Model-based dose calculations for COMS eye plaque brachytherapy using an anatomically realistic eye phantom

    International Nuclear Information System (INIS)

    Lesperance, Marielle; Inglis-Whalen, M.; Thomson, R. M.

    2014-01-01

    Purpose : To investigate the effects of the composition and geometry of ocular media and tissues surrounding the eye on dose distributions for COMS eye plaque brachytherapy with 125 I, 103 Pd, or 131 Cs seeds, and to investigate doses to ocular structures. Methods : An anatomically and compositionally realistic voxelized eye model with a medial tumor is developed based on a literature review. Mass energy absorption and attenuation coefficients for ocular media are calculated. Radiation transport and dose deposition are simulated using the EGSnrc Monte Carlo user-code BrachyDose for a fully loaded COMS eye plaque within a water phantom and our full eye model for the three radionuclides. A TG-43 simulation with the same seed configuration in a water phantom neglecting the plaque and interseed effects is also performed. The impact on dose distributions of varying tumor position, as well as tumor and surrounding tissue media is investigated. Each simulation and radionuclide is compared using isodose contours, dose volume histograms for the lens and tumor, maximum, minimum, and average doses to structures of interest, and doses to voxels of interest within the eye. Results : Mass energy absorption and attenuation coefficients of the ocular media differ from those of water by as much as 12% within the 20–30 keV photon energy range. For all radionuclides studied, average doses to the tumor and lens regions in the full eye model differ from those for the plaque in water by 8%–10% and 13%–14%, respectively; the average doses to the tumor and lens regions differ between the full eye model and the TG-43 simulation by 2%–17% and 29%–34%, respectively. Replacing the surrounding tissues in the eye model with water increases the maximum and average doses to the lens by 2% and 3%, respectively. Substituting the tumor medium in the eye model for water, soft tissue, or an alternate melanoma composition affects tumor dose compared to the default eye model simulation by up

  1. Comparison of radiation doses using weight-based protocol and dose modulation techniques for patients undergoing biphasic abdominal computed tomography examinations

    Directory of Open Access Journals (Sweden)

    Livingstone Roshan

    2009-01-01

    Full Text Available Computed tomography (CT of the abdomen contributes a substantial amount of man-made radiation dose to patients and use of this modality is on the increase. This study intends to compare radiation dose and image quality using dose modulation techniques and weight- based protocol exposure parameters for biphasic abdominal CT. Using a six-slice CT scanner, a prospective study of 426 patients who underwent abdominal CT examinations was performed. Constant tube potentials of 90 kV and 120 kV were used for all arterial and portal venous phase respectively. The tube current-time product for weight-based protocol was optimized according to patient′s body weight; this was automatically selected in dose modulations. The effective dose using weight-based protocol, angular and z-axis dose modulation was 11.3 mSv, 9.5 mSv and 8.2 mSv respectively for the patient′s body weight ranging from 40 to 60 kg. For patients of body weights ranging 60 to 80 kg, the effective doses were 13.2 mSv, 11.2 mSv and 10.6 mSv respectively. The use of dose modulation technique resulted in a reduction of 16 to 28% in radiation dose with acceptable diagnostic accuracy in comparison to the use of weight-based protocol settings.

  2. SU-F-19A-10: Recalculation and Reporting Clinical HDR 192-Ir Head and Neck Dose Distributions Using Model Based Dose Calculation

    Energy Technology Data Exchange (ETDEWEB)

    Carlsson Tedgren, A [Linkoping University, Linkoping, Linkoping (Sweden); Persson, M; Nilsson, J [Karolinska hospital, Stockholm, Stockholm (Sweden)

    2014-06-15

    Purpose: To retrospectively re-calculate dose distributions for selected head and neck cancer patients, earlier treated with HDR 192Ir brachytherapy, using Monte Carlo (MC) simulations and compare results to distributions from the planning system derived using TG43 formalism. To study differences between dose to medium (as obtained with the MC code) and dose to water in medium as obtained through (1) ratios of stopping powers and (2) ratios of mass energy absorption coefficients between water and medium. Methods: The MC code Algebra was used to calculate dose distributions according to earlier actual treatment plans using anonymized plan data and CT images in DICOM format. Ratios of stopping power and mass energy absorption coefficients for water with various media obtained from 192-Ir spectra were used in toggling between dose to water and dose to media. Results: Differences between initial planned TG43 dose distributions and the doses to media calculated by MC are insignificant in the target volume. Differences are moderate (within 4–5 % at distances of 3–4 cm) but increase with distance and are most notable in bone and at the patient surface. Differences between dose to water and dose to medium are within 1-2% when using mass energy absorption coefficients to toggle between the two quantities but increase to above 10% for bone using stopping power ratios. Conclusion: MC predicts target doses for head and neck cancer patients in close agreement with TG43. MC yields improved dose estimations outside the target where a larger fraction of dose is from scattered photons. It is important with awareness and a clear reporting of absorbed dose values in using model based algorithms. Differences in bone media can exceed 10% depending on how dose to water in medium is defined.

  3. SU-F-19A-10: Recalculation and Reporting Clinical HDR 192-Ir Head and Neck Dose Distributions Using Model Based Dose Calculation

    International Nuclear Information System (INIS)

    Carlsson Tedgren, A; Persson, M; Nilsson, J

    2014-01-01

    Purpose: To retrospectively re-calculate dose distributions for selected head and neck cancer patients, earlier treated with HDR 192Ir brachytherapy, using Monte Carlo (MC) simulations and compare results to distributions from the planning system derived using TG43 formalism. To study differences between dose to medium (as obtained with the MC code) and dose to water in medium as obtained through (1) ratios of stopping powers and (2) ratios of mass energy absorption coefficients between water and medium. Methods: The MC code Algebra was used to calculate dose distributions according to earlier actual treatment plans using anonymized plan data and CT images in DICOM format. Ratios of stopping power and mass energy absorption coefficients for water with various media obtained from 192-Ir spectra were used in toggling between dose to water and dose to media. Results: Differences between initial planned TG43 dose distributions and the doses to media calculated by MC are insignificant in the target volume. Differences are moderate (within 4–5 % at distances of 3–4 cm) but increase with distance and are most notable in bone and at the patient surface. Differences between dose to water and dose to medium are within 1-2% when using mass energy absorption coefficients to toggle between the two quantities but increase to above 10% for bone using stopping power ratios. Conclusion: MC predicts target doses for head and neck cancer patients in close agreement with TG43. MC yields improved dose estimations outside the target where a larger fraction of dose is from scattered photons. It is important with awareness and a clear reporting of absorbed dose values in using model based algorithms. Differences in bone media can exceed 10% depending on how dose to water in medium is defined

  4. A microcontroller based lyoluminescence recording system for high dose dosimetry

    International Nuclear Information System (INIS)

    Thakur, Vaishali M.; Raman, Anand; Oommen, I.K.; Choithramani, S.J.; Sharma, D.N.

    2001-01-01

    This paper describes the features of a microcontroller based lyoluminescence (LL) measurement system which provides the peak yield versus time plot and the integrated light yield of the LL process. The peak yield is found to be a better measure of the LL process as compared to the integrated yield. (author)

  5. Toward an organ based dose prescription method for the improved accuracy of murine dose in orthovoltage x-ray irradiators

    International Nuclear Information System (INIS)

    Belley, Matthew D.; Wang, Chu; Nguyen, Giao; Gunasingha, Rathnayaka; Chao, Nelson J.; Chen, Benny J.; Dewhirst, Mark W.; Yoshizumi, Terry T.

    2014-01-01

    Purpose: Accurate dosimetry is essential when irradiating mice to ensure that functional and molecular endpoints are well understood for the radiation dose delivered. Conventional methods of prescribing dose in mice involve the use of a single dose rate measurement and assume a uniform average dose throughout all organs of the entire mouse. Here, the authors report the individual average organ dose values for the irradiation of a 12, 23, and 33 g mouse on a 320 kVp x-ray irradiator and calculate the resulting error from using conventional dose prescription methods. Methods: Organ doses were simulated in the Geant4 application for tomographic emission toolkit using the MOBY mouse whole-body phantom. Dosimetry was performed for three beams utilizing filters A (1.65 mm Al), B (2.0 mm Al), and C (0.1 mm Cu + 2.5 mm Al), respectively. In addition, simulated x-ray spectra were validated with physical half-value layer measurements. Results: Average doses in soft-tissue organs were found to vary by as much as 23%–32% depending on the filter. Compared to filters A and B, filter C provided the hardest beam and had the lowest variation in soft-tissue average organ doses across all mouse sizes, with a difference of 23% for the median mouse size of 23 g. Conclusions: This work suggests a new dose prescription method in small animal dosimetry: it presents a departure from the conventional approach of assigninga single dose value for irradiation of mice to a more comprehensive approach of characterizing individual organ doses to minimize the error and uncertainty. In human radiation therapy, clinical treatment planning establishes the target dose as well as the dose distribution, however, this has generally not been done in small animal research. These results suggest that organ dose errors will be minimized by calibrating the dose rates for all filters, and using different dose rates for different organs

  6. A Study of the Literature on Lab-Based Instruction in Biology

    Science.gov (United States)

    Puttick, Gillian; Drayton, Brian; Cohen, Eliza

    2015-01-01

    We analyzed the practitioner literature on lab-based instruction in biology in "The American Biology Teacher" between 2007 and 2012. We investigated what laboratory learning looks like in biology classrooms, what topics are addressed, what instructional methods and activities are described, and what is being learned about student…

  7. Challenges and Opportunities for Learning Biology in Distance-Based Settings

    Science.gov (United States)

    Hallyburton, Chad L.; Lunsford, Eddie

    2013-01-01

    The history of learning biology through distance education is documented. A review of terminology and unique problems associated with biology instruction is presented. Using published research and their own teaching experience, the authors present recommendations and best practices for managing biology in distance-based formats. They offer ideas…

  8. Early Childhood Education: The Biological Bases: Malnutrition and Behavioral Development

    Science.gov (United States)

    Read, Merrill S.

    1972-01-01

    Malnutrition, contrasted with hunger, is defined as a state of impaired functional ability or development resulting from an inadequate supply of essential nutrients or calories to meet long-term biologic needs. (Author/MB)

  9. Biological dosimetry of low doses (0.05 - 0.4 Gy) with micronucleus dicentrics and chromosome fragments

    International Nuclear Information System (INIS)

    Rodriguez, L.; Sanchez, E.; Linares, C.; Navlet, J.

    1997-01-01

    This study was carried out within the framework of the agreement between the National Nuclear Safety Council and the University of Alcala of Hernares and in co-operation with the Radiological Service and the Radiation Protection Unit of the Gregorio Maranon General Hospital of Madrid, where irradiations were performed. Blood samples were taken of 4 individuals irradiated with 6 doses of gamma rays between 0.05 Gy and 0.40 Gy, leaving an aliquot dose of 0 Gy. Cultures of lymphocytes for the study of dicentric chromosomes (DC) and chromosomal fragments (fr), stopping the first mitosis after postirradiation with Colcemid. A study of micronuclei (MN) in binuclear cells was also performed, interrupting the first cytokinesis after postirradiation with citocalasina B. After the corresponding studies with optical microscope, statistical analysis was made on the observed data on DC, fr and MN. We made a multiple linear regression analysis of the data of the 4 individuals. We obtained the average of the 4 individuals for each variable and dose and performed the variance analysis. According to our study, neither the DC nor the MN are valid dosemeters for lower doses up to 0.4 Gy. Nevertheless there are indications that the fragments are correlated with the dose to these levels. By increasing both the points of dose and the number of metaphases studied, we believe that a dose curve can be done that would allow to estimate with a reasonable degree of confidence the dose received by a sample irradiated

  10. Normal tissue complication probabilities: dependence on choice of biological model and dose-volume histogram reduction scheme

    International Nuclear Information System (INIS)

    Moiseenko, Vitali; Battista, Jerry; Van Dyk, Jake

    2000-01-01

    Purpose: To evaluate the impact of dose-volume histogram (DVH) reduction schemes and models of normal tissue complication probability (NTCP) on ranking of radiation treatment plans. Methods and Materials: Data for liver complications in humans and for spinal cord in rats were used to derive input parameters of four different NTCP models. DVH reduction was performed using two schemes: 'effective volume' and 'preferred Lyman'. DVHs for competing treatment plans were derived from a sample DVH by varying dose uniformity in a high dose region so that the obtained cumulative DVHs intersected. Treatment plans were ranked according to the calculated NTCP values. Results: Whenever the preferred Lyman scheme was used to reduce the DVH, competing plans were indistinguishable as long as the mean dose was constant. The effective volume DVH reduction scheme did allow us to distinguish between these competing treatment plans. However, plan ranking depended on the radiobiological model used and its input parameters. Conclusions: Dose escalation will be a significant part of radiation treatment planning using new technologies, such as 3-D conformal radiotherapy and tomotherapy. Such dose escalation will depend on how the dose distributions in organs at risk are interpreted in terms of expected complication probabilities. The present study indicates considerable variability in predicted NTCP values because of the methods used for DVH reduction and radiobiological models and their input parameters. Animal studies and collection of standardized clinical data are needed to ascertain the effects of non-uniform dose distributions and to test the validity of the models currently in use

  11. The relative biological effectiveness of fractionated doses of fast neutrons (42 MeV sub d yields Be ) for normal tissues. Pt. 3; Effects on lung function

    Energy Technology Data Exchange (ETDEWEB)

    Rezvani, M.; Hopewell, J.W.; Robbins, M.E.C.; Hamlet, R. (Churchill Hospital, Oxford (UK)); Barnes, D.W.H.; Sansom, J.M.; Adams, P.J.V. (Medical Research Council, Harwell (UK). Radiobiological Research Unit)

    1990-11-01

    The effect of single and fractionated doses of fast neutrons (42 MeV{sub d{yields}Bc}) on the early and late radiation responses of the pig lung have been assessed by the measurement of changes in lung function using a {sup 133}Xe washout technique. The results obtained for irradiation schedules with fast neutrons have been compared with those after photon irradiation. There was no statistically significant difference between the values for the relative biological effectiveness (RBE) for the early and late radiation response of the lung. The RBE of the neutron beam increased with decreasing size of dose/fraction with an upper limit value of 4.39 {plus minus} 0.94 for infinitely small X-ray doses per fraction. (author).

  12. 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

  13. Molecular biology-based diagnosis and therapy for pancreatic cancer

    International Nuclear Information System (INIS)

    Fujita, Hayato; Ohuchida, Kenoki; Mizumoto, Kazuhiro; Tanaka, Masao

    2011-01-01

    Mainly described are author's investigations of the title subject through clinical and basic diagnosis/therapeutic approach. Based on their consideration of carcinogenesis and pathological features of pancreatic cancer (PC), analysis of expression of cancer-related genes in clinically available samples like pancreatic juice and cells biopsied can result in attaining their purposes. Desmoplasia, a pathological feature of PC, possibly induces resistance to therapy and one of strategies is probably its suppression. Targeting stem cells of the mesenchyma as well as those of PC is also a strategy in future. Authors' studies have revealed that quantitation of hTERT (coding teromerase) mRNA levels in PC cells micro-dissected from cytological specimens is an accurate molecular biological diagnostic method applicable clinically. Other cancer-related genes are also useful for the diagnosis and mucin (MUC) family genes are shown to be typical ones for differentiating the precancerous PC, PC and chronic pancreatisis. Efficacy of standard gemcitabine chemotherapy can be individualized with molecular markers concerned to metabolism of the drug like dCK. Radiotherapy/radio-chemotherapy are not so satisfactory for PC treatment now. Authors have found elevated MMP-2 expression and HGF/c-Met signal activation in irradiated PC cells, which can increase the invasive capability; and stimulation of phosphorylation and activation of c-Met/MARK in co-culture of irradiated PC cells with messenchymal cells from PC, which possibly leads to progression of malignancy of PC through their interaction, of which suppression, therefore, can be a new approach to increase the efficacy of radiotherapy. Authors are making effort to introducing adenovirus therapy in clinic; exempli gratia (e.g.), the virus carrying wild type p53, a cancer-suppressive gene, induces apoptosis of PC cells often having its mutated gene. (T.T.)

  14. Mucosal dose prescription in endobronchial brachytherapy: a study based on CT-dosimetry

    International Nuclear Information System (INIS)

    Lagerwaard, Frank J.; Murrer, Lars H.P.; Pan, Connie de; Roos, Martin; Senan, Suresh

    2000-01-01

    Purpose: To investigate the consequences of using different dose prescription methods for endobronchial brachytherapy (EB), both with and without the use of a centered applicator. Materials and Methods: A CT scan was performed during EB procedures in 13 patients after insertion of the lung applicator. A dosimetric analysis was subsequently performed in five of these patients using a 3D-brachytherapy treatment planning system (PLATO v13.3, Nucletron). Results: Dose prescription to the mucosa yields uniform dose distributions to the bronchial mucosa when a centrally positioned applicator is used. When non-centrally positioned applicators are used, mucosal dosing results in a significant underdosage to parts of the target volume. Due to the rapid dose fall-off in EB, dose prescription to the mucosa resulted in inadequate coverage of the outer portion of the bronchial wall and adjacent peribronchial space. When compared to mucosal dose prescription, prescription to the outer aspect of the bronchial wall appears to improve target coverage while limiting the hyperdose (i.e., 200%) volume. The diameters of the different bronchial segments, as determined by CT measurements in 13 patients, correlated well with calculated values based upon the tracheal diameter. Conclusions: Mucosal dose prescription should only be used in combination with centered EB applicators. Given the rapid dose fall-off in EB mucosal dose prescription should be used with caution in curative treatments where EB, without additional external radiotherapy, is used as the sole treatment modality. In curative EB, both improved target coverage and a limited hyperdose volume can be achieved by dose prescription to the outer aspect of the bronchial wall

  15. SU-E-P-47: Evaluation of Improvement of Esophagus Sparing in SBRT Lung Patients with Biologically Based IMRT Optimization

    International Nuclear Information System (INIS)

    Liang, X; Penagaricano, J; Paudel, N; Zhang, X; Morrill, S; Corry, P; Han, E; Hardee, M; Ratanatharathorn, V

    2015-01-01

    Purpose: To study the potential of improving esophageal sparing for stereotactic body radiation therapy (SBRT) lung cancer patients by using biological optimization (BO) compared to conventional dose-volume based optimization (DVO) in treatment planning. Methods: Three NSCLC patients (PTV (62.3cc, 65.1cc, and 125.1cc) adjacent to the heart) previously treated with SBRT were re-planned using Varian Eclipse TPS (V11) using DVO and BO. The prescription dose was 60 Gy in 5 fractions normalized to 95% of the PTV volume. Plans were evaluated by comparing esophageal maximum doses, PTV heterogeneity (HI= D5%/D95%), and Paddick’s conformity (CI) indices. Quality of the plans was assessed by clinically-used IMRT QA procedures. Results: By using BO, the maximum dose to the esophagus was decreased 1384 cGy (34.6%), 502 cGy (16.5%) and 532 cGy (16.2%) in patient 1, 2 and 3 respectively. The maximum doses to spinal cord and the doses to 1000 cc and 1500 cc of normal lung were comparable in both plans. The mean doses (Dmean-hrt) and doses to 15cc of the heart (V15-hrt) were comparable for patient 1 and 2. However for patient 3, with the largest PTV, Dmean-hrt and V15-hrt increased by 62.2 cGy (18.3%) and 549.9 cGy (24.9%) respectively for the BO plans. The mean target HI of BO plans (1.13) was inferior to the DVO plans (1.07). The same trend was also observed for mean CI in BO plans (0.77) versus DVO plans (0.83). The QA pass rates (3%, 3mm) were comparable for both plans. Conclusion: This study demonstrated that the use of biological models in treatment planning optimization can substantially improve esophageal sparing without compromising spinal cord and normal lung doses. However, for the large PTV case (125.1cc) we studied here, Dmean-hrt and V15-hrt increased substantially. The target HI and CI were inferior in the BO plans

  16. Influence of length of interval between pulses in PDR brachytherapy (PDRBT on value of Biologically Equivalent Dose (BED in healthy tissues

    Directory of Open Access Journals (Sweden)

    Tomasz Piotrowski

    2010-07-01

    Full Text Available Purpose: Different PDR treatment schemas are used in clinical practice, however optimal length of interval between pulses still remains unclear. The aim of this work was to compare value of BED doses measured in surrounded healthy tissues according to different intervals between pulses in PDRBT. Influence of doses optimization on BED values was analyzed.Material and methods: Fifty-one patients treated in Greater Poland Cancer Centre were qualified for calculations.Calculations of doses were made in 51 patients with head and neck cancer, brain tumor, breast cancer, sarcoma, penis cancer and rectal cancer. Doses were calculated with the use of PLATO planning system in chosen critical points in surrounded healthy tissues. For all treatment plans the doses were compared using Biologically Equivalent Dose formula.Three interval lengths (1, 2 and 4 hours between pulses were chosen for calculations. For statistical analysis Friedman ANOVA test and Kendall ratio were used.Results: The median value of BED in chosen critical points in healthy tissues was statistically related to the length of interval between PDR pulses and decreased exponentially with 1 hour interval to 4 hours (Kendall = from 0.48 to 1.0; p = from 0.002 to 0.00001.Conclusions: Prolongation of intervals between pulses in PDR brachytherapy was connected with lower values of BED doses in healthy tissues. It seems that longer intervals between pulses reduced the risk of late complications, but also decreased the tumour control. Furthermore, optimization influenced the increase of doses in healthy tissues.

  17. Consolidating duodenal and small bowel toxicity data via isoeffective dose calculations based on compiled clinical data.

    Science.gov (United States)

    Prior, Phillip; Tai, An; Erickson, Beth; Li, X Allen

    2014-01-01

    To consolidate duodenum and small bowel toxicity data from clinical studies with different dose fractionation schedules using the modified linear quadratic (MLQ) model. A methodology of adjusting the dose-volume (D,v) parameters to different levels of normal tissue complication probability (NTCP) was presented. A set of NTCP model parameters for duodenum toxicity were estimated by the χ(2) fitting method using literature-based tolerance dose and generalized equivalent uniform dose (gEUD) data. These model parameters were then used to convert (D,v) data into the isoeffective dose in 2 Gy per fraction, (D(MLQED2),v) and convert these parameters to an isoeffective dose at another NTCP (D(MLQED2'),v). The literature search yielded 5 reports useful in making estimates of duodenum and small bowel toxicity. The NTCP model parameters were found to be TD50(1)(model) = 60.9 ± 7.9 Gy, m = 0.21 ± 0.05, and δ = 0.09 ± 0.03 Gy(-1). Isoeffective dose calculations and toxicity rates associated with hypofractionated radiation therapy reports were found to be consistent with clinical data having different fractionation schedules. Values of (D(MLQED2'),v) between different NTCP levels remain consistent over a range of 5%-20%. MLQ-based isoeffective calculations of dose-response data corresponding to grade ≥2 duodenum toxicity were found to be consistent with one another within the calculation uncertainty. The (D(MLQED2),v) data could be used to determine duodenum and small bowel dose-volume constraints for new dose escalation strategies. Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

  18. Inversion-based propofol dosing for intravenous induction of hypnosis

    Science.gov (United States)

    Padula, F.; Ionescu, C.; Latronico, N.; Paltenghi, M.; Visioli, A.; Vivacqua, G.

    2016-10-01

    In this paper we propose an inversion-based methodology for the computation of a feedforward action for the propofol intravenous administration during the induction of hypnosis in general anesthesia. In particular, the typical initial bolus is substituted with a command signal that is obtained by predefining a desired output and by applying an input-output inversion procedure. The robustness of the method has been tested by considering a set of patients with different model parameters, which is representative of a large population.

  19. Investigations on construction material and construction concepts in order to obtain dose-reducing effects in the dismantling of the biological shield of a 1300 MWe-PWR

    International Nuclear Information System (INIS)

    Bittner, A.; Jungwirth, D.; Knell, M.; Schnitzler, L.

    1984-04-01

    Numerical values of neutron fluxes, activations, dose rates etc. as a function of characteristic values of materials required for optimization purposes to reduce the radiation effect of the biological shield of a PWR are not available. Design concepts are presented for biological shields of PWRs made of concrete with respect to both the most suitable application of materials and the design principles aiming at reduced radiation exposure as compared to present designs during entering, waste disposal and ultimate storage. To evaluate the present-state design the above values have been calculated. Suggested alternative designs are biological shields with selective material application, built from precast elements with or without boron carbide layer arranged in front of it. (orig./HP) [de

  20. Fiber optical dose rate measurement based on the luminescence of beryllium oxide

    Directory of Open Access Journals (Sweden)

    Teichmann Tobias

    2018-01-01

    Full Text Available This work presents a fiber optical dose rate measurement system based on the radioluminescence and optically stimulated luminescence of beryllium oxide. The system consists of a small, radiation sensitive probe which is coupled to a light detection unit with a long and flexible light guide. Exposing the beryllium oxide probe to ionizing radiation results in the emission of light with an intensity which is proportional to the dose rate. Additionally, optically stimulated luminescence can be used to obtain dose and dose rate information during irradiation or retrospectively. The system is capable of real time dose rate measurements in fields of high dose rates and dose rate gradients and in complex, narrow geometries. This enables the application for radiation protection measurements as well as for quality control in radiotherapy. One inherent drawback of fiber optical dosimetry systems is the generation of Cherenkov radiation and luminescence in the light guide itself when it is exposed to ionizing radiation. This so called “stem” effect leads to an additional signal which introduces a deviation in the dose rate measurement and reduces the spatial resolution of the system, hence it has to be removed. The current system uses temporal discrimination of the effect for radioluminescence measurements in pulsed radiation fields and modulated optically stimulated luminescence for continuous irradiation conditions. This work gives an overview of the major results and discusses new-found obstacles of the applied methods of stem discrimination.

  1. Construction of boundary-surface-based Chinese female astronaut computational phantom and proton dose estimation

    International Nuclear Information System (INIS)

    Sun Wenjuan; Xie Tianwu; Liu Qian; Jia Xianghong; Xu Feng

    2013-01-01

    With the rapid development of China's space industry, the importance of radiation protection is increasingly prominent. To provide relevant dose data, we first developed the Visible Chinese Human adult Female (VCH-F) phantom, and performed further modifications to generate the VCH-F Astronaut (VCH-FA) phantom, incorporating statistical body characteristics data from the first batch of Chinese female astronauts as well as reference organ mass data from the International Commission on Radiological Protection (ICRP; both within 1% relative error). Based on cryosection images, the original phantom was constructed via Non-Uniform Rational B-Spline (NURBS) boundary surfaces to strengthen the deformability for fitting the body parameters of Chinese female astronauts. The VCH-FA phantom was voxelized at a resolution of 2 x 2 x 4 mm 3 for radioactive particle transport simulations from isotropic protons with energies of 5000 - 10 000 MeV in Monte Carlo N-Particle eXtended (MCNPX) code. To investigate discrepancies caused by anatomical variations and other factors, the obtained doses were compared with corresponding values from other phantoms and sex-averaged doses. Dose differences were observed among phantom calculation results, especially for effective dose with low-energy protons. Local skin thickness shifts the breast dose curve toward high energy, but has little impact on inner organs. Under a shielding layer, organ dose reduction is greater for skin than for other organs. The calculated skin dose per day closely approximates measurement data obtained in low-Earth orbit (LEO). (author)

  2. Effects of emitter junction and passive base region on low dose rate effect in bipolar devices

    International Nuclear Information System (INIS)

    Pershenkov, V.S.; Cherepko, S.V.; Maslov, V.B.; Belyakov, V.V.; Sogoyan, A.V.; Ulimov, N.; Emelianov, V.V.

    1999-01-01

    Low dose rate effect in bipolar devices consists in the increase of peripheral surface recombination current with dose rate decrease. This is due to the more rapid positive oxide charge and interface trap density build-up as the dose rate becomes lower. High dose rate elevated temperature irradiation is proposed for simulation if the low dose rate effect. In the present we tried to separate the effect of radiation-induced charge in the thick passivation oxide over the emitter junction and passive base regions of npn bipolar transistor. Its goal is to improve bipolar device design for use in space environments and nuclear installations. Three experiments were made during this work. 1. Experiment on radiation-induced charge neutralization (RICN) effect under elevated temperature was performed to show transistor degradation dependence on emitter-base bias. 2. High dose rate elevated and room temperature irradiation of bipolar transistors were performed to separate effects of emitter-junction and passive base regions. 3. Pre- and post- irradiation hydrogen ambient storage was used to investigate its effect on radiation-induced charge build-up over the passive base region. All experiments were performed with npn and pnp transistors. (authors)

  3. Biological and ecological responses to carbon-based nanomaterials

    Science.gov (United States)

    Ratnikova, Tatsiana A.

    This dissertation examines the biological and ecological responses to carbon nanoparticles, a major class of nanomaterials which have been mass produced and extensively studied for their rich physical properties and commercial values. Chapter I of this dissertation offers a comprehensive review on the structures, properties, applications, and implications of carbon nanomaterials, especially related to the perspectives of biological and ecosystems. Given that there are many types of carbon nanomaterials available, this chapter is focused on three major types of carbon-based nanomaterials only, namely, fullerenes, single walled and multi-walled carbon nanotubes. On the whole organism level, specifically, Chapter II presents a first study on the fate of fullerenes and multiwalled carbon nanotubes in rice plants, which was facilitated by the self assembly of these nanomaterials with NOM. The aspects of fullerene uptake, translocation, biodistribution, and generational transfer in the plants were examined and quantified using bright field and electron microscopy, FT-Raman, and FTIR spectroscopy. The uptake and transport of fullerene in the plant vascular system were attributed to water transpiration, convection, capillary force, and the fullerene concentration gradient from the roots to the leaves of the plants. On the cellular level, Chapter III documents the differential uptake of hydrophilic C60(OH)20 vs. amphiphilic C70-NOM complex in Allium cepa plant cells and HT-29 colon carcinoma cells. This study was conducted using a plant cell viability assay, and complemented by bright field, fluorescence and electron microscopy imaging. In particular, C60(OH)20 and C70-NOM showed contrasting uptake in both the plant and mammalian cells, due to their significant differences in physicochemistry and the presence of an extra hydrophobic plant cell wall in the plant cells. Consequently, C60(OH)20 was found to induce toxicity in Allium cepa cells but not in HT-29 cells, while C70

  4. 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

  5. SU-E-T-602: Patient-Specific Online Dose Verification Based On Transmission Detector Measurements

    International Nuclear Information System (INIS)

    Thoelking, J; Yuvaraj, S; Jens, F; Lohr, F; Wenz, F; Wertz, H; Wertz, H

    2015-01-01

    Purpose: Intensity modulated radiotherapy requires a comprehensive quality assurance program in general and ideally independent verification of dose delivery. Since conventional 2D detector arrays allow only pre-treatment verification, there is a debate concerning the need of online dose verification. This study presents the clinical performance, including dosimetric plan verification in 2D as well as in 3D and the error detection abilities of a new transmission detector (TD) for online dose verification of 6MV photon beam. Methods: To validate the dosimetric performance of the new device, dose reconstruction based on TD measurements were compared to a conventional pre-treatment verification method (reference) and treatment planning system (TPS) for 18 IMRT and VMAT treatment plans. Furthermore, dose reconstruction inside the patient based on TD read-out was evaluated by comparing various dose volume indices and 3D gamma evaluations against independent dose computation and TPS. To investigate the sensitivity of the new device, different types of systematic and random errors for leaf positions and linac output were introduced in IMRT treatment sequences. Results: The 2D gamma index evaluation of transmission detector based dose reconstruction showed an excellent agreement for all IMRT and VMAT plans compared to reference measurements (99.3±1.2)% and TPS (99.1±0.7)%. Good agreement was also obtained for 3D dose reconstruction based on TD read-out compared to dose computation (mean gamma value of PTV = 0.27±0.04). Only a minimal dose underestimation within the target volume was observed when analyzing DVH indices (<1%). Positional errors in leaf banks larger than 1mm and errors in linac output larger than 2% could clearly identified with the TD. Conclusion: Since 2D and 3D evaluations for all IMRT and VMAT treatment plans were in excellent agreement with reference measurements and dose computation, the new TD is suitable to qualify for routine treatment plan

  6. SU-E-T-602: Patient-Specific Online Dose Verification Based On Transmission Detector Measurements

    Energy Technology Data Exchange (ETDEWEB)

    Thoelking, J; Yuvaraj, S; Jens, F; Lohr, F; Wenz, F; Wertz, H; Wertz, H [University Medical Center Mannheim, University of Heidelberg, Mannheim, Baden-Wuerttemberg (Germany)

    2015-06-15

    Purpose: Intensity modulated radiotherapy requires a comprehensive quality assurance program in general and ideally independent verification of dose delivery. Since conventional 2D detector arrays allow only pre-treatment verification, there is a debate concerning the need of online dose verification. This study presents the clinical performance, including dosimetric plan verification in 2D as well as in 3D and the error detection abilities of a new transmission detector (TD) for online dose verification of 6MV photon beam. Methods: To validate the dosimetric performance of the new device, dose reconstruction based on TD measurements were compared to a conventional pre-treatment verification method (reference) and treatment planning system (TPS) for 18 IMRT and VMAT treatment plans. Furthermore, dose reconstruction inside the patient based on TD read-out was evaluated by comparing various dose volume indices and 3D gamma evaluations against independent dose computation and TPS. To investigate the sensitivity of the new device, different types of systematic and random errors for leaf positions and linac output were introduced in IMRT treatment sequences. Results: The 2D gamma index evaluation of transmission detector based dose reconstruction showed an excellent agreement for all IMRT and VMAT plans compared to reference measurements (99.3±1.2)% and TPS (99.1±0.7)%. Good agreement was also obtained for 3D dose reconstruction based on TD read-out compared to dose computation (mean gamma value of PTV = 0.27±0.04). Only a minimal dose underestimation within the target volume was observed when analyzing DVH indices (<1%). Positional errors in leaf banks larger than 1mm and errors in linac output larger than 2% could clearly identified with the TD. Conclusion: Since 2D and 3D evaluations for all IMRT and VMAT treatment plans were in excellent agreement with reference measurements and dose computation, the new TD is suitable to qualify for routine treatment plan

  7. Data base of dose coefficients called ecrin-V1-internet reference handbook

    International Nuclear Information System (INIS)

    Perrin, M.L.

    2003-07-01

    The objective of this data base is to dispose on a only computer medium the values of radiation doses allowing to guarantee the tracing and the coherence of radiation doses received by man. These data are usable to evaluate the risks in the frame of studies or expertise. They include the doses coming from external irradiations, internal contamination by inhalation or ingestion and receive by workers or public. The definitions and reference values come from international publications (the list is given). (N.C.)

  8. Predicting standard-dose PET image from low-dose PET and multimodal MR images using mapping-based sparse representation

    International Nuclear Information System (INIS)

    Wang, Yan; Zhou, Jiliu; Zhang, Pei; An, Le; Ma, Guangkai; Kang, Jiayin; Shi, Feng; Shen, Dinggang; Wu, Xi; Lalush, David S; Lin, Weili

    2016-01-01

    Positron emission tomography (PET) has been widely used in clinical diagnosis for diseases and disorders. To obtain high-quality PET images requires a standard-dose radionuclide (tracer) injection into the human body, which inevitably increases risk of radiation exposure. One possible solution to this problem is to predict the standard-dose PET image from its low-dose counterpart and its corresponding multimodal magnetic resonance (MR) images. Inspired by the success of patch-based sparse representation (SR) in super-resolution image reconstruction, we propose a mapping-based SR (m-SR) framework for standard-dose PET image prediction. Compared with the conventional patch-based SR, our method uses a mapping strategy to ensure that the sparse coefficients, estimated from the multimodal MR images and low-dose PET image, can be applied directly to the prediction of standard-dose PET image. As the mapping between multimodal MR images (or low-dose PET image) and standard-dose PET images can be particularly complex, one step of mapping is often insufficient. To this end, an incremental refinement framework is therefore proposed. Specifically, the predicted standard-dose PET image is further mapped to the target standard-dose PET image, and then the SR is performed again to predict a new standard-dose PET image. This procedure can be repeated for prediction refinement of the iterations. Also, a patch selection based dictionary construction method is further used to speed up the prediction process. The proposed method is validated on a human brain dataset. The experimental results show that our method can outperform benchmark methods in both qualitative and quantitative measures. (paper)

  9. Moving from gamma passing rates to patient DVH-based QA metrics in pretreatment dose QA

    Energy Technology Data Exchange (ETDEWEB)

    Zhen, Heming; Nelms, Benjamin E.; Tome, Wolfgang A. [Department of Medical Physics, University of Wisconsin, Madison, Wisconsin 53705 (United States); Department of Human Oncology, University of Wisconsin, Madison, Wisconsin 53792 and Canis Lupus LLC, Merrimac, Wisconsin 53561 (United States); Department of Medical Physics, University of Wisconsin, Madison, Wisconsin 53705 and Department of Human Oncology, University of Wisconsin, Madison, Wisconsin 53792 (United States)

    2011-10-15

    Purpose: The purpose of this work is to explore the usefulness of the gamma passing rate metric for per-patient, pretreatment dose QA and to validate a novel patient-dose/DVH-based method and its accuracy and correlation. Specifically, correlations between: (1) gamma passing rates for three 3D dosimeter detector geometries vs clinically relevant patient DVH-based metrics; (2) Gamma passing rates of whole patient dose grids vs DVH-based metrics, (3) gamma passing rates filtered by region of interest (ROI) vs DVH-based metrics, and (4) the capability of a novel software algorithm that estimates corrected patient Dose-DVH based on conventional phan-tom QA data are analyzed. Methods: Ninety six unique ''imperfect'' step-and-shoot IMRT plans were generated by applying four different types of errors on 24 clinical Head/Neck patients. The 3D patient doses as well as the dose to a cylindrical QA phantom were then recalculated using an error-free beam model to serve as a simulated measurement for comparison. Resulting deviations to the planned vs simulated measured DVH-based metrics were generated, as were gamma passing rates for a variety of difference/distance criteria covering: dose-in-phantom comparisons and dose-in-patient comparisons, with the in-patient results calculated both over the whole grid and per-ROI volume. Finally, patient dose and DVH were predicted using the conventional per-beam planar data as input into a commercial ''planned dose perturbation'' (PDP) algorithm, and the results of these predicted DVH-based metrics were compared to the known values. Results: A range of weak to moderate correlations were found between clinically relevant patient DVH metrics (CTV-D95, parotid D{sub mean}, spinal cord D1cc, and larynx D{sub mean}) and both 3D detector and 3D patient gamma passing rate (3%/3 mm, 2%/2 mm) for dose-in-phantom along with dose-in-patient for both whole patient volume and filtered per-ROI. There was

  10. Feasibility of CBCT-based dose calculation: Comparative analysis of HU adjustment techniques

    International Nuclear Information System (INIS)

    Fotina, Irina; Hopfgartner, Johannes; Stock, Markus; Steininger, Thomas; Lütgendorf-Caucig, Carola; Georg, Dietmar

    2012-01-01

    Background and purpose: The aim of this work was to compare the accuracy of different HU adjustments for CBCT-based dose calculation. Methods and materials: Dose calculation was performed on CBCT images of 30 patients. In the first two approaches phantom-based (Pha-CC) and population-based (Pop-CC) conversion curves were used. The third method (WAB) represents override of the structures with standard densities for water, air and bone. In ROI mapping approach all structures were overridden with average HUs from planning CT. All techniques were benchmarked to the Pop-CC and CT-based plans by DVH comparison and γ-index analysis. Results: For prostate plans, WAB and ROI mapping compared to Pop-CC showed differences in PTV D median below 2%. The WAB and Pha-CC methods underestimated the bladder dose in IMRT plans. In lung cases PTV coverage was underestimated by Pha-CC method by 2.3% and slightly overestimated by the WAB and ROI techniques. The use of the Pha-CC method for head–neck IMRT plans resulted in difference in PTV coverage up to 5%. Dose calculation with WAB and ROI techniques showed better agreement with pCT than conversion curve-based approaches. Conclusions: Density override techniques provide an accurate alternative to the conversion curve-b