WorldWideScience

Sample records for biologically based dose

  1. Patient Preference for Dosing Frequency Based on Prior Biologic Experience.

    Science.gov (United States)

    Zhang, Mingliang; Carter, Chureen; Olson, William H; Johnson, Michael P; Brennem, Susan K; Lee, Seina; Farahi, Kamyar

    2017-03-01

    There is limited research exploring patient preferences regarding dosing frequency of biologic treatment of psoriasis. Patients with moderate-to-severe plaque psoriasis identified in a healthcare claims database completed a survey regarding experience with psoriasis treatments and preferred dosing frequency. Survey questions regarding preferences were posed in two ways: (1) by likelihood of choosing once per week or 2 weeks, or 12 weeks; and (2) by choosing one option among once every 1-2 or 3-4 weeks or 1-2 or 2-3 months. Data were analyzed by prior biologic history (biologic-experienced vs biologic-naïve, and with one or two specific biologics). Overall, 426 patients completed the survey: 163 biologic-naïve patients and 263 biologic-experienced patients (159 had some experience with etanercept, 105 with adalimumab, and 49 with ustekinumab). Among patients who indicated experience with one or two biologics, data were available for 219 (30 with three biologics and 14 did not specify which biologic experience). The majority of biologic-naïve (68.8%) and overall biologic-experienced (69.4%) patients indicated that they were very likely to choose the least frequent dosing option of once every 12 weeks (Table 1). In contrast, fewer biologic-naïve (9.1% and 16.7%) and biologic-experienced (22.5% and 25.3%) patients indicated that they were very likely to choose the 1-week and 2-week dosing interval options, respectively. In each cohort grouped by experience with specific biologics, among those with no experience with ustekinumab, the most chosen option was 1-2 weeks. The most frequently chosen option was every 2-3 months, among patients with any experience with ustekinumab, regardless of their experience with other biologics. The least frequent dosing interval was preferred among biologic naïve patients and patients who had any experience with ustekinumab. Dosing interval may influence the shared decision-making process for psoriasis treatment with biologics. J

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

    Energy Technology Data Exchange (ETDEWEB)

    Deasy, J. [Memorial Sloan Kettering Cancer Center, New York, NY (United States)

    2015-06-15

    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.

  3. WE-B-304-01: Treatment Planning Evaluation and Optimization Should Be Dose/volume and Not Biologically Based

    Energy Technology Data Exchange (ETDEWEB)

    Mayo, C. [Mayo Clinic (United States)

    2015-06-15

    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.

  4. 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...

  5. 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...

  6. 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 (EQD2) was calculated using biological effective dose (BED) based on the LQL model. The software calculation and the manual calculation were compared for EQD2 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 D90%, 0.56% in the bladder, 1.74% in the rectum when determined by D2cc, and less than 1% in Pinnacle. The difference in the EQD2 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.

  7. 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...

  8. Clinically applicable Monte Carlo-based biological dose optimization for the treatment of head and neck cancers with spot-scanning proton therapy

    CERN Document Server

    Tseung, H Wan Chan; Kreofsky, C R; Ma, D; Beltran, C

    2016-01-01

    Purpose: 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: 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 IMPT optimizer. Besides dose, the dose-averaged linear energy transfer (LETd) can be simultaneously scored, which makes biological dose (BD) optimization possible. To convert from LETd to BD, a linear relation was assumed. Using this novel optimizer, inverse biological planning was applied to 4 patients: 2 small and 1 large thyroid tumor targets, and 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 IMRT and IMPT plans were created for each case in Eclipse (Varian, Inc). The same critical structure PD constraints were use...

  9. Segmentation of biological target volumes on multi-tracer PET images based on information fusion for achieving dose painting in radiotherapy.

    Science.gov (United States)

    Lelandais, Benoît; Gardin, Isabelle; Mouchard, Laurent; Vera, Pierre; Ruan, Su

    2012-01-01

    Medical imaging plays an important role in radiotherapy. Dose painting consists in the application of a nonuniform dose prescription on a tumoral region, and is based on an efficient segmentation of biological target volumes (BTV). It is derived from PET images, that highlight tumoral regions of enhanced glucose metabolism (FDG), cell proliferation (FLT) and hypoxia (FMiso). In this paper, a framework based on Belief Function Theory is proposed for BTV segmentation and for creating 3D parametric images for dose painting. We propose to take advantage of neighboring voxels for BTV segmentation, and also multi-tracer PET images using information fusion to create parametric images. The performances of BTV segmentation was evaluated on an anthropomorphic phantom and compared with two other methods. Quantitative results show the good performances of our method. It has been applied to data of five patients suffering from lung cancer. Parametric images show promising results by highlighting areas where a high frequency or dose escalation could be planned.

  10. Establishment of a γ-H2AX foci-based assay to determine biological dose of radon to red bone marrow in rats

    Science.gov (United States)

    Wang, Jing; He, Linfeng; Fan, Dunhuang; Ding, Defang; Wang, Xufei; Gao, Yun; Zhang, Xuxia; Li, Qiang; Chen, Honghong

    2016-07-01

    The biodosimetric information is critical for assessment of cancer risk in populations exposed to high radon. However, no tools are available for biological dose estimation following radon exposure. Here, we established a γ-H2AX foci-based assay to determine biological dose to red bone marrow (RBM) in radon-inhaled rats. After 1–3 h of in vitro radon exposure, a specific pattern of γ-H2AX foci, linear tracks with individual p-ATM and p-DNA-PKcs foci, was observed, and the yield of γ-H2AX foci and its linear tracks displayed a linear dose-response manner in both rat peripheral blood lymphocytes (PBLs) and bone-marrow lymphocytes (BMLs). When the cumulative doses of radon inhaled by rats reached 14, 30 and 60 working level months (WLM), the yields of three types of foci markedly increased in both PBLs and BMLs, and γ-H2AX foci-based dose estimates to RBM were 0.97, 2.06 and 3.94 mGy, respectively. Notably, BMLs displayed a more profound increase of three types of foci than PBLs, and the absorbed dose ratio between BMLs and PBLs was similar between rats exposed to 30 and 60 WLM of radon. Taken together, γ-H2AX foci quantitation in PBLs is able to estimate RBM-absorbed doses with the dose-response curve of γ-H2AX foci after in vitro radon exposure and the ratio of RBM- to PBL-absorbed doses in rats following radon exposure.

  11. Establishment of a γ-H2AX foci-based assay to determine biological dose of radon to red bone marrow in rats

    Science.gov (United States)

    Wang, Jing; He, Linfeng; Fan, Dunhuang; Ding, Defang; Wang, Xufei; Gao, Yun; Zhang, Xuxia; Li, Qiang; Chen, Honghong

    2016-01-01

    The biodosimetric information is critical for assessment of cancer risk in populations exposed to high radon. However, no tools are available for biological dose estimation following radon exposure. Here, we established a γ-H2AX foci-based assay to determine biological dose to red bone marrow (RBM) in radon-inhaled rats. After 1–3 h of in vitro radon exposure, a specific pattern of γ-H2AX foci, linear tracks with individual p-ATM and p-DNA-PKcs foci, was observed, and the yield of γ-H2AX foci and its linear tracks displayed a linear dose-response manner in both rat peripheral blood lymphocytes (PBLs) and bone-marrow lymphocytes (BMLs). When the cumulative doses of radon inhaled by rats reached 14, 30 and 60 working level months (WLM), the yields of three types of foci markedly increased in both PBLs and BMLs, and γ-H2AX foci-based dose estimates to RBM were 0.97, 2.06 and 3.94 mGy, respectively. Notably, BMLs displayed a more profound increase of three types of foci than PBLs, and the absorbed dose ratio between BMLs and PBLs was similar between rats exposed to 30 and 60 WLM of radon. Taken together, γ-H2AX foci quantitation in PBLs is able to estimate RBM-absorbed doses with the dose-response curve of γ-H2AX foci after in vitro radon exposure and the ratio of RBM- to PBL-absorbed doses in rats following radon exposure. PMID:27445126

  12. Dose response biology: the case of resveratrol.

    Science.gov (United States)

    Calabrese, Edward J; Mattson, Mark P; Calabrese, Vittorio

    2010-12-01

    Resveratrol often displays hormesis-like biphasic dose responses. This occurs in a broad range of biological models and for numerous endpoints of biomedical interest and public health concern. Recognition of the widespread occurrence of the hormetic nature of many of the responses of resveratrol is important on multiple levels. It can help optimize study design protocols by investigators, create a dose-response framework for better addressing dose-related biological complexities and assist in the development of public health and medical guidance with respect to considerations for what is an optimal dose not just for an agent such as resveratrol, but also for the plethora of agents that also act via hormetic mechanisms.

  13. Modeling Dose-response at Low Dose: A Systems Biology Approach for Ionization Radiation.

    Science.gov (United States)

    Zhao, Yuchao; Ricci, Paolo F

    2010-03-18

    For ionization radiation (IR) induced cancer, a linear non-threshold (LNT) model at very low doses is the default used by a number of national and international organizations and in regulatory law. This default denies any positive benefit from any level of exposure. However, experimental observations and theoretical biology have found that both linear and J-shaped IR dose-response curves can exist at those very low doses. We develop low dose J-shaped dose-response, based on systems biology, and thus justify its use regarding exposure to IR. This approach incorporates detailed, molecular and cellular descriptions of biological/toxicological mechanisms to develop a dose-response model through a set of nonlinear, differential equations describing the signaling pathways and biochemical mechanisms of cell cycle checkpoint, apoptosis, and tumor incidence due to IR. This approach yields a J-shaped dose response curve while showing where LNT behaviors are likely to occur. The results confirm the hypothesis of the J-shaped dose response curve: the main reason is that, at low-doses of IR, cells stimulate protective systems through a longer cell arrest time per unit of IR dose. We suggest that the policy implications of this approach are an increasingly correct way to deal with precautionary measures in public health.

  14. Three dimensional biological dose distribution of antiprotons

    Energy Technology Data Exchange (ETDEWEB)

    Tegami, Sara; Boll, Rebecca; Sellner, Stefan [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany); Welsch, Carsten P. [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany); Cockcroft Institute, University of Liverpool (United Kingdom); Holzscheiter, Michael H. [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany); University of New Mexico, Albuquerque (United States)

    2010-07-01

    The goal of external beam cancer therapy is to destroy the tumour while sparing the healthy tissue around it. In hadron therapy, the dose profile of heavy charged particles satisfies this request, because most of the energy is deposited at the end of the particle path, in the Bragg peak. Antiprotons are even more promising, thanks to the extra energy released by annihilation when captured in a normal atom at the end of range. The aim of the AD-4/ACE experiment at CERN is to determine the increase in biological dose near the Bragg peak due to densely ionizing particles emanating from the annihilation of antiprotons. Initial experiments showed the damage to cells inflicted at the end of the beam for identical damage at the skin level to be four times higher for antiprotons than for protons. The radiation field in a spread-out Bragg peak produced with antiprotons is highly mixed and for proper dose planning knowledge of linear energy transfer (LET) and relative biological efficiency (RBE) at any point in the target is needed. We are studying a number of detection methods for their response to mixed radiation fields with the goal to obtain a direct measurement of the 3D LET distribution and report on first results.

  15. The biologically effective dose in inhalation nanotoxicology.

    Science.gov (United States)

    Donaldson, Ken; Schinwald, Anja; Murphy, Fiona; Cho, Wan-Seob; Duffin, Rodger; Tran, Lang; Poland, Craig

    2013-03-19

    In all branches of toxicology, the biologically effective dose (BED) is the fraction of the total dose of a toxin that actually drives any toxic effect. Knowledge of the BED has a number of applications including in building structure-activity relationships, the selection of metrics, the design of safe particles, and the determination of when a nanoparticle (NP) can be considered to be "new" for regulatory purposes. In particle toxicology, we define the BED as "the entity within any dose of particles in tissue that drives a critical pathophysiogically relevant form of toxicity (e.g., oxidative stress, inflammation, genotoxicity, or proliferation) or a process that leads to it." In conventional chemical toxicology, researchers generally use the mass as the metric to describe dose (such as mass per unit tissue or cells in culture) because of its convenience. Concentration, calculated from mass, may also figure in any description of dose. In the case of a nanoparticle dose, researchers use either the mass or the surface area. The mass of nanoparticles is not the only driver of their activity: the surfaces of insoluble particles interact with biological systems, and soluble nanoparticles can release factors that interact with these systems. Nanoparticle shape can modify activity. In this Account, we describe the current knowledge of the BED as it pertains to different NP types. Soluble toxins released by NPs represent one potential indicator of BED for wholly or partially soluble NPs composed of copper or zinc. Rapid dissolution of these NPs into their toxic ions in the acidic environment of the macrophage phagolysosome causes those ions to accumulate, which leads to lysosome destabilization and inflammation. In contrast, soluble NPs that release low toxicity ions, such as magnesium oxide NPs, are not inflammogenic. For insoluble NPs, ζ potential can serve as a BED measurement because the exposure of the particle surface to the acidic milieu of the phagolysosome and

  16. 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.

  17. Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Tomohiko, E-mail: matsutomo_llp@yahoo.co.jp [Department of Radiation Oncology, Kumamoto University, Kumamoto (Japan); Kogo, Kasei [Kumamoto Radiosurgery Clinic, Kumamoto (Japan); Oya, Natsuo [Department of Radiation Oncology, Kumamoto University, Kumamoto (Japan)

    2013-03-15

    Purpose: To evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC). Methods and Materials: Between March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy{sub 10}. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method. Results: Local control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement. Conclusions: This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients.

  18. Responses to low doses of ionizing radiation in biological systems.

    Science.gov (United States)

    Feinendegen, Ludwig E; Pollycove, Myron; Sondhaus, Charles A

    2004-07-01

    Biological tissues operate through cells that act together within signaling networks. These assure coordinated cell function in the face of constant exposure to an array of potentially toxic agents, externally from the environment and endogenously from metabolism. Living tissues are indeed complex adaptive systems.To examine tissue effects specific for low-dose radiation, (1) absorbed dose in tissue is replaced by the sum of the energies deposited by each track event, or hit, in a cell-equivalent tissue micromass (1 ng) in all micromasses exposed, that is, by the mean energy delivered by all microdose hits in the exposed micromasses, with cell dose expressing the total energy per micromass from multiple microdoses; and (2) tissue effects are related to cell damage and protective cellular responses per average microdose hit from a given radiation quality for all such hits in the exposed micromasses.The probability of immediate DNA damage per low-linear-energy-transfer (LET) average micro-dose hit is extremely small, increasing over a certain dose range in proportion to the number of hits. Delayed temporary adaptive protection (AP) involves (a) induced detoxification of reactive oxygen species, (b) enhanced rate of DNA repair, (c) induced removal of damaged cells by apoptosis followed by normal cell replacement and by cell differentiation, and (d) stimulated immune response, all with corresponding changes in gene expression. These AP categories may last from less than a day to weeks and be tested by cell responses against renewed irradiation. They operate physiologically against nonradiogenic, largely endogenous DNA damage, which occurs abundantly and continually. Background radiation damage caused by rare microdose hits per micromass is many orders of magnitude less frequent. Except for apoptosis, AP increasingly fails above about 200 mGy of low-LET radiation, corresponding to about 200 microdose hits per exposed micromass. This ratio appears to exceed approximately

  19. Modeling of biological doses and mechanical effects on bone transduction

    CERN Document Server

    Rieger, Romain; Jennane, Rachid; 10.1016/j.jtbi.2011.01.003

    2012-01-01

    Shear stress, hormones like parathyroid and mineral elements like calcium mediate the amplitude of stimulus signal which affects the rate of bone remodeling. The current study investigates the theoretical effects of different metabolic doses in stimulus signal level on bone. The model was built considering the osteocyte as the sensing center mediated by coupled mechanical shear stress and some biological factors. The proposed enhanced model was developed based on previously published works dealing with different aspects of bone transduction. It describes the effects of physiological doses variations of Calcium, Parathyroid Hormone, Nitric Oxide and Prostaglandin E2 on the stimulus level sensed by osteocytes in response to applied shear stress generated by interstitial fluid flow. We retained the metabolic factors (Parathyroid Hormone, Nitric Oxide, and Prostaglandin E2) as parameters of bone cell mechanosensitivity because stimulation/inhibition of induced pathways stimulates osteogenic response in vivo. We t...

  20. 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

  1. Are there dangers in biologic dose reduction strategies?

    Science.gov (United States)

    Chan, Christopher K Y; Holroyd, Christopher R; Mason, Alice; Zarroug, Jalaa; Edwards, Christopher J

    2016-07-01

    Biologic dose reduction strategies, for patients with inflammatory rheumatic diseases, have been assessed in multiple studies to assess outcomes compared to ongoing maintenance dosing. Whilst cessation in established disease usually leads to disease flare, dose tapering approaches for those achieving low disease activity often appear to be successful in the short term. However, tapering can be associated with a higher risk of losing disease control and rates of recapture of disease control using the original biologic dose vary between studies. Over relatively short periods of follow-up, a number of studies have shown no statistical difference in radiographic progression in patients tapering or discontinuing biologics. However, a Cochrane review found that radiographic and functional outcomes may be worse after TNF inhibitor discontinuation, and over long-term disease follow-up flares have been associated with radiographic progression and worse patient reported outcomes. To date, no studies of biological therapy dose reduction have specifically investigated the risk of increased immunogenicity or the effects on cardiovascular risk and other co-morbidities, although these remain important potential risks. In addition, whether there are greater dangers in certain dose reduction approaches such as a reduction in dose at the same frequency or a spacing of doses is not established.

  2. Biological dose representation for carbon-ion radiotherapy of unconventional fractionation

    Science.gov (United States)

    Kanematsu, Nobuyuki; Inaniwa, Taku

    2017-02-01

    In carbon-ion radiotherapy, single-beam delivery each day in alternate directions has been common practice for efficient operation, taking advantage of the Bragg peak and the relative biological effectiveness (RBE) for uniform dose conformation to a tumor. Treatments are usually fractionated and treatment plans are evaluated with the total RBE-weighted dose; however, this is of limited relevance to the biological effect. In this study, we reformulate the biologically effective dose (BED) to normalize the dose-fractionation and cell-repopulation effects as well as the RBE of treating radiation, based on inactivation of a reference cell line by a reference carbon-ion radiation. The BED distribution virtually represents the biological effect of a treatment regardless of radiation modality or fractionation scheme. We applied the BED formulation to simplistic model treatments and to a preclinical survey for hypofractionation based on an actual prostate cancer treatment with carbon ions. The proposed formulation was demonstrated to be practical and to give theoretical implications. For a prostate cancer treatment in 12 fractions, the distributions of BED and of RBE-weighted dose were very similar. With hypofractionation, while the RBE-weighted dose distribution varied significantly, the BED distribution was nearly invariant, implying that carbon-ion radiotherapy would be effectively insensitive to fractionation. However, treatment evaluation with such a simplistic biological dose is intrinsically limited and must be complemented in practice by clinical experience and biological experiments.

  3. Biological effects and equivalent doses in radiotherapy: a software solution

    CERN Document Server

    Voyant, Cyril; Roustit, Rudy; Biffi, Katia; Marcovici, Celine Lantieri

    2013-01-01

    The limits of TDF (time, dose, and fractionation) and linear quadratic models have been known for a long time. Medical physicists and physicians are required to provide fast and reliable interpretations regarding the delivered doses or any future prescriptions relating to treatment changes. We therefore propose a calculation interface under the GNU license to be used for equivalent doses, biological doses, and normal tumor complication probability (Lyman model). The methodology used draws from several sources: the linear-quadratic-linear model of Astrahan, the repopulation effects of Dale, and the prediction of multi-fractionated treatments of Thames. The results are obtained from an algorithm that minimizes an ad-hoc cost function, and then compared to the equivalent dose computed using standard calculators in seven French radiotherapy centers.

  4. 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

  5. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-06-15

    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. Analysis of clinical trials with biologics using dose-time-response models.

    Science.gov (United States)

    Lange, Markus R; Schmidli, Heinz

    2015-09-30

    Biologics such as monoclonal antibodies are increasingly and successfully used for the treatment of many chronic diseases. Unlike conventional small drug molecules, which are commonly given as tablets once daily, biologics are typically injected at much longer time intervals, that is, weeks or months. Hence, both the dose and the time interval have to be optimized during the drug development process for biologics. To identify an adequate regimen for the investigated biologic, the dose-time-response relationship must be well characterized, based on clinical trial data. The proposed approach uses semi-mechanistic nonlinear regression models to describe and predict the time-changing response for complex dosing regimens. Both likelihood-based and Bayesian methods for inference and prediction are discussed. The methodology is illustrated with data from a clinical study in an auto-immune disease.

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

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y., E-mail: yingchen29@yahoo.com.cn [Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850 (China); Yan, X.K. [Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850 (China); Department of Radiation Safety, Beijing Institute of Nuclear and Chemical Safety, 14 Guan-cun, Dongcheng District, Beijing 100077 (China); Du, J.; Wang, Z.D.; Zhang, X.Q.; Zeng, F.G.; Zhou, P.K. [Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, 27 Taiping Road, Haidian District, Beijing 100850 (China)

    2011-09-15

    To correctly estimate the biological dose of victims accidentally exposed to a very high dose of {sup 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 {sup 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{sup -3}D{sup 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 {gamma}-irradiation from a supra-high dose {sup 60}Co gamma-ray accident.

  9. 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 Outlier status was defined as a patient having received at least 1 dose 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

  10. Evaluation of HER-2/neu amplification and other biological markers as predictors of response to neoadjuvant anthracycline-based chemotherapy in primary breast cancer: the role of anthracycline dose intensity.

    Science.gov (United States)

    Bozzetti, Cecilia; Musolino, Antonino; Camisa, Roberta; Bisagni, Giancarlo; Flora, Marcella; Bassano, Cristina; Martella, Eugenia; Lagrasta, Costanza; Nizzoli, Rita; Personeni, Nicola; Leonardi, Francesco; Cocconi, Giorgio; Ardizzoni, Andrea

    2006-04-01

    The value of HER-2/neu status as a predictor of response to anthracycline-based chemotherapy is still a matter of debate. We evaluated the contribution of HER-2/neu gene amplification and other biologic markers in predicting response to different doses of neoadjuvant anthracycline-based chemotherapy. Clinical and pathologic records of 115 primary breast cancer patients were reviewed. Forty-eight and 67 patients received high (doxorubicin > or =20 mg/m2/wk; epirubicin > or =30 mg/m2/wk) and moderate-low anthracycline dose intensity regimens, respectively. Pathologic diagnosis, hormonal receptor status (HR), Ki67, and HER-2/neu status were assessed on tumor samples before neoadjuvant chemotherapy. HER-2/neu was determined by fluorescence in situ hybridization (FISH). HER-2/neu amplification was observed in 29/115 (25%) tumors, 18 from moderate-low-dose and 11 from high-dose group. In the univariate analysis, a high Ki67 index (> or =20%) and positive clinical axillary nodes were predictive of an objective tumor response (P = 0.033 and 0.001, respectively). In the multivariate analysis, Ki67 was the only factor predictive of response (OR = 3.08, 95% CI = 1.1-8.5, P = 0.03). HER-2/neu status was not a factor in predicting objective response to different anthracycline dose intensities. The same finding was observed with regards to HR and Ki67. In our series, no significant dose-response relationship was found according to HER-2/neu status.

  11. 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 ...

  12. Dose escalation in permanent brachytherapy for prostate cancer: dosimetric and biological considerations

    Energy Technology Data Exchange (ETDEWEB)

    Li, X Allen [Department of Radiation Oncology, University of Maryland, School of Medicine, 22 South Greene Street, Baltimore, MD 21201-1595 (United States); Wang, Jian Z [Department of Radiation Oncology, University of Maryland, School of Medicine, 22 South Greene Street, Baltimore, MD 21201-1595 (United States); Stewart, Robert D [School of Health Sciences, Purdue University, West Lafayette, IN 47907-1338 (United States); Di Biase, Steven J [Department of Radiation Oncology, University of Maryland, School of Medicine, 22 South Greene Street, Baltimore, MD 21201-1595 (United States)

    2003-09-07

    No prospective dose escalation study for prostate brachytherapy (PB) with permanent implants has been reported. In this work, we have performed a dosimetric and biological analysis to explore the implications of dose escalation in PB using {sup 125}I and {sup 103}Pd implants. The concept of equivalent uniform dose (EUD), proposed originally for external-beam radiotherapy (EBRT), is applied to low dose rate brachytherapy. For a given {sup 125}I or {sup 103}Pd PB, the EUD for tumour that corresponds to a dose distribution delivered by EBRT is calculated based on the linear quadratic model. The EUD calculation is based on the dose volume histogram (DVH) obtained retrospectively from representative actual patient data. Tumour control probabilities (TCPs) are also determined in order to compare the relative effectiveness of different dose levels. The EUD for normal tissue is computed using the Lyman model. A commercial inverse treatment planning algorithm is used to investigate the feasibility of escalating the dose to prostate with acceptable dose increases in the rectum and urethra. The dosimetric calculation is performed for five representative patients with different prostate sizes. A series of PB dose levels are considered for each patient using {sup 125}I and {sup 103}Pd seeds. It is found that the PB prescribed doses (minimum peripheral dose) that give an equivalent EBRT dose of 64.8, 70.2, 75.6 and 81 Gy with a fraction size of 1.8 Gy are 129, 139, 150 and 161 Gy for {sup 125}I and 103, 112, 122 and 132 Gy for {sup 103}Pd implants, respectively. Estimates of the EUD and TCP for a series of possible prescribed dose levels (e.g., 145, 160, 170 and 180 Gy for {sup 125}I and 125, 135, 145 and 155 for {sup 103}Pd implants) are tabulated. The EUD calculation was found to depend strongly on DVHs and radiobiological parameters. The dosimetric calculations suggest that the dose to prostate can be escalated without a substantial increase in both rectal and urethral dose

  13. Biologically effective doses of postoperative radiotherapy in the prevention of keloids. Dose-effect relationship

    Energy Technology Data Exchange (ETDEWEB)

    Kal, H.B.; Veen, R.E. [University Medical Center Utrecht (Netherlands). Dept. of Radiotherapy

    2005-11-01

    Purpose: To review the recurrence rates of keloids after surgical excision followed by radiotherapy, and to answer the question whether after normalization of the dose, a dose-effect relationship could be derived. Material and Methods: A literature search was performed to identify studies dealing with the efficacy of various irradiation regimes for the prevention of keloids after surgery. Biologically effective doses (BEDs) of the various irradiation regimens were calculated using the linear-quadratic concept. A distinction between recurrence rates of keloids in the face and neck region and those in other parts of the body was made. Results: 31 reports were identified with PubMed with the search terms keloids, surgery, radiation therapy, radiotherapy. 13 reports were excluded, because no link could be found between recurrence rate and dose, or if less than ten patients per dose group. The recurrence rate for surgery only was 50-80%. For BED values >10 Gy the recurrence rate decreased as a function of BED. For BED values >30 Gy the recurrence rate was <10%. For a given dose, the recurrence rates of keloids in the sites with high stretch tension were not significantly higher than in sites without stretch tension. Conclusion: The results of this study indicate that for effectively treating keloids postoperatively, a relatively high dose must be applied in a short overall treatment time. The optimal treatment probably is an irradiation scheme resulting in a BED value of at least 30 Gy. A BED value of 30 Gy can be obtained with, for instance, a single acute dose of 13 Gy, two fractions of 8 Gy two fractions of 8 Gy or three fractions of 6 Gy, or a single dose of 27 Gy at low dose rate. The radiation treatment should be administered within 2 days after surgery. (orig.)

  14. Systems Cancer Biology and the Controlling Mechanisms for the J-Shaped Cancer Dose Response: Towards Relaxing the LNT Hypothesis

    OpenAIRE

    Lou, In Chio; Zhao, Yuchao; Wu, YingJie; Ricci, Paolo F

    2012-01-01

    The hormesis phenomena or J-shaped dose response have been accepted as a common phenomenon regardless of the involved biological model, endpoint measured and chemical class/physical stressor. This paper first introduced a mathematical dose response model based on systems biology approach. It links molecular-level cell cycle checkpoint control information to clonal growth cancer model to predict the possible shapes of the dose response curves of Ionizing Radiation (IR) induced tumor transforma...

  15. Biological equivalent dose studies for dose escalation in the stereotactic synchrotron radiation therapy clinical trials

    Energy Technology Data Exchange (ETDEWEB)

    Prezado, Y.; Fois, G.; Edouard, M.; Nemoz, C.; Renier, M.; Requardt, H.; Esteve, F.; Adam, JF.; Elleaume, H.; Bravin, A., E-mail: prezado@esrf.fr [ID17 Biomedical Beamline, European Synchrotron Radiation Facility (ESRF), 6 rue Jules Horowitz, BP 220, 38043 Grenoble Cedex (France)

    2009-03-15

    Synchrotron radiation is an innovative tool for the treatment of brain tumors. In the stereotactic synchrotron radiation therapy (SSRT) technique a radiation dose enhancement specific to the tumor is obtained. The tumor is loaded with a high atomic number (Z) element and it is irradiated in stereotactic conditions from several entrance angles. The aim of this work was to assess dosimetric properties of the SSRT for preparing clinical trials at the European Synchrotron Radiation Facility (ESRF). To estimate the possible risks, the doses received by the tumor and healthy tissues in the future clinical conditions have been calculated by using Monte Carlo simulations (PENELOPE code). The dose enhancement factors have been determined for different iodine concentrations in the tumor, several tumor positions, tumor sizes, and different beam sizes. A scheme for the dose escalation in the various phases of the clinical trials has been proposed. The biological equivalent doses and the normalized total doses received by the skull have been calculated in order to assure that the tolerance values are not reached.

  16. 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

  17. Dose inhomogeneities at various levels of biological organization

    Energy Technology Data Exchange (ETDEWEB)

    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 /sup 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.

  18. Biological dose representation for carbon-ion radiotherapy of unconventional fractionation

    CERN Document Server

    Kanematsu, Nobuyuki

    2016-01-01

    In carbon-ion radiotherapy, single-beam delivery each day in alternate directions has been commonly practiced for operational efficiency, taking advantage of the Bragg peak and the relative biological effectiveness (RBE) for uniform dose conformation to a tumor. The treatment plans are usually evaluated with total RBE-weighted dose, which is however deficient in relevance to the biological effect in the linear-quadratic model due to its quadratic-dose term, or the dose-fractionation effect. In this study, we reformulate the extrapolated response dose (ERD), or synonymously BED, which normalizes the dose-fractionation and cell-repopulation effects as well as the RBE of treating radiation, based on inactivation of a single model cell system and a typical treating radiation in carbon-ion RT. The ERD distribution virtually represents the biological effect of the treatment regardless of radiation modality or fractionation scheme. We applied the ERD formulation to simplistic model treatments and to a preclinical su...

  19. Biological UV-doses and the effect of an ozone layer depletion.

    Science.gov (United States)

    Dahlback, A; Henriksen, T; Larsen, S H; Stamnes, K

    1989-05-01

    Effective UV-doses were calculated based on the integrated product of the biological action spectrum (the one proposed by IEC, which extends to 400 nm, was adopted) and the spectral irradiance. The calculations include absorption and scattering of UV-radiation in the atmosphere, both for normal ozone conditions as well as for a depleted ozone layer. For Scandinavian latitudes the effective annual UV-dose increases by approximately 4% per degrees of latitude towards the Equator. An ozone depletion of one percent increases the annual UV-dose by approximately 1% at 60 degrees N (increases slightly at lower latitudes). A large depletion of 50% over Scandinavia (60 degrees N) would give these countries an effective UV-dose similar to that obtained, with normal ozone conditions, at a latitude of 40 degrees 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 at 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.

  20. Interaction between the biological effects of high- and low-LET radiation dose components in a mixed field exposure

    DEFF Research Database (Denmark)

    Mason, Anna J.; Giusti, Valerio; Green, Stuart

    2011-01-01

    The relative biological effectiveness of two epithermal neutron sources, a reactor based source at Studsvik, Sweden, and a proton accelerator-based source in Birmingham, UK, was studied in relation to the proportional absorbed dose distribution as a function of neutron energy. Evidence for any in...... interactions between the effects of biological damage induced by high- and low-linear energy transfer (LET) dose components, in this 'mixed field' irradiation, was also examined......The relative biological effectiveness of two epithermal neutron sources, a reactor based source at Studsvik, Sweden, and a proton accelerator-based source in Birmingham, UK, was studied in relation to the proportional absorbed dose distribution as a function of neutron energy. Evidence for any...

  1. Systems Cancer Biology and the Controlling Mechanisms for the J-Shaped Cancer Dose Response: Towards Relaxing the LNT Hypothesis.

    Science.gov (United States)

    Lou, In Chio; Zhao, Yuchao; Wu, Yingjie; Ricci, Paolo F

    2012-01-01

    The hormesis phenomena or J-shaped dose response have been accepted as a common phenomenon regardless of the involved biological model, endpoint measured and chemical class/physical stressor. This paper first introduced a mathematical dose response model based on systems biology approach. It links molecular-level cell cycle checkpoint control information to clonal growth cancer model to predict the possible shapes of the dose response curves of Ionizing Radiation (IR) induced tumor transformation frequency. J-shaped dose response curves have been captured with consideration of cell cycle checkpoint control mechanisms. The simulation results indicate the shape of the dose response curve relates to the behavior of the saddle-node points of the model in the bifurcation diagram. A simplified version of the model in previous work of the authors was used mathematically to analyze behaviors relating to the saddle-node points for the J-shaped dose response curve. It indicates that low-linear energy transfer (LET) is more likely to have a J-shaped dose response curve. This result emphasizes the significance of systems biology approach, which encourages collaboration of multidiscipline of biologists, toxicologists and mathematicians, to illustrate complex cancer-related events, and confirm the biphasic dose-response at low doses.

  2. 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...

  3. 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

    -volumes dose escalation were defined by a threshold-based method for both tracers and five dose escalation levels were in each sub-volume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions 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 of dose distribution density maps and quality volume histograms (QVH). Correlation between high-dose regions was investigated with Dice correlation coefficients...... 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...

  4. 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)

  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. 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.

  7. Biologically adapted radiotherapy and evaluation of non-uniform dose distributions

    Energy Technology Data Exchange (ETDEWEB)

    Soevik, Aaste

    2007-07-01

    Radiation therapy plays an integral part in cancer management. Over the last decade, the fraction of patients in the Nordic countries receiving radiation therapy at some stage in their disease has increased by around 50%, and approximately half of the treatments arc given with curative intent. While only 20% of patients with primary tumors receive radiation therapy as the only form of treatment, curative radiation therapy given in combination with other treatment modalities has been shown to be of benefit for the majority of the most common cancers. The future requirements for radiation therapy are expected to increase along with the increase in cancer incidence. The aim of curing the patient is not always achieved, due to distant metastasis and/or lack of locoregional control. Locoregional failure occurs when the delivered tumor dose fails to eradicate the cancer cells, and can result from a radioresistant subpopulation of tumor cells. As the tumor dose is limited by the probability of inducing normal tissue complications, novel treatment strategies are needed to improve locoregional tumor control. Over the recent years, there has been an increasing interest in complex treatment delivery strategies in radiation therapy. Intensity modulated radiation therapy (IMRT) can be used to provide a distribution of radiation dose that conforms closely to irregularly shaped tumors, while sparing the surrounding normal tissues. However, IMRT can also be used to deliver non-uniform dose distributions, based on patient specific biological information, i.e. biologically conformal radiation therapy (BCRT). Functional and molecular imaging can be used to demonstrate both the distribution of and the extent of heterogeneity in parameters that influence tumor radiation sensitivity. Non-invasive images of radiobiological parameters form the basis of biologically conformal radiation therapy and are needed to create individually optimized radiation therapy plans. Recent advances in the

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

    Science.gov (United States)

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

    2008-03-01

    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 alpha/beta), 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

  9. Application of Benchmark Dose (BMD) in Estimating Biological Exposure Limit (BEL) to Cadmium

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To estimate the biological exposure limit (BEL) using benchmark dose (BMD) based on two sets of data from occupational epidemiology. Methods Cadmium-exposed workers were selected from a cadmium smelting factory and a zinc product factory. Doctors, nurses or shop assistants living in the same area served as a control group. Urinary cadmium (UCd) was used as an exposure biomarker and urinary β2-microgloburin (B2M), N-acetyl-β-D-glucosaminidase (NAG) and albumin (ALB) as effect biomarkers. All urine parameters were adjusted by urinary creatinine. Software of BMDS (Version 1.3.2, EPA.U.S.A) was used to calculate BMD. Results The cut-off point (abnormal values) was determined based on the upper limit of 95% of effect biomarkers in control group. There was a significant dose response relationship between the effect biomarkers (urinary B2M, NAG, and ALB) and exposure biomarker (UCd). BEL value was 5 μg/g creatinine for UB2M as an effect biomarker, consistent with the recommendation of WHO. BEL could be estimated by using the method of BMD. BEL value was 3 μg/g creatinine for UNAG as an effect biomarker. The more sensitive the used biomarker is, the more occupational population will be protected. Conclusion BMD can be used in estimating the biological exposure limit (BEL). UNAG is a sensitive biomarker for estimating BEL after cadmium exposure.

  10. Responses to Low Doses of Ionizing Radiation in Biological Systems

    OpenAIRE

    Feinendegen, Ludwig E.; Pollycove, Myron; Sondhaus, Charles A.

    2004-01-01

    Biological tissues operate through cells that act together within signaling networks. These assure coordinated cell function in the face of constant exposure to an array of potentially toxic agents, externally from the environment and endogenously from metabolism. Living tissues are indeed complex adaptive systems.

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

    Science.gov (United States)

    2009-11-01

    providing radiation biological dose estimates using the dicentric chromosome assay (DCA). As indicated in the CRTI-06-0146RD charter, the existing...laboratories of the National Biological Dose Response Plan plus two US laboratories. Samples were scored for the dicentric chromosome assay and the CBMN...Wilkins, R.C. QuickScan dicentric chromosome analysis for radiation biodosimetry , Health Physics Journal, In Press (2009). 2. McNamee, J.P., Flegal

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

    Energy Technology Data Exchange (ETDEWEB)

    Yamaoka, K. [Okayama University Medical School, Okayama (Japan); Nomura, T. [Central Research Institute of Electric Power Industry, Tokyo (Japan); Kojima, S. [Science University of Tokyo, Chiba (Japan)

    2000-05-01

    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 {alpha}-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{sub 2}- to H{sub 2}O{sub 2}, the question as to whether the resultant H{sub 2}O{sub 2} is further detoxicated into H{sub 2}O and O{sub 2} or not must

  13. 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

  14. 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.

  15. Biological radiation dose from secondary particles in a Milky Way gamma-ray burst

    Science.gov (United States)

    Atri, Dimitra; Melott, Adrian L.; Karam, Andrew

    2014-07-01

    Gamma-ray bursts (GRBs) are a class of highly energetic explosions emitting radiation in a very short timescale of a few seconds and with a very narrow opening angle. Although, all GRBs observed so far are extragalactic in origin, there is a high probability of a GRB of galactic origin beaming towards the Earth in the past ~0.5 Gyr. We define the level of catastrophic damage to the biosphere as approximation 100 kJ m-2, based on Thomas et al. (2005a, b). Using results in Melott & Thomas (2011), we estimate the probability of the Earth receiving this fluence from a GRB of any type, as 87% during the last 500 Myr. Such an intense burst of gamma rays would ionize the atmosphere and deplete the ozone (O3) layer. With depleted O3, there will be an increased flux of Solar UVB on the Earth's surface with potentially harmful biological effects. In addition to the atmospheric damage, secondary particles produced by gamma ray-induced showers will reach the surface. Among all secondary particles, muons dominate the ground-level secondary particle flux (99% of the total number of particles) and are potentially of biological significance. Using the Monte Carlo simulation code CORSIKA, we modelled the air showers produced by gamma-ray primaries up to 100 GeV. We found that the number of muons produced by the electromagnetic component of hypothetical galactic GRBs significantly increases the total muon flux. However, since the muon production efficiency is extremely low for photon energies below 100 GeV, and because GRBs radiate strongly for only a very short time, we find that the biological radiation dose from secondary muons is negligible. The main mechanism of biological damage from GRBs is through Solar UVB irradiation from the loss of O3 in the upper atmosphere.

  16. Nonlinear Effects of Nanoparticles: Biological Variability From Hormetic Doses, Small Particle Sizes, and Dynamic Adaptive Interactions

    OpenAIRE

    Bell, Iris R.; Ives, John A.; Wayne B. Jonas

    2013-01-01

    Researchers are increasingly focused on the nanoscale level of organization where biological processes take place in living systems. Nanoparticles (NPs, e.g., 1–100 nm diameter) are small forms of natural or manufactured source material whose properties differ markedly from those of the respective bulk forms of the “same” material. Certain NPs have diagnostic and therapeutic uses; some NPs exhibit low-dose toxicity; other NPs show ability to stimulate low-dose adaptive responses (hormesis). B...

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Is Biology based on Physics?

    Science.gov (United States)

    Goradia, Shantilal

    2015-04-01

    The equation on Boltsmann's tomb is S = K log W, giving 137 = 10E60 where 10E60 closely stands for the age of the universe in Plank times. We wish we could add ``137 = 10E60'' on his tomb as a contribution leading physics towards information in biology as explained in our book ``Quantum Consciousness - the Road to Reality.'' (1) We draft our speculation that such a step may explain the underlying physical cause for mutations. Tiny immeasurable and slow changes well beyond the tenth digit of fine structure constant may suffice to change the information system in constituent particles of nucleotides with their external effects forcing changes in the genetic code with successful changes resulting into mutations. (2) Our quantum mechanical published derivation of the strong coupling implies gravity as a cumulative effect of quantum mechanical particles further implying that the universal constant of gravity (G) can not be constant everywhere. (1) and (2) put together should remove Darwin's confusion about the constancy of gravity. Moving planets and Sunstorms should also cause changes in G on earth unnoticeable to mankind, but large enough to have an impact on the internal particles of nucleotides which should implicitly have an external effect on the genetic code per our theory.

  2. 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.

  3. 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.

  4. The role of nuclear reactions in Monte Carlo calculations of absorbed and biological effective dose distributions in hadron therapy

    CERN Document Server

    Brons, S; Elsässer, T; Ferrari, A; Gadioli, E; Mairani, A; Parodi, K; Sala, P; Scholz, M; Sommerer, F

    2010-01-01

    Monte Carlo codes are rapidly spreading among hadron therapy community due to their sophisticated nuclear/electromagnetic models which allow an improved description of the complex mixed radiation field produced by nuclear reactions in therapeutic irradiation. In this contribution results obtained with the Monte Carlo code FLUKA are presented focusing on the production of secondary fragments in carbon ion interaction with water and on CT-based calculations of absorbed and biological effective dose for typical clinical situations. The results of the simulations are compared with the available experimental data and with the predictions of the GSI analytical treatment planning code TRiP.

  5. 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

  6. Biological bases of human musicality.

    Science.gov (United States)

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

    2017-01-20

    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.

  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. SU-E-T-456: Impact of Dose Calculation Algorithms On Biologically Optimized VMAT Plans for Esophageal Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thiyagarajan, Rajesh; Vikraman, S; Karrthick, KP; Ramu, M; Sambasivaselli, R; Senniandavar, V; Kataria, Tejinder [Medanta The Medicity, Gurgaon, Haryana (India); Nambiraj, N Arunai; Sigamani, Ashokkumar [VIT University, Vellore, Tamil Nadu (India); Subbarao, Bargavan [Elekta India, Chennai, Tamil Nadu (India)

    2015-06-15

    Purpose: To evaluate the impact of dose calculation algorithm on the dose distribution of biologically optimized Volumatric Modulated Arc Therapy (VMAT) plans for Esophgeal cancer. Methods: Eighteen retrospectively treated patients with carcinoma esophagus were studied. VMAT plans were optimized using biological objectives in Monaco (5.0) TPS for 6MV photon beam (Elekta Infinity). These plans were calculated for final dose using Monte Carlo (MC), Collapsed Cone Convolution (CCC) & Pencil Beam Convolution (PBC) algorithms from Monaco and Oncentra Masterplan TPS. A dose grid of 2mm was used for all algorithms and 1% per plan uncertainty maintained for MC calculation. MC based calculations were considered as the reference for CCC & PBC. Dose volume histogram (DVH) indices (D95, D98, D50 etc) of Target (PTV) and critical structures were compared to study the impact of all three algorithms. Results: Beam models were consistent with measured data. The mean difference observed in reference with MC calculation for D98, D95, D50 & D2 of PTV were 0.37%, −0.21%, 1.51% & 1.18% respectively for CCC and 3.28%, 2.75%, 3.61% & 3.08% for PBC. Heart D25 mean difference was 4.94% & 11.21% for CCC and PBC respectively. Lung Dmean mean difference was 1.5% (CCC) and 4.1% (PBC). Spinal cord D2 mean difference was 2.35% (CCC) and 3.98% (PBC). Similar differences were observed for liver and kidneys. The overall mean difference found for target and critical structures was 0.71±1.52%, 2.71±3.10% for CCC and 3.18±1.55%, 6.61±5.1% for PBC respectively. Conclusion: We observed a significant overestimate of dose distribution by CCC and PBC as compared to MC. The dose prediction of CCC is closer (<3%) to MC than that of PBC. This can be attributed to poor performance of CCC and PBC in inhomogeneous regions around esophagus. CCC can be considered as an alternate in the absence of MC algorithm.

  9. Fully Automated Treatment Planning for Head and Neck Radiotherapy using a Voxel-Based Dose Prediction and Dose Mimicking Method

    CERN Document Server

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

    2016-01-01

    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 an atlas-based approach which learns a dose prediction model for each patient (atlas) in a training database, and then learns to match novel patients to the most relevant atlases. The method creates a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces any requirement for specifying dose-volume objectives for conveying the goals of treatment planning. A probabilistic dose distribution is inferred from the most relevant atlases, and is scalarized using a conditional random field to determine the most likely spatial distribution of dose to yield a specific dose prior (histogram) for relevant regions of interest. Voxel-based dose mimicking then converts the predicted dose distribution to a deliverable treatment plan dose distribution. In this study, we ...

  10. Biological shielding assessment and dose rate calculation for a neutron inspection portal

    Science.gov (United States)

    Donzella, A.; Bonomi, G.; Giroletti, E.; Zenoni, A.

    2012-04-01

    With reference to the prototype of neutron inspection portal built and successfully tested in the Rijeka seaport (Croatia) within the EURITRACK (EURopean Illicit Trafficking Countermeasures Kit) project, an assessment of the biological shielding in different set-up configurations of a future portal has been calculated with MCNP Monte Carlo code in the frame of the Eritr@C (European Riposte against Illicit TR@ffiCking) project. In the configurations analyzed the compliance with the dose limits for workers and the population stated by the European legislation is provided by appropriate shielding of the neutron sources and by the delimitation of a controlled area.

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

    Science.gov (United States)

    Strolin, Silvia; Bossi, Gianluca; Strigari, Lidia

    2017-01-01

    Background 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. Methods 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. Results 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. Conclusion 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. PMID:28222111

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

    Science.gov (United States)

    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

    2007-07-01

    Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines.

  13. The calculation of radial dose from heavy ions: predictions of biological action cross sections

    Science.gov (United States)

    Katz, Robert; Cucinotta, Francis A.; Zhang, C. X.

    1996-02-01

    The track structure model of heavy ion cross sections was developed by Katz and co-workers in the 1960s. In this model the action cross section is evaluated by mapping the dose-response of a detector to γ rays (modeled from biological target theory) onto the radial dose distribution from δ rays about the path of the ion. This is taken to yield the radial distribution of probability for a "hit" (an interaction leading to an observable end-point). Radial integration of the probability yields the cross section. When different response from ions of different Z having the same stopping power is observed this model may be indicated. Since the 1960s there have been several developments in the computation of the radial dose distribution, in the measurement of these distributions, and in new radiobiological data against which to test the model. The earliest model, by Butts and Katz, made use of simplified δ ray distribution functions, of simplified electron range-energy relations, and neglected angular distributions. Nevertheless it made possible the calculation of cross sections for the inactivation of enzymes and viruses, and allowed extension to tracks in nuclear emulsions and other detectors and to biological cells. It set the pattern for models of observable effects in the matter through which the ion passed. Here we outline subsequent calculations of radial dose which make use of improved knowledge of the electron emission spectrum, the electron range-energy relation, the angular distribution, and some considerations of molecular excitation, of particular interest both close to the path of the ion and the outer limits of electron penetration. These are applied to the modeling of action cross sections for the inactivation of several strains of E-coli and B. subtilis spores where extensive measurements in the "thin-down" region have been made with heavy ion beams. Such calculations serve to test the radial dose calculations at the outer limit of electron penetration

  14. Instance-Based Generative Biological Shape Modeling.

    Science.gov (United States)

    Peng, Tao; Wang, Wei; Rohde, Gustavo K; Murphy, Robert F

    2009-01-01

    Biological shape modeling is an essential task that is required for systems biology efforts to simulate complex cell behaviors. Statistical learning methods have been used to build generative shape models based on reconstructive shape parameters extracted from microscope image collections. However, such parametric modeling approaches are usually limited to simple shapes and easily-modeled parameter distributions. Moreover, to maximize the reconstruction accuracy, significant effort is required to design models for specific datasets or patterns. We have therefore developed an instance-based approach to model biological shapes within a shape space built upon diffeomorphic measurement. We also designed a recursive interpolation algorithm to probabilistically synthesize new shape instances using the shape space model and the original instances. The method is quite generalizable and therefore can be applied to most nuclear, cell and protein object shapes, in both 2D and 3D.

  15. The dose-dependence biological effect of laser fluence on rabbit fibroblasts derived from urethral scar.

    Science.gov (United States)

    Yang, Yong; Yu, Bo; Sun, Dongchong; Wu, Yuanyi; Xiao, Yi

    2015-04-01

    Two-micrometer laser vaporization resection has been used in clinic for years, but some patients received the treatment are still faced with excessive and abnormal wound repair which leads to the recurrent of urethral stricture eventually. Fibroblasts play a key role in the processes of "narrow-expansion/operation-restenosis" recurring problems. Here, we investigated the effect of laser fluence biomodulation on urethral scar fibroblasts as well as the underlying mechanism. Urethral scar fibroblasts were isolated and cultured, and laser irradiation (2 μm) was applied at different laser fluence or doses (0, 0.125, 0.5, 2, 8, 32 J/cm(2)) with a single exposure in 1 day. The effect of 2-μm laser irradiation on cell proliferation, viability, and expression of scar formation related genes were investigated. Two-micrometer laser irradiation with intermediate dose (8 J/cm(2)) promoted scar fibroblasts proliferation and reactive oxygen species (ROS) production, while higher doses of 32 J/cm(2) are suppressive as it decreased the survival rate, viability, and proliferation of fibroblasts. In addition, qRT-PCR and Western blotting results both proven that collagen type I, collagen IV, MMP9, and CTGF display significant increase, yet the TGF-β1 expression was severely reduced at intermediate dose (8 J/cm(2)) group when compared with the others groups. Our findings suggest the scar formation-related genes are sensitive to intermediate laser irradiation dose, the most in scar fibroblasts. We revealed the bioeffect and molecular mechanism of 2-μm laser irradiation on rabbit urethral scar fibroblasts. Our study provides new insights into the mechanisms which involved in the excessive and abnormal wound repair of 2-μm laser vaporization resection. These results could potentially contribute to further study on biological effects and application of 2-μm laser irradiation in urethral stricture therapy.

  16. 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).

  17. An analogy between effects of ultra-low doses of biologically active substances on biological objects and properties of spin supercurrents in superfluid 3He-B.

    Science.gov (United States)

    Boldyreva, Liudmila B

    2011-07-01

    The effects of ultra-low doses (ULDs) of biologically active substances (BASs) (with concentrations of 10(-13)M or lower) on biological objects (BOs), such as cells, organisms, etc., and the properties of spin supercurrents in superfluid (3)He-B are discussed. It is shown that the effects of ULDs of BASs on biologic objects can be specified by the same set of physical characteristics and described by the same mathematical relations as those used for the specification and description of the properties of spin supercurrents between spin structures in superfluid (3)He-B. This is based on the up-to-date physical concepts: 1) the physical vacuum has the properties of superfluid (3)He-B; 2) all quantum entities (hence, the BAS and the BO, which consist of such entities) produce spin structures in the physical vacuum. The photon being a quantum entity, the features of the effects of low-intensity electromagnetic radiation on BOs can be explained using the same approach.

  18. Ambient and biological monitoring of cokeoven workers: determinants of the internal dose of polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Jongeneelen, F J; van Leeuwen, F E; Oosterink, S; Anzion, R B; van der Loop, F; Bos, R P; van Veen, H G

    1990-07-01

    Polycyclic aromatic hydrocarbons (PAH) were measured in the breathing zone air of 56 battery workers at two cokeovens during three consecutive days. The concentration of total PAH ranged up to 186 micrograms/m3. Preshift and end of shift urine samples were collected to determine 1-hydroxypyrene, a metabolite of pyrene. Control urine samples were available from 44 workers in the shipping yard of a hot rolling mill. The median values of 1-hydroxypyrene in urine of smoking and non-smoking controls were 0.51 and 0.17 mumol/mol creatinine, respectively. Concentrations of 1-hydroxypyrene up to 11.2 mumol/mol were found in the urine of the cokeoven workers. At the start of the three day working period after 32 hours off work, the 1-hydroxypyrene concentrations were four times higher and at the end of the working period 10 times higher compared with control concentrations. Excretion of 1-hydroxypyrene occurred with a half life of 6-35 hours. Both the ambient air monitoring data and the biological monitoring data showed that the topside workers were the heaviest exposed workers. The relation between air monitoring data and biological monitoring data was not strong. Multiple regression analysis was performed to identify determinants of the internal dose. The combination of exposure and smoking amplify each other and the use of a protective airstream helmet decreases the internal dose. An effect of alcohol consumption and the use of medication on the toxicokinetics of pyrene was not found.

  19. 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

  20. Antibody-based biological toxin detection

    Energy Technology Data Exchange (ETDEWEB)

    Menking, D.E.; Goode, M.T. [Army Edgewood Research, Development and Engineering Center, Aberdeen Proving Ground, MD (United States)

    1995-12-01

    Fiber optic evanescent fluorosensors are under investigation in our laboratory for the study of drug-receptor interactions for detection of threat agents and antibody-antigen interactions for detection of biological toxins. In a direct competition assay, antibodies against Cholera toxin, Staphylococcus Enterotoxin B or ricin were noncovalently immobilized on quartz fibers and probed with fluorescein isothiocyanate (FITC) - labeled toxins. In the indirect competition assay, Cholera toxin or Botulinum toxoid A was immobilized onto the fiber, followed by incubation in an antiserum or partially purified anti-toxin IgG. These were then probed with FITC-anti-IgG antibodies. Unlabeled toxins competed with labeled toxins or anti-toxin IgG in a dose dependent manner and the detection of the toxins was in the nanomolar range.

  1. 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.

  2. 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

  3. 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

  4. Stochastic description of the ligand-receptor interaction of biologically active substances at extremely low doses.

    Science.gov (United States)

    Gurevich, Konstantin G; Agutter, Paul S; Wheatley, Denys N

    2003-04-01

    Signalling molecules can be effective at extraordinarily low concentrations (down to attomolar levels). To handle such cases, probabilistic methods have been used to describe the formal kinetics of action of biologically active substances in these low doses, although it has been necessary to review what is meant by such a term. The mean numbers of transformed/degraded molecules and their dispersions were calculated for the possible range of ligand-receptor binding schemes. We used both analytical equations and numerical simulations to calculate the coefficients of variation (ratio of standard deviation to mean) and demonstrated that the distribution of the coefficient is highly dependent on the reaction scheme. It may, therefore, be used as an additional factor for discriminating between cooperative and noncooperative models of ligand-receptor interaction over extreme ranges of ligand dilution. The relevance to signalling behaviour is discussed.

  5. EUD-based biological optimization for carbon ion therapy

    Energy Technology Data Exchange (ETDEWEB)

    Brüningk, Sarah C., E-mail: sarah.brueningk@icr.ac.uk; Kamp, Florian; Wilkens, Jan J. [Department of Radiation Oncology, Technische Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, München 81675, Germany and Physik-Department, Technische Universität München, James-Franck-Str. 1, Garching 85748 (Germany)

    2015-11-15

    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

  6. 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

  7. Cytogenetic dose-response in vitro for biological dosimetry after exposure to high doses of gamma-rays.

    Science.gov (United States)

    Vinnikov, Volodymyr A; Maznyk, Nataliya A

    2013-04-01

    The dose response for dicentrics plus centric rings and total unstable chromosome-type aberrations was studied in the first mitoses of cultured human peripheral blood lymphocytes irradiated in vitro to doses of ∼2, 4, 6, 8, 10, 16 and 20 Gy of acute (60)Со gamma-rays. A dose-dependent increase of aberration yield was accompanied by a tendency to the underdispersion of dicentrics and centric rings among cells distributions compared with Poisson statistics at doses ≥6 Gy. The formal fitting of the data to a linear-quadratic model resulted in an equation with the linear and quadratic coefficients ranged 0.098-0.129×cell(-1)×Gy(-1) and 0.039-0.034×cell(-1)×Gy(-2), respectively, depending on the fitting method. The actual radiation-induced aberration yield was markedly lower than expected from a calibration curve, generated earlier within a lower dose range. Interlaboratory variations in reported dicentric yields induced by medium-to-high radiation doses in vitro are discussed.

  8. Gamma Knife radiosurgery with CT image-based dose calculation.

    Science.gov (United States)

    Xu, Andy Yuanguang; Bhatnagar, Jagdish; Bednarz, Greg; Niranjan, Ajay; Kondziolka, Douglas; Flickinger, John; Lunsford, L Dade; Huq, M Saiful

    2015-11-08

    The Leksell GammaPlan software version 10 introduces a CT image-based segmentation tool for automatic skull definition and a convolution dose calculation algorithm for tissue inhomogeneity correction. The purpose of this work was to evaluate the impact of these new approaches on routine clinical Gamma Knife treatment planning. Sixty-five patients who underwent CT image-guided Gamma Knife radiosurgeries at the University of Pittsburgh Medical Center in recent years were retrospectively investigated. The diagnoses for these cases include trigeminal neuralgia, meningioma, acoustic neuroma, AVM, glioma, and benign and metastatic brain tumors. Dose calculations were performed for each patient with the same dose prescriptions and the same shot arrangements using three different approaches: 1) TMR 10 dose calculation with imaging skull definition; 2) convolution dose calculation with imaging skull definition; 3) TMR 10 dose calculation with conventional measurement-based skull definition. For each treatment matrix, the total treatment time, the target coverage index, the selectivity index, the gradient index, and a set of dose statistics parameters were compared between the three calculations. The dose statistics parameters investigated include the prescription isodose volume, the 12 Gy isodose volume, the minimum, maximum and mean doses on the treatment targets, and the critical structures under consideration. The difference between the convolution and the TMR 10 dose calculations for the 104 treatment matrices were found to vary with the patient anatomy, location of the treatment shots, and the tissue inhomogeneities around the treatment target. An average difference of 8.4% was observed for the total treatment times between the convolution and the TMR algorithms. The maximum differences in the treatment times, the prescription isodose volumes, the 12 Gy isodose volumes, the target coverage indices, the selectivity indices, and the gradient indices from the convolution

  9. Dosing down with biologic therapies: a systematic review and clinicians' perspective.

    Science.gov (United States)

    Edwards, Christopher J; Fautrel, Bruno; Schulze-Koops, Hendrik; Huizinga, Tom W J; Kruger, Klaus

    2017-02-16

    The effectiveness of biologic therapies now means that remission or low disease activity are realistic targets for treatment. However, after achieving remission/low disease activity, the next steps remain unclear. The aim of this publication was to conduct a broad systematic literature review to evaluate dosing down of biologics. After screening papers and abstracts for relevance and application of inclusion/exclusion criteria, a structured extraction process was used to collect information on the included studies. Fifty-two papers were included in the analysis across rheumatic disease. In patients who discontinue therapy, remission is not typically sustained, with reported rates of relapse and flare across early RA (48-54%), established RA (2-84%), axial spondyloarthritis (11-53%) and PsA (44.9%). In many cases, an acceptable disease activity can be regained upon retreatment. More research is needed to understand the long-term impacts of these strategies on efficacy, safety and cost. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology.

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

    Science.gov (United States)

    Tomita, Masanori; Maeda, Munetoshi

    2015-03-01

    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 bystander 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. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  11. Biological effects of long-term exposure to low dose-rate radiation -- Comparisons of WAM model and LQ model

    CERN Document Server

    Wada, Takahiro; Nakamura, Issei; Tsunoyama, Yuichi; Nakajima, Hiroo; Bando, Masako

    2015-01-01

    Newly proposed Whack-A-Mole (WAM) model which is to be used to estimate the biological effects of artificial radiations is compared with conventionally used Linear-Quadratic model. Basic properties of WAM model are discussed emphasizing on the dose-rate dependence. By adopting the parameters that are determined to fit the mega mouse experiments, biological effects of long-term exposure to extremely low dose-rate radiation are discussed. In WAM model, the effects of the long-term exposure show a saturation property, which makes a clear distinction from the LNT hypothesis which predicts a linear increase of the effects with time.

  12. Language Based Techniques for Systems Biology

    DEFF Research Database (Denmark)

    Pilegaard, Henrik

    on the π calculus fragment of BioAmbients. In both cases the analyses compute very precise estimates of the temporal structure of the underlying pathways; hence they are applicable across a family of widely used bio-ware languages that descend from Milner’s Calculus of Communicating Systems. The presented...... calculi have similarly been used for the study of bio-chemical reactive systems. In this dissertation it is argued that techniques rooted in the theory and practice of programming languages, language based techniques if you will, constitute a strong basis for the investigation of models of biological...

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

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Ken; Mitomo, Masanori [Osaka National Hospital (Japan); Nose, Takayuki; Koizumi, Masahiko; Nishiyama, Kinji [Osaka Prefectural Center for Adult Diseases (Japan); Yoshida, Mineo [Sanda City Hospital, Hyogo (Japan)

    2002-12-01

    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

  14. The biological effect of large single doses: a possible role for non-targeted effects in cell inactivation.

    Directory of Open Access Journals (Sweden)

    Marlon R Veldwijk

    Full Text Available BACKGROUND AND PURPOSE: Novel radiotherapy techniques increasingly use very large dose fractions. It has been argued that the biological effect of large dose fractions may differ from that of conventional fraction sizes. The purpose was to study the biological effect of large single doses. MATERIAL AND METHODS: Clonogenic cell survival of MCF7 and MDA-MB-231 cells was determined after direct X-ray irradiation, irradiation of feeder cells, or transfer of conditioned medium (CM. Cell-cycle distributions and the apoptotic sub-G1 fraction were measured by flow cytometry. Cytokines in CM were quantified by a cytokine antibody array. γH2AX foci were detected by immunofluorescence microscopy. RESULTS: The surviving fraction of MCF7 cells irradiated in vitro with 12 Gy showed an 8.5-fold decrease (95% c.i.: 4.4-16.3; P<0.0001 when the density of irradiated cells was increased from 10 to 50×10(3 cells per flask. Part of this effect was due to a dose-dependent transferrable factor as shown in CM experiments in the dose range 5-15 Gy. While no effect on apoptosis and cell cycle distribution was observed, and no differentially expressed cytokine could be identified, the transferable factor induced prolonged expression of γH2AX DNA repair foci at 1-12 h. CONCLUSIONS: A dose-dependent non-targeted effect on clonogenic cell survival was found in the dose range 5-15 Gy. The dependence of SF on cell numbers at high doses would represent a "cohort effect" in vivo. These results support the hypothesis that non-targeted effects may contribute to the efficacy of very large dose fractions in radiotherapy.

  15. 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.

  16. Using rule-based shot dose assignment in model-based MPC applications

    Science.gov (United States)

    Bork, Ingo; Buck, Peter; Wang, Lin; Müller, Uwe

    2014-10-01

    Shrinking feature sizes and the need for tighter CD (Critical Dimension) control require the introduction of new technologies in mask making processes. One of those methods is the dose assignment of individual shots on VSB (Variable Shaped Beam) mask writers to compensate CD non-linearity effects and improve dose edge slope. Using increased dose levels only for most critical features, generally only for the smallest CDs on a mask, the change in mask write time is minimal while the increase in image quality can be significant. This paper describes a method combining rule-based shot dose assignment with model-based shot size correction. This combination proves to be very efficient in correcting mask linearity errors while also improving dose edge slope of small features. Shot dose assignment is based on tables assigning certain dose levels to a range of feature sizes. The dose to feature size assignment is derived from mask measurements in such a way that shape corrections are kept to a minimum. For example, if a 50nm drawn line on mask results in a 45nm chrome line using nominal dose, a dose level is chosen which is closest to getting the line back on target. Since CD non-linearity is different for lines, line-ends and contacts, different tables are generated for the different shape categories. The actual dose assignment is done via DRC rules in a pre-processing step before executing the shape correction in the MPC engine. Dose assignment to line ends can be restricted to critical line/space dimensions since it might not be required for all line ends. In addition, adding dose assignment to a wide range of line ends might increase shot count which is undesirable. The dose assignment algorithm is very flexible and can be adjusted based on the type of layer and the best balance between accuracy and shot count. These methods can be optimized for the number of dose levels available for specific mask writers. The MPC engine now needs to be able to handle different dose

  17. On expedient properties of common biological score functions for multi-modality, adaptive and 4D dose optimization

    Energy Technology Data Exchange (ETDEWEB)

    Sobotta, B; Alber, M [Section for Biomedical Physics, Radioonkologische Uniklinik, Universitaet Tuebingen, 72076 Tuebingen (Germany); Soehn, M [Department of Radiation Oncology, University Hospital Grosshadern, LMU Muenchen, 81377 Muenchen (Germany); Shaw, W, E-mail: benjamin.sobotta@med.uni-tuebingen.de [Department of Medical Physics, Faculty of Health Sciences, University of the Free State, PO Box 339, Bloemfontein 9300 (South Africa)

    2011-05-21

    Frequently, radiotherapy treatments are comprised of several dose distributions computed or optimized in different patient geometries. Therefore, the need arises to compute the comprehensive biological effect or physical figure of merit of the combined dose of a number of distinct geometry instances. For that purpose the dose is typically accumulated in a reference geometry through deformation fields obtained from deformable image registration. However, it is difficult to establish precise voxel-by-voxel relationships between different anatomical images in many cases. In this work, the mathematical properties of commonly used score functions are exploited to derive an upper boundary for the maximum effect for normal tissue and a lower boundary for the minimum effect for the target of accumulated doses on multiple geometry instances. (note)

  18. On expedient properties of common biological score functions for multi-modality, adaptive and 4D dose optimization.

    Science.gov (United States)

    Sobotta, B; Söhn, M; Shaw, W; Alber, M

    2011-05-21

    Frequently, radiotherapy treatments are comprised of several dose distributions computed or optimized in different patient geometries. Therefore, the need arises to compute the comprehensive biological effect or physical figure of merit of the combined dose of a number of distinct geometry instances. For that purpose the dose is typically accumulated in a reference geometry through deformation fields obtained from deformable image registration. However, it is difficult to establish precise voxel-by-voxel relationships between different anatomical images in many cases. In this work, the mathematical properties of commonly used score functions are exploited to derive an upper boundary for the maximum effect for normal tissue and a lower boundary for the minimum effect for the target of accumulated doses on multiple geometry instances.

  19. Estimation of breast dose reduction potential for organ-based tube current modulated CT with wide dose reduction arc

    Science.gov (United States)

    Fu, Wanyi; Sturgeon, Gregory M.; Agasthya, Greeshma; Segars, W. Paul; Kapadia, Anuj J.; Samei, Ehsan

    2017-03-01

    This study aimed to estimate the organ dose reduction potential for organ-dose-based tube current modulated (ODM) thoracic CT with wide dose reduction arc. Twenty-one computational anthropomorphic phantoms (XCAT, age range: 27- 75 years, weight range: 52.0-105.8 kg) were used to create a virtual patient population with clinical anatomic variations. For each phantom, two breast tissue compositions were simulated: 50/50 and 20/80 (glandular-to-adipose ratio). A validated Monte Carlo program was used to estimate the organ dose for standard tube current modulation (TCM) (SmartmA, GE Healthcare) and ODM (GE Healthcare) for a commercial CT scanner (Revolution, GE Healthcare) with explicitly modeled tube current modulation profile, scanner geometry, bowtie filtration, and source spectrum. Organ dose was determined using a typical clinical thoracic CT protocol. Both organ dose and CTDIvol-to-organ dose conversion coefficients (h factors) were compared between TCM and ODM. ODM significantly reduced all radiosensitive organ doses (psaw an increase or no significant change. The organ-dose-based tube current modulation significantly reduced organ doses especially for radiosensitive superficial anterior organs such as the breasts.

  20. 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 advanta

  1. Practical aspects and uncertainty analysis of biological effective dose (BED) regarding its three-dimensional calculation in multiphase radiotherapy treatment plans

    Energy Technology Data Exchange (ETDEWEB)

    Kauweloa, Kevin I., E-mail: Kauweloa@livemail.uthscsa.edu; Gutierrez, Alonso N.; Bergamo, Angelo; Stathakis, Sotirios; Papanikolaou, Nikos; Mavroidis, Panayiotis [Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229 and Cancer Therapy and Research Center, San Antonio, Texas 78229 (United States)

    2014-07-15

    Purpose: There is a growing interest in the radiation oncology community to use the biological effective dose (BED) rather than the physical dose (PD) in treatment plan evaluation and optimization due to its stronger correlation with radiobiological effects. Radiotherapy patients may receive treatments involving a single only phase or multiple phases (e.g., primary and boost). Since most treatment planning systems cannot calculate the analytical BED distribution in multiphase treatments, an approximate multiphase BED expression, which is based on the total physical dose distribution, has been used. The purpose of this paper is to reveal the mathematical properties of the approximate BED formulation, relative to the true BED. Methods: The mathematical properties of the approximate multiphase BED equation are analyzed and evaluated. In order to better understand the accuracy of the approximate multiphase BED equation, the true multiphase BED equation was derived and the mathematical differences between the true and approximate multiphase BED equations were determined. The magnitude of its inaccuracies under common clinical circumstances was also studied. All calculations were performed on a voxel-by-voxel basis using the three-dimensional dose matrices. Results: Results showed that the approximate multiphase BED equation is accurate only when the dose-per-fractions (DPFs) in both the first and second phases are equal, which occur when the dose distribution does not significantly change between the phases. In the case of heterogeneous dose distributions, which significantly vary between the phases, there are fewer occurrences of equal DPFs and hence the inaccuracy of the approximate multiphase BED is greater. These characteristics are usually seen in the dose distributions being delivered to organs at risk rather than to targets. Conclusions: The finding of this study indicates that the true multiphase BED equation should be implemented in the treatment planning

  2. 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)

  3. 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.

  4. Biologically effective dose in fractionated molecular radiotherapy—application to treatment of neuroblastoma with 131I-mIBG

    Science.gov (United States)

    Mínguez, Pablo; Gustafsson, Johan; Flux, Glenn; Sjögreen Gleisner, Katarina

    2016-03-01

    In this work, the biologically effective dose (BED) is investigated for fractionated molecular radiotherapy (MRT). A formula for the Lea-Catcheside G-factor is derived which takes the possibility of combinations of sub-lethal damage due to radiation from different administrations of activity into account. In contrast to the previous formula, the new G-factor has an explicit dependence on the time interval between administrations. The BED of tumour and liver is analysed in MRT of neuroblastoma with 131I-mIBG, following a common two-administration protocol with a mass-based activity prescription. A BED analysis is also made for modified schedules, when due to local regulations there is a maximum permitted activity for each administration. Modifications include both the simplistic approach of delivering this maximum permitted activity in each of the two administrations, and also the introduction of additional administrations while maintaining the protocol-prescribed total activity. For the cases studied with additional (i.e. more than two) administrations, BED of tumour and liver decreases at most 12% and 29%, respectively. The decrease in BED of the tumour is however modest compared to the two-administration schedule using the maximum permitted activity, where the decrease compared to the original schedule is 47%.

  5. [Ecological and biological characteristics of Drosophila melanogaster features depending on the dose of electromagnetic radiation of various types].

    Science.gov (United States)

    Babkina, V V; Chernova, G V; Allenova, E A; Endebera, O P; Naumkina, E N

    2013-01-01

    Biological effects of exposure to red light (lambda = 660 +/- 10 nm) on the viability and morphophysiological characteristics of Drosophila melanogaster have been studied. The ability of this physical agent to modify these features is shown. The degree of expression and impact of biological effects depend on the dose, functional and genetic status of the organism. The study of the life expectancy of the exposed to EHF and white light D. melanogaster has revealed that expression of the features depends on the radiation doses, genotype, sex, the nature of the position of wings and lighting conditions. It has been found that the dark mode (24 h-night) is more favorable than the artificial lighting. Individuals with the left wing at the top are more sensitive to the external factors.

  6. Total and secondary gamma doses in ilmenite-limonite concrete biological shields

    Energy Technology Data Exchange (ETDEWEB)

    Makarious, A.S. (AEA, Cairo (Egypt). Reactor and Neutron Physics Dept.); El-Kolaly, M.A. (AEA, Cairo (Egypt). Radiation Protection Dept.); Bashter, I.I. (Zagazig Univ. (Egypt). Physics Dept.); Kansouh, W.A. (AEA, Cairo (Egypt). Nuclear Research Centre)

    1991-10-01

    The attenuation and distribution of total gamma ray doses in a bulk shield of ilmenite-limonite concrete of density 2.9 g cm{sup -3} have been measured. Direct, cadmium filtered and B{sub 4}C filtered collimated reactor beam emitted from one of the horizontal channels of the ET-RR-1 reactor have been utilized in the present work. The distribution of the secondary gamma ray doses generated from the interaction of reactor neutrons of definite energy ranges has also been obtained for ilmenite-limonite concrete. The gamma doses were measured using {sup 7}LiF Teflon disc TL dosimeters. A semiempirical formula was derived to calculate total gamma dose distributions for bare, cadmium filtered and B{sub 4}C filtered reactor beams at different thickness along the beam axis in ordinary concrete, with density 2.3 g cm{sup -3}, using the corresponding measured value in ilmenite-limonite concrete. Good agreement has been achieved between the values of the total gamma doses and those calculated using the derived empirical formula. Isodose curves were constructed for both the total gamma-ray doses and the secondary gamma-ray doses shields together with the corresponding values for ordinary concrete shields. The thickness of ilmenite-limonite concrete required to attenuate the total gamma dose intensity to a certain factor is approximately 94% of the thickness when the shield is made of ordinary concrete. (orig./HP).

  7. Relative biological effectiveness and tolerance dose of fission neutrons in canine skin for a potential combination of neutron capture therapy and fast-neutron therapy.

    Science.gov (United States)

    Kadosawa, Tsuyoshi; Ohashi, Fumihito; Nishimura, Ryohei; Sasaki, Nobuo; Saito, Isao; Wakabayashi, Hiroaki; Takeuchi, Akira

    2003-10-01

    To investigate the potential efficacy of fission neutrons from a fast-neutron reactor for the treatment of radioresistant tumors, the relative biological effectiveness (RBE) and tolerance dose of fission neutrons in canine skin were determined. The forelimbs of 34 healthy mongrel dogs received a single dose of fission neutrons (5.6, 6.8, 8.2, 9.6 or 11 Gy) or 137Cs gamma rays (10, 15, 20, 25 or 30 Gy). Based on observations of radiodermatitis for each radiation, the single-fraction RBE of fission neutrons in the sixth month was calculated as approximately 3. The tolerance doses of fission neutrons and gamma rays, defined as the highest doses giving no moist desquamation on the irradiated skin in the recovery phase, were estimated as 7.6 Gy and 20 Gy, respectively. The tolerance dose of 7.6 Gy of fission neutrons included 5.0 Gy of fast neutrons possessing high anti-tumor effects and 1.4 x 10(12) n/cm2 of thermal neutrons, which could be applicable to neutron capture therapy (NCT). The combination of fast-neutron therapy and NCT using a fast-neutron reactor might be useful for the treatment of radioresistant tumors.

  8. Biological dose escalation and hypofractionation: what is there to be gained and how will it best be done?

    Science.gov (United States)

    Tree, A C; Alexander, E J; Van As, N J; Dearnaley, D P; Khoo, V

    2013-08-01

    The evidence supporting dose escalation for localised prostate cancer is widely accepted, but in tandem with improvements in biochemical control, dose escalation increases side-effects. In a scenario where most patients achieve control of their cancer, quality of life concerns predominate. Here we examine the biological ways in which an effective dose can be escalated without an unacceptable increase in toxicity. Possible avenues include exploiting the unusual radiobiology of prostate cancer by hypofractionation, the use of image guidance, adaptive planning and prostate motion management. We await with anticipation the results of large randomised trials of hypofractionation, moderate and profound, to establish whether we can further improve the balance between cure and quality of life.

  9. Effects of dose-delivery time structure on biological effectiveness for therapeutic carbon-ion beams evaluated with microdosimetric kinetic model.

    Science.gov (United States)

    Inaniwa, Taku; Suzuki, Masao; Furukawa, Takuji; Kase, Yuki; Kanematsu, Nobuyuki; Shirai, Toshiyuki; Hawkins, Roland B

    2013-07-01

    Treatment plans of carbon-ion radiotherapy have been made on the assumption that the beams are delivered instantaneously irrespective to the dose delivery time as well as the interruption time. The advanced therapeutic techniques such as a hypofractionation and a respiratory gating usually require more time to deliver a fractioned dose than conventional techniques. The purpose of this study was to investigate the effects of dose-delivery time structure on biological effectiveness in carbon-ion radiotherapy. The rate equations defined in the microdosimetric kinetic model (MKM) for primary lesions caused in the DNA were reanalyzed and applied to continuous or interrupted irradiation with therapeutic carbon-ion beams. The rate constants characterizing the time of the primary nonlethal lesions to repair or to convert to lethal lesion were experimentally determined for human salivary gland (HSG) tumor cells. Treatment plans were made for a patient case on the assumption that the beam is delivered instantaneously. The RBE weighted absorbed doses of 2.65, 3.45 and 6.86 Gy (RBE) was prescribed to the target. These plans were recalculated by varying the dose delivery time and the interruption time ranging from 1-60 min based on the MKM with the determined parameters. The sum of rate constants for nonlethal lesion to repair a and to convert to lethal lesion c, (a + c), is 2.19 ± 0.40 h⁻¹. The biological effectiveness in the target decreases with the dose delivery time T in continuous irradiation compared to the planned one due to the repair of nonlethal lesions during the irradiation. The biological effectiveness in terms of equivalent acute dose decreases to 99.7% and 96.4% for T = 3 and 60 min in 2.65 Gy (RBE), 99.5% and 94.3% in 4.35 Gy (RBE), and 99.4% and 91.7% in 6.86 Gy (RBE), respectively. For all the cases, the decrease of biological effectiveness is larger at the proximal side with low-LET than the distal side with high-LET. Similar reductions of biological

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

    OpenAIRE

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

    2010-01-01

    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 V...

  11. Weight-Based Adaptation of TNF-Antagonist Induction versus Maintenance Dose

    Directory of Open Access Journals (Sweden)

    Marco A. Muster

    2011-06-01

    Full Text Available Biologics are highly specific and exhibit few problems in regard to overdosages. In clinical practice, induction schemes with an initial loading dose and a subsequent lower maintenance dose have been established and are of higher efficacy for psoriasis than starting directly with the maintenance dose. As obese patients sometimes respond less well to standard dosages, increases of the maintenance dose, but not the loading doses, have been tried with variable success. In our study, we increased the loading (160 mg instead of 80 mg but not the maintenance dose of adalimumab in an obese patient with severe psoriasis resistant to previous biologics and methotrexate. Within 12 weeks, both PASI (11 to 1.6 and DLQI (22/30 to 5/30 decreased. This strategy might be an effective and less costly alternative to doubling the maintenance doses, and could be further evaluated for psoriasis patients refractory to previous treatments.

  12. 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

  13. 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.

  14. Statistical analysis of MRI-only based dose planning

    DEFF Research Database (Denmark)

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

    2012-01-01

    Head and Neck (HN) patients treated with static IMRT, 5 sarcoma (extremities only) patients treated with APPA. 21 prostate and 5 pelvic (not prostate) patients treated with VMAT. Data for each patient contains a CT scan (Phillips Big Bore CT) and a T2 weighted MRI scan (1T Panorama Phillips) as well...... 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...... and the CT. The differences in dose distributions of the MRI bulk, MRI unit and CT data are quantified using DVH points. The reported DVH points for the PTV and CTV are Dmedian, D98% and D2% in accordance with ICRU report 83. The DVH points for the organs at risk are based on clinically guidelines used...

  15. PET/CT Based Dose Planning in Radiotherapy

    DEFF Research Database (Denmark)

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

    2011-01-01

    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...... 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...... 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. 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.

  17. Biological Bases of Space Radiation Risk

    Science.gov (United States)

    1997-01-01

    In this session, Session JP4, the discussion focuses on the following topics: Hematopoiesis Dynamics in Irradiated Mammals, Mathematical Modeling; Estimating Health Risks in Space from Galactic Cosmic Rays; Failure of Heavy Ions to Affect Physiological Integrity of the Corneal Endothelial Monolayer; Application of an Unbiased Two-Gel CDNA Library Screening Method to Expression Monitoring of Genes in Irradiated Versus Control Cells; Detection of Radiation-Induced DNA Strand Breaks in Mammalian Cells By Enzymatic Post-Labeling; Evaluation of Bleomycin-Induced Chromosome Aberrations Under Microgravity Conditions in Human Lymphocytes, Using "Fish" Techniques; Technical Description of the Space Exposure Biology Assembly Seba on ISS; and Cytogenetic Research in Biological Dosimetry.

  18. Biological Based Risk Assessment for Space Exploration

    Science.gov (United States)

    Cucinotta, Francis A.

    2011-01-01

    Exposures from galactic cosmic rays (GCR) - made up of high-energy protons and high-energy and charge (HZE) nuclei, and solar particle events (SPEs) - comprised largely of low- to medium-energy protons are the primary health concern for astronauts for long-term space missions. Experimental studies have shown that HZE nuclei produce both qualitative and quantitative differences in biological effects compared to terrestrial radiation, making risk assessments for cancer and degenerative risks, such as central nervous system effects and heart disease, highly uncertain. The goal for space radiation protection at NASA is to be able to reduce the uncertainties in risk assessments for Mars exploration to be small enough to ensure acceptable levels of risks are not exceeded and to adequately assess the efficacy of mitigation measures such as shielding or biological countermeasures. We review the recent BEIR VII and UNSCEAR-2006 models of cancer risks and their uncertainties. These models are shown to have an inherent 2-fold uncertainty as defined by ratio of the 95% percent confidence level to the mean projection, even before radiation quality is considered. In order to overcome the uncertainties in these models, new approaches to risk assessment are warranted. We consider new computational biology approaches to modeling cancer risks. A basic program of research that includes stochastic descriptions of the physics and chemistry of radiation tracks and biochemistry of metabolic pathways, to emerging biological understanding of cellular and tissue modifications leading to cancer is described.

  19. Nucleic Acid--Based Nanodevices in Biological Imaging

    Science.gov (United States)

    Chakraborty, Kasturi; Veetil, Aneesh T.

    2017-01-01

    The nanoscale engineering of nucleic acids has led to exciting molecular technologies for high-end biological imaging. The predictable base pairing, high programmability, and superior new chemical and biological methods used to access nucleic acids with diverse lengths and in high purity, coupled with computational tools for their design, have allowed the creation of a stunning diversity of nucleic acid--based nanodevices. Given their biological origin, such synthetic devices have a tremendous capacity to interface with the biological world, and this capacity lies at the heart of several nucleic acid--based technologies that are finding applications in biological systems. We discuss these diverse applications and emphasize the advantage, in terms of physicochemical properties, that the nucleic acid scaffold brings to these contexts. As our ability to engineer this versatile scaffold increases, its applications in structural, cellular, and organismal biology are clearly poised to massively expand. PMID:27294440

  20. Nucleic Acid-Based Nanodevices in Biological Imaging.

    Science.gov (United States)

    Chakraborty, Kasturi; Veetil, Aneesh T; Jaffrey, Samie R; Krishnan, Yamuna

    2016-06-02

    The nanoscale engineering of nucleic acids has led to exciting molecular technologies for high-end biological imaging. The predictable base pairing, high programmability, and superior new chemical and biological methods used to access nucleic acids with diverse lengths and in high purity, coupled with computational tools for their design, have allowed the creation of a stunning diversity of nucleic acid-based nanodevices. Given their biological origin, such synthetic devices have a tremendous capacity to interface with the biological world, and this capacity lies at the heart of several nucleic acid-based technologies that are finding applications in biological systems. We discuss these diverse applications and emphasize the advantage, in terms of physicochemical properties, that the nucleic acid scaffold brings to these contexts. As our ability to engineer this versatile scaffold increases, its applications in structural, cellular, and organismal biology are clearly poised to massively expand.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Low-dose rituximab in adult patients with idiopathic autoimmune hemolytic anemia: clinical efficacy and biologic studies.

    Science.gov (United States)

    Barcellini, Wilma; Zaja, Francesco; Zaninoni, Anna; Imperiali, Francesca Guia; Battista, Marta Lisa; Di Bona, Eros; Fattizzo, Bruno; Consonni, Dario; Cortelezzi, Agostino; Fanin, Renato; Zanella, Alberto

    2012-04-19

    This prospective study investigated the efficacy, safety, and response duration of low-dose rituximab (100 mg fixed dose for 4 weekly infusions) together with a short course of steroids as first- or second-line therapy in 23 patients with primary autoimmune hemolytic anemia (AIHA). The overall response was 82.6% at month +2, and subsequently stabilized to ∼ 90% at months +6 and +12; the response was better in warm autoimmune hemolytic anemia (WAIHA; overall response, 100% at all time points) than in cold hemagglutinin disease (CHD; average, 60%); the relapse-free survival was 100% for WAIHA at +6 and +12 months versus 89% and 59% in CHD, respectively, and the estimated relapse-free survival at 2 years was 81% and 40% for the warm and cold forms, respectively. The risk of relapse was higher in CHD and in patients with a longer interval between diagnosis and enrollment. Steroid administration was reduced both as cumulative dose (∼ 50%) and duration compared with the patient's past history. Treatment was well tolerated and no adverse events or infections were recorded; retreatment was also effective. The clinical response was correlated with amelioration biologic markers such as cytokine production (IFN-γ, IL-12, TNF-α, and IL-17), suggesting that low-dose rituximab exerts an immunomodulating activity. This study is registered at www.clinicaltrials.gov as NCT01345708.

  8. Mechanism of Action for Anti-Radiation Vaccine in Reducing the Biological Impact of High-Dose Irradiation

    Science.gov (United States)

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

    2006-01-01

    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. We partially analyzed the biochemical characteristics of the SRDs. 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.

  9. Specification of absorbed dose to water using model-based dose calculation algorithms for treatment planning in brachytherapy.

    Science.gov (United States)

    Tedgren, Åsa Carlsson; Carlsson, Gudrun Alm

    2013-04-21

    Model-based dose calculation algorithms (MBDCAs), recently introduced in treatment planning systems (TPS) for brachytherapy, calculate tissue absorbed doses. In the TPS framework, doses have hereto been reported as dose to water and water may still be preferred as a dose specification medium. Dose to tissue medium Dmed then needs to be converted into dose to water in tissue Dw,med. Methods to calculate absorbed dose to differently sized water compartments/cavities inside tissue, infinitesimal (used for definition of absorbed dose), small, large or intermediate, are reviewed. Burlin theory is applied to estimate photon energies at which cavity sizes in the range 1 nm-10 mm can be considered small or large. Photon and electron energy spectra are calculated at 1 cm distance from the central axis in cylindrical phantoms of bone, muscle and adipose tissue for 20, 50, 300 keV photons and photons from (125)I, (169)Yb and (192)Ir sources; ratios of mass-collision-stopping powers and mass energy absorption coefficients are calculated as applicable to convert Dmed into Dw,med for small and large cavities. Results show that 1-10 nm sized cavities are small at all investigated photon energies; 100 µm cavities are large only at photon energies <20 keV. A choice of an appropriate conversion coefficient Dw, med/Dmed is discussed in terms of the cavity size in relation to the size of important cellular targets. Free radicals from DNA bound water of nanometre dimensions contribute to DNA damage and cell killing and may be the most important water compartment in cells implying use of ratios of mass-collision-stopping powers for converting Dmed into Dw,med.

  10. 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.

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

    OpenAIRE

    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-...

  12. Biological and hemodynamic effects of low doses of fludrocortisone and hydrocortisone, alone or in combination, in healthy volunteers with hypoaldosteronism.

    Science.gov (United States)

    Laviolle, B; Le Maguet, P; Verdier, M-C; Massart, C; Donal, E; Lainé, F; Lavenu, A; Pape, D; Bellissant, E

    2010-08-01

    Low doses of hydrocortisone (HC) and fludrocortisone (FC) administered together improve the prognosis after septic shock; however, there continues to be disagreement about the utility of FC for this indication. The biological and hemodynamic effects of HC (50 mg intravenously) and FC (50 microg orally) were assessed in 12 healthy male volunteers with saline-induced hypoaldosteronism in a placebo-controlled, randomized, double-blind, crossover study performed according to a 2 x 2 factorial design. HC and FC significantly decreased urinary sodium and potassium levels (from -58% at 4 h to -28% at 10 h and from -35% at 8 h to -24% at 12 h, respectively) with additive effects. At 4 h after administration, HC significantly increased cardiac output (+14%), decreased systemic vascular resistances (-14%), and slightly increased heart rate (+4 beats/min), whereas FC had no hemodynamic effect. At doses used in septic shock, HC induced greater mineralocorticoid effect than FC did. HC also induced transient systemic hemodynamic effects, whereas FC did not. New studies are required to better define the optimal dose of FC in septic shock.

  13. 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.

  14. Biological radiation dose from secondary particles in a Milky Way gamma ray burst

    CERN Document Server

    Atri, Dimitra; Karam, Andrew

    2013-01-01

    Gamma ray bursts (GBRs) are a class of highly energetic explosions emitting radiation in a very short timescale of a few seconds and with a very narrow opening angle. Although, all GRBs observed so far are extragalactic in origin, there is a high probability of a GRB of galactic origin beaming towards the Earth in the past ~ 0.5 Gyr. Such an intense burst of gamma rays would ionize the atmosphere and deplete the ozone layer. With depleted ozone, there will be an increased flux of solar UVB on the Earth\\~Os surface with harmful biological effects. In addition to the atmospheric damage, secondary particles produced by gamma ray-induced showers will reach the surface. Amongst all secondary particles, muons dominate the ground-level secondary particle flux (99% of the total number of particles) and are potentially of biological significance. Using the Monte Carlo simulation code CORSIKA, we modeled the air showers produced by gamma ray primaries up to 100 GeV. We found that the number of muons produced by hypothe...

  15. [CUDA-based fast dose calculation in radiotherapy].

    Science.gov (United States)

    Wang, Xianliang; Liu, Cao; Hou, Qing

    2011-10-01

    Dose calculation plays a key role in treatment planning of radiotherapy. Algorithms for dose calculation require high accuracy and computational efficiency. Finite size pencil beam (FSPB) algorithm is a method commonly adopted in the treatment planning system for radiotherapy. However, improvement on its computational efficiency is still desirable for such purpose as real time treatment planning. In this paper, we present an implementation of the FSPB, by which the most time-consuming parts in the algorithm are parallelized and ported on graphic processing unit (GPU). Compared with the FSPB completely running on central processing unit (CPU), the GPU-implemented FSPB can speed up the dose calculation for 25-35 times on a low price GPU (Geforce GT320) and for 55-100 times on a Tesla C1060, indicating that the GPU-implemented FSPB can provide fast enough dose calculations for real-time treatment planning.

  16. 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.)

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

    Science.gov (United States)

    Lahanas, M; Baltas, D; Zamboglou, N

    2003-02-07

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Lahanas, M [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach, 63069 Offenbach (Germany); Baltas, D [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach, 63069 Offenbach (Germany); Zamboglou, N [Department of Medical Physics and Engineering, Strahlenklinik, Klinikum Offenbach, 63069 Offenbach (Germany)

    2003-02-07

    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.

  19. 86Y based PET radiopharmaceuticals: radiochemistry and biological applications.

    Science.gov (United States)

    Nayak, Tapan K; Brechbiel, Martin W

    2011-09-01

    Development of targeted radionuclide therapy with (90)Y labeled antibodies and peptides has gained momentum in the past decade due to the successes of (90)Y-ibritumomab tiuxetan and (90)Y-DOTA-Phe(1)-Tyr(3)-octreotide in treatment of cancer. (90)Y is a pure β(-)-emitter and cannot be imaged for patient-specific dosimetry which is essential for pre-therapeutic treatment planning and accurate absorbed dose estimation in individual patients to mitigate radiation related risks. This review article describes the utility of (86)Y, a positron emitter (33%) with a 14.7-h half-life that can be imaged by positron emission tomography and used as an isotopically matched surrogate radionuclide for (90)Y radiation doses estimations. This review discusses various aspects involved in the development of (86)Y labeled radiopharmaceuticals with the specific emphasis on the radiochemistry and biological applications with antibodies and peptides.

  20. 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

  1. 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.

  2. Parameter identifiability-based optimal observation remedy for biological networks.

    Science.gov (United States)

    Wang, Yulin; Miao, Hongyu

    2017-05-04

    To systematically understand the interactions between numerous biological components, a variety of biological networks on different levels and scales have been constructed and made available in public databases or knowledge repositories. Graphical models such as structural equation models have long been used to describe biological networks for various quantitative analysis tasks, especially key biological parameter estimation. However, limited by resources or technical capacities, partial observation is a common problem in experimental observations of biological networks, and it thus becomes an important problem how to select unobserved nodes for additional measurements such that all unknown model parameters become identifiable. To the best knowledge of our authors, a solution to this problem does not exist until this study. The identifiability-based observation problem for biological networks is mathematically formulated for the first time based on linear recursive structural equation models, and then a dynamic programming strategy is developed to obtain the optimal observation strategies. The efficiency of the dynamic programming algorithm is achieved by avoiding both symbolic computation and matrix operations as used in other studies. We also provided necessary theoretical justifications to the proposed method. Finally, we verified the algorithm using synthetic network structures and illustrated the application of the proposed method in practice using a real biological network related to influenza A virus infection. The proposed approach is the first solution to the structural identifiability-based optimal observation remedy problem. It is applicable to an arbitrary directed acyclic biological network (recursive SEMs) without bidirectional edges, and it is a computerizable method. Observation remedy is an important issue in experiment design for biological networks, and we believe that this study provides a solid basis for dealing with more challenging design

  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 approaches

  4. 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

  5. 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)

  6. Semantic Search among Heterogeneous Biological Databases Based on Gene Ontology

    Institute of Scientific and Technical Information of China (English)

    Shun-Liang CAO; Lei QIN; Wei-Zhong HE; Yang ZHONG; Yang-Yong ZHU; Yi-Xue LI

    2004-01-01

    Semantic search is a key issue in integration of heterogeneous biological databases. In thispaper, we present a methodology for implementing semantic search in BioDW, an integrated biological datawarehouse. Two tables are presented: the DB2GO table to correlate Gene Ontology (GO) annotated entriesfrom BioDW data sources with GO, and the semantic similarity table to record similarity scores derived fromany pair of GO terms. Based on the two tables, multifarious ways for semantic search are provided and thecorresponding entries in heterogeneous biological databases in semantic terms can be expediently searched.

  7. Pharmacogenetically based dosing of thiopurines in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Rotevatn, Elisabeth Orskov; Rosthøj, Susanne

    2014-01-01

    BACKGROUND: Previous studies have indicated that patients with thiopurine methyltransferase (TPMT) low activity (TPMT(LA)) have reduced risk of relapse but increased risk of second malignant neoplasm (SMN) compared to patients with TPMT wild-type (TPMT(WT)) when treated with 6 MP maintenance...... therapy starting doses of 75 mg/m(2)/day. To reduce SMN risk, 6MP starting doses were reduced to 50 mg/m(2)/day for patients with TPMT heterozygosity in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2000 protocol. PROCEDURE: We explored the pattern of SMN and relapse in the NOPHO...... relapse or SMN, the risk of SMN versus leukemia relapse was significantly lower in the ALL2000 cohort for patients with a 6MP starting dose

  8. A Theme-Based Approach to Teaching Nonmajors Biology: Helping Students Connect Biology to Their Lives

    Science.gov (United States)

    Chaplin, Susan B.; Manske, Jill M.

    2005-01-01

    This article describes the curriculum for a highly student-centered human biology course constructed around a series of themes that enables the integration of the same basic paradigms found in a traditional survey lecture course without sacrificing essential content. The theme-based model enhances student interest, ability to integrate knowledge,…

  9. 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)

  10. Computational Systems Biology and Dose Response Modeling Workshop, September 22-26, 2008

    Science.gov (United States)

    The recently published National Academy of Sciences (NAS) report “Toxicity Testing in the 21st Century” recommends a new approach to toxicity testing, based on evaluating cellular responses in a suite of toxicity pathway assays in human cells or cells lines in vitro. Such a parad...

  11. Systems Biology Approach for Understanding MOA, Dose-Response and Susceptibility to Environmental Chemicals

    Science.gov (United States)

    There is an increasing need for assays for the rapid and efficient assessment of toxicities of large numbers of environmental chemicals. To meet this need, we have developed a battery of cell-based reporter assays that measure the activation of key cellular stress pathways. These...

  12. Development of dose-based release limits for unrestricted release of a radiochemistry laboratory.

    Science.gov (United States)

    Rima, Steven D

    2003-02-01

    Current regulations for unrestricted release are based on annual dose equivalent. Unless one desires to use very conservative "screening levels," dose modeling must be accomplished to derive an areal or volumetric limit or concentration value for release purposes. Such derived limits are referred to as "Derived Concentration Guideline Levels" (DCGL). This paper describes the process employed to derive DCGLs for building surfaces contaminated with uranium and its decay progeny based on annual dose equivalent and the innovative means employed during the derivation.

  13. Modeling Low-Dose-Rate Effects in Irradiated Bipolar-Base Oxides

    Energy Technology Data Exchange (ETDEWEB)

    Cirba, C.R.; Fleetwood, D.M.; Graves, R.J.; Michez, A.; Milanowski, R.J.; Saigne, F.; Schrimpf, R.D.; Witczak, S.C.

    1998-10-26

    A physical model is developed to quantify the contribution of oxide-trapped charge to enhanced low-dose-rate gain degradation in bipolar junction transistors. Multiple-trapping simulations show that space charge limited transport is partially responsible for low-dose-rate enhancement. At low dose rates, more holes are trapped near the silicon-oxide interface than at high dose rates, resulting in larger midgap voltage shifts at lower dose rates. The additional trapped charge near the interface may cause an exponential increase in excess base current, and a resultant decrease in current gain for some NPN bipolar technologies.

  14. Comparison of radon doses based on different radon monitoring approaches.

    Science.gov (United States)

    Vaupotič, Janja; Smrekar, Nataša; Žunić, Zora S

    2017-04-01

    In 43 places (23 schools, 3 kindergartens, 16 offices and one dwelling), indoor radon has been monitored as an intercomparison experiment, using α-scintillation cells (SC - Jožef Stefan Institute, Slovenia), various kinds of solid state nuclear track detectors (KfK - Karlsruhe Institute of Technology, Germany; UFO - National Institute of Radiological Sciences, Chiba, Japan; RET - University College Dublin, Ireland) and active electronic devices (EQF, Sarad, Germany). At the same place, the radon levels and, consequently, the effective doses obtained with different radon devices differed substantially (by a factor of 2 or more), and no regularity was observed as regards which detector would show a higher or lower dose. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. 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.

  16. The effect of the beta-emitting yttrium-90 citrate on the dose-response of dicentric chromosomes in human lymphocytes: a basis for biological dosimetry after radiosynoviorthesis.

    Science.gov (United States)

    Schmid, E; Selbach, H-J; Voth, M; Pinkert, J; Gildehaus, F J; Klett, R; Haney, M

    2006-07-01

    The production of dicentric chromosomes in human lymphocytes by beta-particles of yttrium-90 (Y-90) was studied in vitro to provide a basis of biological dosimetry after radiosynoviorthesis (RSO) of persistent synovitis by intra-articular administration of yttrium-90 citrate colloid. Since the injected colloid may leak into the lymphatic drainage exposing other parts of the body to radiation, the measurement of biological damage induced by beta-particles of Y-90 is important for the assessment of radiation risk to the patients. A linear dose-response relationship (alpha = 0.0229 +/- 0.0028 dicentric chromosomes per cell per gray) was found over the dose range of 0.2176-2.176 Gy. The absorbed doses were calculated for exposure of blood samples to Y-90 activities from 40 to 400 kBq using both Monte Carlo simulation and an analytical model. The maximum low-dose RBE, the RBE(M) which is equivalent to the ratio of the alpha coefficients of the dose-response curves, is well in line with published results obtained earlier for irradiation of blood of the same donor with heavily filtered 220 kV X-rays (3.35 mm copper), but half of the RBE(M) relative to weakly filtered 220 kV X-rays. Therefore, it can be concluded that for estimating an absorbed dose during RSO by the technique of biological dosimetry, in vitro and in vivo data for the same radiation quality are necessary.

  17. Voxel-Based Dose Prediction with Multi-Patient Atlas Selection for Automated Radiotherapy Treatment Planning

    CERN Document Server

    McIntosh, Chris

    2016-01-01

    Automating the radiotherapy treatment planning process is a technically challenging problem. The majority of automated approaches have focused on customizing and inferring dose volume objectives to used in plan optimization. In this work we outline a multi-patient atlas-based dose prediction approach that learns to predict the dose-per-voxel for a novel patient directly from the computed tomography (CT) planning scan without the requirement of specifying any objectives. Our method learns to automatically select the most effective atlases for a novel patient, and then map the dose from those atlases onto the novel patient. We extend our previous work to include a conditional random field for the optimization of a joint distribution prior that matches the complementary goals of an accurately spatially distributed dose distribution while still adhering to the desired dose volume histograms. The resulting distribution can then be used for inverse-planning with a new spatial dose objective, or to create typical do...

  18. 4D cone beam CT-based dose assessment for SBRT lung cancer treatment

    Science.gov (United States)

    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.

  19. 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

  20. 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

    2016-05-21

    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 ([Formula: see text]) 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 [Formula: see text] values that quantified the regional dose field for each organ. The organ dose was estimated by multiplying [Formula: see text] with the organ dose coefficients ([Formula: see text]). 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 discrepancy between the estimated organ dose and dose simulated using TCM Monte Carlo program was quantified. We further compared the

  1. 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…

  2. 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…

  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. Characterization of tumor dose heterogeneity for 90Y microsphere therapies using voxel- based dosimetry

    Directory of Open Access Journals (Sweden)

    Justin Mikell

    2014-03-01

    Full Text Available Purpose: Dosimetry for 90Y microsphere therapies (YMT with Standard (SM and Partition (PM models provide only uniform dose estimates to tumor and liver. Our objective is to calculate tumor dose heterogeneity, known to effect response, using voxel-based dosimetry and investigate the limitations of SM and PM.Methods: Voxel-based dosimetry was performed on 17 YMT patients using Monte Carlo DOSXYZnrc. 90Y activity and tissue/density distributions were based on quantitative 90Y bremsstrahlung SPECT/CT. Tumors (n=31, liver, and treatment lobe/segments were segmented on diagnostic CT or MR. Dose volume histograms (DVH were created for tumors and normal liver. Bland-Altman analysis compared voxel-based mean absorbed doses to tumor and liver with SM and PM. Tumor and normal liver absorbed dose heterogeneity were investigated through metrics: integral uniformity (IU, D10/D90, COV. Correlations of heterogeneity with voxel-based mean doses and volumes were evaluated.Results: Heterogeneity metrics (mean ± 1σ for tumor dose were COV = 0.48 ± 0.28, D10/D90 = 4.7 ± 3.9, and IU = 0.8 ± 0.18. Heterogeneity metrics correlated with tumor volume (r > 0.58 but not tumor mean doses (r < 0.20. Voxel-based tumor mean doses correlated with PM (r = 0.84 but not SM (r = 0.08. Both yielded poor limits of agreement with of 83 ± 174 and -28 ± 181 Gy, respectively. Normal liver heterogeneity metrics (mean ± 1σ were COV = 0.83 ± 0.29, D10/D90 = 12 ± 15, and IU = 0.97 ± 0.03. Only D10/D90 (r = 0.49 correlated with mean normal liver absorbed dose. Voxel-based normal liver/lobe mean doses correlated with PM (r = 0.96, but had poor limits of agreement (26 ± 29 Gy.Conclusion: Tumor doses have high levels of heterogeneity that increase with volume but are independent of dose. Voxel-based DVH and dose heterogeneity metrics will promote accurate characterization of tumor response following YMT.--------------------------------------Cite this article as: Mikell J, Mourtada F

  6. 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.

  7. 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 ...

  8. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    d’Espaux, Leo [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint BioEnergy Inst.; Mendez-Perez, Daniel [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint BioEnergy Inst.; Li, Rachel [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint BioEnergy Inst.; Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology; Keasling, Jay D. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Joint BioEnergy Inst.; Univ. of California, Berkeley, CA (United States). Dept. of Plant and Microbial Biology; Univ. of California, Berkeley, CA (United States). Dept. of Bioengineering, QB3 Inst.; Univ. of California, Berkeley, CA (United States). Dept. of Chemical and Biomolecular Engineering, QB3 Inst.

    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.

  10. 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.

  11. Estimated fluoride doses from toothpastes should be based on total soluble fluoride.

    Science.gov (United States)

    Oliveira, Maria José L; Martins, Carolina C; Paiva, Saul M; Tenuta, Livia M A; Cury, Jaime A

    2013-11-01

    The fluoride dose ingested by young children may be overestimated if based on levels of total fluoride (TF) rather than levels of bioavailable fluoride (total soluble fluoride-TSF) in toothpaste. The aim of the present study was to compare doses of fluoride intake based on TF and TSF. Fluoride intake in 158 Brazilian children aged three and four years was determined after tooth brushing with their usual toothpaste (either family toothpaste (n = 80) or children's toothpaste (n = 78)). The estimated dose (mg F/day/Kg of body weight) of TF or TSF ingested was calculated from the chemical analysis of the toothpastes. Although the ingested dose of TF from the family toothpastes was higher than that from the children's toothpastes (0.074 ± 0.007 and 0.039 ± 0.003 mg F/day/Kg, respectively; p toothpaste was found regarding the ingested dose based on TSF (0.039 ± 0.005 and 0.039 ± 0.005 mg F/day/Kg, respectively; p > 0.05). The fluoride dose ingested by children from toothpastes may be overestimated if based on the TF of the product. This finding suggests that the ingested dose should be calculated based on TSF. Dose of TSF ingested by children is similar whether family or children's toothpaste is used.

  12. 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.

  13. 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.

  14. 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.

  15. 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.)

  16. Adaptive neural-based fuzzy modeling for biological systems.

    Science.gov (United States)

    Wu, Shinq-Jen; Wu, Cheng-Tao; Chang, Jyh-Yeong

    2013-04-01

    The inverse problem of identifying dynamic biological networks from their time-course response data set is a cornerstone of systems biology. Hill and Michaelis-Menten model, which is a forward approach, provides local kinetic information. However, repeated modifications and a large amount of experimental data are necessary for the parameter identification. S-system model, which is composed of highly nonlinear differential equations, provides the direct identification of an interactive network. However, the identification of skeletal-network structure is challenging. Moreover, biological systems are always subject to uncertainty and noise. Are there suitable candidates with the potential to deal with noise-contaminated data sets? Fuzzy set theory is developed for handing uncertainty, imprecision and complexity in the real world; for example, we say "driving speed is high" wherein speed is a fuzzy variable and high is a fuzzy set, which uses the membership function to indicate the degree of a element belonging to the set (words in Italics to denote fuzzy variables or fuzzy sets). Neural network possesses good robustness and learning capability. In this study we hybrid these two together into a neural-fuzzy modeling technique. A biological system is formulated to a multi-input-multi-output (MIMO) Takagi-Sugeno (T-S) fuzzy system, which is composed of rule-based linear subsystems. Two kinds of smooth membership functions (MFs), Gaussian and Bell-shaped MFs, are used. The performance of the proposed method is tested with three biological systems.

  17. Modern methods for vancomycin determination in biological fluids by methods based on high-performance liquid chromatography--A review.

    Science.gov (United States)

    Javorska, Lenka; Krcmova, Lenka Kujovska; Solichova, Dagmar; Solich, Petr; Kaska, Milan

    2016-01-01

    Vancomycin is a glycopeptide antibiotic used in the therapy of severe bacterial infection. The monitoring of vancomycin levels is recommended because of its narrow therapeutic index and toxicity. This measurement is especially appropriate in patients with unstable renal functions, who receive high doses of vancomycin or present serious bacterial infections accompanied by important sequestration of liquids when it could be difficult to achieve the optimal therapeutic dose. Most of the methods for vancomycin determination in routine practice are immunoassays. However, chromatography-based techniques in combination with UV or mass spectrometry detection provide results with greater accuracy and precision also in complicated biological matrices. This review provides a detailed overview of modern approaches for the chromatographic separation of vancomycin in various biological samples and useful sample preparation procedures for vancomycin determination in various biological fluids.

  18. GTV-based prescription in SBRT for lung lesions using advanced dose calculation algorithms.

    Science.gov (United States)

    Lacornerie, Thomas; Lisbona, Albert; Mirabel, Xavier; Lartigau, Eric; Reynaert, Nick

    2014-10-16

    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

  19. 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

  20. 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.

  1. 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.

  2. Confidence Level Based Approach to Total Dose Specification for Spacecraft Electronics

    Science.gov (United States)

    Xapsos, M. A.; Stauffer, C.; Phan, A.; McClure, S. S.; Ladbury, R. L.; Pellish, J. A.; Campola, M. J.; Label, K. A.

    2017-01-01

    A confidence level based approach to total dose radiation hardness assurance is presented for spacecraft electronics. It is applicable to both ionizing and displacement damage dose. Results are compared to the traditional approach that uses radiation design margin and advantages of the new approach are discussed.

  3. 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.

  4. Stepwise Method Based on Confidence Bound and Information Incorporation for Identifying the Maximum Tolerable Dose

    Institute of Scientific and Technical Information of China (English)

    王雪丽; 陶剑; 史宁中

    2005-01-01

    The primary goal of a phase I clinical trial is to find the maximum tolerable dose of a treatment. In this paper, we propose a new stepwise method based on confidence bound and information incorporation to determine the maximum tolerable dose among given dose levels. On the one hand, in order to avoid severe even fatal toxicity to occur and reduce the experimental subjects, the new method is executed from the lowest dose level, and then goes on in a stepwise fashion. On the other hand,in order to improve the accuracy of the recommendation, the final recommendation of the maximum tolerable dose is accomplished through the information incorporation of an additional experimental cohort at the same dose level. Furthermore, empirical simulation results show that the new method has some real advantages in comparison with the modified continual reassessment method.

  5. 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.)

  6. 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

  7. Designing the Cloud-based DOE Systems Biology Knowledgebase

    Energy Technology Data Exchange (ETDEWEB)

    Lansing, Carina S.; Liu, Yan; Yin, Jian; Corrigan, Abigail L.; Guillen, Zoe C.; Kleese van Dam, Kerstin; Gorton, Ian

    2011-09-01

    Systems Biology research, even more than many other scientific domains, is becoming increasingly data-intensive. Not only have advances in experimental and computational technologies lead to an exponential increase in scientific data volumes and their complexity, but increasingly such databases themselves are providing the basis for new scientific discoveries. To engage effectively with these community resources, integrated analyses, synthesis and simulation software is needed, regularly supported by scientific workflows. In order to provide a more collaborative, community driven research environment for this heterogeneous setting, the Department of Energy (DOE) has decided to develop a federated, cloud based cyber infrastructure - the Systems Biology Knowledgebase (Kbase). Pacific Northwest National Laboratory (PNNL) with its long tradition in data intensive science lead two of the five initial pilot projects, these two focusing on defining and testing the basic federated cloud-based system architecture and develop a prototype implementation. Hereby the community wide accessibility of biological data and the capability to integrate and analyze this data within its changing research context were seen as key technical functionalities the Kbase needed to enable. In this paper we describe the results of our investigations into the design of a cloud based federated infrastructure for: (1) Semantics driven data discovery, access and integration; (2) Data annotation, publication and sharing; (3) Workflow enabled data analysis; and (4) Project based collaborative working. We describe our approach, exemplary use cases and our prototype implementation that demonstrates the feasibility of this approach.

  8. Competency-based reforms of the undergraduate biology curriculum: integrating the physical and biological sciences.

    Science.gov (United States)

    Thompson, Katerina V; Chmielewski, Jean; Gaines, Michael S; Hrycyna, Christine A; LaCourse, William R

    2013-06-01

    The National Experiment in Undergraduate Science Education project funded by the Howard Hughes Medical Institute is a direct response to the Scientific Foundations for Future Physicians report, which urged a shift in premedical student preparation from a narrow list of specific course work to a more flexible curriculum that helps students develop broad scientific competencies. A consortium of four universities is working to create, pilot, and assess modular, competency-based curricular units that require students to use higher-order cognitive skills and reason across traditional disciplinary boundaries. Purdue University; the University of Maryland, Baltimore County; and the University of Miami are each developing modules and case studies that integrate the biological, chemical, physical, and mathematical sciences. The University of Maryland, College Park, is leading the effort to create an introductory physics for life sciences course that is reformed in both content and pedagogy. This course has prerequisites of biology, chemistry, and calculus, allowing students to apply strategies from the physical sciences to solving authentic biological problems. A comprehensive assessment plan is examining students' conceptual knowledge of physics, their attitudes toward interdisciplinary approaches, and the development of specific scientific competencies. Teaching modules developed during this initial phase will be tested on multiple partner campuses in preparation for eventual broad dissemination.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Widya Saraswati

    2010-06-01

    Full Text Available 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 monomer that may induce toxicity in pulp fibroblast cells. Method: The method of this study was experimental laboratory with post test control group design. Primary cell culture was made from dental pulp fibroblast cells, and was given with HEMA resin bonding material in various concentrations (5 µg/ml–2560 µg/ml, and then subjected to toxicity test (MTT assay. Result: HEMA optimum concentration was 320 µg/ml to induce cytotoxicity in pulp fibroblast cells. Conclusion: The used of HEMA - base bonding material with the concentration of 200 µg/ml may induced pulp fibroblas cell toxicity.Latar belakang: Keberhasilan suatu bahan bonding secara klinis tergantung pada kandungan fisik, kimia dan keamanan secara biologis. HEMA (2-hydroxyethyl methacrylate adalah bahan resin yang paling banyak digunakan karena memiliki sifat fisik-kimia yang baik. Beberapa penelitian pendahuluan menyebutkan bahwa resin merupakan bahan yang mampu menyebabkan gangguan pada kompleks dentin pulpa sehingga perlu dilakukan penelitian lebih lanjut menyangkut segi keamanan secara biologis bagi jaringan keras dan jaringan lunak di rongga mulut. Tujuan: Penelitian ini akan menguji secara in vitro (pada kultur sel fibroblas pulpa gigi untuk mengetahui dosis optimal monomer resin HEMA yang dapat menyebabkan toksisitas pada sel fibroblas pulpa. Metode: Metode penelitian ini adalah eksperimental laboratoris dengan rancangan penelitian post test control group design. Kultur sel primer dibuat dari

  11. 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)

    Gonzalez, Sara Josefina; Pozzi, Emiliano C C; Monti Hughes, Andrea; Provenzano, Lucas; Koivunoro, Hanna; Carando, Daniel Germán; Thorp, Silvia Inés; Casal, Mariana Rosalía; Bortolussi, Silva; Trivillin, Verónica A; Garabalino, Marcela A; Curotto, Paula; Heber, Elisa M; Santa Cruz, Gustavo A; Kankaanranta, Leena; Joensuu, Heikki; Schwint, Amanda E

    2017-08-31

    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 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 model are

  12. 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.

  13. 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.

  14. Performance-based testing for drugs of abuse: dose and time profiles of marijuana, amphetamine, alcohol, and diazepam.

    Science.gov (United States)

    Kelly, T H; Foltin, R W; Emurian, C S; Fischman, M W

    1993-09-01

    The time courses of the effects of acute doses of amphetamine (5 and 10 mg/70 kg), alcohol (0.3 and 0.6 g/kg), diazepam (5 and 10 mg/70 kg), and marijuana (2.0% and 3.5% delta 9-THC) on performance engendered by each of four computerized behavioral tasks were evaluated in six human subjects. These performance-based tasks have potential commercial utility for drug-use detection in the workplace. Alcohol and marijuana effects were reliably detected for up to three hours following dose administration with most procedures. Amphetamine and diazepam effects were also detected, but the dose effects and time courses were variable. The profile of behavioral effects varied across drugs, suggesting that performance-based testing procedures might be useful in discriminating which drug was administered and the time course of the drug's effects. Results indicate that repeated measurement with performance-based drug detection procedures can provide immediate indications of performance impairment in a cost-effective and noninvasive manner and, as such, would be a useful supplement to biological sample testing for drug-use detection.

  15. Variability of marker-based rectal dose evaluation in HDR cervical brachytherapy.

    Science.gov (United States)

    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.

  16. Toward an organ based dose prescription method for the improved accuracy of murine dose in orthovoltage x-ray irradiators

    Energy Technology Data Exchange (ETDEWEB)

    Belley, Matthew D.; Wang, Chu [Medical Physics Graduate Program, Duke University Medical Center, Durham, North Carolina 27705 (United States); Nguyen, Giao; Gunasingha, Rathnayaka [Duke Radiation Dosimetry Laboratory, Duke University Medical Center, Durham, North Carolina 27710 (United States); Chao, Nelson J. [Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710 and Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Chen, Benny J. [Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710 (United States); Dewhirst, Mark W. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Yoshizumi, Terry T., E-mail: terry.yoshizumi@duke.edu [Duke Radiation Dosimetry Laboratory, Duke University Medical Center, Durham, North Carolina 27710 (United States); Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710 (United States)

    2014-03-15

    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.

  17. Estimated Fluoride Doses from Toothpastes Should be Based on Total Soluble Fluoride

    Directory of Open Access Journals (Sweden)

    Jaime A. Cury

    2013-11-01

    Full Text Available The fluoride dose ingested by young children may be overestimated if based on levels of total fluoride (TF rather than levels of bioavailable fluoride (total soluble fluoride—TSF in toothpaste. The aim of the present study was to compare doses of fluoride intake based on TF and TSF. Fluoride intake in 158 Brazilian children aged three and four years was determined after tooth brushing with their usual toothpaste (either family toothpaste (n = 80 or children’s toothpaste (n = 78. The estimated dose (mg F/day/Kg of body weight of TF or TSF ingested was calculated from the chemical analysis of the toothpastes. Although the ingested dose of TF from the family toothpastes was higher than that from the children’s toothpastes (0.074 ± 0.007 and 0.039 ± 0.003 mg F/day/Kg, respectively; p 0.05. The fluoride dose ingested by children from toothpastes may be overestimated if based on the TF of the product. This finding suggests that the ingested dose should be calculated based on TSF. Dose of TSF ingested by children is similar whether family or children’s toothpaste is used.

  18. Estimated Fluoride Doses from Toothpastes Should be Based on Total Soluble Fluoride

    Science.gov (United States)

    Oliveira, Maria José L.; Martins, Carolina C.; Paiva, Saul M.; Tenuta, Livia M. A.; Cury, Jaime A.

    2013-01-01

    The fluoride dose ingested by young children may be overestimated if based on levels of total fluoride (TF) rather than levels of bioavailable fluoride (total soluble fluoride—TSF) in toothpaste. The aim of the present study was to compare doses of fluoride intake based on TF and TSF. Fluoride intake in 158 Brazilian children aged three and four years was determined after tooth brushing with their usual toothpaste (either family toothpaste (n = 80) or children’s toothpaste (n = 78)). The estimated dose (mg F/day/Kg of body weight) of TF or TSF ingested was calculated from the chemical analysis of the toothpastes. Although the ingested dose of TF from the family toothpastes was higher than that from the children’s toothpastes (0.074 ± 0.007 and 0.039 ± 0.003 mg F/day/Kg, respectively; p 0.05). The fluoride dose ingested by children from toothpastes may be overestimated if based on the TF of the product. This finding suggests that the ingested dose should be calculated based on TSF. Dose of TSF ingested by children is similar whether family or children’s toothpaste is used. PMID:24189183

  19. Improving abdomen tumor low-dose CT images using a fast dictionary learning based processing

    Science.gov (United States)

    Chen, Yang; Yin, Xindao; Shi, Luyao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis; Toumoulin, Christine

    2013-08-01

    In abdomen computed tomography (CT), repeated radiation exposures are often inevitable for cancer patients who receive surgery or radiotherapy guided by CT images. Low-dose scans should thus be considered in order to avoid the harm of accumulative x-ray radiation. This work is aimed at improving abdomen tumor CT images from low-dose scans by using a fast dictionary learning (DL) based processing. Stemming from sparse representation theory, the proposed patch-based DL approach allows effective suppression of both mottled noise and streak artifacts. The experiments carried out on clinical data show that the proposed method brings encouraging improvements in abdomen low-dose CT images with tumors.

  20. Estimated Fluoride Doses from Toothpastes Should be Based on Total Soluble Fluoride

    OpenAIRE

    Cury,Jaime A.; Saul M Paiva; Tenuta,Livia M.A; Oliveira,Maria José L.; Martins, Carolina C.

    2013-01-01

    The fluoride dose ingested by young children may be overestimated if based on levels of total fluoride (TF) rather than levels of bioavailable fluoride (total soluble fluoride-TSF) in toothpaste. The aim of the present study was to compare doses of fluoride intake based on TF and TSF. Fluoride intake in 158 Brazilian children aged three and four years was determined after tooth brushing with their usual toothpaste (either family toothpaste (n = 80) or children's toothpaste (n = 78)). The esti...

  1. An atlas-based organ dose estimator for tomosynthesis and radiography

    Science.gov (United States)

    Hoye, Jocelyn; Zhang, Yakun; Agasthya, Greeshma; Sturgeon, Greg; Kapadia, Anuj; Segars, W. Paul; Samei, Ehsan

    2017-03-01

    The purpose of this study was to provide patient-specific organ dose estimation based on an atlas of human models for twenty tomosynthesis and radiography protocols. The study utilized a library of 54 adult computational phantoms (age: 18-78 years, weight 52-117 kg) and a validated Monte-Carlo simulation (PENELOPE) of a tomosynthesis and radiography system to estimate organ dose. Positioning of patient anatomy was based on radiographic positioning handbooks. The field of view for each exam was calculated to include relevant organs per protocol. Through simulations, the energy deposited in each organ was binned to estimate normalized organ doses into a reference database. The database can be used as the basis to devise a dose calculator to predict patient-specific organ dose values based on kVp, mAs, exposure in air, and patient habitus for a given protocol. As an example of the utility of this tool, dose to an organ was studied as a function of average patient thickness in the field of view for a given exam and as a function of Body Mass Index (BMI). For tomosynthesis, organ doses can also be studied as a function of x-ray tube position. This work developed comprehensive information for organ dose dependencies across tomosynthesis and radiography. There was a general exponential decrease dependency with increasing patient size that is highly protocol dependent. There was a wide range of variability in organ dose across the patient population, which needs to be incorporated in the metrology of organ dose.

  2. Radiation dose dependent change in physiochemical, mechanical and barrier properties of guar gum based films.

    Science.gov (United States)

    Saurabh, Chaturbhuj K; Gupta, Sumit; Bahadur, Jitendra; Mazumder, S; Variyar, Prasad S; Sharma, Arun

    2013-11-06

    Mechanical and water vapor barrier properties of biodegradable films prepared from radiation processed guar gum were investigated. Films prepared from GG irradiated up to 500 Gy demonstrated significantly higher tensile strength as compared to non-irradiated control films. This improvement in tensile strength observed was demonstrated to be due to the ordering of polymer structures as confirmed by small angle X-ray scattering analysis. Exposure to doses higher than 500 Gy, however, resulted in a dose dependent decrease in tensile strength. A dose dependent decrease in puncture strength with no significant differences in the percent elongation was also observed at all the doses studied. Water vapor barrier properties of films improved up to 15% due to radiation processing. Radiation processing at lower doses for improving mechanical and barrier properties of guar based packaging films is demonstrated here for the first time. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Dose calculation using a numerical method based on Haar wavelets integration

    Energy Technology Data Exchange (ETDEWEB)

    Belkadhi, K., E-mail: khaled.belkadhi@ult-tunisie.com [Unité de Recherche de Physique Nucléaire et des Hautes Énergies, Faculté des Sciences de Tunis, Université Tunis El-Manar (Tunisia); Manai, K. [Unité de Recherche de Physique Nucléaire et des Hautes Énergies, Faculté des Sciences de Tunis, Université Tunis El-Manar (Tunisia); College of Science and Arts, University of Bisha, Bisha (Saudi Arabia)

    2016-03-11

    This paper deals with the calculation of the absorbed dose in an irradiation cell of gamma rays. Direct measurement and simulation have shown that they are expensive and time consuming. An alternative to these two operations is numerical methods, a quick and efficient way can furnish an estimation of the absorbed dose by giving an approximation of the photon flux at a specific point of space. To validate the numerical integration method based on the Haar wavelet for absorbed dose estimation, a study with many configurations was performed. The obtained results with the Haar wavelet method showed a very good agreement with the simulation highlighting good efficacy and acceptable accuracy. - Highlights: • A numerical integration method using Haar wavelets is detailed. • Absorbed dose is estimated with Haar wavelets method. • Calculated absorbed dose using Haar wavelets and Monte Carlo simulation using Geant4 are compared.

  4. Voxel-based dose prediction with multi-patient atlas selection for automated radiotherapy treatment planning

    Science.gov (United States)

    McIntosh, Chris; Purdie, Thomas G.

    2017-01-01

    Automating the radiotherapy treatment planning process is a technically challenging problem. The majority of automated approaches have focused on customizing and inferring dose volume objectives to be used in plan optimization. In this work we outline a multi-patient atlas-based dose prediction approach that learns to predict the dose-per-voxel for a novel patient directly from the computed tomography planning scan without the requirement of specifying any objectives. Our method learns to automatically select the most effective atlases for a novel patient, and then map the dose from those atlases onto the novel patient. We extend our previous work to include a conditional random field for the optimization of a joint distribution prior that matches the complementary goals of an accurately spatially distributed dose distribution while still adhering to the desired dose volume histograms. The resulting distribution can then be used for inverse-planning with a new spatial dose objective, or to create typical dose volume objectives for the canonical optimization pipeline. We investigated six treatment sites (633 patients for training and 113 patients for testing) and evaluated the mean absolute difference in all DVHs for the clinical and predicted dose distribution. The results on average are favorable in comparison to our previous approach (1.91 versus 2.57). Comparing our method with and without atlas-selection further validates that atlas-selection improved dose prediction on average in whole breast (0.64 versus 1.59), prostate (2.13 versus 4.07), and rectum (1.46 versus 3.29) while it is less important in breast cavity (0.79 versus 0.92) and lung (1.33 versus 1.27) for which there is high conformity and minimal dose shaping. In CNS brain, atlas-selection has the potential to be impactful (3.65 versus 5.09), but selecting the ideal atlas is the most challenging.

  5. Web-based software tool for constraint-based design specification of synthetic biological systems.

    Science.gov (United States)

    Oberortner, Ernst; Densmore, Douglas

    2015-06-19

    miniEugene provides computational support for solving combinatorial design problems, enabling users to specify and enumerate designs for novel biological systems based on sets of biological constraints. This technical note presents a brief tutorial for biologists and software engineers in the field of synthetic biology on how to use miniEugene. After reading this technical note, users should know which biological constraints are available in miniEugene, understand the syntax and semantics of these constraints, and be able to follow a step-by-step guide to specify the design of a classical synthetic biological system-the genetic toggle switch.1 We also provide links and references to more information on the miniEugene web application and the integration of the miniEugene software library into sophisticated Computer-Aided Design (CAD) tools for synthetic biology ( www.eugenecad.org ).

  6. Monte Carlo-based revised values of dose rate constants at discrete photon energies

    Directory of Open Access Journals (Sweden)

    T Palani Selvam

    2014-01-01

    Full Text Available Absorbed dose rate to water at 0.2 cm and 1 cm due to a point isotropic photon source as a function of photon energy is calculated using the EDKnrc user-code of the EGSnrc Monte Carlo system. This code system utilized widely used XCOM photon cross-section dataset for the calculation of absorbed dose to water. Using the above dose rates, dose rate constants are calculated. Air-kerma strength S k needed for deriving dose rate constant is based on the mass-energy absorption coefficient compilations of Hubbell and Seltzer published in the year 1995. A comparison of absorbed dose rates in water at the above distances to the published values reflects the differences in photon cross-section dataset in the low-energy region (difference is up to 2% in dose rate values at 1 cm in the energy range 30-50 keV and up to 4% at 0.2 cm at 30 keV. A maximum difference of about 8% is observed in the dose rate value at 0.2 cm at 1.75 MeV when compared to the published value. S k calculations based on the compilation of Hubbell and Seltzer show a difference of up to 2.5% in the low-energy region (20-50 keV when compared to the published values. The deviations observed in the values of dose rate and S k affect the values of dose rate constants up to 3%.

  7. Construction of boundary-surface-based Chinese female astronaut computational phantom and proton dose estimation.

    Science.gov (United States)

    Sun, Wenjuan; Jia, Xianghong; Xie, Tianwu; Xu, Feng; Liu, Qian

    2013-03-01

    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 × 2 × 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).

  8. Biologic

    CERN Document Server

    Kauffman, L H

    2002-01-01

    In this paper we explore the boundary between biology and the study of formal systems (logic). In the end, we arrive at a summary formalism, a chapter in "boundary mathematics" where there are not only containers but also extainers ><, entities open to interaction and distinguishing the space that they are not. The boundary algebra of containers and extainers is to biologic what boolean algebra is to classical logic. We show how this formalism encompasses significant parts of the logic of DNA replication, the Dirac formalism for quantum mechanics, formalisms for protein folding and the basic structure of the Temperley Lieb algebra at the foundations of topological invariants of knots and links.

  9. Predicting standard-dose PET image from low-dose PET and multimodal MR images using mapping-based sparse representation

    Science.gov (United States)

    Wang, Yan; Zhang, Pei; An, Le; Ma, Guangkai; Kang, Jiayin; Shi, Feng; Wu, Xi; Zhou, Jiliu; Lalush, David S.; Lin, Weili; Shen, Dinggang

    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.

  10. 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.

  11. A GEM-based dose imaging detector with optical readout for proton radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Klyachko, A.V., E-mail: aklyachk@indiana.edu [Indiana University Cyclotron Operations, Indiana University Integrated Science and Accelerator Technology Hall, 2401 Milo. B. Sampson Ln., Bloomington, IN 47408 (United States); Moskvin, V. [Department of Radiation Oncology, School of Medicine, Indiana University, Indianapolis, IN 46202 (United States); Nichiporov, D.F.; Solberg, K.A. [Indiana University Cyclotron Operations, Indiana University Integrated Science and Accelerator Technology Hall, 2401 Milo. B. Sampson Ln., Bloomington, IN 47408 (United States)

    2012-12-01

    New techniques in proton radiation therapy and advances in beam delivery systems design such as beam scanning require accurate 2D dosimetry systems to verify the delivered dose distribution. Dose imaging detectors based on gas electron multipliers (GEMs) are capable of providing high sensitivity, improved dose measurement linearity, position resolution, fast response and accurate characterization of depth-dose distributions. In this work, we report on the development of a GEM-based dose imaging detector with optical readout using a CCD camera. A 10 Multiplication-Sign 10 cm{sup 2} detector has been tested in a 205 MeV proton beam in single- and double-GEM configurations. The detector demonstrates linearity in dose rate up to 100 Gy/min and position resolution ({sigma}) of 0.42 mm. Transverse non-uniformity of the detector response is {<=}10% before correction and the stability of the detector output throughout the day is within {+-}1%, with day-to-day reproducibility of about 10%. The depth-dose response of the detector is close to that of a wide-aperture air-filled ionization chamber and is in good agreement with Monte Carlo simulations.

  12. Dose estimation based on a behavior survey of residents around the JCO facility.

    Science.gov (United States)

    Fujimoto, K; Yonehara, H; Yamaguchi, Y; Endo, A

    2001-09-01

    The NIRS staff interviewed the residents in the evacuated zone around the JCO facility in Tokai-mura on 19 and 20 November, 1999, to obtain the following parameters every 30 minutes starting from 10:35 A.M. on 30 September to 6:15 A.M. on 1 October: the distance from the precipitation tank, the type of the house, positions in the house, wall materials and their thickness in order to estimate individual doses due to the accident. The ambient dose equivalents were obtained based on monitoring data during the accident. In addition, computer calculations were conducted to evaluate the conversion factor from ambient dose equivalent to effective dose equivalent as well as the shielding effect of the house or factory to estimate the effective dose equivalent to the residents. The estimated individual doses based on the behavior survey were in the range from zero to 21 mSv. The individual doses were reported to the residents during the second visit to each house and factory at the end of January, 2000.

  13. 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

  14. Dose calculation based on Cone Beam CT images

    DEFF Research Database (Denmark)

    Slot Thing, Rune

    , several other factors contributing to the image quality degradation, and while one should, theoretically, be able to obtain CT-like image quality from CBCT scans, clinical image quality is often very far from this ideal realisation. The present thesis describes the investigation of potential image quality...... improvements in clinical CBCT imaging achieved through post-processing of the clinical image data. A Monte Carlo model was established to predict patient specific scattered radiation in CBCT imaging, based on anatomical information from the planning CT scan. This allowed the time consuming Monte Carlo......Cone beam CT (CBCT) imaging is frequently used in modern radiotherapy to ensure the proper positioning of the patient prior to each treatment fraction. With the increasing use of CBCT imaging for image guidance, interest has grown in exploring the potential use of these 3– or 4–D medical images...

  15. A phenomenological relative biological effectiveness approach for proton therapy based on an improved description of the mixed radiation field

    Science.gov (United States)

    Mairani, A.; Dokic, I.; Magro, G.; Tessonnier, T.; Bauer, J.; Böhlen, T. T.; Ciocca, M.; Ferrari, A.; Sala, P. R.; Jäkel, O.; Debus, J.; Haberer, T.; Abdollahi, A.; Parodi, K.

    2017-02-01

    Proton therapy treatment planning systems (TPSs) are based on the assumption of a constant relative biological effectiveness (RBE) of 1.1 without taking into account the found in vitro experimental variations of the RBE as a function of tissue type, linear energy transfer (LET) and dose. The phenomenological RBE models available in literature are based on the dose-averaged LET (LET D ) as an indicator of the physical properties of the proton radiation field. The LET D values are typically calculated taking into account primary and secondary protons, neglecting the biological effect of heavier secondaries. In this work, we have introduced a phenomenological RBE approach which considers the biological effect of primary protons, and of secondary protons, deuterons, tritons (Z  =  1) and He fragments (3He and 4He, Z  =  2). The calculation framework, coupled with a Monte Carlo (MC) code, has been successfully benchmarked against clonogenic in vitro data measured in this work for two cell lines and then applied to determine biological quantities for spread-out Bragg peaks and a prostate and a head case. The introduced RBE formalism, which depends on the mixed radiation field, the dose and the ratio of the linear–quadratic model parameters for the reference radiation {{≤ft(α /β \\right)}\\text{ph}} , predicts, when integrated in an MC code, higher RBE values in comparison to LET D -based parameterizations. This effect is particular enhanced in the entrance channel of the proton field and for low {{≤ft(α /β \\right)}\\text{ph}} tissues. For the prostate and the head case, we found higher RBE-weighted dose values up to about 5% in the entrance channel when including or neglecting the Z  =  2 secondaries in the RBE calculation. TPSs able to proper account for the mixed radiation field in proton therapy are thus recommended for an accurate determination of the RBE in the whole treatment field.

  16. Clinical evaluation of a dose monitoring software tool based on Monte Carlo Simulation in assessment of eye lens doses for cranial CT scans

    Energy Technology Data Exchange (ETDEWEB)

    Guberina, Nika; Suntharalingam, Saravanabavaan; Nassenstein, Kai; Forsting, Michael; Theysohn, Jens; Wetter, Axel; Ringelstein, Adrian [University Hospital Essen, Institute of Diagnostic and Interventional Radiology and Neuroradiology, Essen (Germany)

    2016-10-15

    The aim of this study was to verify the results of a dose monitoring software tool based on Monte Carlo Simulation (MCS) in assessment of eye lens doses for cranial CT scans. In cooperation with the Federal Office for Radiation Protection (Neuherberg, Germany), phantom measurements were performed with thermoluminescence dosimeters (TLD LiF:Mg,Ti) using cranial CT protocols: (I) CT angiography; (II) unenhanced, cranial CT scans with gantry angulation at a single and (III) without gantry angulation at a dual source CT scanner. Eye lens doses calculated by the dose monitoring tool based on MCS and assessed with TLDs were compared. Eye lens doses are summarized as follows: (I) CT angiography (a) MCS 7 mSv, (b) TLD 5 mSv; (II) unenhanced, cranial CT scan with gantry angulation, (c) MCS 45 mSv, (d) TLD 5 mSv; (III) unenhanced, cranial CT scan without gantry angulation (e) MCS 38 mSv, (f) TLD 35 mSv. Intermodality comparison shows an inaccurate calculation of eye lens doses in unenhanced cranial CT protocols at the single source CT scanner due to the disregard of gantry angulation. On the contrary, the dose monitoring tool showed an accurate calculation of eye lens doses at the dual source CT scanner without gantry angulation and for CT angiography examinations. The dose monitoring software tool based on MCS gave accurate estimates of eye lens doses in cranial CT protocols. However, knowledge of protocol and software specific influences is crucial for correct assessment of eye lens doses in routine clinical use. (orig.)

  17. 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

  18. 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…

  19. 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…

  20. Model-based dose calculations for {sup 125}I lung brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Sutherland, J. G. H.; Furutani, K. M.; Garces, Y. I.; Thomson, R. M. [Carleton Laboratory for Radiotherapy Physics, Department of Physics, Carleton University, Ottawa, Ontario K1S 5B6 (Canada); Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905 (United States); Carleton Laboratory for Radiotherapy Physics, Department of Physics, Carleton University, Ottawa, Ontario K1S 5B6 (Canada)

    2012-07-15

    Purpose: Model-baseddose calculations (MBDCs) are performed using patient computed tomography (CT) data for patients treated with intraoperative {sup 125}I lung brachytherapy at the Mayo Clinic Rochester. Various metallic artifact correction and tissue assignment schemes are considered and their effects on dose distributions are studied. Dose distributions are compared to those calculated under TG-43 assumptions. Methods: Dose distributions for six patients are calculated using phantoms derived from patient CT data and the EGSnrc user-code BrachyDose. {sup 125}I (GE Healthcare/Oncura model 6711) seeds are fully modeled. Four metallic artifact correction schemes are applied to the CT data phantoms: (1) no correction, (2) a filtered back-projection on a modified virtual sinogram, (3) the reassignment of CT numbers above a threshold in the vicinity of the seeds, and (4) a combination of (2) and (3). Tissue assignment is based on voxel CT number and mass density is assigned using a CT number to mass density calibration. Three tissue assignment schemes with varying levels of detail (20, 11, and 5 tissues) are applied to metallic artifact corrected phantoms. Simulations are also performed under TG-43 assumptions, i.e., seeds in homogeneous water with no interseed attenuation. Results: Significant dose differences (up to 40% for D{sub 90}) are observed between uncorrected and metallic artifact corrected phantoms. For phantoms created with metallic artifact correction schemes (3) and (4), dose volume metrics are generally in good agreement (less than 2% differences for all patients) although there are significant local dose differences. The application of the three tissue assignment schemes results in differences of up to 8% for D{sub 90}; these differences vary between patients. Significant dose differences are seen between fully modeled and TG-43 calculations with TG-43 underestimating the dose (up to 36% in D{sub 90}) for larger volumes containing higher proportions of

  1. 49. Biological dose assessment by the analyses of chromosomal aberrations and CB micronuclei in two victims accidentally exposed to 60Co gamma-rays

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    @@Biological doses were estimated by using the yields of dicentrics plus rings(dic+r) and cytokinesis-block micronuclei (CBMN) for two victims of the 60Co radiation source accident occurred on Mar 6,2001 in the City of Xuchang(victim A), and Jun 26,2001 in the City of Kaifeng(victim B), Henan Province, respectively. The whole blood of the victim A (male, 37 years old) and the victim B (female, 27 years old)

  2. A measurement-based generalized source model for Monte Carlo dose simulations of CT scans

    Science.gov (United States)

    Ming, Xin; Feng, Yuanming; Liu, Ransheng; Yang, Chengwen; Zhou, Li; Zhai, Hezheng; Deng, Jun

    2017-03-01

    The goal of this study is to develop a generalized source model for accurate Monte Carlo dose simulations of CT scans based solely on the measurement data without a priori knowledge of scanner specifications. The proposed generalized source model consists of an extended circular source located at x-ray target level with its energy spectrum, source distribution and fluence distribution derived from a set of measurement data conveniently available in the clinic. Specifically, the central axis percent depth dose (PDD) curves measured in water and the cone output factors measured in air were used to derive the energy spectrum and the source distribution respectively with a Levenberg–Marquardt algorithm. The in-air film measurement of fan-beam dose profiles at fixed gantry was back-projected to generate the fluence distribution of the source model. A benchmarked Monte Carlo user code was used to simulate the dose distributions in water with the developed source model as beam input. The feasibility and accuracy of the proposed source model was tested on a GE LightSpeed and a Philips Brilliance Big Bore multi-detector CT (MDCT) scanners available in our clinic. In general, the Monte Carlo simulations of the PDDs in water and dose profiles along lateral and longitudinal directions agreed with the measurements within 4%/1 mm for both CT scanners. The absolute dose comparison using two CTDI phantoms (16 cm and 32 cm in diameters) indicated a better than 5% agreement between the Monte Carlo-simulated and the ion chamber-measured doses at a variety of locations for the two scanners. Overall, this study demonstrated that a generalized source model can be constructed based only on a set of measurement data and used for accurate Monte Carlo dose simulations of patients’ CT scans, which would facilitate patient-specific CT organ dose estimation and cancer risk management in the diagnostic and therapeutic radiology.

  3. Quantification of confounding factors in MRI-based dose calculations as applied to prostate IMRT

    Science.gov (United States)

    Maspero, Matteo; Seevinck, Peter R.; Schubert, Gerald; Hoesl, Michaela A. U.; van Asselen, Bram; Viergever, Max A.; Lagendijk, Jan J. W.; Meijer, Gert J.; van den Berg, Cornelis A. T.

    2017-02-01

    Magnetic resonance (MR)-only radiotherapy treatment planning requires pseudo-CT (pCT) images to enable MR-based dose calculations. To verify the accuracy of MR-based dose calculations, institutions interested in introducing MR-only planning will have to compare pCT-based and computer tomography (CT)-based dose calculations. However, interpreting such comparison studies may be challenging, since potential differences arise from a range of confounding factors which are not necessarily specific to MR-only planning. Therefore, the aim of this study is to identify and quantify the contribution of factors confounding dosimetric accuracy estimation in comparison studies between CT and pCT. The following factors were distinguished: set-up and positioning differences between imaging sessions, MR-related geometric inaccuracy, pCT generation, use of specific calibration curves to convert pCT into electron density information, and registration errors. The study comprised fourteen prostate cancer patients who underwent CT/MRI-based treatment planning. To enable pCT generation, a commercial solution (MRCAT, Philips Healthcare, Vantaa, Finland) was adopted. IMRT plans were calculated on CT (gold standard) and pCTs. Dose difference maps in a high dose region (CTV) and in the body volume were evaluated, and the contribution to dose errors of possible confounding factors was individually quantified. We found that the largest confounding factor leading to dose difference was the use of different calibration curves to convert pCT and CT into electron density (0.7%). The second largest factor was the pCT generation which resulted in pCT stratified into a fixed number of tissue classes (0.16%). Inter-scan differences due to patient repositioning, MR-related geometric inaccuracy, and registration errors did not significantly contribute to dose differences (0.01%). The proposed approach successfully identified and quantified the factors confounding accurate MRI-based dose calculation in

  4. SU-E-T-129: Are Knowledge-Based Planning Dose Estimates Valid for Distensible Organs?

    Energy Technology Data Exchange (ETDEWEB)

    Lalonde, R; Heron, D; Huq, M [UPMC CancerCenter, Pittsburgh, PA (United States); Readshaw, A [D3 Oncology Solutions, Pittsburgh, PA (United States)

    2015-06-15

    Purpose: Knowledge-based planning programs have become available to assist treatment planning in radiation therapy. Such programs can be used to generate estimated DVHs and planning constraints for organs at risk (OARs), based upon a model generated from previous plans. These estimates are based upon the planning CT scan. However, for distensible OARs like the bladder and rectum, daily variations in volume may make the dose estimates invalid. The purpose of this study is to determine whether knowledge-based DVH dose estimates may be valid for distensible OARs. Methods: The Varian RapidPlan™ knowledge-based planning module was used to generate OAR dose estimates and planning objectives for 10 prostate cases previously planned with VMAT, and final plans were calculated for each. Five weekly setup CBCT scans of each patient were then downloaded and contoured (assuming no change in size and shape of the target volume), and rectum and bladder DVHs were recalculated for each scan. Dose volumes were then compared at 75, 60,and 40 Gy for the bladder and rectum between the planning scan and the CBCTs. Results: Plan doses and estimates matched well at all dose points., Volumes of the rectum and bladder varied widely between planning CT and the CBCTs, ranging from 0.46 to 2.42 for the bladder and 0.71 to 2.18 for the rectum, causing relative dose volumes to vary between planning CT and CBCT, but absolute dose volumes were more consistent. The overall ratio of CBCT/plan dose volumes was 1.02 ±0.27 for rectum and 0.98 ±0.20 for bladder in these patients. Conclusion: Knowledge-based planning dose volume estimates for distensible OARs are still valid, in absolute volume terms, between treatment planning scans and CBCT’s taken during daily treatment. Further analysis of the data is being undertaken to determine how differences depend upon rectum and bladder filling state. This work has been supported by Varian Medical Systems.

  5. Dose rate effects in radiation degradation of polymer-based cable materials

    Science.gov (United States)

    Plaček, V.; Bartoníček, B.; Hnát, V.; Otáhal, B.

    2003-08-01

    Cable ageing under the nuclear power plant (NPP) conditions must be effectively managed to ensure that the required plant safety and reliability are maintained throughout the plant service life. Ionizing radiation is one of the main stressors causing age-related degradation of polymer-based cable materials in air. For a given absorbed dose, radiation-induced damage to a polymer in air environment usually depends on the dose rate of the exposure. In this work, the effect of dose rate on the degradation rate has been studied. Three types of NPP cables (with jacket/insulation combinations PVC/PVC, PVC/PE, XPE/XPE) were irradiated at room temperature using 60Co gamma ray source at average dose rates of 7, 30 and 100 Gy/h with the doses up to 590 kGy. The irradiated samples have been tested for their mechanical properties, thermo-oxidative stability (using differential scanning calorimetry, DSC), and density. In the case of PVC and PE samples, the tested properties have shown evident dose rate effects, while the XPE material has shown no noticeable ones. The values of elongation at break and the thermo-oxidative stability decrease with the advanced degradation, density tends to increase with the absorbed dose. For XPE samples this effect can be partially explained by the increase of crystallinity. It was tested by the DSC determination of the crystalline phase amount.

  6. A fully model-based MPC solution including VSB shot dose assignment and shape correction

    Science.gov (United States)

    Bork, Ingo; Buck, Peter; Reddy, Murali; Durvasula, Bhardwaj

    2015-10-01

    The value of using multiple dose levels for individual shots on VSB (Variable Shaped Beam) mask writers has been demonstrated earlier [1][2]. The main advantage of modulating dose on a per shot basis is the fact that higher dose levels can be used selectively for critical features while other areas of the mask with non-critical feature types can be exposed at lower dose levels. This reduces the amount of backscattering and mask write time penalty compared to a global overdose-undersize approach. While dose assignment to certain polygons or parts of polygons (VSB shots) can easily be accomplished via DRC rules on layers with limited shape variations like contact or VIA layers, it can be challenging to come up with consistent rules for layers consisting of a very broad range of shapes, generally found on metal layers. This work introduces a method for fully model-based modulation of shot dose for VSB machines supporting between two and eight dose levels and demonstrates results achieved with this method.

  7. BIOLOGICAL CONTROL OF Melolontha melolontha L. LARVAE WITH ENTOMOPATHOGENIC BIOINSECTICIDE BASED ON Beauveria brongniartii

    Directory of Open Access Journals (Sweden)

    Ana-Cristina FĂTU

    2015-10-01

    Full Text Available From 2010 to 2013 tests were conducted with entomopathogenic bioproduct based on Beauveria brongniartii, in nurseries of the Botosani, Neamt and Suceava Forest Departments. At RDPP Bucharest a technology for multiplication on nutrtive solid substrate of entomopathogenic fungus B. brongniartii was developed, on the basis of which the experimental bioinsecticide BioMelCon (G was obtained. Soil treatments were performed with the BioMelCon (G in doses ranging from 100 to200 kg/ha. The tested dosages were achieved by applying two treatments per year. Application of biological product held generally early spring on surfaces free from crops, to ensure a uniform distribution and to create the possibility of periodic inspection of the treatment effect by soil surveys. Checking the effectiveness of treatment was carried out in several stages, in different site conditions. The paper presents results concerning the effect of applying several biological treatments on Melolontha melolontha larvae (L2-L3. The cumulative effect of the biological product and the agricultural practices of experimental fields have led to a decreased density of larval populations under economic threshold level.

  8. A CT-based analytical dose calculation method for HDR {sup 192}Ir brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Poon, Emily; Verhaegen, Frank [Medical Physics Unit, McGill University, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4 (Canada); Medical Physics Unit, McGill University, 1650 Cedar Avenue, Montreal, Quebec H3G 1A4 (Canada) and Department of Radiation Oncology (MAASTRO), GROW, University Hospital Maastricht, Maastricht 6229ET (Netherlands)

    2009-09-15

    esophagus patient plans, P{sub {gamma}{>=}1} are {>=}99% for both calculation methods. Conclusions: A correction-based dose calculation method has been validated for HDR {sup 192}Ir brachytherapy. Its high calculation efficiency makes it feasible for use in treatment planning. Because tissue inhomogeneity effects are small and primary dose predominates in the near-source region, TG-43 is adequate for target dose estimation provided shielding and contrast solution are not used.

  9. A CT-based analytical dose calculation method for HDR 192Ir brachytherapy.

    Science.gov (United States)

    Poon, Emily; Verhaegen, Frank

    2009-09-01

    = 99% for both calculation methods. A correction-based dose calculation method has been validated for HDR 192Ir brachytherapy. Its high calculation efficiency makes it feasible for use in treatment planning. Because tissue inhomogeneity effects are small and primary dose predominates in the near-source region, TG-43 is adequate for target dose estimation provided shielding and contrast solution are not used.

  10. Process-based design of dynamical biological systems

    Science.gov (United States)

    Tanevski, Jovan; Todorovski, Ljupčo; Džeroski, Sašo

    2016-09-01

    The computational design of dynamical systems is an important emerging task in synthetic biology. Given desired properties of the behaviour of a dynamical system, the task of design is to build an in-silico model of a system whose simulated be- haviour meets these properties. We introduce a new, process-based, design methodology for addressing this task. The new methodology combines a flexible process-based formalism for specifying the space of candidate designs with multi-objective optimization approaches for selecting the most appropriate among these candidates. We demonstrate that the methodology is general enough to both formulate and solve tasks of designing deterministic and stochastic systems, successfully reproducing plausible designs reported in previous studies and proposing new designs that meet the design criteria, but have not been previously considered.

  11. Reference dosimetry of proton pencil beams based on dose-area product: a proof of concept

    Science.gov (United States)

    Gomà, Carles; Safai, Sairos; Vörös, Sándor

    2017-06-01

    This paper describes a novel approach to the reference dosimetry of proton pencil beams based on dose-area product (DAPw ). It depicts the calibration of a large-diameter plane-parallel ionization chamber in terms of dose-area product in a 60Co beam, the Monte Carlo calculation of beam quality correction factors—in terms of dose-area product—in proton beams, the Monte Carlo calculation of nuclear halo correction factors, and the experimental determination of DAPw of a single proton pencil beam. This new approach to reference dosimetry proves to be feasible, as it yields DAPw values in agreement with the standard and well-established approach of determining the absorbed dose to water at the centre of a broad homogeneous field generated by the superposition of regularly-spaced proton pencil beams.

  12. Postmarketing review of intravenous acetaminophen dosing based on Food and Drug Administration prescribing guidelines.

    Science.gov (United States)

    dela Cruz Ubaldo, Catherine; Hall, Natalie Semaan; Le, Brenden

    2014-12-01

    To evaluate the appropriateness of intravenous acetaminophen dosing-prescribed dose, frequency, duration, and indication-based on United States Food and Drug Administration (FDA)-approved prescribing guidelines and to evaluate the adverse effect profile of intravenous acetaminophen. Retrospective chart review. United States Navy medical center. Three hundred patients who received intravenous acetaminophen from August 1, 2011, to August 1, 2012. The indications, dose, frequency, and duration of intravenous acetaminophen were recorded for each patient. Adverse effects of intravenous acetaminophen were analyzed by thoroughly reviewing any adverse effects documented, including nausea, vomiting, headache, or any symptom specifically attributed to the drug. Baseline liver function tests, including aspartate aminotransferase and alanine aminotransferase levels, and elevations 3 times the upper limit of normal during intravenous acetaminophen therapy were recorded. The average patient weight was 78±21 kg, with 12 patients (4%) weighing less than 50 kg and 288 (96%) patients weighing 50 kg or greater. Two hundred forty-one patients (80%) were appropriately dosed, whereas 59 (20%) patients were not appropriately dosed based on the FDA-approved dosing. No patients exceeded the FDA-approved maximum daily dosing recommendations for intravenous acetaminophen (4 g). Sixty-five patients (22%) received intravenous acetaminophen for longer than 24 hours. Intravenous acetaminophen was well tolerated, without any reported adverse effects, including the commonly reported adverse effects of nausea, vomiting, headache, and insomnia. Ten patients (3%) had a documented history of liver disease and did not experience any adverse effects or increases in liver function tests after the administration of intravenous acetaminophen. Intravenous acetaminophen appeared to be a safe and effective analgesic and antipyretic agent. Dosing for patients weighing less than 50 kg needs to be appropriately

  13. Development of modern approach to absorbed dose assessment in radionuclide therapy, based on Monte Carlo method simulation of patient scintigraphy

    Science.gov (United States)

    Lysak, Y. V.; Klimanov, V. A.; Narkevich, B. Ya

    2017-01-01

    One of the most difficult problems of modern radionuclide therapy (RNT) is control of the absorbed dose in pathological volume. This research presents new approach based on estimation of radiopharmaceutical (RP) accumulated activity value in tumor volume, based on planar scintigraphic images of the patient and calculated radiation transport using Monte Carlo method, including absorption and scattering in biological tissues of the patient, and elements of gamma camera itself. In our research, to obtain the data, we performed modeling scintigraphy of the vial with administered to the patient activity of RP in gamma camera, the vial was placed at the certain distance from the collimator, and the similar study was performed in identical geometry, with the same values of activity of radiopharmaceuticals in the pathological target in the body of the patient. For correct calculation results, adapted Fisher-Snyder human phantom was simulated in MCNP program. In the context of our technique, calculations were performed for different sizes of pathological targets and various tumors deeps inside patient’s body, using radiopharmaceuticals based on a mixed β-γ-radiating (131I, 177Lu), and clear β- emitting (89Sr, 90Y) therapeutic radionuclides. Presented method can be used for adequate implementing in clinical practice estimation of absorbed doses in the regions of interest on the basis of planar scintigraphy of the patient with sufficient accuracy.

  14. 3D delivered dose assessment using a 4DCT-based motion model

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Weixing; Hurwitz, Martina H.; Williams, Christopher L.; Dhou, Salam; Berbeco, Ross I.; Mishra, Pankaj, E-mail: wcai@lroc.harvard.edu, E-mail: jhlewis@lroc.harvard.edu; Lewis, John H., E-mail: wcai@lroc.harvard.edu, E-mail: jhlewis@lroc.harvard.edu [Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States); Seco, Joao [Francis H. Burr Proton Therapy Center, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115 (United States)

    2015-06-15

    Purpose: The purpose of this work is to develop a clinically feasible method of calculating actual delivered dose distributions for patients who have significant respiratory motion during the course of stereotactic body radiation therapy (SBRT). Methods: A novel approach was proposed to calculate the actual delivered dose distribution for SBRT lung treatment. This approach can be specified in three steps. (1) At the treatment planning stage, a patient-specific motion model is created from planning 4DCT data. This model assumes that the displacement vector field (DVF) of any respiratory motion deformation can be described as a linear combination of some basis DVFs. (2) During the treatment procedure, 2D time-varying projection images (either kV or MV projections) are acquired, from which time-varying “fluoroscopic” 3D images of the patient are reconstructed using the motion model. The DVF of each timepoint in the time-varying reconstruction is an optimized linear combination of basis DVFs such that the 2D projection of the 3D volume at this timepoint matches the projection image. (3) 3D dose distribution is computed for each timepoint in the set of 3D reconstructed fluoroscopic images, from which the total effective 3D delivered dose is calculated by accumulating deformed dose distributions. This approach was first validated using two modified digital extended cardio-torso (XCAT) phantoms with lung tumors and different respiratory motions. The estimated doses were compared to the dose that would be calculated for routine 4DCT-based planning and to the actual delivered dose that was calculated using “ground truth” XCAT phantoms at all timepoints. The approach was also tested using one set of patient data, which demonstrated the application of our method in a clinical scenario. Results: For the first XCAT phantom that has a mostly regular breathing pattern, the errors in 95% volume dose (D95) are 0.11% and 0.83%, respectively for 3D fluoroscopic images

  15. SU-E-T-616: Plan Quality Assessment of Both Treatment Planning System Dose and Measurement-Based 3D Reconstructed Dose in the Patient

    Energy Technology Data Exchange (ETDEWEB)

    Olch, A [University of Southern California, Los Angeles, CA (United States)

    2015-06-15

    Purpose: Systematic radiotherapy plan quality assessment promotes quality improvement. Software tools can perform this analysis by applying site-specific structure dose metrics. The next step is to similarly evaluate the quality of the dose delivery. This study defines metrics for acceptable doses to targets and normal organs for a particular treatment site and scores each plan accordingly. The input can be the TPS or the measurement-based 3D patient dose. From this analysis, one can determine whether the delivered dose distribution to the patient receives a score which is comparable to the TPS plan score, otherwise replanning may be indicated. Methods: Eleven neuroblastoma patient plans were exported from Eclipse to the Quality Reports program. A scoring algorithm defined a score for each normal and target structure based on dose-volume parameters. Each plan was scored by this algorithm and the percentage of total possible points was obtained. Each plan also underwent IMRT QA measurements with a Mapcheck2 or ArcCheck. These measurements were input into the 3DVH program to compute the patient 3D dose distribution which was analyzed using the same scoring algorithm as the TPS plan. Results: The mean quality score for the TPS plans was 75.37% (std dev=14.15%) compared to 71.95% (std dev=13.45%) for the 3DVH dose distribution. For 3/11 plans, the 3DVH-based quality score was higher than the TPS score, by between 0.5 to 8.4 percentage points. Eight/11 plans scores decreased based on IMRT QA measurements by 1.2 to 18.6 points. Conclusion: Software was used to determine the degree to which the plan quality score differed between the TPS and measurement-based dose. Although the delivery score was generally in good agreement with the planned dose score, there were some that improved while there was one plan whose delivered dose quality was significantly less than planned. This methodology helps evaluate both planned and delivered dose quality. Sun Nuclear Corporation has

  16. Biological agent detection based on principal component analysis

    Science.gov (United States)

    Mudigonda, Naga R.; Kacelenga, Ray

    2006-05-01

    This paper presents an algorithm, based on principal component analysis for the detection of biological threats using General Dynamics Canada's 4WARN Sentry 3000 biodetection system. The proposed method employs a statistical method for estimating background biological activity so as to make the algorithm adaptive to varying background situations. The method attempts to characterize the pattern of change that occurs in the fluorescent particle counts distribution and uses the information to suppress false-alarms. The performance of the method was evaluated using a total of 68 tests including 51 releases of Bacillus Globigii (BG), six releases of BG in the presence of obscurants, six releases of obscurants only, and five releases of ovalbumin at the Ambient Breeze Tunnel Test facility, Battelle, OH. The peak one-minute average concentration of BG used in the tests ranged from 10 - 65 Agent Containing Particles per Liter of Air (ACPLA). The obscurants used in the tests included diesel smoke, white grenade smoke, and salt solution. The method successfully detected BG at a sensitivity of 10 ACPLA and resulted in an overall probability of detection of 94% for BG without generating any false-alarms for obscurants at a detection threshold of 0.6 on a scale of 0 to 1. Also, the method successfully detected BG in the presence of diesel smoke and salt water fumes. The system successfully responded to all the five ovalbumin releases with noticeable trends in algorithm output and alarmed for two releases at the selected detection threshold.

  17. Estimating radiation effective doses from whole body computed tomography scans based on U.S. soldier patient height and weight

    Directory of Open Access Journals (Sweden)

    Quinn Brian

    2011-10-01

    Full Text Available Abstract Background The purpose of this study is to explore how a patient's height and weight can be used to predict the effective dose to a reference phantom with similar height and weight from a chest abdomen pelvis computed tomography scan when machine-based parameters are unknown. Since machine-based scanning parameters can be misplaced or lost, a predictive model will enable the medical professional to quantify a patient's cumulative radiation dose. Methods One hundred mathematical phantoms of varying heights and weights were defined within an x-ray Monte Carlo based software code in order to calculate organ absorbed doses and effective doses from a chest abdomen pelvis scan. Regression analysis was used to develop an effective dose predictive model. The regression model was experimentally verified using anthropomorphic phantoms and validated against a real patient population. Results Estimates of the effective doses as calculated by the predictive model were within 10% of the estimates of the effective doses using experimentally measured absorbed doses within the anthropomorphic phantoms. Comparisons of the patient population effective doses show that the predictive model is within 33% of current methods of estimating effective dose using machine-based parameters. Conclusions A patient's height and weight can be used to estimate the effective dose from a chest abdomen pelvis computed tomography scan. The presented predictive model can be used interchangeably with current effective dose estimating techniques that rely on computed tomography machine-based techniques.

  18. On-site gamma dose rates at the Andreeva Bay shore technical base, northwest Russia.

    Science.gov (United States)

    Reistad, O; Dowdall, M; Standring, W J F; Selnaes, Ø G; Hustveit, S; Steinhusen, F; Sørlie, A

    2008-07-01

    The spent nuclear fuel (SNF) and radioactive waste (RAW) storage facility at Andreeva Bay shore technical base (STB) is one of the largest and most hazardous nuclear legacy sites in northwest Russia. Originally commissioned in the 1960s the facility now stores large amounts of SNF and RAW associated with the Russian Northern Fleet of nuclear powered submarines. The objective of the present study was to map ambient gamma dose rates throughout the facility, in particular at a number of specific sites where SNF and RAW are stored. The data presented here are taken from a Norwegian-Russian collaboration enabling the first publication in the scientific literature of the complete survey of on-site dose rates. Results indicate that elevated gamma dose rates are found primarily at discrete sites within the facility; maximum dose rates of up to 1000 microSv/h close to the ground (0.1m) and up to 3000 microSv/h at 1m above ground were recorded, higher doses at the 1m height being indicative primarily of the presence of contaminated equipment as opposed to ground contamination. Highest dose rates were measured at sites located in the immediate vicinity of buildings used for storing SNF and sites associated with storage of solid and liquid radioactive wastes. Elevated dose rates were also observed near the former channel of a small brook that became heavily contaminated as a result of radioactive leaks from the SNF storage at Building 5 starting in 1982. Isolated patches of elevated dose rates were also observed throughout the STB. A second paper detailing the radioactive soil contamination at the site is published in this issue of Journal of Environmental Radioactivity.

  19. Clinical transition to model-based dose calculation algorithm: A retrospective analysis of high-dose-rate tandem and ring brachytherapy of the cervix.

    Science.gov (United States)

    Jacob, Dayee; Lamberto, Melissa; DeSouza Lawrence, Lana; Mourtada, Firas

    To retrospectively compare clinical dosimetry of CT-based tandem-ring treatment plans using a model-based dose calculation algorithm (MBDCA) with the standard TG-43-based dose formalism. A cohort of 10 cervical cancer cohorts treated using the tandem and ring high-dose-rate applicators were evaluated. The original treatment plans were created using the department CT-based volume optimization clinical standards. All plans originally calculated with TG-43 dose calculation formalism were recalculated using the MBDCA algorithm. The gross target volume and organs at risk (OARs) were contoured on each data set along with significant heterogeneities like air in cavity and high-density plastic tandem and ring components. The patient tissue was modeled as homogenous liquid water. D90, D95, and D100 for gross target volume, D0.1cm(3), D1.0cm(3), and D2.0cm(3) for bladder, rectum, and sigmoid were extracted from dose-volume histograms for TG-43 and MBDCA calculated plans. Mean absolute difference ± 2σ in the above metrics was calculated for each plan. Using the manual applicator contouring method, MBDCA plans (n = 10) showed 2.1 ± 1.1% reduction in dose to Point A average, 2.6 ± 0.9% reduction in Target D90 dose, and 2.1 ± 0.3% dose reduction to OARs. Results from plans using vendor supplied solid applicator models (n = 5) showed 2.2 ± 1.10% reduction in dose to Point A average, 2.7 ± 0.2% reduction in Target D90 dose, and 2.7 ± 1.0% dose reduction on average to OARs. For unshielded plastic gynecologic applicators, minimal dosimetric changes (<5%) were found using MBDCA relative to standard TG-43. Use of solid applicator model is more efficient than manual applicator contouring and also yielded similar MBDCA dosimetric results. Currently, TG-186 dose calculations should be reported along TG-43 until we obtain studies with larger cohorts to fully realize the potential of MBDCA dosimetry. Copyright © 2017 American Brachytherapy Society. Published by

  20. Coumarin Based Neutral Sensor for Biologically Important Anions

    Institute of Scientific and Technical Information of China (English)

    SHAO Jie

    2011-01-01

    A coumarin Shiff-base derivative,salicylaldehyde-N-(6-phenylazo-coumarin-3-formyl)-hydrazone(1),was obtained by simple organic synthesis from cheap and commercially available starting materials.Sensor 1 exhibits a very weak fluorescence emission,however,in the presence of acetate ions “turn-on” fluorescence is observed,which results from binding-induced conformational restriction of the fluorophore.Importantly,sensor 1 can also be used as colorimetric chemosensor for the anions with strong basicity,which is easily observed from yellow to red by naked eyes.Consequently,compound l can behave as a colorimetric and fluorescence sensor for biologically important F,CH3COO and H2PO4- in the presence of the other anions tested such as Cl-,Br- and I- in dimethyl sulfoxide(DMSO).

  1. 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

  2. A new label dosimetry system based on pentacosa-diynoic acid monomer for low dose applications

    Science.gov (United States)

    Abdel-Fattah, A. A.; Abdel-Rehim, F.; Soliman, Y. S.

    2012-01-01

    The dosimetric characteristics of γ-radiation sensitive labels based on polyvinyl butyral (PVB) and a conjugated diacetylene monomer, 10,12-pentacosa-diynoic acid (PCDA) have been investigated using reflectance colorimeter. Two types of labels (colourless and yellow) based on PCDA monomer were prepared using an Automatic Film Applicator System. Upon γ-ray exposure, the colourless label turns progressively blue, while the yellow colour label turns to green then to dark blue. The colour intensity of the labels is proportional to the radiation absorbed dose. The useful dose range was 15 Gy-2 kGy depending on PCDA monomer concentration. The expanded uncertainty of dose measurement of the colourless label was 6.06 (2 σ).

  3. Heart-on-a-chip based on stem cell biology.

    Science.gov (United States)

    Jastrzebska, Elzbieta; Tomecka, Ewelina; Jesion, Iwona

    2016-01-15

    Heart diseases are one of the main causes of death around the world. The great challenge for scientists is to develop new therapeutic methods for these types of ailments. Stem cells (SCs) therapy could be one of a promising technique used for renewal of cardiac cells and treatment of heart diseases. Conventional in vitro techniques utilized for investigation of heart regeneration do not mimic natural cardiac physiology. Lab-on-a-chip systems may be the solution which could allow the creation of a heart muscle model, enabling the growth of cardiac cells in conditions similar to in vivo conditions. Microsystems can be also used for differentiation of stem cells into heart cells, successfully. It will help better understand of proliferation and regeneration ability of these cells. In this review, we present Heart-on-a-chip systems based on cardiac cell culture and stem cell biology. This review begins with the description of the physiological environment and the functions of the heart. Next, we shortly described conventional techniques of stem cells differentiation into the cardiac cells. This review is mostly focused on describing Lab-on-a-chip systems for cardiac tissue engineering. Therefore, in the next part of this article, the microsystems for both cardiac cell culture and SCs differentiation into cardiac cells are described. The section about SCs differentiation into the heart cells is divided in sections describing biochemical, physical and mechanical stimulations. Finally, we outline present challenges and future research concerning Heart-on-a-chip based on stem cell biology. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Functional proteomic analysis revealed ground-base ion radiations cannot reflect biological effects of space radiations of rice

    Science.gov (United States)

    Wang, Wei; Sun, Yeqing; Zhao, Qian; Han, Lu

    2016-07-01

    Highly ionizing radiation (HZE) in space is considered as main factor causing biological effects. Radiobiological studies during space flights are unrepeatable due to the variable space radiation environment, ground-base ion radiations are usually performed to simulate of the space biological effect. Spaceflights present a low-dose rate (0.1˜~0.3mGy/day) radiation environment inside aerocrafts while ground-base ion radiations present a much higher dose rate (100˜~500mGy/min). Whether ground-base ion radiation can reflect effects of space radiation is worth of evaluation. In this research, we compared the functional proteomic profiles of rice plants between on-ground simulated HZE particle radiation and spaceflight treatments. Three independent ground-base seed ionizing radiation experiments with different cumulative doses (dose range: 2˜~20000mGy) and different liner energy transfer (LET) values (13.3˜~500keV/μμm) and two independent seed spaceflight experiments onboard Chinese 20th satellite and SZ-6 spacecraft were carried out. Alterations in the proteome were analyzed by two-dimensional difference gel electrophoresis (2-D DIGE) with MALDI-TOF/TOF mass spectrometry identifications. 45 and 59 proteins showed significant (pmetabolic process, protein folding and phosphorylation. The results implied that ground-base radiations cannot truly reflect effects of spaceflight radiations, ground-base radiation was a kind of indirect effect to rice causing oxidation and metabolism stresses, but space radiation was a kind of direct effect leading to macromolecule (DNA and protein) damage and signal pathway disorders. This functional proteomic analysis work might provide a new evaluation method for further on-ground simulated HZE radiation experiments.

  5. LESM: a laser-driven sub-MeV electron source delivering ultra-high dose rate on thin biological samples

    Science.gov (United States)

    Labate, L.; Andreassi, M. G.; Baffigi, F.; Bizzarri, R.; Borghini, A.; Bussolino, G. C.; Fulgentini, L.; Ghetti, F.; Giulietti, A.; Köster, P.; Lamia, D.; Levato, T.; Oishi, Y.; Pulignani, S.; Russo, G.; Sgarbossa, A.; Gizzi, L. A.

    2016-07-01

    We present a laser-driven source of electron bunches with average energy 260~\\text{keV} and picosecond duration, which has been setup for radiobiological tests covering the previously untested sub-MeV energy range. Each bunch combines high charge with short duration and sub-millimeter range into a record instantaneous dose rate, as high as {{10}9}~\\text{Gy}~{{\\text{s}}-1} . The source can be operated at 10~\\text{Hz} and its average dose rate is 35~\\text{mGy}~{{\\text{s}}-1} . Both the high instantaneous dose rate and high level of relative biological effectiveness, attached to sub-MeV electrons, make this source very attractive for studies of ultrafast radiobiology on thin cell samples. The source reliability, in terms of shot-to-shot stability of features such as mean energy, bunch charge and transverse beam profile, is discussed, along with a dosimetric characterization. Finally, a few preliminary biological tests performed with this source are presented.

  6. Assessment of target volume doses in radiotherapy based on the standard and measured calibration curves

    Directory of Open Access Journals (Sweden)

    Gholamreza Fallah Mohammadi

    2015-01-01

    Full Text Available Context: In radiation treatments, estimation of the dose distribution in the target volume is one of the main components of the treatment planning procedure. To estimate the dose distribution, the information of electron densities is necessary. The standard curves determined by computed tomography (CT scanner that may be different from that of other oncology centers. In this study, the changes of dose calculation due to the different calibration curves (HU-ρel were investigated. Materials and Methods: Dose values were calculated based on the standard calibration curve that was predefined for the treatment planning system (TPS. The calibration curve was also extracted from the CT images of the phantom, and dose values were calculated based on this curve. The percentage errors of the calculated values were determined. Statistical Analysis Used: The statistical analyses of the mean differences were performed using the Wilcoxon rank-sum test for both of the calibration curves. Results and Discussion: The results show no significant difference for both of the measured and standard calibration curves (HU-ρel in 6, 15, and 18 MeV energies. In Wilcoxon ranked sum nonparametric test for independent samples with P < 0.05, the equality of monitor units for both of the curves to transfer 200 cGy doses to reference points was resulted. The percentage errors of the calculated values were lower than 2% and 1.5% in 6 and 15 MeV, respectively. Conclusion: From the results, it could be concluded that the standard calibration curve could be used in TPS dose calculation accurately.

  7. Daily fraction dose recalculation based on rigid registration using Cone Beam CT

    Directory of Open Access Journals (Sweden)

    Courtney Bosse

    2014-03-01

    Full Text Available Purpose: To calculate the daily fraction dose for CBCT recalculations based on rigid registration and compare it to the planned CT doses.Methods: For this study, 30 patients that were previously treated (10 SBRT lung, 10 prostate and 10 abdomen were considered. The daily CBCT images were imported into the Pinnacle treatment planning system from Mosaic. Pinnacle was used to re-contour the regions of interest (ROI for the specific CBCT by copying the contours from the original CT plan, planned by the prescribing physician, onto each daily CBCT and then manually reshaping contours to match the ROIs. A new plan is then created with the re-contoured CBCT as primary image in order to calculate the daily dose delivered to each ROI. The DVH values are then exported into Excel and overlaid onto the original CT DVH to produce a graph.Results: For the SBRT lung patients, we found that there were small daily volume changes in the lungs, trachea and esophagus. For almost all regions of interest we found that the dose received each day was less than the predicted dose of the planned CT while the PTV dose was relatively the same each day. The results for the prostate patients were similar, showing slight differences in the DVH values for different days in the rectum and bladder but similar PTV.Conclusion: By comparing daily fraction dose between the re-contoured CBCT images and the original planned CT show that PTV coverage for both prostate and SBRT, it has been shown that for PTV coverage, a planned CT is adequate. However, there are differences between the dose for the organs surrounding the PTV. The dose difference is less than the planned in most instances.-----------------------Cite this article as: Bosse C, Tuohy R, Mavroidis P, Shi Z, Crownover R, Gutierrez A, Papanikolaou N, Stathakis S. Daily fraction dose recalculation based on rigid registration using Cone Beam CT. Int J Cancer Ther Oncol 2014; 2(2:020217. DOI: 10.14319/ijcto.0202.17

  8. Image quality and dose distributions of three linac-based imaging modalities

    Energy Technology Data Exchange (ETDEWEB)

    Dzierma, Yvonne; Ames, Evemarie; Nuesken, Frank; Palm, Jan; Licht, Norbert; Ruebe, Christian [Universitaetsklinikum des Saarlandes, Klinik fuer Strahlentherapie und Radioonkologie, Homburg/Saar (Germany)

    2015-04-01

    Linac-based patient imaging is possible with a variety of techniques using different photon energies. The purpose of this work is to compare three imaging systems operating at 6 MV, flattening free filter (FFF) 1 MV, and 121 kV. The dose distributions of all pretreatment set-up images (over 1,000) were retrospectively calculated on the planning computed tomography (CT) images for all patients with prostate and head-and-neck cancer treated at our institution in 2013. We analyzed the dose distribution and the dose to organs at risk. For head-and-neck cancer patients, the imaging dose from 6-MV cone beam CT (CBCT) reached maximum values at around 8 cGy. The 1-MV CBCT dose was about 63-79 % of the 6-MV CBCT dose for all organs at risk. Planar imaging reduced the imaging dose from CBCT to 30-40 % for both megavoltage modalities. The dose from the kilovoltage CBCT was 4-10 % of the 6-MV CBCT dose. For prostate cancer patients, the maximum dose from 6-MV CBCT reached 13-15 cGy, and was reduced to 66-73 % for 1 MV. Planar imaging reduces the MV CBCT dose to 10-20 %. The kV CBCT dose is 15-20 % of the 6-MV CBCT dose, slightly higher than the dose from MV axes. The dose distributions differ markedly in response to the different beam profiles and dose-depth characteristics. (orig.) [German] Linac-basierte Bildgebung zur Patientenlagerung ist mit einer Vielzahl von Techniken unterschiedlicher Photonenenergien moeglich. Ziel dieser Arbeit ist der Vergleich dreier Bildgebungssysteme mit 6 MV (Megavolt), FFF 1 MV, und 121 kV (Kilovolt). Fuer alle im Jahr 2013 an unserer Klinik behandelten Prostata- und HNO-Patienten wurden retrospektiv die Dosisverteilungen aller Verifikationsaufnahmen (ueber 1000 insgesamt) auf der Planungs-Computertomographie (CT) berechnet. Wir analysierten die Dosisverteilung und die Dosis an den Risikoorganen. Bei HNO-Patienten erreichte die Dosis von 6 MV ''Cone-beam''-CT (CBCT)Maximalwerte um 8 cGy. Mit 1 MV wird die Dosis auf 63

  9. 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

    Background: Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The 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)diac...

  10. Effects of Low-Dose Mindfulness-Based Stress Reduction (MBSR-ld) on Working Adults

    Science.gov (United States)

    Klatt, Maryanna D.; Buckworth, Janet; Malarkey, William B.

    2009-01-01

    Mindfulness-based stress reduction (MBSR) has produced behavioral, psychological, and physiological benefits, but these programs typically require a substantial time commitment from the participants. This study assessed the effects of a shortened (low-dose [ld]) work-site MBSR intervention (MBSR-ld) on indicators of stress in healthy working…

  11. Surface membrane based bladder registration for evaluation of accumulated dose during brachytherapy in cervical cancer

    DEFF Research Database (Denmark)

    Noe, Karsten Østergaard; Tanderup, Kari; Sørensen, Thomas Sangild

    2011-01-01

    of the fixed surface. Optional landmark based matches can be included in the suggested iterative solver. The technique is demonstrated for bladder registration in brachytherapy treatment evaluation of cervical cancer. It holds promise to better estimate the accumulated but unintentional dose delivered...

  12. Calibrating passive sampling and passive dosing techniques to lipid based concentrations

    DEFF Research Database (Denmark)

    Mayer, Philipp; Schmidt, Stine Nørgaard; Annika, A.

    2011-01-01

    coated vials and with Head Space Solid Phase Microextraction (HS-SPME) yielded lipid based concentrations that were in good agreement with each other, but about a factor of two higher than measured lipid-normalized concentrations in the organisms. Passive dosing was applied to bioconcentration...

  13. Biological characterization of radiation exposure and dose estimates for inhaled uranium milling effluents. Annual progress report April 1, 1982-March 31, 1983

    Energy Technology Data Exchange (ETDEWEB)

    Eidson, A.F.

    1984-05-01

    The problems addressed are the protection of uranium mill workers from occupational exposure to uranium through routine bioassay programs and the assessment of accidental worker exposures. Comparisons of chemical properties and the biological behavior of refined uranium ore (yellowcake) are made to identify important properties that influence uranium distribution patterns among organs. These studies will facilitate calculations of organ doses for specific exposures and associated health risk estimates and will identify important bioassay procedures to improve evaluations of human exposures. A quantitative analytical method for yellowcake was developed based on the infrared absorption of ammonium diuranate and U/sub 3/O/sub 8/ mixtures in KBr. The method was applied to yellowcake samples obtained from six operating mills. The composition of yellowcake from the six mills ranged from nearly pure ammonium diuranate to nearly pure U/sub 3/O/sub 8/. The composition of yellowcake samples taken from lots from the same mill was only somewhat less variable. Because uranium mill workers might be exposed to yellowcake either by contamination of a wound or by inhalation, a study of retention and translocation of uranium after subcutaneous implantation in rats was done. The results showed that 49% of the implanted yellowcake cleared from the body with a half-time (T sub 1/2) in the body of 0.3 days, and the remainder was cleared with a T sub 1/2 of 11 to 30 days. Exposures of Beagle dogs by nose-only inhalation to aerosols of commercial yellowcake were completed. Biochemical indicators of kidney dysfunction that appeared in blood and urine 4 to 8 days after exposure to the more soluble yellowcake showed significant changes in dogs, but levels returned to normal by 16 days after exposure. No biochemical evidence of kidney dysfunction was observed in dogs exposed to the less soluble yellowcake form. 18 figures, 9 tables.

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

    DEFF Research Database (Denmark)

    Bertelsen, Anders; Schytte, Tine; Bentzen, Søren M;

    2011-01-01

    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....

  15. 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

  16. A graphical user interface (GUI) toolkit for the calculation of three-dimensional (3D) multi-phase biological effective dose (BED) distributions including statistical analyses.

    Science.gov (United States)

    Kauweloa, Kevin I; Gutierrez, Alonso N; Stathakis, Sotirios; Papanikolaou, Niko; Mavroidis, Panayiotis

    2016-07-01

    A toolkit has been developed for calculating the 3-dimensional biological effective dose (BED) distributions in multi-phase, external beam radiotherapy treatments such as those applied in liver stereotactic body radiation therapy (SBRT) and in multi-prescription treatments. This toolkit also provides a wide range of statistical results related to dose and BED distributions. MATLAB 2010a, version 7.10 was used to create this GUI toolkit. The input data consist of the dose distribution matrices, organ contour coordinates, and treatment planning parameters from the treatment planning system (TPS). The toolkit has the capability of calculating the multi-phase BED distributions using different formulas (denoted as true and approximate). Following the calculations of the BED distributions, the dose and BED distributions can be viewed in different projections (e.g. coronal, sagittal and transverse). The different elements of this toolkit are presented and the important steps for the execution of its calculations are illustrated. The toolkit is applied on brain, head & neck and prostate cancer patients, who received primary and boost phases in order to demonstrate its capability in calculating BED distributions, as well as measuring the inaccuracy and imprecision of the approximate BED distributions. Finally, the clinical situations in which the use of the present toolkit would have a significant clinical impact are indicated.

  17. Dose evaluation of therapeutic radiolabeled bleomycin complexes based on biodistribution data in wild-type rats:Effect of radionuclides in absorbed dose of different organs

    Institute of Scientific and Technical Information of China (English)

    Hassan Yousefnia; Samaneh Zolghadri; Amir Reza Jalilian; Mohammad Ghannadi-Maragheh

    2015-01-01

    Bleomycins (BLMs), as tumor-seeking antibiotics, have been used for over 20 years in treatment of several types of cancers. Several radioisotopes are used in radiolabeling of BLMs for therapeutic and diagnostic purpos-es. An important points in developing new radiopharmaceuticals, especially therapeutic agents, is the absorbed dose delivered in critical organs. In this work, absorbed dose to organs after injection of 153Sm-, 177Lu-and 166Ho-labeled BLM was investigated by radiation dose assessment resource (RADAR) method based on biodis-tribution data in wild-type rats. The absorbed dose effect of the radionuclides was evaluated. The maximum absorbed dose for the complexes was observed in the kidneys, liver and lungs. For all the radiolabeled BLMs, bone and red marrow received considerable absorbed dose. Due to the high energy beta particles emitted by 166Ho, higher absorbed dose is observed for 166Ho-BLM in the most organs. The reported data can be useful for the determination of the maximum permissible injected activity of the radiolabeled BLMs in the treatment planning programs.

  18. Particle induced X-ray emission and ion dose distribution in a biological micro-beam: Geant4 Monte Carlo simulations

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Syed Bilal, E-mail: ahmadsb@mcmaster.ca [TAB-104D, Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada L8S 4K1 (Canada); Thompson, Jeroen E., E-mail: Jeroen.thompson@gmail.com [Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada L8S 4K1 (Canada); McNeill, Fiona E., E-mail: fmcneill@mcmaster.ca [Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada L8S 4K1 (Canada); Byun, Soo Hyun, E-mail: soohyun@mcmaster.ca [Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada L8S 4K1 (Canada); Prestwich, William V., E-mail: prestwic@mcmaster.ca [Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ontario, Canada L8S 4K1 (Canada)

    2013-01-15

    The goal of a microbeam is to deliver a highly localized and small dose to the biological medium. This can be achieved by using a set of collimators that confine the charged particle beam to a very small spatial area of the order of microns in diameter. By using a system that combines an appropriate beam detection method that signals to a beam shut-down mechanism, a predetermined and counted number of energetic particles can be delivered to targeted biological cells. Since the shutter and the collimators block a significant proportion of the beam, there is a probability of the production of low energy X-rays and secondary electrons through interactions with the beam. There is little information in the biological microbeam literature on potential X-ray production. We therefore used Monte Carlo simulations to investigate the potential production of particle-induced X-rays and secondary electrons in the collimation system (which is predominantly made of tungsten) and the subsequent possible effects on the total absorbed dose delivered to the biological medium. We found, through the simulation, no evidence of the escape of X-rays or secondary electrons from the collimation system for proton energies up to 3 MeV as we found that the thickness of the collimators is sufficient to reabsorb all of the generated low energy X-rays and secondary electrons. However, if the proton energy exceeds 3 MeV our simulations suggest that 10 keV X-rays can escape the collimator and expose the overlying layer of cells and medium. If the proton energy is further increased to 4.5 MeV or beyond, the collimator can become a significant source of 10 keV and 59 keV X-rays. These additional radiation fields could have effects on cells and these results should be verified through experimental measurement. We suggest that researchers using biological microbeams at higher energies need to be aware that cells may be exposed to a mixed LET radiation field and be careful in their interpretation of

  19. Small field dose delivery evaluations using cone beam optical computed tomography-based polymer gel dosimetry

    Directory of Open Access Journals (Sweden)

    Timothy Olding

    2011-01-01

    Full Text Available This paper explores the combination of cone beam optical computed tomography with an N-isopropylacrylamide (NIPAM-based polymer gel dosimeter for three-dimensional dose imaging of small field deliveries. Initial investigations indicate that cone beam optical imaging of polymer gels is complicated by scattered stray light perturbation. This can lead to significant dosimetry failures in comparison to dose readout by magnetic resonance imaging (MRI. For example, only 60% of the voxels from an optical CT dose readout of a 1 l dosimeter passed a two-dimensional Low′s gamma test (at a 3%, 3 mm criteria, relative to a treatment plan for a well-characterized pencil beam delivery. When the same dosimeter was probed by MRI, a 93% pass rate was observed. The optical dose measurement was improved after modifications to the dosimeter preparation, matching its performance with the imaging capabilities of the scanner. With the new dosimeter preparation, 99.7% of the optical CT voxels passed a Low′s gamma test at the 3%, 3 mm criteria and 92.7% at a 2%, 2 mm criteria. The fitted interjar dose responses of a small sample set of modified dosimeters prepared (a from the same gel batch and (b from different gel batches prepared on the same day were found to be in agreement to within 3.6% and 3.8%, respectively, over the full dose range. Without drawing any statistical conclusions, this experiment gives a preliminary indication that intrabatch or interbatch NIPAM dosimeters prepared on the same day should be suitable for dose sensitivity calibration.

  20. A phantom-based method to standardize dose-calibrators for new β+-emitters.

    Science.gov (United States)

    Morgat, Clément; Mazère, Joachim; Fernandez, Philippe; Buj, Sébastien; Vimont, Delphine; Schulz, Jürgen; Lamare, Frédéric

    2015-02-01

    Quantitative imaging with PET requires accurate measurements of the amount of radioactivity injected into the patient and the concentration of radioactivity in a given region. Recently, new positron emitters, such as (124)I, (89)Zr, (82)Rb, (68)Ga, and (64)Cu, have emerged to promote PET development, but standards are still largely lacking. Therefore, we propose to validate a simple, robust, and replicable methodology, not requiring the use of any standards, to accurately calibrate a dose-calibrator for any β(+)-emitter. On the basis of (18)F cross-calibration, routinely performed with fluorine-18-fluorodeoxyglucose (F-FDG) in nuclear medicine departments, a methodology was developed using β(+)-emitting' phantoms to cross-calibrate the dose-calibrator for measuring the activity of positron emitters and quantifying the standardized uptake value (SUV). Ga phantoms filled with activities measured with various dose-calibrator settings were imaged to establish calibration curves (SUV values as a function of the dose-calibrator settings) and to identify the setting value, yielding an SUV value of 1.00 g/ml, reflecting an accurate measurement of (68)Ga activity. Activities measured with the identified setting were finally checked with a γ-counter. The setting of 772±1 was identified as ensuring that the studied dose-calibrator is correctly calibrated for (68)Ga to ensure an SUV value of 1.00±0.01 g/ml. γ-Ray spectrometry confirmed the accurate measurement of Ga activities by the dose-calibrator (relative error of 2.9±1.5%). We have developed a phantom-based method to accurately standardize dose-calibrators for any β(+)-emitter, without any standards.

  1. GPU-based fast Monte Carlo simulation for radiotherapy dose calculation.

    Science.gov (United States)

    Jia, Xun; Gu, Xuejun; Graves, Yan Jiang; Folkerts, Michael; Jiang, Steve B

    2011-11-21

    Monte Carlo (MC) simulation is commonly considered to be the most accurate dose calculation method in radiotherapy. However, its efficiency still requires improvement for many routine clinical applications. In this paper, we present our recent progress toward the development of a graphics processing unit (GPU)-based MC dose calculation package, gDPM v2.0. It utilizes the parallel computation ability of a GPU to achieve high efficiency, while maintaining the same particle transport physics as in the original dose planning method (DPM) code and hence the same level of simulation accuracy. In GPU computing, divergence of execution paths between threads can considerably reduce the efficiency. Since photons and electrons undergo different physics and hence attain different execution paths, we use a simulation scheme where photon transport and electron transport are separated to partially relieve the thread divergence issue. A high-performance random number generator and a hardware linear interpolation are also utilized. We have also developed various components to handle the fluence map and linac geometry, so that gDPM can be used to compute dose distributions for realistic IMRT or VMAT treatment plans. Our gDPM package is tested for its accuracy and efficiency in both phantoms and realistic patient cases. In all cases, the average relative uncertainties are less than 1%. A statistical t-test is performed and the dose difference between the CPU and the GPU results is not found to be statistically significant in over 96% of the high dose region and over 97% of the entire region. Speed-up factors of 69.1 ∼ 87.2 have been observed using an NVIDIA Tesla C2050 GPU card against a 2.27 GHz Intel Xeon CPU processor. For realistic IMRT and VMAT plans, MC dose calculation can be completed with less than 1% standard deviation in 36.1 ∼ 39.6 s using gDPM.

  2. Anatomy-based three-dimensional dose optimization in brachytherapy using multiobjective genetic algorithms.

    Science.gov (United States)

    Lahanas, M; Baltas, D; Zamboglou, N

    1999-09-01

    In conventional dose optimization algorithms, in brachytherapy, multiple objectives are expressed in terms of an aggregating function which combines individual objective values into a single utility value, making the problem single objective, prior to optimization. A multiobjective genetic algorithm (MOGA) was developed for dose optimization based on an a posteriori approach, leaving the decision-making process to a planner and offering a representative trade-off surface of the various objectives. The MOGA provides a flexible search engine which provides the maximum of information for a decision maker. Tests performed with various treatment plans in brachytherapy have shown that MOGA gives solutions which are superior to those of traditional dose optimization algorithms. Objectives were proposed in terms of the COIN distribution and differential volume histograms, taking into account patient anatomy in the optimization process.

  3. Fast CPU-based Monte Carlo simulation for radiotherapy dose calculation.

    Science.gov (United States)

    Ziegenhein, Peter; Pirner, Sven; Ph Kamerling, Cornelis; Oelfke, Uwe

    2015-08-07

    Monte-Carlo (MC) simulations are considered to be the most accurate method for calculating dose distributions in radiotherapy. Its clinical application, however, still is limited by the long runtimes conventional implementations of MC algorithms require to deliver sufficiently accurate results on high resolution imaging data. In order to overcome this obstacle we developed the software-package PhiMC, which is capable of computing precise dose distributions in a sub-minute time-frame by leveraging the potential of modern many- and multi-core CPU-based computers. PhiMC is based on the well verified dose planning method (DPM). We could demonstrate that PhiMC delivers dose distributions which are in excellent agreement to DPM. The multi-core implementation of PhiMC scales well between different computer architectures and achieves a speed-up of up to 37[Formula: see text] compared to the original DPM code executed on a modern system. Furthermore, we could show that our CPU-based implementation on a modern workstation is between 1.25[Formula: see text] and 1.95[Formula: see text] faster than a well-known GPU implementation of the same simulation method on a NVIDIA Tesla C2050. Since CPUs work on several hundreds of GB RAM the typical GPU memory limitation does not apply for our implementation and high resolution clinical plans can be calculated.

  4. Dose monitoring for boron neutron capture therapy using a reactor-based epithermal neutron beam

    Science.gov (United States)

    Raaijmakers, C. P. J.; Nottelman, E. L.; Konijnenberg, M. W.; Mijnheer, B. J.

    1996-12-01

    The aims of this study were (i) to determine the variation with time of the relevant beam parameters of a clinical reactor-based epithermal neutron beam for boron neutron capture therapy (BNCT) and (ii) to test a monitoring system for its applicability to monitor the dose delivered to the dose specification point in a patient treated with BNCT. For this purpose two fission chambers covered with Cd and two GM counters were positioned in the beam-shaping collimator assembly of the epithermal neutron beam. The monitor count rates were compared with in-phantom reference measurements of the thermal neutron fluence rate, the gamma-ray dose rate and the fast neutron dose rate, at a constant reactor power, over a period of 2 years. Differences in beam output, defined as the thermal neutron fluence rate at 2 cm depth in a phantom, of up to 15% were observed between various reactor cycles. A decrease in beam output of about 5% was observed in each reactor cycle. An unacceptable decrease of 50% in beam output due to malfunctioning of the beam filter assembly was detected. For safe and accurate treatment of patients, on-line monitoring of the beam is essential. Using the calibrated monitor system, the standard uncertainty in the total dose at depth due to variations with time of the beam output parameters has been reduced to a clinically acceptable value of 1% (one standard deviation).

  5. Absorbed Dose Calculations Using Mesh-based Human Phantoms And Monte Carlo Methods

    Science.gov (United States)

    Kramer, Richard

    2011-08-01

    Health risks attributable to the exposure to ionizing radiation are considered to be a function of the absorbed or equivalent dose to radiosensitive organs and tissues. However, as human tissue cannot express itself in terms of equivalent dose, exposure models have to be used to determine the distribution of equivalent dose throughout the human body. An exposure model, be it physical or computational, consists of a representation of the human body, called phantom, plus a method for transporting ionizing radiation through the phantom and measuring or calculating the equivalent dose to organ and tissues of interest. The FASH2 (Female Adult meSH) and the MASH2 (Male Adult meSH) computational phantoms have been developed at the University of Pernambuco in Recife/Brazil based on polygon mesh surfaces using open source software tools and anatomical atlases. Representing standing adults, FASH2 and MASH2 have organ and tissue masses, body height and body mass adjusted to the anatomical data published by the International Commission on Radiological Protection for the reference male and female adult. For the purposes of absorbed dose calculations the phantoms have been coupled to the EGSnrc Monte Carlo code, which can transport photons, electrons and positrons through arbitrary media. This paper reviews the development of the FASH2 and the MASH2 phantoms and presents dosimetric applications for X-ray diagnosis and for prostate brachytherapy.

  6. Mechanisms of Action and Dose-Response Relationships Governing Biological Control of Fusarium Wilt of Tomato by Nonpathogenic Fusarium spp.

    Science.gov (United States)

    Larkin, R P; Fravel, D R

    1999-12-01

    ABSTRACT Three isolates of nonpathogenic Fusarium spp. (CS-1, CS-20, and Fo47), previously shown to reduce the incidence of Fusarium wilt diseases of multiple crops, were evaluated to determine their mechanisms of action and antagonist-pathogen inoculum density relationships. Competition for nutrients, as represented by a reduction in pathogen saprophytic growth in the presence of the biocontrol isolates, was observed to be an important mechanism of action for isolate Fo47, but not for isolates CS-1 and CS-20. All three biocontrol isolates demonstrated some degree of induced systemic resistance in tomato (Lycopersicon esculentum) and watermelon (Citrullus lanatus) plants, as determined by split-root tests, but varied in their relative abilities to reduce disease. Isolate CS-20 provided the most effective control (39 to 53% disease reduction), while Fo47 provided the least effective control (23 to 25% reduction) in split-root tests. Dose-response relationships also differed considerably among the three biocon-trol isolates, with CS-20 significantly reducing disease incidence at antagonist doses as low as 100 chlamydospores per g of soil (cgs) and at pathogen densities up to 10(5) cgs. Isolate CS-1 also was generally effective at antagonist densities of 100 to 5,000 cgs, but only when pathogen densities were below 10(4) cgs. Isolate Fo47 was effective only at antagonist densities of 10(4) to 10(5) cgs, regardless of pathogen density. Epidemiological dose-response models (described by linear, negative exponential, hyperbolic saturation [HS], and logistic [LG] functions) fit to the observed data were used to quantify differences among the biocontrol isolates and establish biocontrol characteristics. Each isolate required a different model to best describe its dose-response characteristics, with the HS/HS, LG/HS, and LG/LG models (pathogen/biocontrol components) providing the best fit for isolates CS-1, CS-20, and Fo47, respectively. Model parameters (defining effective

  7. SU-E-P-47: Evaluation of Improvement of Esophagus Sparing in SBRT Lung Patients with Biologically Based IMRT Optimization

    Energy Technology Data Exchange (ETDEWEB)

    Liang, X; Penagaricano, J; Paudel, N; Zhang, X; Morrill, S; Corry, P; Han, E; Hardee, M; Ratanatharathorn, V [University of Arkansas Medical Science, Little Rock, AR (United States)

    2015-06-15

    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.

  8. Evaluation of heparin dosing based on adjusted body weight in obese patients.

    Science.gov (United States)

    Fan, Jingyang; John, Billee; Tesdal, Emily

    2016-10-01

    Results of a study to determine whether heparin dosing based on adjusted body weight (BWAdj) instead of actual body weight (ABW) can lead to faster achievement of therapeutic activated partial thromboplastin time (aPTT) values in obese patients are presented. A single-center retrospective cohort study was conducted to assess aPTT outcomes before and after implementation of a revised heparin protocol specifying BWAdj-based dosing for obese patients. The primary outcome was the percentage of first aPTT values within the target range after heparin initiation. Secondary outcomes included the median time to the first on-target aPTT and the rate of clinically significant bleeding. After protocol implementation, there was no significant difference between obese and nonobese patients in the primary outcome (17% and 21%, respectively, had first aPTT values in the target range) or in the median time to achieve the first on-target aPTT value. Among obese patients, on-target aPTT values were achieved significantly faster with BWAdj-versus ABW-based dosing (14 hours versus 24 hours, p = 0.002). Prior to implementation of BWAdj-based heparin dosing, obese patients had a higher rate of clinically significant bleeding than nonobese patients (11% versus 1%, p = 0.01); postimplementation bleeding rates did not differ significantly. The percentages of first aPTT values in the targeted range did not differ significantly in obese and nonobese patients before and after protocol implementation. The use of BWAdj for dose calculation in obese patients was associated with faster achievement of an aPTT value in the target range. Copyright © 2016 by the American Society of Health-System Pharmacists, Inc. All rights reserved.

  9. Validation of a deformable image registration technique for cone beam CT-based dose verification

    Energy Technology Data Exchange (ETDEWEB)

    Moteabbed, M., E-mail: mmoteabbed@partners.org; Sharp, G. C.; Wang, Y.; Trofimov, A.; Efstathiou, J. A.; Lu, H.-M. [Massachusetts General Hospital, Boston, Massachusetts 02114 and Harvard Medical School, Boston, Massachusetts 02115 (United States)

    2015-01-15

    Purpose: As radiation therapy evolves toward more adaptive techniques, image guidance plays an increasingly important role, not only in patient setup but also in monitoring the delivered dose and adapting the treatment to patient changes. This study aimed to validate a method for evaluation of delivered intensity modulated radiotherapy (IMRT) dose based on multimodal deformable image registration (DIR) for prostate treatments. Methods: A pelvic phantom was scanned with CT and cone-beam computed tomography (CBCT). Both images were digitally deformed using two realistic patient-based deformation fields. The original CT was then registered to the deformed CBCT resulting in a secondary deformed CT. The registration quality was assessed as the ability of the DIR method to recover the artificially induced deformations. The primary and secondary deformed CT images as well as vector fields were compared to evaluate the efficacy of the registration method and it’s suitability to be used for dose calculation. PLASTIMATCH, a free and open source software was used for deformable image registration. A B-spline algorithm with optimized parameters was used to achieve the best registration quality. Geometric image evaluation was performed through voxel-based Hounsfield unit (HU) and vector field comparison. For dosimetric evaluation, IMRT treatment plans were created and optimized on the original CT image and recomputed on the two warped images to be compared. The dose volume histograms were compared for the warped structures that were identical in both warped images. This procedure was repeated for the phantom with full, half full, and empty bladder. Results: The results indicated mean HU differences of up to 120 between registered and ground-truth deformed CT images. However, when the CBCT intensities were calibrated using a region of interest (ROI)-based calibration curve, these differences were reduced by up to 60%. Similarly, the mean differences in average vector field

  10. Altered natural killer cell biology in C57BL/6 mice after leukemogenic split-dose irradiation. [/sup 137/Cs

    Energy Technology Data Exchange (ETDEWEB)

    Parkinson, D.R.; Brightman, R.P.; Waksal, S.D.

    1981-04-01

    Natural killer (NK) cell activity was examined in the spleens of C57BL/6 mice given leukemogenic split-dose irradiation. The radiation protocol resulted in severe depression of spontaneous NK cell activity; this activity was not fully restored after treatment with the interferon inducer poly I:C. In vitro mixing studies provided no evidence for active suppression in vivo as a mechanism for this decrease in activity. In addition, spontaneous activity was restored towards control levels after bone marrow transfusion from nonirradiated mice. The results are most compatible with the radiation-induced loss of a cell with normal NK activity from spleen and bone marrow after the split-dose radiation protocol. In addition, a population of cells able to competitively block normal NK cell lysis of YAC-1 tumor cells is found in the bone marrow, spleen, and thymus of the irradiated mice lacking NK cell activity.

  11. STS-based education in non-majors college biology

    Science.gov (United States)

    Henderson, Phyllis Lee

    The study explored the effect of the science-technology-society (STS) and traditional teaching methods in non-majors biology classes at a community college. It investigated the efficacy of the two methods in developing cognitive abilities at Bloom's first three levels of learning. It compared retention rates in classes taught in the two methods. Changes in student attitude relating to anxiety, fear, and interest in biology were explored. The effect of each method on grade attainment among men and women was investigated. The effect of each method on grade attainment among older and younger students was examined. Results of the study indicated that no significant differences, relating to retention or student attitude, existed in classes taught in the two methods. The study found no significant cognitive gains at Bloom's first three levels in classes taught in the traditional format. In the STS classes no significant gains were uncovered at Bloom's first level of cognition. Statistically significant gains were found in the STS classes at Bloom's second and third levels of cognition. In the classes taught in the traditional format no difference was identified in grade attainment between males and females. In the STS-based classes a small correlational difference between males and females was found with males receiving lower grades than expected. No difference in grade attainment was found between older and younger students taught in the traditional format. In the STS-based classes a small statistically significant difference in grade attainment was uncovered between older and younger students with older students receiving more A's and fewer C's than expected. This study found no difference in the grades of older, female students as compared to all other students in the traditionally taught classes. A weak statistically significant difference was discovered between grade attainment of older, female students and all other students in the STS classes with older, female

  12. The Impact of Adaptive and Non-targeted Effects in the Biological Responses to Low Dose/Low Fluence Ionizing-Radiation: The Modulating Effect of Linear Energy Transfer

    OpenAIRE

    de Toledo, Sonia M.; Buonanno, Manuela; Li, Min; Asaad, Nesrin; Qin, Yong; Zhang, Jie; Azzam, Edouard I.

    2011-01-01

    A large volume of laboratory and human epidemiological studies have shown that high doses of ionizing radiation engender significant health risks. In contrast, the health risks of low level radiation remain ambiguous and have been the subject of intense debate. To reduce the uncertainty in evaluating these risks, research advances in cellular and molecular biology are being used to characterize the biological effects of low dose radiation exposures and their underlying mechanisms. Radiation t...

  13. Dose sparing of induction dose of propofol by fentanyl and butorphanol: A comparison based on entropy analysis

    Directory of Open Access Journals (Sweden)

    Jasleen Kaur

    2013-01-01

    Full Text Available Background: The induction dose of propofol is reduced with concomitant use of opioids as a result of a possible synergistic action. Aim and Objectives: The present study compared the effect of fentanyl and two doses of butorphanol pre-treatment on the induction dose of propofol, with specific emphasis on entropy. Methods: Three groups of 40 patients each, of the American Society of Anaesthesiologistsphysical status I and II, were randomized to receive fentanyl 2 μg/kg (Group F, butorphanol 20 μg/kg (Group B 20 or 40 μg/kg (Group B 40 as pre-treatment. Five minutes later, the degree of sedation was assessed by the observer′s assessment of alertness scale (OAA/S. Induction of anesthesia was done with propofol (30 mg/10 s till the loss of response to verbal commands. Thereafter, rocuronium 1 mg/kg was administered and endotracheal intubation was performed 2 min later. OAA/S, propofol induction dose, heart rate, blood pressure, oxygen saturation and entropy (response and state were compared in the three groups. Statistical Analysis: Data was analyzed using ANOVA test with posthoc significance, Kruskal-Wallis test, Chi-square test and Fischer exact test. A P<0.05 was considered as significant. Results: The induction dose of propofol (mg/kg was observed to be 1.1±0.50 in Group F, 1.05±0.35 in Group B 20 and 1.18±0.41 in Group B40. Induction with propofol occurred at higher entropy values on pre-treatment with both fentanyl as well as butorphanol. Hemodynamic variables were comparable in all the three groups. Conclusion: Butorphanol 20 μg/kg and 40 μg/kg reduce the induction requirement of propofol, comparable to that of fentanyl 2 μg/kg, and confer hemodynamic stability at induction and intubation.

  14. Renal Drug Dosing. Effectiveness of Outpatient Pharmacist-Based vs. Prescriber-Based Clinical Decision Support Systems.

    Science.gov (United States)

    Vogel, Erin A; Billups, Sarah J; Herner, Sheryl J; Delate, Thomas

    2016-07-27

    The purpose of this study was to compare the effectiveness of an outpatient renal dose adjustment alert via a computerized provider order entry (CPOE) clinical decision support system (CDSS) versus a CDSS with alerts made to dispensing pharmacists. This was a retrospective analysis of patients with renal impairment and 30 medications that are contraindicated or require dose-adjustment in such patients. The primary outcome was the rate of renal dosing errors for study medications that were dispensed between August and December 2013, when a pharmacist-based CDSS was in place, versus August through December 2014, when a prescriber-based CDSS was in place. A dosing error was defined as a prescription for one of the study medications dispensed to a patient where the medication was contraindicated or improperly dosed based on the patient's renal function. The denominator was all prescriptions for the study medications dispensed during each respective study period. During the pharmacist- and prescriber-based CDSS study periods, 49,054 and 50,678 prescriptions, respectively, were dispensed for one of the included medications. Of these, 878 (1.8%) and 758 (1.5%) prescriptions were dispensed to patients with renal impairment in the respective study periods. Patients in each group were similar with respect to age, sex, and renal function stage. Overall, the five-month error rate was 0.38%. Error rates were similar between the two groups: 0.36% and 0.40% in the pharmacist- and prescriber-based CDSS, respectively (p=0.523). The medication with the highest error rate was dofetilide (0.51% overall) while the medications with the lowest error rate were dabigatran, fondaparinux, and spironolactone (0.00% overall). Prescriber- and pharmacist-based CDSS provided comparable, low rates of potential medication errors. Future studies should be undertaken to examine patient benefits of the prescriber-based CDSS.

  15. Should dosing of rocuronium in obese patients be based on ideal or corrected body weight?

    DEFF Research Database (Denmark)

    Meyhoff, Christian S; Lund, Jørgen; Jenstrup, Morten T;

    2009-01-01

    BACKGROUND: Pharmacokinetic studies in obese patients suggest that dosing of rocuronium should be based on ideal body weight (IBW). This may, however, result in a prolonged onset time or compromised conditions for tracheal intubation. In this study, we compared onset time, conditions for tracheal...... intubation, and duration of action in obese patients when the intubation dose of rocuronium was based on three different weight corrections. METHODS: Fifty-one obese patients, with a median (range) body mass index of 44 (34-72) kg/m2, scheduled for laparoscopic gastric banding or gastric bypass under...... propofol-remifentanil anesthesia were randomized into three groups. The patients received rocuronium (0.6 mg/kg) based on IBW (IBW group, n = 17), IBW plus 20% of excess weight (corrected body weight [CBW]20% group, n = 17), or IBW plus 40% of excess weight (CBW40% group, n = 17). Propofol was administered...

  16. Effects of CT based Voxel Phantoms on Dose Distribution Calculated with Monte Carlo Method

    Institute of Scientific and Technical Information of China (English)

    Chen Chaobin; Huang Qunying; Wu Yican

    2005-01-01

    A few CT-based voxel phantoms were produced to investigate the sensitivity of Monte Carlo simulations of X-ray beam and electron beam to the proportions of elements and the mass densities of the materials used to express the patient's anatomical structure. The human body can be well outlined by air, lung, adipose, muscle, soft bone and hard bone to calculate the dose distribution with Monte Carlo method. The effects of the calibration curves established by using various CT scanners are not clinically significant based on our investigation. The deviation from the values of cumulative dose volume histogram derived from CT-based voxel phantoms is less than 1% for the given target.

  17. Reinforcement learning-based control of drug dosing for cancer chemotherapy treatment.

    Science.gov (United States)

    Padmanabhan, Regina; Meskin, Nader; Haddad, Wassim M

    2017-08-16

    The increasing threat of cancer to human life and the improvement in survival rate of this disease due to effective treatment has promoted research in various related fields. This research has shaped clinical trials and emphasized the necessity to properly schedule cancer chemotherapy to ensure effective and safe treatment. Most of the control methodologies proposed for cancer chemotherapy scheduling treatment are model-based. In this paper, a reinforcement learning (RL)-based, model-free method is proposed for the closed-loop control of cancer chemotherapy drug dosing. Specifically, the Q-learning algorithm is used to develop an optimal controller for cancer chemotherapy drug dosing. Numerical examples are presented using simulated patients to illustrate the performance of the proposed RL-based controller. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. The biologically equivalent dose BED - Is the approach for calculation of this factor really a reliable basis?; Die biologisch aequivalente Dosis BED - wie solide ist die Berechnung dieses Faktors? Eine Betrachtung der Fehlerbalken der biologisch aequivalenten Dosis

    Energy Technology Data Exchange (ETDEWEB)

    Jensen, J.M. [Kiel Univ. (DE). Klinik fuer Strahlentherapie (Radioonkologie); Zimmermann, J. [Marburg Univ. (DE). Klinik fuer Strahlentherapie (Radioonkologie)

    2000-07-01

    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 {alpha}, {beta}, {gamma}, T{sub p}, T{sub k}, and {rho}, as well as external parameters, so as D, d, n, V, and V{sub 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 {delta}={+-}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 {delta} 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.) [German] Um bei der Strahlentherapie von Tumoren die Wirkung, vor allem hinsichtlich irreversibler Effekte, zu prognostizieren, aber auch retrospektive Beurteilungen durchzufuehren, wird z.Z. auf das sog. LQ-Modell vertraut. Interne organspezifische Parameter, {alpha}, {beta}, {gamma}, T{sub p}, T{sub k} und {rho}, und externe Parameter, wie D, d, n, V und V{sub ref}, (Erlaeuterungen im Text) werden zur Bestimmung einer biologisch aequivalenten Dosis BED herangezogen. Waehrend die externen Parameter mit geringem Fehler bestimmbar sind, unterliegen die internen Parameter biologischen Varianzen und Streuungen, in manchen Faellen ist der

  19. MO-FG-303-03: Demonstration of Universal Knowledge-Based 3D Dose Prediction

    Energy Technology Data Exchange (ETDEWEB)

    Shiraishi, S; Moore, K L [University of California, San Diego, La Jolla, CA (United States)

    2015-06-15

    Purpose: To demonstrate a knowledge-based 3D dose prediction methodology that can accurately predict achievable radiotherapy distributions. Methods: Using previously treated plans as input, an artificial neural network (ANN) was trained to predict 3D dose distributions based on 14 patient-specific anatomical parameters including the distance (r) to planning target volume (PTV) boundary, organ-at-risk (OAR) boundary distances, and angular position ( θ,φ). 23 prostate and 49 stereotactic radiosurgery (SRS) cases with ≥1 nearby OARs were studied. All were planned with volumetric-modulated arc therapy (VMAT) to prescription doses of 81Gy for prostate and 12–30Gy for SRS. Site-specific ANNs were trained using all prostate 23 plans and using a 24 randomly-selected subset for the SRS model. The remaining 25 SRS plans were used to validate the model. To quantify predictive accuracy, the dose difference between the clinical plan and prediction were calculated on a voxel-by-voxel basis δD(r,θ,φ)=Dclin(r,θ,φ)-Dpred(r, θ,φ). Grouping voxels by boundary distance, the mean <δ Dr>=(1/N)Σ -θ,φ D(r,θ,φ) and inter-quartile range (IQR) quantified the accuracy of this method for deriving DVH estimations. The standard deviation (σ) of δ D quantified the 3D dose prediction error on a voxel-by-voxel basis. Results: The ANNs were highly accurate in predictive ability for both prostate and SRS plans. For prostate, <δDr> ranged from −0.8% to +0.6% (max IQR=3.8%) over r=0–32mm, while 3D dose prediction accuracy averaged from σ=5–8% across the same range. For SRS, from r=0–34mm the training set <δDr> ranged from −3.7% to +1.5% (max IQR=4.4%) while the validation set <δDr> ranged from −2.2% to +5.8% (max IQR=5.3%). 3D dose prediction accuracy averaged σ=2.5% for the training set and σ=4.0% over the same interval. Conclusion: The study demonstrates this technique’s ability to predict achievable 3D dose distributions for VMAT SRS and prostate. Future

  20. Interspecies extrapolation based on the RepDose database--a probabilistic approach.

    Science.gov (United States)

    Escher, Sylvia E; Batke, Monika; Hoffmann-Doerr, Simone; Messinger, Horst; Mangelsdorf, Inge

    2013-04-12

    Repeated dose toxicity studies from the RepDose database (DB) were used to determine interspecies differences for rats and mice. NOEL (no observed effect level) ratios based on systemic effects were investigated for three different types of exposure: inhalation, oral food/drinking water and oral gavage. Furthermore, NOEL ratios for local effects in inhalation studies were evaluated. On the basis of the NOEL ratio distributions, interspecies assessment factors (AF) are evaluated. All data sets were best described by a lognormal distribution. No difference was seen between inhalation and oral exposure for systemic effects. Rats and mice were on average equally sensitive at equipotent doses with geometric mean (GM) values of 1 and geometric standard deviation (GSD) values ranging from 2.30 to 3.08. The local AF based on inhalation exposure resulted in a similar distribution with GM values of 1 and GSD values between 2.53 and 2.70. Our analysis confirms former analyses on interspecies differences, including also dog and human data. Furthermore it supports the principle of allometric scaling according to caloric demand in the case that body doses are applied. In conclusion, an interspecies distribution animal/human with a GM equal to allometric scaling and a GSD of 2.5 was derived.

  1. A new label dosimetry system based on pentacosa-diynoic acid monomer for low dose applications

    Energy Technology Data Exchange (ETDEWEB)

    Abdel-Fattah, A.A.; Abdel-Rehim, F. [National Center for Radiation Research and Technology, Atomic Energy Authority, P.O. Box 8029, Nasr City, Cairo (Egypt); Soliman, Y.S., E-mail: yasser_shabaan@hotmail.com [National Center for Radiation Research and Technology, Atomic Energy Authority, P.O. Box 8029, Nasr City, Cairo (Egypt)

    2012-01-15

    The dosimetric characteristics of {gamma}-radiation sensitive labels based on polyvinyl butyral (PVB) and a conjugated diacetylene monomer, 10,12-pentacosa-diynoic acid (PCDA) have been investigated using reflectance colorimeter. Two types of labels (colourless and yellow) based on PCDA monomer were prepared using an Automatic Film Applicator System. Upon {gamma}-ray exposure, the colourless label turns progressively blue, while the yellow colour label turns to green then to dark blue. The colour intensity of the labels is proportional to the radiation absorbed dose. The useful dose range was 15 Gy-2 kGy depending on PCDA monomer concentration. The expanded uncertainty of dose measurement of the colourless label was 6.06 (2{sigma}). - Highlights: > Using 10,12-pentacosa-diynoic acid (PCDA) in preparation of label dosimeter. > PCDA polymerises upon {gamma}-rays exposure producing a blue coloured polymer. > Useful dose range is 15 Gy to 2 kGy depending on concentration of PCDA. > Overall uncertainty of label dosimeter was 6.06 at 2{sigma}.

  2. Raw data-based iterative reconstruction in body CTA: evaluation of radiation dose saving potential

    Energy Technology Data Exchange (ETDEWEB)

    Winklehner, Anna; Karlo, Christoph; Puippe, Gilbert; Goetti, Robert; Pfammatter, Thomas; Frauenfelder, Thomas; Alkadhi, Hatem [University Hospital Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Schmidt, Bernhard; Flohr, Thomas [Siemens Healthcare, Forchheim (Germany)

    2011-12-15

    To evaluate prospectively, in patients undergoing body CTA, the radiation dose saving potential of raw data-based iterative reconstruction as compared to filtered back projection (FBP). Twenty-five patients underwent thoraco-abdominal CTA with 128-slice dual-source CT, operating both tubes at 120 kV. Full-dose (FD) images were reconstructed with FBP and were compared to half-dose (HD) images with FBP and HD-images with sinogram-affirmed iterative reconstruction (SAFIRE), both reconstructed using data from only one tube-detector-system. Image quality and sharpness of the aortic contour were assessed. Vessel attenuation and noise were measured, contrast-to-noise-ratio was calculated. Noise as image quality deteriorating artefact occurred in 24/25 (96%) HD-FBP but not in FD-FBP and HD-raw data-based iterative reconstruction datasets (p < 0.001). Other artefacts occurred with similar prevalence among the datasets. Sharpness of the aortic contour was higher for FD-FBP and HD-raw data-based iterative reconstruction as compared to HD-FBP (p < 0.001). Aortoiliac attenuation was similar among all datasets (p > 0.05). Lowest noise was found for HD-raw data-based iterative reconstruction (7.23HU), being 9.4% lower than that in FD-FBP (7.98HU, p < 0.05) and 30.8% lower than in HD-FBP images (10.44HU, p < 0.001). Contrast-to-noise-ratio was lower in HD-FBP (p < 0.001) and higher in HD-raw data-based iterative reconstruction (p < 0.001) as compared to FD-FBP. Intra-individual comparisons of image quality of body CTA suggest that raw data-based iterative reconstruction allows for dose reduction >50% while maintaining image quality. (orig.)

  3. A Varian DynaLog file-based procedure for patient dose-volume histogram-based IMRT QA.

    Science.gov (United States)

    Calvo-Ortega, Juan F; Teke, Tony; Moragues, Sandra; Pozo, Miquel; Casals-Farran, Joan

    2014-03-06

    In the present study, we describe a method based on the analysis of the dynamic MLC log files (DynaLog) generated by the controller of a Varian linear accelerator in order to perform patient-specific IMRT QA. The DynaLog files of a Varian Millennium MLC, recorded during an IMRT treatment, can be processed using a MATLAB-based code in order to generate the actual fluence for each beam and so recalculate the actual patient dose distribution using the Eclipse treatment planning system. The accuracy of the DynaLog-based dose reconstruction procedure was assessed by introducing ten intended errors to perturb the fluence of the beams of a reference plan such that ten subsequent erroneous plans were generated. In-phantom measurements with an ionization chamber (ion chamber) and planar dose measurements using an EPID system were performed to investigate the correlation between the measured dose changes and the expected ones detected by the reconstructed plans for the ten intended erroneous cases. Moreover, the method was applied to 20 cases of clinical plans for different locations (prostate, lung, breast, and head and neck). A dose-volume histogram (DVH) metric was used to evaluate the impact of the delivery errors in terms of dose to the patient. The ionometric measurements revealed a significant positive correlation (R² = 0.9993) between the variations of the dose induced in the erroneous plans with respect to the reference plan and the corresponding changes indicated by the DynaLog-based reconstructed plans. The EPID measurements showed that the accuracy of the DynaLog-based method to reconstruct the beam fluence was comparable with the dosimetric resolution of the portal dosimetry used in this work (3%/3 mm). The DynaLog-based reconstruction method described in this study is a suitable tool to perform a patient-specific IMRT QA. This method allows us to perform patient-specific IMRT QA by evaluating the result based on the DVH metric of the planning CT image (patient

  4. 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.

  5. A generic TG-186 shielded applicator for commissioning model-based dose calculation algorithms for high-dose-rate (192) Ir brachytherapy.

    Science.gov (United States)

    Ma, Yunzhi; Vijande, Javier; Ballester, Facundo; Carlsson Tedgren, Åsa; Granero, Domingo; Haworth, Annette; Mourtada, Firas; Fonseca, Gabriel Paiva; Zourari, Kyveli; Papagiannis, Panagiotis; Rivard, Mark J; Siebert, Frank André; Sloboda, Ron S; Smith, Ryan; Chamberland, Marc J P; Thomson, Rowan M; Verhaegen, Frank; Beaulieu, Luc

    2017-07-19

    A joint working group was created by the American Association of Physicists in Medicine (AAPM), the European Society for Radiotherapy and Oncology (ESTRO), and the Australasian Brachytherapy Group (ABG) with the charge, among others, to develop a set of well-defined test case plans and perform model-based dose calculation algorithms (MBDCA) dose calculations and comparisons. Its main goal is to facilitate a smooth transition from the AAPM Task Group No. 43 (TG-43) dose calculation formalism, widely being used in clinical practice for brachytherapy, to the one proposed by Task Group No. 186 (TG-186) for MBDCAs. To do so, in this work a hypothetical, generic high-dose rate (HDR) (192) Ir shielded applicator has been designed and benchmarked. A generic HDR (192) Ir shielded applicator was designed based on three commercially available gynecological applicators as well as a virtual cubic water phantom that can be imported into any DICOM-RT compatible treatment planning system (TPS). The absorbed dose distribution around the applicator with the TG-186 (192) Ir source located at one dwell position at its center was computed using two commercial TPSs incorporating MBDCAs (Oncentra(®) Brachy with Advanced Collapsed-cone Engine, ACE(™) , and BrachyVision ACUROS(™) ) and state-of-the-art Monte Carlo (MC) codes, including ALGEBRA, BrachyDose, egs_brachy, Geant4, MCNP6, and Penelope2008. TPS-based volumetric dose distributions for the previously reported "source centered in water" and "source displaced" test cases, and the new "source centered in applicator" test case, were analyzed here using the MCNP6 dose distribution as a reference. Volumetric dose comparisons of TPS results against results for the other MC codes were also performed. Distributions of local and global dose difference ratios are reported. The local dose differences among MC codes are comparable to the statistical uncertainties of the reference datasets for the "source centered in water" and "source

  6. GPU-based fast Monte Carlo dose calculation for proton therapy.

    Science.gov (United States)

    Jia, Xun; Schümann, Jan; Paganetti, Harald; Jiang, Steve B

    2012-12-07

    Accurate radiation dose calculation is essential for successful proton radiotherapy. Monte Carlo (MC) simulation is considered to be the most accurate method. However, the long computation time limits it from routine clinical applications. Recently, graphics processing units (GPUs) have been widely used to accelerate computationally intensive tasks in radiotherapy. We have developed a fast MC dose calculation package, gPMC, for proton dose calculation on a GPU. In gPMC, proton transport is modeled by the class II condensed history simulation scheme with a continuous slowing down approximation. Ionization, elastic and inelastic proton nucleus interactions are considered. Energy straggling and multiple scattering are modeled. Secondary electrons are not transported and their energies are locally deposited. After an inelastic nuclear interaction event, a variety of products are generated using an empirical model. Among them, charged nuclear fragments are terminated with energy locally deposited. Secondary protons are stored in a stack and transported after finishing transport of the primary protons, while secondary neutral particles are neglected. gPMC is implemented on the GPU under the CUDA platform. We have validated gPMC using the TOPAS/Geant4 MC code as the gold standard. For various cases including homogeneous and inhomogeneous phantoms as well as a patient case, good agreements between gPMC and TOPAS/Geant4 are observed. The gamma passing rate for the 2%/2 mm criterion is over 98.7% in the region with dose greater than 10% maximum dose in all cases, excluding low-density air regions. With gPMC it takes only 6-22 s to simulate 10 million source protons to achieve ∼1% relative statistical uncertainty, depending on the phantoms and energy. This is an extremely high efficiency compared to the computational time of tens of CPU hours for TOPAS/Geant4. Our fast GPU-based code can thus facilitate the routine use of MC dose calculation in proton therapy.

  7. Development of Software for dose Records Data Base Access; Programacion para la consulta del Banco de Datos Dosimetricos

    Energy Technology Data Exchange (ETDEWEB)

    Amaro, M.

    1990-07-01

    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.

  8. Knowledge-based prediction of three-dimensional dose distributions for external beam radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Shiraishi, Satomi; Moore, Kevin L., E-mail: kevinmoore@ucsd.edu [Department of Radiation Medicine and Applied Sciences, University of California, San Diego, La Jolla, California 92093 (United States)

    2016-01-15

    Purpose: To demonstrate knowledge-based 3D dose prediction for external beam radiotherapy. Methods: Using previously treated plans as training data, an artificial neural network (ANN) was trained to predict a dose matrix based on patient-specific geometric and planning parameters, such as the closest distance (r) to planning target volume (PTV) and organ-at-risks (OARs). Twenty-three prostate and 43 stereotactic radiosurgery/radiotherapy (SRS/SRT) cases with at least one nearby OAR were studied. All were planned with volumetric-modulated arc therapy to prescription doses of 81 Gy for prostate and 12–30 Gy for SRS. Using these clinically approved plans, ANNs were trained to predict dose matrix and the predictive accuracy was evaluated using the dose difference between the clinical plan and prediction, δD = D{sub clin} − D{sub pred}. The mean (〈δD{sub r}〉), standard deviation (σ{sub δD{sub r}}), and their interquartile range (IQR) for the training plans were evaluated at a 2–3 mm interval from the PTV boundary (r{sub PTV}) to assess prediction bias and precision. Initially, unfiltered models which were trained using all plans in the cohorts were created for each treatment site. The models predict approximately the average quality of OAR sparing. Emphasizing a subset of plans that exhibited superior to the average OAR sparing during training, refined models were created to predict high-quality rectum sparing for prostate and brainstem sparing for SRS. Using the refined model, potentially suboptimal plans were identified where the model predicted further sparing of the OARs was achievable. Replans were performed to test if the OAR sparing could be improved as predicted by the model. Results: The refined models demonstrated highly accurate dose distribution prediction. For prostate cases, the average prediction bias for all voxels irrespective of organ delineation ranged from −1% to 0% with maximum IQR of 3% over r{sub PTV} ∈ [ − 6, 30] mm. The

  9. Indoor biology pollution control based on system-based humidity priority control strategy

    Institute of Scientific and Technical Information of China (English)

    刘亚昱; 谢慧; 石博强

    2009-01-01

    Indoor biological contamination and HVAC system secondary contamination problems caused wide public concerns. Biological contamination control will be the next step to achieve better IAQ. The most efficient and safe way to control biological contamination was to limit relative humidity in HVAC system and conditioned environment in the range that is more unsuitable for microorganism to survive. In this paper,by referring to bio-clean project experiences,a system-based humidity priority control manner came into being by lowering outdoor air humidity ratio to eliminate all indoor latent load and using self recirculation units to bear indoor sensible load. Based on the whole-course residue humidity contaminant control concept,dynamic step models for coil and conditioned zone were developed to describe mass and energy conservation and transformation processes. Then,HVAC system and conditioned zone dynamic models were established on LabVIEW+Matlab platform to investigate optimized regulation types,input signatures and control logics. Decoupling between cooling and dehumidification processes can be achieved and a more simplified and stable control system can be acquired by the system-based humidity priority control strategy. Therefore,it was a promising way for controlling biological pollution in buildings in order to achieve better IAQ.

  10. 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…

  11. Single-Dose Lignocaine-Based Blood Cardioplegia in Single Valve Replacement Patients

    Directory of Open Access Journals (Sweden)

    Jaydip Ramani

    Full Text Available Abstract OBJECTIVE: Myocardial protection is the most important in cardiac surgery. We compared our modified single-dose long-acting lignocaine-based blood cardioplegia with short-acting St Thomas 1 blood cardioplegia in patients undergoing single valve replacement. METHODS: A total of 110 patients who underwent single (aortic or mitral valve replacement surgery were enrolled. Patients were divided in two groups based on the cardioplegia solution used. In group 1 (56 patients, long-acting lignocaine based-blood cardioplegia solution was administered as a single dose while in group 2 (54 patients, standard St Thomas IB (short-acting blood-based cardioplegia solution was administered and repeated every 20 minutes. All the patients were compared for preoperative baseline parameters, intraoperative and all the postoperative parameters. RESULTS: We did not find any statistically significant difference in preoperative baseline parameters. Cardiopulmonary bypass time were 73.8±16.5 and 76.4±16.9 minutes (P=0.43 and cross clamp time were 58.9±10.3 and 66.3±11.2 minutes (P=0.23 in group 1 and group 2, respectively. Mean of maximum inotrope score was 6.3±2.52 and 6.1±2.13 (P=0.65 in group 1 and group 2, respectively. We also did not find any statistically significant difference in creatine-phosphokinase-MB (CPK-MB, Troponin-I levels, lactate level and cardiac functions postoperatively. CONCLUSION: This study proves the safety and efficacy of long-acting lignocaine-based single-dose blood cardioplegia compared to the standard short-acting multi-dose blood cardioplegia in patients requiring the single valve replacement. Further studies need to be undertaken to establish this non-inferiority in situations of complex cardiac procedures especially in compromised patients.

  12. Single-Dose Lignocaine-Based Blood Cardioplegia in Single Valve Replacement Patients.

    Science.gov (United States)

    Ramani, Jaydip; Malhotra, Amber; Wadhwa, Vivek; Sharma, Pranav; Garg, Pankaj; Tarsaria, Malkesh; Pandya, Himani

    2017-01-01

    Myocardial protection is the most important in cardiac surgery. We compared our modified single-dose long-acting lignocaine-based blood cardioplegia with short-acting St Thomas 1 blood cardioplegia in patients undergoing single valve replacement. A total of 110 patients who underwent single (aortic or mitral) valve replacement surgery were enrolled. Patients were divided in two groups based on the cardioplegia solution used. In group 1 (56 patients), long-acting lignocaine based-blood cardioplegia solution was administered as a single dose while in group 2 (54 patients), standard St Thomas IB (short-acting blood-based cardioplegia solution) was administered and repeated every 20 minutes. All the patients were compared for preoperative baseline parameters, intraoperative and all the postoperative parameters. We did not find any statistically significant difference in preoperative baseline parameters. Cardiopulmonary bypass time were 73.8±16.5 and 76.4±16.9 minutes (P=0.43) and cross clamp time were 58.9±10.3 and 66.3±11.2 minutes (P=0.23) in group 1 and group 2, respectively. Mean of maximum inotrope score was 6.3±2.52 and 6.1±2.13 (P=0.65) in group 1 and group 2, respectively. We also did not find any statistically significant difference in creatine-phosphokinase-MB (CPK-MB), Troponin-I levels, lactate level and cardiac functions postoperatively. This study proves the safety and efficacy of long-acting lignocaine-based single-dose blood cardioplegia compared to the standard short-acting multi-dose blood cardioplegia in patients requiring the single valve replacement. Further studies need to be undertaken to establish this non-inferiority in situations of complex cardiac procedures especially in compromised patients.

  13. Investigating the Use of Inquiry & Web-Based Activities with Inclusive Biology Learners

    Science.gov (United States)

    Bodzin, Alec M.; Waller, Patricia L.; Edwards, Lana; Darlene Kale, Santoro

    2007-01-01

    A Web-integrated biology program is used to explore how to best assist inclusive high school students to learn biology with inquiry-based activities. Classroom adaptations and instructional strategies teachers may use to assist in promoting biology learning with inclusive learners are discussed.

  14. 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…

  15. 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…

  16. 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…

  17. Radiation dose evaluation based on exposure scenario during the operation of radioactive waste disposal facility

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Jeong Hyoun; Kim Chang Lak; Choi, Heui Joo; Park, Joo Wan [Korea Electric Power Corporation, Nuclear Environment Technology Institute, Taejon (Korea, Republic of)

    1999-07-01

    Radiation dose to worker in disposal facility was calculated by using point kernel MICROSHIELD V5.02 computer code based on exposure scenarios. An conceptual design model for disposal vaults in disposal facility was used for object of shielding calculation model. Selected radionuclides and their activities among radioactive wastes from nuclear power plants were assumed as radiation sources for the exposure calculation. Annual radiation doses to crane workers and to people working on disposal vaults were calculated according to exposure time and distance from the sources with conservative operation scenarios. The scenarios used for this study were based on assumption for representing disposal activities in a future Korean near surface disposal facility. Calculated exposure rates to worker during normal disposal work were very low comparing with annual allowable limit for radiation worker.

  18. Gadolinium-based contrast media may be nephrotoxic even at approved doses

    Energy Technology Data Exchange (ETDEWEB)

    Thomsen, Henrik S. [Department of Diagnostic Radiology, Copenhagen University Hospital at Herlev, Herlev Ringvej 75, 2730, Herlev (Denmark)

    2004-09-01

    It is generally believed that gadolinium-based contrast media are not nephrotoxic at the approved doses for MR (<0.3 mmol/kg body weight). Recently, a patient with diabetic nephropathy required dialysis because of anuria 6-7 days after MR angiography with 0.14 mmol/kg body weight gadolinium-DTPA-BMA to assess renal artery stenosis. No special precautions (e.g., hydration) had been taken. The serum creatinine levels had been within 200 and 300 {mu}mol/l for the last 3 years with a very slow increase. This case highlights that gadolinium-based contrast media can cause contrast medium-induced nephropathy even at doses below 0.2 mmol/kg body weight in patients with multiple risk factors. (orig.)

  19. GPU-based Monte Carlo radiotherapy dose calculation using phase-space sources

    Science.gov (United States)

    Townson, Reid W.; Jia, Xun; Tian, Zhen; Jiang Graves, Yan; Zavgorodni, Sergei; Jiang, Steve B.

    2013-06-01

    A novel phase-space source implementation has been designed for graphics processing unit (GPU)-based Monte Carlo dose calculation engines. Short of full simulation of the linac head, using a phase-space source is the most accurate method to model a clinical radiation beam in dose calculations. However, in GPU-based Monte Carlo dose calculations where the computation efficiency is very high, the time required to read and process a large phase-space file becomes comparable to the particle transport time. Moreover, due to the parallelized nature of GPU hardware, it is essential to simultaneously transport particles of the same type and similar energies but separated spatially to yield a high efficiency. We present three methods for phase-space implementation that have been integrated into the most recent version of the GPU-based Monte Carlo radiotherapy dose calculation package gDPM v3.0. The first method is to sequentially read particles from a patient-dependent phase-space and sort them on-the-fly based on particle type and energy. The second method supplements this with a simple secondary collimator model and fluence map implementation so that patient-independent phase-space sources can be used. Finally, as the third method (called the phase-space-let, or PSL, method) we introduce a novel source implementation utilizing pre-processed patient-independent phase-spaces that are sorted by particle type, energy and position. Position bins located outside a rectangular region of interest enclosing the treatment field are ignored, substantially decreasing simulation time with little effect on the final dose distribution. The three methods were validated in absolute dose against BEAMnrc/DOSXYZnrc and compared using gamma-index tests (2%/2 mm above the 10% isodose). It was found that the PSL method has the optimal balance between accuracy and efficiency and thus is used as the default method in gDPM v3.0. Using the PSL method, open fields of 4 × 4, 10 × 10 and 30 × 30 cm

  20. GPU-based Monte Carlo radiotherapy dose calculation using phase-space sources.

    Science.gov (United States)

    Townson, Reid W; Jia, Xun; Tian, Zhen; Graves, Yan Jiang; Zavgorodni, Sergei; Jiang, Steve B

    2013-06-21

    A novel phase-space source implementation has been designed for graphics processing unit (GPU)-based Monte Carlo dose calculation engines. Short of full simulation of the linac head, using a phase-space source is the most accurate method to model a clinical radiation beam in dose calculations. However, in GPU-based Monte Carlo dose calculations where the computation efficiency is very high, the time required to read and process a large phase-space file becomes comparable to the particle transport time. Moreover, due to the parallelized nature of GPU hardware, it is essential to simultaneously transport particles of the same type and similar energies but separated spatially to yield a high efficiency. We present three methods for phase-space implementation that have been integrated into the most recent version of the GPU-based Monte Carlo radiotherapy dose calculation package gDPM v3.0. The first method is to sequentially read particles from a patient-dependent phase-space and sort them on-the-fly based on particle type and energy. The second method supplements this with a simple secondary collimator model and fluence map implementation so that patient-independent phase-space sources can be used. Finally, as the third method (called the phase-space-let, or PSL, method) we introduce a novel source implementation utilizing pre-processed patient-independent phase-spaces that are sorted by particle type, energy and position. Position bins located outside a rectangular region of interest enclosing the treatment field are ignored, substantially decreasing simulation time with little effect on the final dose distribution. The three methods were validated in absolute dose against BEAMnrc/DOSXYZnrc and compared using gamma-index tests (2%/2 mm above the 10% isodose). It was found that the PSL method has the optimal balance between accuracy and efficiency and thus is used as the default method in gDPM v3.0. Using the PSL method, open fields of 4 × 4, 10 × 10 and 30 × 30 cm

  1. Radiation Dose Assessments for Fleet-Based Individuals in Operation Tomodachi

    Science.gov (United States)

    2013-09-01

    report. In other cases, some ships were included despite being located outside the 200 nautical-mile (nmi) radius from the FDNPS because the OTR...well outside the 200 nmi radius from FDNPS during the two-month time period. The Seventh Fleet comprises 60–70 ships, 200–300 aircraft, and 40,000 Navy...surfaces. As discussed in the shore-based report, the MEXT systems did not quantify most of the cosmic radiation dose. Although these detection

  2. NMR-based Metabolomics Applications in Biological and Environmental Science

    Science.gov (United States)

    As a complimentary tool to other omics platforms, metabolomics is increasingly being used bybiologists to study the dynamic response of biological systems (cells, tissues, or wholeorganisms) under diverse physiological or pathological conditions. Metabolomics deals with the quali...

  3. Determination of radiation-induced DNA double-strand breaks for the biological dose monitoring in cardiac computerized tomography; Bestimmung von strahleninduzierten DNA-Doppelstrangbruechen zum Monitoring der biologischen Dosis in der Herz-Computertomographie

    Energy Technology Data Exchange (ETDEWEB)

    Wegener, Jasmin

    2013-11-12

    Background and aims: X-rays cause relevant DNA damage to cells. DNA double-strand breaks (DSBs) are considered to be the most biologically significant radiation induced DNA-lesions. Recently a sensitive immunofluorescence microscopic method was developed to quantify x-ray induced DSBs as nuclear foci, even after doses as used in computed tomography. The method is based on the phosphorylation of the histone variant H2AX after formation of DSBs and distinct foci representing DSBs can be visualised. The number of foci correlates well with the delivered radiation dose. The importance of cardiac CT has increased during the last years. The radiation exposure of cardiac CT is rather high compared to other radiologic diagnostic procedures and techniques for dose-reduction receive increasing attention. In this context the purpose of this study was to determine to what extent the γ-H2AX-based method is able to measure x-ray induced DSBs in patients undergoing cardiac CT. Furthermore the objective was to evaluate whether CT-induced DSBs correlate with exposure parameters (dose length product, DLP) and to assess the influence of the scan protocols on the biological radiation damage. Materials and methods: 32 patients undergoing coronary CT angiography either using a 64-slice (n = 5: SOMATOM Sensation 64 {sup registered}) or a dual-source CT scanner (n = 27: SOMATOM Definition {sup registered}) were included in the study. Venous blood samples were taken before and 0.5 h, 2.5 h, and 24 h after the CT scan. Additional venous blood samples obtained before CT were irradiated in-vitro at various radiation doses (10 mGy, 50 mGy, 100 mGy) to obtain reference values of foci. Lymphocytes were separated and incubated with a specific γ-H2AX primary and a fluorescent secondary antibody. The number of γ-H2AX-foci was quantified using a fluorescence microscope. Every distinct focus represents one DNA-DSB. The number of radiation-induced DSBs was calculated by subtracting the foci number

  4. A brief look at model-based dose calculation principles, practicalities, and promise.

    Science.gov (United States)

    Sloboda, Ron S; Morrison, Hali; Cawston-Grant, Brie; Menon, Geetha V

    2017-02-01

    Model-based dose calculation algorithms (MBDCAs) have recently emerged as potential successors to the highly practical, but sometimes inaccurate TG-43 formalism for brachytherapy treatment planning. So named for their capacity to more accurately calculate dose deposition in a patient using information from medical images, these approaches to solve the linear Boltzmann radiation transport equation include point kernel superposition, the discrete ordinates method, and Monte Carlo simulation. In this overview, we describe three MBDCAs that are commercially available at the present time, and identify guidance from professional societies and the broader peer-reviewed literature intended to facilitate their safe and appropriate use. We also highlight several important considerations to keep in mind when introducing an MBDCA into clinical practice, and look briefly at early applications reported in the literature and selected from our own ongoing work. The enhanced dose calculation accuracy offered by a MBDCA comes at the additional cost of modelling the geometry and material composition of the patient in treatment position (as determined from imaging), and the treatment applicator (as characterized by the vendor). The adequacy of these inputs and of the radiation source model, which needs to be assessed for each treatment site, treatment technique, and radiation source type, determines the accuracy of the resultant dose calculations. Although new challenges associated with their familiarization, commissioning, clinical implementation, and quality assurance exist, MBDCAs clearly afford an opportunity to improve brachytherapy practice, particularly for low-energy sources.

  5. A brief look at model-based dose calculation principles, practicalities, and promise

    Directory of Open Access Journals (Sweden)

    Ron S. Sloboda

    2017-02-01

    Full Text Available Model-based dose calculation algorithms (MBDCAs have recently emerged as potential successors to the highly practical, but sometimes inaccurate TG-43 formalism for brachytherapy treatment planning. So named for their capacity to more accurately calculate dose deposition in a patient using information from medical images, these approaches to solve the linear Boltzmann radiation transport equation include point kernel superposition, the discrete ordinates method, and Monte Carlo simulation. In this overview, we describe three MBDCAs that are commercially available at the present time, and identify guidance from professional societies and the broader peer-reviewed literature intended to facilitate their safe and appropriate use. We also highlight several important considerations to keep in mind when introducing an MBDCA into clinical practice, and look briefly at early applications reported in the literature and selected from our own ongoing work. The enhanced dose calculation accuracy offered by a MBDCA comes at the additional cost of modelling the geometry and material composition of the patient in treatment position (as determined from imaging, and the treatment applicator (as characterized by the vendor. The adequacy of these inputs and of the radiation source model, which needs to be assessed for each treatment site, treatment technique, and radiation source type, determines the accuracy of the resultant dose calculations. Although new challenges associated with their familiarization, commissioning, clinical implementation, and quality assurance exist, MBDCAs clearly afford an opportunity to improve brachytherapy practice, particularly for low-energy sources.

  6. Shielding design and dose assessment for accelerator based neutron capture therapy.

    Science.gov (United States)

    Howard, W B; Yanch, J C

    1995-05-01

    Preparations are ongoing to test the viability and usefulness of an accelerator source of epithermal neutrons for ultimate use in a clinical environment. This feasibility study is to be conducted in a shielded room located on the Massachusetts Institute of Technology campus and will not involve patient irradiations. The accelerator production of neutrons is based on the 7Li(p, n)7Be reaction, and a maximum proton beam current of 4 mA at an energy of 2.5 MeV is anticipated. The resultant 3.58 x 10(12) neutrons s-1 have a maximum energy of 800 keV and will be substantially moderated. This paper describes the Monte Carlo methods used to estimate the neutron and photon dose rates in a variety of locations in the vicinity of the accelerator, as well as the shielding configuration required when the device is run at maximum current. Results indicate that the highest absorbed dose rate to which any individual will be exposed is 3 microSv h-1 (0.3 mrem h-1). The highest possible yearly dose is 0.2 microSv (2 x 10(-2) mrem) to the general public or 0.9 mSv (90 mrem) to a radiation worker in close proximity to the accelerator facility. The shielding necessary to achieve these dose levels is also discussed.

  7. Simple weight-based contrast dosing for standardization of portal phase CT liver enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Benbow, M. [Department of Radiology, Royal Bournemouth Hospital, Bournemouth, Dorset (United Kingdom); Bull, R.K., E-mail: russell.bull@rbch.nhs.uk [Department of Radiology, Royal Bournemouth Hospital, Bournemouth, Dorset (United Kingdom)

    2011-10-15

    Aim: To investigate the use of a weight-based volume of contrast media to optimize portal enhancement in patients undergoing abdominal computed tomography (CT). Materials and methods: Thirty-one patients were assessed to establish whether a relationship existed between their weight and the portal liver enhancement achieved. Three methods of estimating weight were evaluated to establish which was the most appropriate to use in clinical practice. One hundred patients were then examined using 100 ml contrast media and 100 further patients using a weight-based contrast volume as dictated by a look-up table. The enhancement achieved by each technique was assessed. Results: A good correlation was shown between patient weight and contrast enhancement when a fixed volume of contrast media was used (r = -0.825, p < 0.0001). Asking the patient was shown to be the most appropriate method for estimating their weight. The mean portal liver enhancement using the fixed dose and weight-adjusted dose were 110 HU (SD = 25.1) and 108 HU (SD = 11.9), respectively. Weight-adjusted dose brought 37% more patients into the 'ideal' enhancement range of 100-125 HU. Conclusion: The use of a simple, practical, weight-based look-up table to decide contrast media volumes during portal phase liver CT can greatly reduce inter-patient variability compared to a fixed-volume technique.

  8. Statistical image reconstruction for low-dose CT using nonlocal means-based regularization.

    Science.gov (United States)

    Zhang, Hao; Ma, Jianhua; Wang, Jing; Liu, Yan; Lu, Hongbing; Liang, Zhengrong

    2014-09-01

    Low-dose computed tomography (CT) imaging without sacrifice of clinical tasks is desirable due to the growing concerns about excessive radiation exposure to the patients. One common strategy to achieve low-dose CT imaging is to lower the milliampere-second (mAs) setting in data scanning protocol. However, the reconstructed CT images by the conventional filtered back-projection (FBP) method from the low-mAs acquisitions may be severely degraded due to the excessive noise. Statistical image reconstruction (SIR) methods have shown potentials to significantly improve the reconstructed image quality from the low-mAs acquisitions, wherein the regularization plays a critical role and an established family of regularizations is based on the Markov random field (MRF) model. Inspired by the success of nonlocal means (NLM) in image processing applications, in this work, we propose to explore the NLM-based regularization for SIR to reconstruct low-dose CT images from low-mAs acquisitions. Experimental results with both digital and physical phantoms consistently demonstrated that SIR with the NLM-based regularization can achieve more gains than SIR with the well-known Gaussian MRF regularization or the generalized Gaussian MRF regularization and the conventional FBP method, in terms of image noise reduction and resolution preservation.

  9. Comparison of Body Surface Area versus Weight-Based Growth Hormone Dosing for Girls with Turner Syndrome

    NARCIS (Netherlands)

    Schrier, L.; Kam, M.L. de; McKinnon, R.; Bakri, A. Che; Oostdijk, W.; Sas, T.C.J.; Menke, L.A.; Otten, B.J.; Keizer-Schrama, S.M.; Kristrom, B.; Ankarberg-Lindgren, C.; Burggraaf, J.; Albertsson-Wikland, K.; Wit, J.M.

    2014-01-01

    Background/Aims: Growth Hormone (GH) dosage in childhood is adjusted for body size, but there is no consensus whether body weight (BW) or body surface area (BSA) should be used. We aimed at comparing the biological effect and cost-effectiveness of GH treatment dosed per m(2) BSA in comparison with d

  10. Comparison of 3-dimensional dose reconstruction system between fluence-based system and dose measurement-guided system.

    Science.gov (United States)

    Nakaguchi, Yuji; Ono, Takeshi; Onitsuka, Ryota; Maruyama, Masato; Shimohigashi, Yoshinobu; Kai, Yudai

    2016-01-01

    COMPASS system (IBA Dosimetry, Schwarzenbruck, Germany) and ArcCHECK with 3DVH software (Sun Nuclear Corp., Melbourne, FL) are commercial quasi-3-dimensional (3D) dosimetry arrays. Cross-validation to compare them under the same conditions, such as a treatment plan, allows for clear evaluation of such measurement devices. In this study, we evaluated the accuracy of reconstructed dose distributions from the COMPASS system and ArcCHECK with 3DVH software using Monte Carlo simulation (MC) for multi-leaf collimator (MLC) test patterns and clinical VMAT plans. In a phantom study, ArcCHECK 3DVH showed clear differences from COMPASS, measurement and MC due to the detector resolution and the dose reconstruction method. Especially, ArcCHECK 3DVH showed 7% difference from MC for the heterogeneous phantom. ArcCHECK 3DVH only corrects the 3D dose distribution of treatment planning system (TPS) using ArcCHECK measurement, and therefore the accuracy of ArcCHECK 3DVH depends on TPS. In contrast, COMPASS showed good agreement with MC for all cases. However, the COMPASS system requires many complicated installation procedures such as beam modeling, and appropriate commissioning is needed. In terms of clinical cases, there were no large differences for each QA device. The accuracy of the compass and ArcCHECK 3DVH systems for phantoms and clinical cases was compared. Both systems have advantages and disadvantages for clinical use, and consideration of the operating environment is important. The QA system selection is depending on the purpose and workflow in each hospital. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  11. A novel model-based approach for dose determination of glycopyrronium bromide in COPD

    Directory of Open Access Journals (Sweden)

    Arievich Helen

    2012-12-01

    Full Text Available Abstract Background Glycopyrronium bromide (NVA237 is an inhaled long-acting muscarinic antagonist in development for treatment of COPD. This study compared the efficacy and safety of once-daily (OD and twice-daily (BID glycopyrronium bromide regimens, using a novel model-based approach, in patients with moderate-to-severe COPD. Methods Double-blind, randomized, dose-finding trial with an eight-treatment, two-period, balanced incomplete block design. Patients (smoking history ≥10 pack-years, post-bronchodilator FEV1 ≥30% and 1/FVC 1 at Day 28. Results 385 patients (mean age 61.2 years; mean post-bronchodilator FEV1 53% predicted were randomized; 88.6% completed. All OD and BID dosing regimens produced dose-dependent bronchodilation; at Day 28, increases in mean trough FEV1 versus placebo were statistically significant for all regimens, ranging from 51 mL (glycopyrronium bromide 12.5 μg OD to 160 mL (glycopyrronium bromide 50 μg BID. Pharmacodynamic steady-state was reached by Day 7. There was a small separation (≤37 mL between BID and OD dose–response curves for mean trough FEV1 at steady-state in favour of BID dosing. Over 24 hours, separation between OD and BID regimens was even smaller (FEV1 AUC0-24h maximum difference for equivalent daily dose regimens: 8 mL. Dose–response results for FEV1 at 12 hours, FEV1 AUC0-12h and FEV1 AUC0-4h at steady-state showed OD regimens provided greater improvement over placebo than BID regimens for total daily doses of 25 μg, 50 μg and 100 μg, while the reverse was true for OD versus BID regimens from 12–24 hours. The 12.5 μg BID dose produced a marginally higher improvement in trough FEV1 versus placebo than 50 μg OD, however, the response at 12 hours over placebo was suboptimal (74 mL. Glycopyrronium bromide was safe and well tolerated at all doses. Conclusions Glycopyrronium bromide 50 μg OD provides significant bronchodilation over a 24 hour period

  12. Ruthenium-106 brachytherapy for thick uveal melanoma: reappraisal of apex and base dose radiation and dose rate

    Directory of Open Access Journals (Sweden)

    Masood Naseripour

    2016-02-01

    Full Text Available Purpose: To evaluate the outcomes of ruthenium-106 ( 106 Ru brachytherapy in terms of radiation parameters in patients with thick uveal melanomas. Material and methods: Medical records of 51 patients with thick (thickness ≥ 7 mm and < 11 mm uveal melanoma treated with 106 Ru brachytherapy during a ten-year period were reviewed. Radiation parameters, tumor regression, best corrected visual acuity (BCVA, and treatment-related complications were assessed. Results: Fifty one eyes of 51 consecutive patients including 25 men and 26 women with a mean age of 50.5 ± 15.2 years were enrolled. Patients were followed for 36.1 ± 26.5 months (mean ± SD. Mean radiation dose to tumor apex and to sclera were 71 (± 19.2 Gy and 1269 (± 168.2 Gy. Radiation dose rates to tumor apex and to sclera were 0.37 (± 0.14 Gy/h and 6.44 (± 1.50 Gy/h. Globe preservation was achieved in 82.4%. Preoperative mean tumor thickness of 8.1 (± 0.9 mm decreased to 4.5 (± 1.6 mm, 3.4 (± 1.4 mm, and 3.0 (± 1.46 mm at 12, 24, and 48 months after brachytherapy (p = 0.03. Four eyes that did not show regression after 6 months of brachytherapy were enucleated. Secondary enucleation was performed in 5 eyes because of tumor recurrence or neovascular glaucoma. Tumor recurrence was evident in 6 (11.8% patients. Mean Log MAR (magnification requirement visual acuity declined from 0.75 (± 0.63 to 0.94 (± 0.5 (p = 0.04. Best corrected visual acuity of 20/200 or worse was recorded in 37% of the patients at the time of diagnosis and 61.7% of the patients at last exam (p = 0.04. Non-proliferative and proliferative radiation-induced retinopathy was observed in 20 and 7 eyes. Conclusions : Thick uveal melanomas are amenable to 106 Ru brachytherapy with less than recommended apex radiation dose and dose rates.

  13. Differential tolerance to biological and subjective effects of four closely spaced doses of N,N-dimethyltryptamine in humans.

    Science.gov (United States)

    Strassman, R J; Qualls, C R; Berg, L M

    1996-05-01

    Tolerance of the behavioral effects of the short-acting, endogenous hallucinogen, N,N-dimethyltryptamine (DMT) is seen inconsistently in animals, and has not been produced in humans. The nature and time course of responses to repetitive, closely spaced administrations of an hallucinogenic dose of DMT were characterized. Thirteen experienced hallucinogen users received intravenous 0.3 mg/kg DMT fumarate, or saline placebo, four times, at 30 min intervals, on 2 separate days, in a randomized, double-blind, design. Tolerance to "psychedelic" subjective effects did not occur according to either clinical interview or Hallucinogen Rating Scale scores. Adrenocorticotropic hormone (ACTH), prolactin, cortisol, and heart rate responses decreased with repeated DMT administration, although blood pressure did not. These data demonstrate the unique properties of DMT relative to other hallucinogens and underscore the differential regulation of the multiple processes mediating the effects of DMT.

  14. A framework for organ dose estimation in x-ray angiography and interventional radiology based on dose-related data in DICOM structured reports

    Science.gov (United States)

    Omar, Artur; Bujila, Robert; Fransson, Annette; Andreo, Pedro; Poludniowski, Gavin

    2016-04-01

    Although interventional x-ray angiography (XA) procedures involve relatively high radiation doses that can lead to deterministic tissue reactions in addition to stochastic effects, convenient and accurate estimation of absorbed organ doses has traditionally been out of reach. This has mainly been due to the absence of practical means to access dose-related data that describe the physical context of the numerous exposures during an XA procedure. The present work provides a comprehensive and general framework for the determination of absorbed organ dose, based on non-proprietary access to dose-related data by utilizing widely available DICOM radiation dose structured reports. The framework comprises a straightforward calculation workflow to determine the incident kerma and reconstruction of the geometrical relation between the projected x-ray beam and the patient’s anatomy. The latter is difficult in practice, as the position of the patient on the table top is unknown. A novel patient-specific approach for reconstruction of the patient position on the table is presented. The proposed approach was evaluated for 150 patients by comparing the estimated position of the primary irradiated organs (the target organs) with their position in clinical DICOM images. The approach is shown to locate the target organ position with a mean (max) deviation of 1.3 (4.3), 1.8 (3.6) and 1.4 (2.9) cm for neurovascular, adult and paediatric cardiovascular procedures, respectively. To illustrate the utility of the framework for systematic and automated organ dose estimation in routine clinical practice, a prototype implementation of the framework with Monte Carlo simulations is included.

  15. Dose calculation in biological samples in a mixed neutron-gamma field at the TRIGA reactor of the University of Mainz.

    Science.gov (United States)

    Schmitz, Tobias; Blaickner, Matthias; Schütz, Christian; Wiehl, Norbert; Kratz, Jens V; Bassler, Niels; Holzscheiter, Michael H; Palmans, Hugo; Sharpe, Peter; Otto, Gerd; Hampel, Gabriele

    2010-10-01

    To establish Boron Neutron Capture Therapy (BNCT) for non-resectable liver metastases and for in vitro experiments at the TRIGA Mark II reactor at the University of Mainz, Germany, it is necessary to have a reliable dose monitoring system. The in vitro experiments are used to determine the relative biological effectiveness (RBE) of liver and cancer cells in our mixed neutron and gamma field. We work with alanine detectors in combination with Monte Carlo simulations, where we can measure and characterize the dose. To verify our calculations we perform neutron flux measurements using gold foil activation and pin-diodes. Material and methods. When L-α-alanine is irradiated with ionizing radiation, it forms a stable radical which can be detected by electron spin resonance (ESR) spectroscopy. The value of the ESR signal correlates to the amount of absorbed dose. The dose for each pellet is calculated using FLUKA, a multipurpose Monte Carlo transport code. The pin-diode is augmented by a lithium fluoride foil. This foil converts the neutrons into alpha and tritium particles which are products of the (7)Li(n,α)(3)H-reaction. These particles are detected by the diode and their amount correlates to the neutron fluence directly. Results and discussion. Gold foil activation and the pin-diode are reliable fluence measurement systems for the TRIGA reactor, Mainz. Alanine dosimetry of the photon field and charged particle field from secondary reactions can in principle be carried out in combination with MC-calculations for mixed radiation fields and the Hansen & Olsen alanine detector response model. With the acquired data about the background dose and charged particle spectrum, and with the acquired information of the neutron flux, we are capable of calculating the dose to the tissue. Conclusion. Monte Carlo simulation of the mixed neutron and gamma field of the TRIGA Mainz is possible in order to characterize the neutron behavior in the thermal column. Currently we also

  16. Detection of biological thiols based on a colorimetric method

    Institute of Scientific and Technical Information of China (English)

    Yuan-yuan XU; Yang-yang SUN; Yu-juan ZHANG; Chen-he LU; Jin-feng MIAO‡

    2016-01-01

    Biological thiols (biothiols), an important kind of functional biomolecules, such as cysteine (Cys) and glutathione (GSH), play vital roles in maintaining the stability of the intracellular environment. In past decades, studies have demonstrated that metabolic disorder of biothiols is related to many serious disease processes and wil lead to extreme damage in human and numerous animals. We carried out a series of experiments to detect biothiols in bi-osamples, including bovine plasma and cel lysates of seven different cel lines based on a simple colorimetric method. In a typical test, the color of the test solution could gradualy change from blue to colorless after the addition of biothiols. Based on the color change displayed, experimental results reveal that the percentage of biothiols in the embryonic fibroblast cell line is significantly higher than those in the other six cell lines, which provides the basis for the following biothiols-related study.%中文概要题目:生物巯化物的可视化检测目的:通过简单可靠的可视化检测方法评估牛血清及各细胞系中生物巯化物的含量。创新点:基于银纳米颗粒形成的比色变化过程对牛血清及细胞中生物巯化物进行了检测。方法:将6组不同的细胞系培养后进行裂解,其裂解产物分别与3,3',5,5'-四甲基联苯胺(TMB)和硝酸银(AgNO3)的混合液室温孵育后,用紫外可见分光光度计测量细胞中生物巯化物的含量。结论:通过不同细胞系中生物巯化物含量的比对,证实胚胎成纤维细胞中生物巯化物的含量明显高于其他细胞。

  17. Proton radiography and proton computed tomography based on time-resolved dose measurements

    Science.gov (United States)

    Testa, Mauro; Verburg, Joost M.; Rose, Mark; Min, Chul Hee; Tang, Shikui; Hassane Bentefour, El; Paganetti, Harald; Lu, Hsiao-Ming

    2013-11-01

    We present a proof of principle study of proton radiography and proton computed tomography (pCT) based on time-resolved dose measurements. We used a prototype, two-dimensional, diode-array detector capable of fast dose rate measurements, to acquire proton radiographic images expressed directly in water equivalent path length (WEPL). The technique is based on the time dependence of the dose distribution delivered by a proton beam traversing a range modulator wheel in passive scattering proton therapy systems. The dose rate produced in the medium by such a system is periodic and has a unique pattern in time at each point along the beam path and thus encodes the WEPL. By measuring the time dose pattern at the point of interest, the WEPL to this point can be decoded. If one measures the time-dose patterns at points on a plane behind the patient for a beam with sufficient energy to penetrate the patient, the obtained 2D distribution of the WEPL forms an image. The technique requires only a 2D dosimeter array and it uses only the clinical beam for a fraction of second with negligible dose to patient. We first evaluated the accuracy of the technique in determining the WEPL for static phantoms aiming at beam range verification of the brain fields of medulloblastoma patients. Accurate beam ranges for these fields can significantly reduce the dose to the cranial skin of the patient and thus the risk of permanent alopecia. Second, we investigated the potential features of the technique for real-time imaging of a moving phantom. Real-time tumor tracking by proton radiography could provide more accurate validations of tumor motion models due to the more sensitive dependence of proton beam on tissue density compared to x-rays. Our radiographic technique is rapid (˜100 ms) and simultaneous over the whole field, it can image mobile tumors without the problem of interplay effect inherently challenging for methods based on pencil beams. Third, we present the reconstructed p

  18. Evaluation of fluence-based dose delivery incorporating the spatial variation of dosimetric leaf gap (DLG).

    Science.gov (United States)

    Kumaraswamy, Lalith K; Xu, Zhengzheng; Bailey, Daniel W; Schmitt, Jonathan D; Podgorsak, Matthew B

    2016-01-08

    The Eclipse treatment planning system uses a single dosimetric leaf gap (DLG) value to retract all multileaf collimator leaf positions during dose calculation to model the rounded leaf ends. This study evaluates the dosimetric impact of the 2D variation of DLG on clinical treatment plans based on their degree of fluence modulation. In-house software was developed to retrospectively apply the 2D variation of DLG to 61 clinically treated VMAT plans, as well as to several test plans. The level of modulation of the VMAT cases were determined by calculating their modulation complexity score (MCS). Dose measurements were done using the MapCHECK device at a depth of 5.0 cm for plans with and without the 2D DLG correction. Measurements were compared against predicted dose planes from the TPS using absolute 3%/3 mm and 2%/2 mm gamma criteria for test plans and for VMAT cases, respectively. The gamma pass rate for the 2 mm, 4 mm, and 6 mm sweep test plans increased by 23.2%, 28.7%, and 26.0%, respectively, when the measurements were corrected with 2D variation of DLG. The clinical anal VMAT cases, which had very high MLC modulation, showed the most improvement. The majority of the improvement occurred for doses created by the 1.0 cm width leaves for both the test plans and the VMAT cases. The gamma pass rates for the highly modulated head and neck (H&N) cases, moderately modulated prostate and esophageal cases, and minimally modulated brain cases improved only slightly when corrected with 2D variation of DLG. This is because these cases did not employ the 1.0 cm width leaves for dose calculation and delivery. These data suggest that, at the very least, the TPS plans with highly modulated fluences created by the 1.0 cm fields require 2D DLG correction. Incorporating the 2D variation of DLG for the highly modulated clinical treatment plans improves their planar dose gamma pass rates, especially for fields employing the outer 1.0 cm width MLC leaves. This is because there are

  19. 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

  20. Bladder dose accumulation based on a biomechanical deformable image registration algorithm in volumetric modulated arc therapy for prostate cancer

    DEFF Research Database (Denmark)

    Andersen, E S; Muren, L P; Sørensen, T S

    2012-01-01

    ) to improve the accuracy of bladder dose assessment. For each of nine prostate cancer patients, the initial treatment plan was re-calculated on eight to nine repeat computed tomography (CT) scans. The planned bladder dose–volume histogram (DVH) parameters were compared to corresponding parameters derived from...... DIR-based accumulations and DVH summation were small and well within 1 Gy. For the investigated treatment scenario, DIR- based bladder dose accumulation did not result in substantial improvement of dose estimation as compared to the straightforward DVH summation. Large variations were found...... in individual patients between the doses from the initial treatment plan and the accumulated bladder doses. Hence, the use of repeat imaging has a potential for improved accuracy in treatment dose reporting....

  1. A generic high-dose rate (192)Ir brachytherapy source for evaluation of model-based dose calculations beyond the TG-43 formalism.

    Science.gov (United States)

    Ballester, Facundo; Carlsson Tedgren, Åsa; Granero, Domingo; Haworth, Annette; Mourtada, Firas; Fonseca, Gabriel Paiva; Zourari, Kyveli; Papagiannis, Panagiotis; Rivard, Mark J; Siebert, Frank-André; Sloboda, Ron S; Smith, Ryan L; Thomson, Rowan M; Verhaegen, Frank; Vijande, Javier; Ma, Yunzhi; Beaulieu, Luc

    2015-06-01

    In order to facilitate a smooth transition for brachytherapy dose calculations from the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) formalism to model-based dose calculation algorithms (MBDCAs), treatment planning systems (TPSs) using a MBDCA require a set of well-defined test case plans characterized by Monte Carlo (MC) methods. This also permits direct dose comparison to TG-43 reference data. Such test case plans should be made available for use in the software commissioning process performed by clinical end users. To this end, a hypothetical, generic high-dose rate (HDR) (192)Ir source and a virtual water phantom were designed, which can be imported into a TPS. A hypothetical, generic HDR (192)Ir source was designed based on commercially available sources as well as a virtual, cubic water phantom that can be imported into any TPS in DICOM format. The dose distribution of the generic (192)Ir source when placed at the center of the cubic phantom, and away from the center under altered scatter conditions, was evaluated using two commercial MBDCAs [Oncentra(®) Brachy with advanced collapsed-cone engine (ACE) and BrachyVision ACUROS™ ]. Dose comparisons were performed using state-of-the-art MC codes for radiation transport, including ALGEBRA, BrachyDose, GEANT4, MCNP5, MCNP6, and PENELOPE2008. The methodologies adhered to recommendations in the AAPM TG-229 report on high-energy brachytherapy source dosimetry. TG-43 dosimetry parameters, an along-away dose-rate table, and primary and scatter separated (PSS) data were obtained. The virtual water phantom of (201)(3) voxels (1 mm sides) was used to evaluate the calculated dose distributions. Two test case plans involving a single position of the generic HDR (192)Ir source in this phantom were prepared: (i) source centered in the phantom and (ii) source displaced 7 cm laterally from the center. Datasets were independently produced by different investigators. MC results were then

  2. A generic high-dose rate {sup 192}Ir brachytherapy source for evaluation of model-based dose calculations beyond the TG-43 formalism

    Energy Technology Data Exchange (ETDEWEB)

    Ballester, Facundo, E-mail: Facundo.Ballester@uv.es [Department of Atomic, Molecular and Nuclear Physics, University of Valencia, Burjassot 46100 (Spain); Carlsson Tedgren, Åsa [Department of Medical and Health Sciences (IMH), Radiation Physics, Faculty of Health Sciences, Linköping University, Linköping SE-581 85, Sweden and Department of Medical Physics, Karolinska University Hospital, Stockholm SE-171 76 (Sweden); Granero, Domingo [Department of Radiation Physics, ERESA, Hospital General Universitario, Valencia E-46014 (Spain); Haworth, Annette [Department of Physical Sciences, Peter MacCallum Cancer Centre and Royal Melbourne Institute of Technology, Melbourne, Victoria 3000 (Australia); Mourtada, Firas [Department of Radiation Oncology, Helen F. Graham Cancer Center, Christiana Care Health System, Newark, Delaware 19713 (United States); Fonseca, Gabriel Paiva [Instituto de Pesquisas Energéticas e Nucleares – IPEN-CNEN/SP, São Paulo 05508-000, Brazil and Department of Radiation Oncology (MAASTRO), GROW, School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6201 BN (Netherlands); Zourari, Kyveli; Papagiannis, Panagiotis [Medical Physics Laboratory, Medical School, University of Athens, 75 MikrasAsias, Athens 115 27 (Greece); Rivard, Mark J. [Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts 02111 (United States); Siebert, Frank-André [Clinic of Radiotherapy, University Hospital of Schleswig-Holstein, Campus Kiel, Kiel 24105 (Germany); Sloboda, Ron S. [Department of Medical Physics, Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada and Department of Oncology, University of Alberta, Edmonton, Alberta T6G 2R3 (Canada); and others

    2015-06-15

    Purpose: In order to facilitate a smooth transition for brachytherapy dose calculations from the American Association of Physicists in Medicine (AAPM) Task Group No. 43 (TG-43) formalism to model-based dose calculation algorithms (MBDCAs), treatment planning systems (TPSs) using a MBDCA require a set of well-defined test case plans characterized by Monte Carlo (MC) methods. This also permits direct dose comparison to TG-43 reference data. Such test case plans should be made available for use in the software commissioning process performed by clinical end users. To this end, a hypothetical, generic high-dose rate (HDR) {sup 192}Ir source and a virtual water phantom were designed, which can be imported into a TPS. Methods: A hypothetical, generic HDR {sup 192}Ir source was designed based on commercially available sources as well as a virtual, cubic water phantom that can be imported into any TPS in DICOM format. The dose distribution of the generic {sup 192}Ir source when placed at the center of the cubic phantom, and away from the center under altered scatter conditions, was evaluated using two commercial MBDCAs [Oncentra{sup ®} Brachy with advanced collapsed-cone engine (ACE) and BrachyVision ACUROS{sup TM}]. Dose comparisons were performed using state-of-the-art MC codes for radiation transport, including ALGEBRA, BrachyDose, GEANT4, MCNP5, MCNP6, and PENELOPE2008. The methodologies adhered to recommendations in the AAPM TG-229 report on high-energy brachytherapy source dosimetry. TG-43 dosimetry parameters, an along-away dose-rate table, and primary and scatter separated (PSS) data were obtained. The virtual water phantom of (201){sup 3} voxels (1 mm sides) was used to evaluate the calculated dose distributions. Two test case plans involving a single position of the generic HDR {sup 192}Ir source in this phantom were prepared: (i) source centered in the phantom and (ii) source displaced 7 cm laterally from the center. Datasets were independently produced by

  3. Improving Low-dose Cardiac CT Images based on 3D Sparse Representation

    Science.gov (United States)

    Shi, Luyao; Hu, Yining; Chen, Yang; Yin, Xindao; Shu, Huazhong; Luo, Limin; Coatrieux, Jean-Louis

    2016-03-01

    Cardiac computed tomography (CCT) is a reliable and accurate tool for diagnosis of coronary artery diseases and is also frequently used in surgery guidance. Low-dose scans should be considered in order to alleviate the harm to patients caused by X-ray radiation. However, low dose CT (LDCT) images tend to be degraded by quantum noise and streak artifacts. In order to improve the cardiac LDCT image quality, a 3D sparse representation-based processing (3D SR) is proposed by exploiting the sparsity and regularity of 3D anatomical features in CCT. The proposed method was evaluated by a clinical study of 14 patients. The performance of the proposed method was compared to the 2D spares representation-based processing (2D SR) and the state-of-the-art noise reduction algorithm BM4D. The visual assessment, quantitative assessment and qualitative assessment results show that the proposed approach can lead to effective noise/artifact suppression and detail preservation. Compared to the other two tested methods, 3D SR method can obtain results with image quality most close to the reference standard dose CT (SDCT) images.

  4. Low-Dose Cyclophosphamide Synergizes with Dendritic Cell-Based Immunotherapy in Antitumor Activity

    Directory of Open Access Journals (Sweden)

    Joris D. Veltman

    2010-01-01

    Full Text Available Clinical immunotherapy trials like dendritic cell-based vaccinations are hampered by the tumor's offensive repertoire that suppresses the incoming effector cells. Regulatory T cells are instrumental in suppressing the function of cytotoxic T cells. We studied the effect of low-dose cyclophosphamide on the suppressive function of regulatory T cells and investigated if the success rate of dendritic cell immunotherapy could be improved. For this, mesothelioma tumor-bearing mice were treated with dendritic cell-based immunotherapy alone or in combination with low-dose of cyclophosphamide. Proportions of regulatory T cells and the cytotoxic T cell functions at different stages of disease were analyzed. We found that low-dose cyclophosphamide induced beneficial immunomodulatory effects by preventing the induction of Tregs, and as a consequence, cytotoxic T cell function was no longer affected. Addition of cyclophosphamide improved immunotherapy leading to an increased median and overall survival. Future studies are needed to address the usefulness of this combination treatment for mesothelioma patients.

  5. [Methodological aspects in environmental and biological monitoring of exposure to low doses of benzene: problems and possible solutions].

    Science.gov (United States)

    Tranfo, Giovanna; Paci, Enrico; Fustinoni, Silvia; Barbieri, Anna; Carrieri, Mariella

    2013-01-01

    This paper aims to examine some methods to measure human exposure to benzene, both in life and occupational environments, through environmental and biological monitoring, examining the critical issues and optimal conditions of use. The overall performance of environmental monitoring, from the analytical point of view, strongly depend on the choice of an appropriate method of sampling and analysis. Urinary SPMA and t, t-MA are the biomarkers listed by ACGIH to evaluate occupational exposure: most of the recent studies use HPLC with tandem mass spectrometry, but since t, t-MA is present in the urine in larger quantities it is also determinable with UV detectors. The urinary benzene is an index not officially included in the list of the ACGIH BEIs, but it is useful to assess exposure and benzene at low concentrations, that most frequently are found today in the occupational and life environments.

  6. SYNTHESIS OF SULFONAMIDE BASED SCHIFF’S BASES AND THEIR BIOLOGICAL EVALUATION TOWARDS COLLETOTRICHUM GLOEOSPORIOIDES

    Directory of Open Access Journals (Sweden)

    Siliveru Swamy

    2012-11-01

    Full Text Available The purpose of research was to synthesize the better antifungal compounds, different substituted aromatic aldehydes are chosen as the starting materials for the synthesis of Schiff’s bases with sulfonamides in presence of alcohol and acidic reagent. The structures of synthesized compounds were confirmed by HRMS spectral analysis data. The derivatives were subjected to Colletotrichum gloeosporioides spore germination to evaluate their biological activity.

  7. MO-AB-BRA-03: Calorimetry-Based Absorbed Dose to Water Measurements Using Interferometry

    Energy Technology Data Exchange (ETDEWEB)

    Flores-Martinez, E; Malin, M; DeWerd, L [University of WI-Madison/ADCL, Madison, WI (United States)

    2015-06-15

    Purpose: Interferometry-based calorimetry is a novel technique to measure radiation-induced temperature changes allowing the measurement of absorbed dose to water (ADW). There are no mechanical components in the field. This technique also has the possibility of obtaining 2D dose distributions. The goal of this investigation is to calorimetrically-measure doses between 2.5 and 5 Gy over a single projection in a photon beam using interferometry and compare the results with doses calculated using the TG-51 linac calibration. Methods: ADW was determined by measuring radiation-induced phase shifts (PSs) of light passing through water irradiated with a 6 MV photon beam. A 9×9×9 cm{sup 3} glass phantom filled with water and placed in an arm of a Michelson interferometer was irradiated with 300, 400, 500 and 600 monitor units. The whole system was thermally insulated to achieve sufficient passive temperature control. The depth of measurement was 4.5 cm with a field size of 7×7 cm{sup 2}. The intensity of the fringe pattern was monitored with a photodiode and used to calculate the time-dependent PS curve. Data was acquired 60 s before and after the irradiation. The radiation-induced PS was calculated by taking the difference in the pre- and post-irradiation drifts extrapolated to the midpoint of the irradiation. Results were compared to computed doses. Results: Average comparison of calculated ADW values with interferometry-measured values showed an agreement to within 9.5%. k=1 uncertainties were 4.3% for calculations and 14.7% for measurements. The dominant source of uncertainty for the measurements was a temperature drift of about 30 µK/s caused by heat conduction from the interferometer’s surroundings. Conclusion: This work presented the first absolute ADW measurements using interferometry in the dose range of linac-based radiotherapy. Future work to improve measurements’ reproducibility includes the implementation of active thermal control techniques.

  8. GPU-based fast Monte Carlo simulation for radiotherapy dose calculation

    CERN Document Server

    Jia, Xun; Graves, Yan Jiang; Folkerts, Michael; Jiang, Steve B

    2011-01-01

    Monte Carlo (MC) simulation is commonly considered to be the most accurate dose calculation method in radiotherapy. However, its efficiency still requires improvement for many routine clinical applications. In this paper, we present our recent progress towards the development a GPU-based MC dose calculation package, gDPM v2.0. It utilizes the parallel computation ability of a GPU to achieve high efficiency, while maintaining the same particle transport physics as in the original DPM code and hence the same level of simulation accuracy. In GPU computing, divergence of execution paths between threads can considerably reduce the efficiency. Since photons and electrons undergo different physics and hence attain different execution paths, we use a simulation scheme where photon transport and electron transport are separated to partially relieve the thread divergence issue. High performance random number generator and hardware linear interpolation are also utilized. We have also developed various components to hand...

  9. State of the Science: Biologically Based Modeling in Risk Assessment [Editorial

    Science.gov (United States)

    The health risk assessment from exposure to a particular agent is preferred when the assessment is based on a relevant measure of internal dose (e.g., maximal concentration of an active metabolite in target tissue) rather than simply the administered dose or exposure concentratio...

  10. 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

    illness and low level of income were all significant independent risk factors for offspring's suicide attempts. CONCLUSIONS: Knowledge of the effect of multiple risk factors on the likelihood of suicide attempts in children and adolescents is important for risk assessment. Dose-response effects......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...... 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...

  11. SU-E-J-68: Adaptive Radiotherapy of Head and Neck Cancer: Re-Planning Based On Prior Dose

    Energy Technology Data Exchange (ETDEWEB)

    Dogan, N; Padgett, K [University of Miami Miller School of Medicine, Miami, FL (United States); Evans, J; Sleeman, W; Song, S [Virginia Commonwealth University, Richmond, VA (United States); Fatyga, M [Mayo Clinic Arizona, Phoenix, AZ (United States)

    2015-06-15

    Purpose: Adaptive Radiotherapy (ART) with frequent CT imaging has been used to improve dosimetric accuracy by accounting for anatomical variations, such as primary tumor shrinkage and/or body weight loss, in Head and Neck (H&N) patients. In most ART strategies, the difference between the planned and the delivered dose is estimated by generating new plans on repeated CT scans using dose-volume constraints used with the initial planning CT without considering already delivered dose. The aim of this study was to assess the dosimetric gains achieved by re-planning based on prior dose by comparing them to re-planning not based-on prior dose for H&N patients. Methods: Ten locally-advanced H&N cancer patients were selected for this study. For each patient, six weekly CT imaging were acquired during the course of radiotherapy. PTVs, parotids, cord, brainstem, and esophagus were contoured on both planning and six weekly CT images. ART with weekly re-plans were done by two strategies: 1) Generating a new optimized IMRT plan without including prior dose from previous fractions (NoPriorDose) and 2) Generating a new optimized IMRT plan based on the prior dose given from previous fractions (PriorDose). Deformable image registration was used to accumulate the dose distributions between planning and six weekly CT scans. The differences in accumulated doses for both strategies were evaluated using the DVH constraints for all structures. Results: On average, the differences in accumulated doses for PTV1, PTV2 and PTV3 for NoPriorDose and PriorDose strategies were <2%. The differences in Dmean to the cord and brainstem were within 3%. The esophagus Dmean was reduced by 2% using PriorDose. PriorDose strategy, however, reduced the left parotid D50 and Dmean by 15% and 14% respectively. Conclusion: This study demonstrated significant parotid sparing, potentially reducing xerostomia, by using ART with IMRT optimization based on prior dose for weekly re-planning of H&N cancer patients.

  12. Systems Biology based studies on anti-inflammatory compounds

    NARCIS (Netherlands)

    Verhoeckx, Kitty Catharina Maria

    2005-01-01

    The introduction of the ‘omics’ techniques (transcriptomics, proteomics, and metabolomics) and systems biology, has caused fundamental changes in the drug discovery process and many other fields in the life science area. In this thesis we explored the possibilities to apply these holistic technologi

  13. Systems Biology and Mode of Action Based Risk Assessment.

    Science.gov (United States)

    The application of systems biology approaches has greatly increased in the past decade largely as a consequence of the human genome project and technological advances in genomics and proteomics. Systems approaches have been used in the medical & pharmaceutical realm for diagnost...

  14. Web Based Learning Support for Experimental Design in Molecular Biology.

    Science.gov (United States)

    Wilmsen, Tinri; Bisseling, Ton; Hartog, Rob

    An important learning goal of a molecular biology curriculum is a certain proficiency level in experimental design. Currently students are confronted with experimental approaches in textbooks, in lectures and in the laboratory. However, most students do not reach a satisfactory level of competence in the design of experimental approaches. This…

  15. A Generic Language for Biological Systems based on Bigraphs

    DEFF Research Database (Denmark)

    Damgaard, Troels Christoffer; Krivine, Jean

    Several efforts have shown that process calculi developed for reasoning about concurrent and mobile systems may be employed for modelling biological systems at the molecular level. In this paper, we initiate investigation of the meta-language framework bigraphical reactive systems, due to Milner et...

  16. A GPU-based Monte Carlo dose calculation code for photon transport in a voxel phantom

    Energy Technology Data Exchange (ETDEWEB)

    Bellezzo, M.; Do Nascimento, E.; Yoriyaz, H., E-mail: mbellezzo@gmail.br [Instituto de Pesquisas Energeticas e Nucleares / CNEN, Av. Lineu Prestes 2242, Cidade Universitaria, 05508-000 Sao Paulo (Brazil)

    2014-08-15

    As the most accurate method to estimate absorbed dose in radiotherapy, Monte Carlo method has been widely used in radiotherapy treatment planning. Nevertheless, its efficiency can be improved for clinical routine applications. In this paper, we present the CUBMC code, a GPU-based Mc photon transport algorithm for dose calculation under the Compute Unified Device Architecture platform. The simulation of physical events is based on the algorithm used in Penelope, and the cross section table used is the one generated by the Material routine, als present in Penelope code. Photons are transported in voxel-based geometries with different compositions. To demonstrate the capabilities of the algorithm developed in the present work four 128 x 128 x 128 voxel phantoms have been considered. One of them is composed by a homogeneous water-based media, the second is composed by bone, the third is composed by lung and the fourth is composed by a heterogeneous bone and vacuum geometry. Simulations were done considering a 6 MeV monoenergetic photon point source. There are two distinct approaches that were used for transport simulation. The first of them forces the photon to stop at every voxel frontier, the second one is the Woodcock method, where the photon stop in the frontier will be considered depending on the material changing across the photon travel line. Dose calculations using these methods are compared for validation with Penelope and MCNP5 codes. Speed-up factors are compared using a NVidia GTX 560-Ti GPU card against a 2.27 GHz Intel Xeon CPU processor. (Author)

  17. A Systems Biology Approach Reveals the Dose- and Time-Dependent Effect of Primary Human Airway Epithelium Tissue Culture After Exposure to Cigarette Smoke In Vitro

    OpenAIRE

    2015-01-01

    To establish a relevant in vitro model for systems toxicology-based mechanistic assessment of environmental stressors such as cigarette smoke (CS), we exposed human organotypic bronchial epithelial tissue cultures at the air liquid interface (ALI) to various CS doses. Previously, we compared in vitro gene expression changes with published human airway epithelia in vivo data to assess their similarities. Here, we present a follow-up evaluation of these in vitro transcriptomics data, using comp...

  18. Comparison of CT number calibration techniques for CBCT-based dose calculation

    Energy Technology Data Exchange (ETDEWEB)

    Dunlop, Alex [The Royal Marsden NHS Foundation Trust, Joint Department of Physics, Institute of Cancer Research, London (United Kingdom); The Royal Marsden Hospital, Sutton, Surrey, Downs Road (United Kingdom); McQuaid, Dualta; Nill, Simeon; Hansen, Vibeke N.; Oelfke, Uwe [The Royal Marsden NHS Foundation Trust, Joint Department of Physics, Institute of Cancer Research, London (United Kingdom); Murray, Julia; Bhide, Shreerang; Harrington, Kevin [The Royal Marsden Hospital, Sutton, Surrey, Downs Road (United Kingdom); The Institute of Cancer Research, London (United Kingdom); Poludniowski, Gavin [Karolinska University Hospital, Department of Medical Physics, Stockholm (Sweden); Nutting, Christopher [The Institute of Cancer Research, London (United Kingdom); Newbold, Kate [The Royal Marsden Hospital, Sutton, Surrey, Downs Road (United Kingdom)

    2015-12-15

    The aim of this work was to compare and validate various computed tomography (CT) number calibration techniques with respect to cone beam CT (CBCT) dose calculation accuracy. CBCT dose calculation accuracy was assessed for pelvic, lung, and head and neck (H and N) treatment sites for two approaches: (1) physics-based scatter correction methods (CBCT{sub r}); (2) density override approaches including assigning water density to the entire CBCT (W), assignment of either water or bone density (WB), and assignment of either water or lung density (WL). Methods for CBCT density assignment within a commercially available treatment planning system (RS{sub auto}), where CBCT voxels are binned into six density levels, were assessed and validated. Dose-difference maps and dose-volume statistics were used to compare the CBCT dose distributions with the ground truth of a planning CT acquired the same day as the CBCT. For pelvic cases, all CTN calibration methods resulted in average dose-volume deviations below 1.5 %. RS{sub auto} provided larger than average errors for pelvic treatments for patients with large amounts of adipose tissue. For H and N cases, all CTN calibration methods resulted in average dose-volume differences below 1.0 % with CBCT{sub r} (0.5 %) and RS{sub auto} (0.6 %) performing best. For lung cases, WL and RS{sub auto} methods generated dose distributions most similar to the ground truth. The RS{sub auto} density override approach is an attractive option for CTN adjustments for a variety of anatomical sites. RS{sub auto} methods were validated, resulting in dose calculations that were consistent with those calculated on diagnostic-quality CT images, for CBCT images acquired of the lung, for patients receiving pelvic RT in cases without excess adipose tissue, and for H and N cases. (orig.) [German] Ziel dieser Arbeit ist der Vergleich und die Validierung mehrerer CT-Kalibrierungsmethoden zur Dosisberechnung auf der Grundlage von Kegelstrahlcomputertomographie

  19. GPU-based ultra fast dose calculation using a finite pencil beam model

    CERN Document Server

    Gu, Xuejun; Men, Chunhua; Pan, Hubert; Majumdar, Amitava; Jiang, Steve B

    2009-01-01

    Online adaptive radiation therapy (ART) is an attractive concept that promises the ability to deliver an optimal treatment in response to the inter-fraction variability in patient anatomy. However, it has yet to be realized due to technical limitations. Fast dose deposit coefficient calculation is a critical component of the online planning process that is required for plan optimization of intensity modulated radiation therapy (IMRT). Computer graphics processing units (GPUs) are well-suited to provide the requisite fast performance for the data-parallel nature of dose calculation. In this work, we develop a dose calculation engine based on a finite-size pencil beam (FSPB) algorithm and a GPU parallel computing framework. The developed framework can accommodate any FSPB model. We test our implementation on a case of a water phantom and a case of a prostate cancer patient with varying beamlet and voxel sizes. All testing scenarios achieved speedup ranging from 200~400 times when using a NVIDIA Tesla C1060 card...

  20. Langerhans Cell Histiocytosis of the Cranial Base: Is Low-Dose Radiotherapy Effective?

    Directory of Open Access Journals (Sweden)

    Andreas Meyer

    2012-01-01

    Full Text Available Introduction. Langerhans cell histiocytosis (LCH is a rare disease of unknown etiology with different clinical features. A standardised treatment has not been established so far. Case Report. We report a case of a 28-year-old patient who initially presented with hypesthesia of the fifth cranial nerve and pain of the left ear. Diagnosis showed a tumour localised in the cranial base with a maximum diameter of 4.1 cm. The diagnosis of LCH was confirmed histologically by biopsy. Diagnostic workup verified the cranial lesion as the sole manifestation of LCH. A total dose of 9 Gy (single dose 1.8 Gy was delivered. The symptoms dissolved completely within 6 months after radiation; repeated CT and MRI scans revealed a reduction in size of the lesion and a remineralisation of the bone. After a followup of 13 years the patient remains free of symptoms without relapse or any side effects from therapy. Discussion. Due to the indolent course of the disease with a high rate of spontaneous remissions the choice of treatment strongly depends on the individual clinical situation. In the presented case low-dose radiotherapy was sufficient to obtain long-term local control in a region with critical structures and tissues.

  1. Reconstructing Organophosphorus Pesticide Doses Using the Reversed Dosimetry Approach in a Simple Physiologically-Based Pharmacokinetic Model

    Directory of Open Access Journals (Sweden)

    Chensheng Lu

    2012-01-01

    Full Text Available We illustrated the development of a simple pharmacokinetic (SPK model aiming to estimate the absorbed chlorpyrifos doses using urinary biomarker data, 3,5,6-trichlorpyridinol as the model input. The effectiveness of the SPK model in the pesticide risk assessment was evaluated by comparing dose estimates using different urinary composite data. The dose estimates resulting from the first morning voids appeared to be lower than but not significantly different to those using before bedtime, lunch or dinner voids. We found similar trend for dose estimates using three different urinary composite data. However, the dose estimates using the SPK model for individual children were significantly higher than those from the conventional physiologically based pharmacokinetic (PBPK modeling using aggregate environmental measurements of chlorpyrifos as the model inputs. The use of urinary data in the SPK model intuitively provided a plausible alternative to the conventional PBPK model in reconstructing the absorbed chlorpyrifos dose.

  2. Moving GPU-OpenCL-based Monte Carlo dose calculation toward clinical use: Automatic beam commissioning and source sampling for treatment plan dose calculation.

    Science.gov (United States)

    Tian, Zhen; Li, Yongbao; Hassan-Rezaeian, Nima; Jiang, Steve B; Jia, Xun

    2017-03-01

    We have previously developed a GPU-based Monte Carlo (MC) dose engine on the OpenCL platform, named goMC, with a built-in analytical linear accelerator (linac) beam model. In this paper, we report our recent improvement on goMC to move it toward clinical use. First, we have adapted a previously developed automatic beam commissioning approach to our beam model. The commissioning was conducted through an optimization process, minimizing the discrepancies between calculated dose and measurement. We successfully commissioned six beam models built for Varian TrueBeam linac photon beams, including four beams of different energies (6 MV, 10 MV, 15 MV, and 18 MV) and two flattening-filter-free (FFF) beams of 6 MV and 10 MV. Second, to facilitate the use of goMC for treatment plan dose calculations, we have developed an efficient source particle sampling strategy. It uses the pre-generated fluence maps (FMs) to bias the sampling of the control point for source particles already sampled from our beam model. It could effectively reduce the number of source particles required to reach a statistical uncertainty level in the calculated dose, as compared to the conventional FM weighting method. For a head-and-neck patient treated with volumetric modulated arc therapy (VMAT), a reduction factor of ~2.8 was achieved, accelerating dose calculation from 150.9 s to 51.5 s. The overall accuracy of goMC was investigated on a VMAT prostate patient case treated with 10 MV FFF beam. 3D gamma index test was conducted to evaluate the discrepancy between our calculated dose and the dose calculated in Varian Eclipse treatment planning system. The passing rate was 99.82% for 2%/2 mm criterion and 95.71% for 1%/1 mm criterion. Our studies have demonstrated the effectiveness and feasibility of our auto-commissioning approach and new source sampling strategy for fast and accurate MC dose calculations for treatment plans. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by

  3. Heart region segmentation from low-dose CT scans: an anatomy based approach

    Science.gov (United States)

    Reeves, Anthony P.; Biancardi, Alberto M.; Yankelevitz, David F.; Cham, Matthew D.; Henschke, Claudia I.

    2012-02-01

    Cardiovascular disease is a leading cause of death in developed countries. The concurrent detection of heart diseases during low-dose whole-lung CT scans (LDCT), typically performed as part of a screening protocol, hinges on the accurate quantification of coronary calcification. The creation of fully automated methods is ideal as complete manual evaluation is imprecise, operator dependent, time consuming and thus costly. The technical challenges posed by LDCT scans in this context are mainly twofold. First, there is a high level image noise arising from the low radiation dose technique. Additionally, there is a variable amount of cardiac motion blurring due to the lack of electrocardiographic gating and the fact that heart rates differ between human subjects. As a consequence, the reliable segmentation of the heart, the first stage toward the implementation of morphologic heart abnormality detection, is also quite challenging. An automated computer method based on a sequential labeling of major organs and determination of anatomical landmarks has been evaluated on a public database of LDCT images. The novel algorithm builds from a robust segmentation of the bones and airways and embodies a stepwise refinement starting at the top of the lungs where image noise is at its lowest and where the carina provides a good calibration landmark. The segmentation is completed at the inferior wall of the heart where extensive image noise is accommodated. This method is based on the geometry of human anatomy and does not involve training through manual markings. Using visual inspection by an expert reader as a gold standard, the algorithm achieved successful heart and major vessel segmentation in 42 of 45 low-dose CT images. In the 3 remaining cases, the cardiac base was over segmented due to incorrect hemidiaphragm localization.

  4. Dose estimation in CT exams of the abdomen based on values of DLP; Estimativa da dose em exames de tomografia de abdome com base nos valores de DLP

    Energy Technology Data Exchange (ETDEWEB)

    Kikuti, C.F.; Medeiros, R.B.; Salvadori, P.S.; Costa, D.M.C; D' lppolito, G., E-mail: kikuticf@gmail.com, E-mail: rbitelli2011@gmail.com [Universidade Federal de Sao Paulo (UNIFESP), SP (Brazil). Coordenadoria de Fisica e Higiene das Radiacoes. Departamento de Diagnostico por Imagem

    2013-10-01

    One of the challenges of multidetector computerized tomography is to minimize the risk of ionizing radiation using optimized protocols since higher doses are necessary to obtain high image quality. It was also noted that, due to the geometry in image acquisition using MDCT becomes necessary to estimate dose values consistent with the hypothesis clinically and with the specificities of the tomographic equipment. The aim of this study was to estimate the doses in abdomen exams from the data recorded on the MDCT console and dimensions obtained from DICOM images of patients undergoing different clinical protocols. Were collected, from the image DICOM of 101 exams, values of the dose length product (DLP) provided by Philips Health Care - Brilliance 64 equipment console, in order to relate them with the dose values obtained by means of thermoluminescent dosimeters ( TLD ) of CasSo{sub 4}:Mn placed on the surface of a cylindrical simulator abdomen acrylic manufactured under the technical - operational conditions for a typical abdomen exam. From the data obtained, it was possible to find a factor of 1.16 ( 5 % ) indicating that the DLP values Brilliance 64 console underestimate the doses and this should be used with correction factor to estimate the total dose of the patient. (author)

  5. CMOS based sensor for dielectric spectroscopy of biological cell suspension

    Science.gov (United States)

    Guha, S.; Schmalz, K.; Meliani, C.; Wenger, Ch

    2013-04-01

    In this work we investigate the use of microwave frequency range to measure the concentration of cells in a biological cell suspension. A theoretical model is discussed and the advantage of high frequency, which is to avoid dispersion mechanisms due to the cell parameters at lower frequencies (for example membrane capacitance), has been described. Interdigitated capacitor (IDC) has been proposed as the sensor for analysing the concentration of a cell species in the suspension. The read-out circuit is a VCO using the IDC and a pair of inductors as resonator. The capacitance of the IDC which is the function of the permittivity of the biological cell suspension determines the resonant frequency of the LC tank oscillator. Thus the concentration of cells in a solution, affecting its permittivity, is read out as the frequency of the oscillator.

  6. Culture and social support: neural bases and biological impact.

    Science.gov (United States)

    Sherman, David K; Kim, Heejung S; Taylor, Shelley E

    2009-01-01

    Social support is an effective means by which people cope with stressful events, and consequently, it beneficially affects health and well-being. Yet there are profound cultural differences in the effectiveness of different types of support and how people use their support networks. In this paper, we examine research on the impact of culture on social support, the neural underpinnings of social support, and how cultural differences in social support seeking are manifested biologically. We focus on cultural factors that may affect individuals' decisions to seek or not to seek social support and how culture moderates the impact of support seeking on biological and psychological health outcomes. We also examine recent research on the interaction between genes and culture in social support use. Discussion centers on the importance of developing an overarching framework of social support that integrates health psychology, cultural psychology, social neuroscience, and genetics.

  7. Biological adhesive based on carboxymethyl chitin derivatives and chitin nanofibers.

    Science.gov (United States)

    Azuma, Kazuo; Nishihara, Masahiro; Shimizu, Haruki; Itoh, Yoshiki; Takashima, Osamu; Osaki, Tomohiro; Itoh, Norihiko; Imagawa, Tomohiro; Murahata, Yusuke; Tsuka, Takeshi; Izawa, Hironori; Ifuku, Shinsuke; Minami, Saburo; Saimoto, Hiroyuki; Okamoto, Yoshiharu; Morimoto, Minoru

    2015-02-01

    Novel biological adhesives made from chitin derivatives were prepared and evaluated for their adhesive properties and biocompatibility. Chitin derivatives with acrylic groups, such as 2-hydroxy-3-methacryloyloxypropylated carboxymethyl chitin (HMA-CM-chitin), were synthesized and cured by the addition of an aqueous hydrogen peroxide solution as a radical initiator. The adhesive strength of HMA-CM-chitin increased when it was blended with chitin nanofibers (CNFs) or surface-deacetylated chitin nanofibers (S-DACNFs). HMA-CM-chitin/CNFs or HMA-CM-chitin/S-DACNFs have almost equal adhesive strength compared to that of a commercial cyanoacrylate adhesive. Moreover, quick adhesion and induction of inflammatory cells migration were observed in HMA-CM-chitin/CNF and HMA-CM-chitin/S-DACNF. These findings indicate that the composites prepared in this study are promising materials as new biological adhesives.

  8. GPU-based Monte Carlo radiotherapy dose calculation using phase-space sources

    CERN Document Server

    Townson, Reid; Tian, Zhen; Graves, Yan Jiang; Zavgorodni, Sergei; Jiang, Steve B

    2013-01-01

    A novel phase-space source implementation has been designed for GPU-based Monte Carlo dose calculation engines. Due to the parallelized nature of GPU hardware, it is essential to simultaneously transport particles of the same type and similar energies but separated spatially to yield a high efficiency. We present three methods for phase-space implementation that have been integrated into the most recent version of the GPU-based Monte Carlo radiotherapy dose calculation package gDPM v3.0. The first method is to sequentially read particles from a patient-dependent phase-space and sort them on-the-fly based on particle type and energy. The second method supplements this with a simple secondary collimator model and fluence map implementation so that patient-independent phase-space sources can be used. Finally, as the third method (called the phase-space-let, or PSL, method) we introduce a novel strategy to pre-process patient-independent phase-spaces and bin particles by type, energy and position. Position bins l...

  9. Knowledge-based iterative model reconstruction: comparative image quality and radiation dose with a pediatric computed tomography phantom

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Young Jin; Choi, Young Hun [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Cheon, Jung-Eun; Kim, Woo Sun; Kim, In-One [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of); Ha, Seongmin [New York-Presbyterian Hospital and the Weill Cornell Medical College, Dalio Institute of Cardiovascular Imaging, New York, NY (United States)

    2016-03-15

    CT of pediatric phantoms can provide useful guidance to the optimization of knowledge-based iterative reconstruction CT. To compare radiation dose and image quality of CT images obtained at different radiation doses reconstructed with knowledge-based iterative reconstruction, hybrid iterative reconstruction and filtered back-projection. We scanned a 5-year anthropomorphic phantom at seven levels of radiation. We then reconstructed CT data with knowledge-based iterative reconstruction (iterative model reconstruction [IMR] levels 1, 2 and 3; Philips Healthcare, Andover, MA), hybrid iterative reconstruction (iDose{sup 4}, levels 3 and 7; Philips Healthcare, Andover, MA) and filtered back-projection. The noise, signal-to-noise ratio and contrast-to-noise ratio were calculated. We evaluated low-contrast resolutions and detectability by low-contrast targets and subjective and objective spatial resolutions by the line pairs and wire. With radiation at 100 peak kVp and 100 mAs (3.64 mSv), the relative doses ranged from 5% (0.19 mSv) to 150% (5.46 mSv). Lower noise and higher signal-to-noise, contrast-to-noise and objective spatial resolution were generally achieved in ascending order of filtered back-projection, iDose{sup 4} levels 3 and 7, and IMR levels 1, 2 and 3, at all radiation dose levels. Compared with filtered back-projection at 100% dose, similar noise levels were obtained on IMR level 2 images at 24% dose and iDose{sup 4} level 3 images at 50% dose, respectively. Regarding low-contrast resolution, low-contrast detectability and objective spatial resolution, IMR level 2 images at 24% dose showed comparable image quality with filtered back-projection at 100% dose. Subjective spatial resolution was not greatly affected by reconstruction algorithm. Reduced-dose IMR obtained at 0.92 mSv (24%) showed similar image quality to routine-dose filtered back-projection obtained at 3.64 mSv (100%), and half-dose iDose{sup 4} obtained at 1.81 mSv. (orig.)

  10. A CRISPR-based MLST Scheme for Understanding the Population Biology and Epidemiology of Salmonella Enterica

    Science.gov (United States)

    2015-05-26

    June 2015 to begin a tenure-track position as an Assistant Professor in the Department of Biology . In her research lab, her focus will continue to be...Approved for Public Release; Distribution Unlimited Final Report: A CRISPR-based MLST Scheme for Understanding the Population Biology and Epidemiology of...Understanding the Population Biology and Epidemiology of Salmonella Enterica Report Title Salmonella enterica subsp. enterica is the most common cause of

  11. A simple dosing scheme for intravenous busulfan based on retrospective population pharmacokinetic analysis in korean patients.

    Science.gov (United States)

    Choe, Sangmin; Kim, Gayeong; Lim, Hyeong-Seok; Cho, Sang-Heon; Ghim, Jong-Lyul; Jung, Jin Ah; Kim, Un-Jib; Noh, Gyujeong; Bae, Kyun-Seop; Lee, Dongho

    2012-08-01

    Busulfan is an antineoplastic agent with a narrow therapeutic window. A post-hoc population pharmacokinetic analysis of a prospective randomized trial for comparison of four-times daily versus once-daily intravenous busulfan was carried out to search for predictive factors of intravenous busulfan (iBu) pharmacokinetics (PK). In this study the population PK of iBu was characterized to provide suitable dosing recommendations. Patients were randomized to receive iBu, either as 0.8 mg/kg every 6 h or 3.2 mg/kg daily over 4 days prior to hematopoietic stem cell transplantation. In total, 295 busulfan concentrations were analyzed with NONMEM. Actual body weight and sex were significant covariates affecting the PK of iBu. Sixty patients were included in the study (all Korean; 23 women, 37 men; mean [SD] age, 36.5 [10.9] years; weight, 66.5 [11.3] kg). Population estimates for a typical patient weighing 65 kg were: clearance (CL) 7.6 l/h and volume of distribution (V(d)) 32.2 l for men and 29.1 L for women. Inter-individual random variabilities of CL and V(d) were 16% and 9%. Based on a CL estimate from the final PK model, a simple dosage scheme to achieve the target AUC(0-inf) (defined as median AUC(0-inf) with a once-daily dosage) of 26.18 mg/l·hr, was proposed: 24.79·ABW(0.5) mg q24h, where ABW represents the actual body weight in kilograms. The dosing scheme reduced the unexplained interindividual variabilities of CL and Vd of iBu with ABW being a significant covariate affecting clearance of iBU. We propose a new simple dosing scheme for iBu based only on ABW.

  12. Comparison in the determination of absorbed dose by biological and physical methods to patients in treatment of cardiac intervention; Comparacion en la determinacion de dosis absorbida por metodos biologicos y fisicos a pacientes en tratamiento de intervencionismo cardiaco

    Energy Technology Data Exchange (ETDEWEB)

    Guerrero C, C.; Arceo M, C., E-mail: citlali.guerrero@inin.gob.mx [ININ, Departamento de Biologia, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2014-10-15

    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)

  13. Standardizing Benchmark Dose Calculations to Improve Science-Based Decisions in Human Health Assessments

    Science.gov (United States)

    Wignall, Jessica A.; Shapiro, Andrew J.; Wright, Fred A.; Woodruff, Tracey J.; Chiu, Weihsueh A.; Guyton, Kathryn Z.

    2014-01-01

    Background: Benchmark dose (BMD) modeling computes the dose associated with a prespecified response level. While offering advantages over traditional points of departure (PODs), such as no-observed-adverse-effect-levels (NOAELs), BMD methods have lacked consistency and transparency in application, interpretation, and reporting in human health assessments of chemicals. Objectives: We aimed to apply a standardized process for conducting BMD modeling to reduce inconsistencies in model fitting and selection. Methods: We evaluated 880 dose–response data sets for 352 environmental chemicals with existing human health assessments. We calculated benchmark doses and their lower limits [10% extra risk, or change in the mean equal to 1 SD (BMD/L10/1SD)] for each chemical in a standardized way with prespecified criteria for model fit acceptance. We identified study design features associated with acceptable model fits. Results: We derived values for 255 (72%) of the chemicals. Batch-calculated BMD/L10/1SD values were significantly and highly correlated (R2 of 0.95 and 0.83, respectively, n = 42) with PODs previously used in human health assessments, with values similar to reported NOAELs. Specifically, the median ratio of BMDs10/1SD:NOAELs was 1.96, and the median ratio of BMDLs10/1SD:NOAELs was 0.89. We also observed a significant trend of increasing model viability with increasing number of dose groups. Conclusions: BMD/L10/1SD values can be calculated in a standardized way for use in health assessments on a large number of chemicals and critical effects. This facilitates the exploration of health effects across multiple studies of a given chemical or, when chemicals need to be compared, providing greater transparency and efficiency than current approaches. Citation: Wignall JA, Shapiro AJ, Wright FA, Woodruff TJ, Chiu WA, Guyton KZ, Rusyn I. 2014. Standardizing benchmark dose calculations to improve science-based decisions in human health assessments. Environ Health

  14. SU-C-BRB-02: Symmetric and Asymmetric MLC Based Lung Shielding and Dose Optimization During Translating Bed TBI

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, S; Kakakhel, MB [Pakistan Institute of Engineering & Applied Sciences (PIEAS), Islamabad (Pakistan); Ahmed, SBS; Hussain, A [Aga Khan University Hospital (AKUH), Karachi (Pakistan)

    2015-06-15

    Purpose: The primary aim was to introduce a dose optimization method for translating bed total body irradiation technique that ensures lung shielding dynamically. Symmetric and asymmetric dynamic MLC apertures were employed for this purpose. Methods: The MLC aperture sizes were defined based on the radiological depth values along the divergent ray lines passing through the individual CT slices. Based on these RD values, asymmetrically shaped MLC apertures were defined every 9 mm of the phantom in superior-inferior direction. Individual MLC files were created with MATLAB™ and were imported into Eclipse™ treatment planning system for dose calculations. Lungs can be shielded to an optimum level by reducing the MLC aperture width over the lungs. The process was repeated with symmetrically shaped apertures. Results: Dose-volume histogram (DVH) analysis shows that the asymmetric MLC based technique provides better dose coverage to the body and optimum shielding of the lungs compared to symmetrically shaped beam apertures. Midline dose homogeneity is within ±3% with asymmetric MLC apertures whereas it remains within ±4.5% with symmetric ones (except head region where it drops down to −7%). The substantial over and under dosage of ±5% at tissue interfaces has been reduced to ±2% with asymmetric MLC technique. Lungs dose can be reduced to any desired limit. In this experiment lungs dose was reduced to 80% of the prescribed dose, as was desired. Conclusion: The novel asymmetric MLC based technique assures optimum shielding of OARs (e.g. lungs) and better 3-D dose homogeneity and body-dose coverage in comparison with the symmetric MLC aperture optimization. The authors acknowledge the financial and infrastructural support provided by Pakistan Institute of Engineering & Applied Sciences (PIEAS), Islamabad and Aga Khan University Hospital (AKUH), Karachi during the course of this research project. Authors have no conflict of interest with any national / international

  15. An approach to using conventional brachytherapy software for clinical treatment planning of complex, Monte Carlo-based brachytherapy dose distributions

    Energy Technology Data Exchange (ETDEWEB)

    Rivard, Mark J.; Melhus, Christopher S.; Granero, Domingo; Perez-Calatayud, Jose; Ballester, Facundo [Department of Radiation Oncology, Tufts University School of Medicine, Boston, Massachusetts 02111 (United States); Radiation Oncology Department, Physics Section, ' ' La Fe' ' University Hospital, Avenida Campanar 21, E-46009 Valencia (Spain); Department of Atomic, Molecular, and Nuclear Physics, University of Valencia, C/Dr. Moliner 50, E-46100 Burjassot, Spain and IFIC (University of Valencia-CSIC), C/Dr. Moliner 50, E-46100 Burjassot (Spain)

    2009-06-15

    Certain brachytherapy dose distributions, such as those for LDR prostate implants, are readily modeled by treatment planning systems (TPS) that use the superposition principle of individual seed dose distributions to calculate the total dose distribution. However, dose distributions for brachytherapy treatments using high-Z shields or having significant material heterogeneities are not currently well modeled using conventional TPS. The purpose of this study is to establish a new treatment planning technique (Tufts technique) that could be applied in some clinical situations where the conventional approach is not acceptable and dose distributions present cylindrical symmetry. Dose distributions from complex brachytherapy source configurations determined with Monte Carlo methods were used as input data. These source distributions included the 2 and 3 cm diameter Valencia skin applicators from Nucletron, 4-8 cm diameter AccuBoost peripheral breast brachytherapy applicators from Advanced Radiation Therapy, and a 16 mm COMS-based eye plaque using {sup 103}Pd, {sup 125}I, and {sup 131}Cs seeds. Radial dose functions and 2D anisotropy functions were obtained by positioning the coordinate system origin along the dose distribution cylindrical axis of symmetry. Origin:tissue distance and active length were chosen to minimize TPS interpolation errors. Dosimetry parameters were entered into the PINNACLE TPS, and dose distributions were subsequently calculated and compared to the original Monte Carlo-derived dose distributions. The new planning technique was able to reproduce brachytherapy dose distributions for all three applicator types, producing dosimetric agreement typically within 2% when compared with Monte Carlo-derived dose distributions. Agreement between Monte Carlo-derived and planned dose distributions improved as the spatial resolution of the fitted dosimetry parameters improved. For agreement within 5% throughout the clinical volume, spatial resolution of

  16. Patient-based estimation of organ dose for a population of 58 adult patients across 13 protocol categories

    Energy Technology Data Exchange (ETDEWEB)

    Sahbaee, Pooyan, E-mail: psahbae@ncsu.edu [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Duke University Medical Center, Durham, North Carolina 27705 and Department of Physics, North Carolina State University, Raleigh, North Carolina 27607 (United States); Segars, W. Paul [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Medical Physics Graduate Program, Duke University Medical Center, Durham, North Carolina 27705 (United States); Samei, Ehsan [Carl E. Ravin Advanced Imaging Laboratories, Department of Radiology, Medical Physics Graduate Program, Department of Physics, Electrical and Computer Engineering, and Biomedical Engineering, Duke University Medical Center, Durham, North Carolina 27705 (United States)

    2014-07-15

    Purpose: This study aimed to provide a comprehensive patient-specific organ dose estimation across a multiplicity of computed tomography (CT) examination protocols. Methods: A validated Monte Carlo program was employed to model a common CT system (LightSpeed VCT, GE Healthcare). The organ and effective doses were estimated from 13 commonly used body and neurological CT examination. The dose estimation was performed on 58 adult computational extended cardiac-torso phantoms (35 male, 23 female, mean age 51.5 years, mean weight 80.2 kg). The organ dose normalized by CTDI{sub vol} (h factor) and effective dose normalized by the dose length product (DLP) (k factor) were calculated from the results. A mathematical model was derived for the correlation between the h and k factors with the patient size across the protocols. Based on this mathematical model, a dose estimation iPhone operating system application was designed and developed to be used as a tool to estimate dose to the patients for a variety of routinely used CT examinations. Results: The organ dose results across all the protocols showed an exponential decrease with patient body size. The correlation was generally strong for the organs which were fully or partially located inside the scan coverage (Pearson sample correlation coefficient (r) of 0.49). The correlation was weaker for organs outside the scan coverage for which distance between the organ and the irradiation area was a stronger predictor of dose to the organ. For body protocols, the effective dose before and after normalization by DLP decreased exponentially with increasing patient's body diameter (r > 0.85). The exponential relationship between effective dose and patient's body diameter was significantly weaker for neurological protocols (r < 0.41), where the trunk length was a slightly stronger predictor of effective dose (0.15 < r < 0.46). Conclusions: While the most accurate estimation of a patient dose requires specific modeling of

  17. Web based dosimetry system for reading and monitoring dose through internet access

    Energy Technology Data Exchange (ETDEWEB)

    Perle, S.C.; Bennett, K.; Kahilainen, J.; Vuotila, M. [Mirion Technologies (United States); Mirion Technologies (Finland)

    2010-07-01

    The Instadose{sup TM} dosemeter from Mirion Technologies is a small, rugged device based on patented direct ion storage technology and is accredited by the National Voluntary Laboratory Accreditation Program (NVLAP) through NIST, bringing radiation monitoring into the digital age. Smaller than a flash drive, this dosemeter provides an instant read-out when connected to any computer with internet access and a USB connection. Instadose devices provide radiation workers with more flexibility than today's dosemeters. Non Volatile Analog Memory Cell surrounded by a Gas Filled Ion Chamber. Dose changes the amount of Electric Charge in the DIS Analog Memory. The total charge storage capacity of the memory determines the available dose range. The state of the Analog Memory is determined by measuring the voltage across the memory cell. AMP (Account Management Program) provides secure real time access to account details, device assignments, reports and all pertinent account information. Access can be restricted based on the role assignment assigned to an individual. A variety of reports are available for download and customizing. The Advantages of the Instadose dosemeter are: - Unlimited reading capability, - Concerns about a possible exposure can be addressed immediately, - Re-readability without loss of exposure data, with cumulative exposure maintained. (authors)

  18. RADAR DOSE ESTIMATE REPORT: A COMPENDIUM OF RADIOPHARMACEUTICAL DOSE ESTIMATES BASED ON OLINDA/EXM VERSION 2.0.

    Science.gov (United States)

    Stabin, Michael; Siegel, Jeffry A

    2017-09-08

    We present here a compendium of about 100 radiopharmaceuticals, using the new OLINDA/EXM version 2.0 software. A totally new generation of voxel-based, realistic human computational phantoms, based on 2007 recommendations of the International Commission on Radiological Protection (ICRP) was used to develop the phantoms, and the most recent biokinetic models were employed as well. These estimates should serve the worldwide user community for many years, and they can be modified and updated as models are changed, and new radiopharmaceuticals are added, as they will be maintained in electronic form. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  19. Repeatability of dose painting by numbers treatment planning in prostate cancer radiotherapy based on multiparametric magnetic resonance imaging

    Science.gov (United States)

    van Schie, Marcel A.; Steenbergen, Peter; Viet Dinh, Cuong; Ghobadi, Ghazaleh; van Houdt, Petra J.; Pos, Floris J.; Heijmink, Stijn W. T. J. P.; van der Poel, Henk G.; Renisch, Steffen; Vik, Torbjørn; van der Heide, Uulke A.

    2017-07-01

    Dose painting by numbers (DPBN) refers to a voxel-wise prescription of radiation dose modelled from functional image characteristics, in contrast to dose painting by contours which requires delineations to define the target for dose escalation. The direct relation between functional imaging characteristics and DPBN implies that random variations in images may propagate into the dose distribution. The stability of MR-only prostate cancer treatment planning based on DPBN with respect to these variations is as yet unknown. We conducted a test-retest study to investigate the stability of DPBN for prostate cancer in a semi-automated MR-only treatment planning workflow. Twelve patients received a multiparametric MRI on two separate days prior to prostatectomy. The tumor probability (TP) within the prostate was derived from image features with a logistic regression model. Dose mapping functions were applied to acquire a DPBN prescription map that served to generate an intensity modulated radiation therapy (IMRT) treatment plan. Dose calculations were done on a pseudo-CT derived from the MRI. The TP and DPBN map and the IMRT dose distribution were compared between both MRI sessions, using the intraclass correlation coefficient (ICC) to quantify repeatability of the planning pipeline. The quality of each treatment plan was measured with a quality factor (QF). Median ICC values for the TP and DPBN map and the IMRT dose distribution were 0.82, 0.82 and 0.88, respectively, for linear dose mapping and 0.82, 0.84 and 0.94 for square root dose mapping. A median QF of 3.4% was found among all treatment plans. We demonstrated the stability of DPBN radiotherapy treatment planning in prostate cancer, with excellent overall repeatability and acceptable treatment plan quality. Using validated tumor probability modelling and simple dose mapping techniques it was shown that despite day-to-day variations in imaging data still consistent treatment plans were obtained.

  20. Web-based training course for evaluating radiological dose assessment in NRC's license termination process.

    Science.gov (United States)

    Lepoire, D; Richmond, P; Cheng, J-J; Kamboj, S; Arnish, J; Chen, S Y; Barr, C; McKenney, C

    2008-08-01

    As part of the requirement for terminating the licenses of nuclear power plants or other nuclear facilities, license termination plans or decommissioning plans are submitted by the licensee to the U.S. Nuclear Regulatory Commission (NRC) for review and approval. Decommissioning plans generally refer to the decommissioning of nonreactor facilities, while license termination plans specifically refer to the decommissioning of nuclear reactor facilities. To provide a uniform and consistent review of dose modeling aspects of these plans and to address NRC-wide knowledge management issues, the NRC, in 2006, commissioned Argonne National Laboratory to develop a Web-based training course on reviewing radiological dose assessments for license termination. The course, which had first been developed in 2005 to target specific aspects of the review processes for license termination plans and decommissioning plans, evolved from a live classroom course into a Web-based training course in 2006. The objective of the Web-based training course is to train NRC staff members (who have various relevant job functions and are located at headquarters, regional offices, and site locations) to conduct an effective review of dose modeling in accordance with the latest NRC guidance, including NUREG-1757, Volumes 1 and 2. The exact size of the staff population who will receive the training has not yet been accurately determined but will depend on various factors such as the decommissioning activities at the NRC. This Web-based training course is designed to give NRC staff members modern, flexible access to training. To this end, the course is divided into 16 modules: 9 core modules that deal with basic topics, and 7 advanced modules that deal with complex issues or job-specific topics. The core and advanced modules are tailored to various NRC staff members with different job functions. The Web-based system uses the commercially available software Articulate, which incorporates audio, video

  1. Event-based text mining for biology and functional genomics

    Science.gov (United States)

    Thompson, Paul; Nawaz, Raheel; McNaught, John; Kell, Douglas B.

    2015-01-01

    The assessment of genome function requires a mapping between genome-derived entities and biochemical reactions, and the biomedical literature represents a rich source of information about reactions between biological components. However, the increasingly rapid growth in the volume of literature provides both a challenge and an opportunity for researchers to isolate information about reactions of interest in a timely and efficient manner. In response, recent text mining research in the biology domain has been largely focused on the identification and extraction of ‘events’, i.e. categorised, structured representations of relationships between biochemical entities, from the literature. Functional genomics analyses necessarily encompass events as so defined. Automatic event extraction systems facilitate the development of sophisticated semantic search applications, allowing researchers to formulate structured queries over extracted events, so as to specify the exact types of reactions to be retrieved. This article provides an overview of recent research into event extraction. We cover annotated corpora on which systems are trained, systems that achieve state-of-the-art performance and details of the community shared tasks that have been instrumental in increasing the quality, coverage and scalability of recent systems. Finally, several concrete applications of event extraction are covered, together with emerging directions of research. PMID:24907365

  2. Nanowire-Based Sensors for Biological and Medical Applications.

    Science.gov (United States)

    Wang, Zongjie; Lee, Suwon; Koo, Kyo; Kim, Keekyoung

    2016-04-01

    Nanomaterials such as nanowires, carbon nanotubes, and nanoparticles have already led to breakthroughs in the field of biological and medical sensors. The quantum size effects of the nanomaterials and their similarity in size to natural and synthetic nanomaterials are anticipated to improve sensor sensitivity dramatically. Nanowires are considered as key nanomaterials because of their electrical controllability for accurate measurement, and chemical-friendly surface for various sensing applications. This review covers the working principles and fabrication of silicon nanowire sensors. Furthermore, we review their applications for the detection of viruses, biomarkers, and DNA, as well as for drug discovery. Advances in the performance and functionality of nanowire sensors are also surveyed to highlight recent progress in this area. These advances include the improvements in reusability, sensitivity in high ionic strength solvent, long-term stability, and self-powering. Overall, with the advantages of ultra-sensitivity and the ease of fabrication, it is expected that nanowires will contribute significantly to the development of biological and medical sensors in the immediate future.

  3. Event-based text mining for biology and functional genomics.

    Science.gov (United States)

    Ananiadou, Sophia; Thompson, Paul; Nawaz, Raheel; McNaught, John; Kell, Douglas B

    2015-05-01

    The assessment of genome function requires a mapping between genome-derived entities and biochemical reactions, and the biomedical literature represents a rich source of information about reactions between biological components. However, the increasingly rapid growth in the volume of literature provides both a challenge and an opportunity for researchers to isolate information about reactions of interest in a timely and efficient manner. In response, recent text mining research in the biology domain has been largely focused on the identification and extraction of 'events', i.e. categorised, structured representations of relationships between biochemical entities, from the literature. Functional genomics analyses necessarily encompass events as so defined. Automatic event extraction systems facilitate the development of sophisticated semantic search applications, allowing researchers to formulate structured queries over extracted events, so as to specify the exact types of reactions to be retrieved. This article provides an overview of recent research into event extraction. We cover annotated corpora on which systems are trained, systems that achieve state-of-the-art performance and details of the community shared tasks that have been instrumental in increasing the quality, coverage and scalability of recent systems. Finally, several concrete applications of event extraction are covered, together with emerging directions of research.

  4. Monte Carlo-based adaptive EPID dose kernel accounting for different field size responses of imagers.

    Science.gov (United States)

    Wang, Song; Gardner, Joseph K; Gordon, John J; Li, Weidong; Clews, Luke; Greer, Peter B; Siebers, Jeffrey V

    2009-08-01

    The aim of this study is to present an efficient method to generate imager-specific Monte Carlo (MC)-based dose kernels for amorphous silicon-based electronic portal image device dose prediction and determine the effective backscattering thicknesses for such imagers. EPID field size-dependent responses were measured for five matched Varian accelerators from three institutions with 6 MV beams at the source to detector distance (SDD) of 105 cm. For two imagers, measurements were made with and without the imager mounted on the robotic supporting arm. Monoenergetic energy deposition kernels with 0-2.5 cm of water backscattering thicknesses were simultaneously computed by MC to a high precision. For each imager, the backscattering thickness required to match measured field size responses was determined. The monoenergetic kernel method was validated by comparing measured and predicted field size responses at 150 cm SDD, 10 x 10 cm2 multileaf collimator (MLC) sliding window fields created with 5, 10, 20, and 50 mm gaps, and a head-and-neck (H&N) intensity modulated radiation therapy (IMRT) patient field. Field size responses for the five different imagers deviated by up to 1.3%. When imagers were removed from the robotic arms, response deviations were reduced to 0.2%. All imager field size responses were captured by using between 1.0 and 1.6 cm backscatter. The predicted field size responses by the imager-specific kernels matched measurements for all involved imagers with the maximal deviation of 0.34%. The maximal deviation between the predicted and measured field size responses at 150 cm SDD is 0.39%. The maximal deviation between the predicted and measured MLC sliding window fields is 0.39%. For the patient field, gamma analysis yielded that 99.0% of the pixels have gamma < 1 by the 2%, 2 mm criteria with a 3% dose threshold. Tunable imager-specific kernels can be generated rapidly and accurately in a single MC simulation. The resultant kernels are imager position

  5. Low-dose computed tomography image denoising based on joint wavelet and sparse representation.

    Science.gov (United States)

    Ghadrdan, Samira; Alirezaie, Javad; Dillenseger, Jean-Louis; Babyn, Paul

    2014-01-01

    Image denoising and signal enhancement are the most challenging issues in low dose computed tomography (CT) imaging. Sparse representational methods have shown initial promise for these applications. In this work we present a wavelet based sparse representation denoising technique utilizing dictionary learning and clustering. By using wavelets we extract the most suitable features in the images to obtain accurate dictionary atoms for the denoising algorithm. To achieve improved results we also lower the number of clusters which reduces computational complexity. In addition, a single image noise level estimation is developed to update the cluster centers in higher PSNRs. Our results along with the computational efficiency of the proposed algorithm clearly demonstrates the improvement of the proposed algorithm over other clustering based sparse representation (CSR) and K-SVD methods.

  6. Simple, inexpensive method of determining total body water using a tracer dose of D/sub 2/O and infrared absorption of biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Lukaski, H.C.; Johnson, P.E.

    1985-02-01

    An improved infrared spectrophotometric method using tracer doses of D/sub 2/O for determination of total body water (TBW) is described. Evaluation of sample preparation procedures showed that only vacuum sublimation yielded acceptable recoveries of D/sub 2/O standards in the range of 0.01-0.30 mg/ml in urine and plasma (101 +/- 2.5 and 99.6 +/- 2.6%, mean +/- SD, respectively). Oral administration of a 10 g dose of D/sub 2/O was shown to equilibrate within 2 hr in the saliva and plasma of 10 healthy men and women, including obese (30% body fat) subjects. Calculated TBW was 39.1 +/- 6.4 L which represented 74 +/- 1.6% of the fat free mass determined by hydrodensitometry. The precision of the described infrared method was 2.5%. Based upon the observed sensitivity of this method, it would be possible to administer smaller oral D/sub 2/O doses, 5-6 g, and obtain reliable TBW values. The practical advantages of this method are low cost and a simple analysis that permits repeated TBW measurements over brief periods without an undue buildup of background deuterium levels in the body.

  7. Dose prescription and treatment planning based on FMISO-PET hypoxia

    Energy Technology Data Exchange (ETDEWEB)

    Toma-Dasu, Iuliana; Antonovic, Laura (Medical Radiation Physics, Stockholm Univ. and Karolinska Institutet, Stockholm (Sweden)), E-mail: iuliana.livia.dasu@ki.se; Uhrdin, Johan (RaySearch Laboratories AB, Stockholm (Sweden)); Dasu, Alexandru (Dept. of Radiation Physics UHL, County Council of Oestergoetland, Linkoeping (Sweden); Radiation Physics, Dept. of Medical and Health Sciences, Faculty of Health Sciences, Linkoeping Univ., Linkoeping (Sweden)); Nuyts, Sandra; Dirix, Piet; Haustermans, Karin (Leuven Univ. Hospitals, Gasthuisberg, Dept. of Radiotherapy, Leuven (Belgium)); Brahme, Anders (Dept. of Oncology and Pathology, Karolinska Institutet, Stockholm (Sweden))

    2012-02-15

    Purpose. The study presents the implementation of a novel method for incorporating hypoxia information from PET-CT imaging into treatment planning and estimates the efficiency of various optimization approaches. Its focuses on the feasibility of optimizing treatment plans based on the non-linear conversion of PET hypoxia images into radiosensitivity maps from the uptake properties of the tracers used. Material and methods. PET hypoxia images of seven head-and-neck cancer patients were used to determine optimal dose distributions needed to counteract the radiation resistance associated with tumor hypoxia assuming various scenarios regarding the evolution of the hypoxic compartment during the treatment. A research planning system for advanced studies has been used to optimize IMRT plans based on hypoxia information from patient PET images. These resulting plans were compared in terms of target coverage for the same fulfilled constraints regarding the organs at risk. Results. The results of a planning study indicated the clinical feasibility of the proposed method for treatment planning based on PET hypoxia. Antihypoxic strategies would lead to small improvements in all the patients, but higher effects are expected for the fraction of patients with hypoxic tumors. For these, individualization of the treatment based on hypoxia PET imaging could lead to improved treatment outcome while creating the premises for limiting the irradiation of the surrounding normal tissues. Conclusions. The proposed approach offers the possibility of improved treatment results as it takes into consideration the heterogeneity and the dynamics of the hypoxic regions. It also provides early identification of the clinical cases that might benefit from dose escalation as well as the cases that could benefit from other counter-hypoxic measures

  8. Radiation dose reduction in medical x-ray CT via Fourier-based iterative reconstruction.

    Science.gov (United States)

    Fahimian, Benjamin P; Zhao, Yunzhe; Huang, Zhifeng; Fung, Russell; Mao, Yu; Zhu, Chun; Khatonabadi, Maryam; DeMarco, John J; Osher, Stanley J; McNitt-Gray, Michael F; Miao, Jianwei

    2013-03-01

    A Fourier-based iterative reconstruction technique, termed Equally Sloped Tomography (EST), is developed in conjunction with advanced mathematical regularization to investigate radiation dose reduction in x-ray CT. The method is experimentally implemented on fan-beam CT and evaluated as a function of imaging dose on a series of image quality phantoms and anonymous pediatric patient data sets. Numerical simulation experiments are also performed to explore the extension of EST to helical cone-beam geometry. EST is a Fourier based iterative algorithm, which iterates back and forth between real and Fourier space utilizing the algebraically exact pseudopolar fast Fourier transform (PPFFT). In each iteration, physical constraints and mathematical regularization are applied in real space, while the measured data are enforced in Fourier space. The algorithm is automatically terminated when a proposed termination criterion is met. Experimentally, fan-beam projections were acquired by the Siemens z-flying focal spot technology, and subsequently interleaved and rebinned to a pseudopolar grid. Image quality phantoms were scanned at systematically varied mAs settings, reconstructed by EST and conventional reconstruction methods such as filtered back projection (FBP), and quantified using metrics including resolution, signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs). Pediatric data sets were reconstructed at their original acquisition settings and additionally simulated to lower dose settings for comparison and evaluation of the potential for radiation dose reduction. Numerical experiments were conducted to quantify EST and other iterative methods in terms of image quality and computation time. The extension of EST to helical cone-beam CT was implemented by using the advanced single-slice rebinning (ASSR) method. Based on the phantom and pediatric patient fan-beam CT data, it is demonstrated that EST reconstructions with the lowest scanner flux setting of 39 m

  9. Biological transformation, kinetics and dose-response assessments of bound musk ketone hemoglobin adducts in rainbow trout as biomarkers of environmental exposure

    Institute of Scientific and Technical Information of China (English)

    M A Mottaleb; J H Zimmerman; T W Moy

    2008-01-01

    Low levels (ng/g) of musk ketone (MK), used as a fragrance additive in the formulation of personal care products, are frequently detected in the water and other environment. Thus, aquatic organisms can be continuously exposed to MK. In this study, kinetics and dose-response assessments of 2-amino-MK (AMK) metabolite, bound to cysteine-hemoglobin (Hb) in rainbow trout, formed by enzymatic nitro-reduction of MK have been demonstrated. Trout were exposed to a single exposure of 0.010, 0.030, 0.10, and or 0.30 mg MK/g of fish. Twenty-six Hb samples were collected from exposed- and control fish subsequent to exposure intervals of 1 d (24 h), 3 d (72 h), and 7 d (168 h). Basic hydrolysis released bound AMK metabolite was extracted into n-hexane and then concentrated and analyzed by gas chromatography (GC) electron capture negative ion chemical ionization (NICI) mass spectrometry (MS) using selected ion monitoring (SIM). The presence of the AMK metabolite in Hb extracts was confirmed by agreement of similar mass spectral features and retention time with a standard. In the dose-response study, maximum adduct formation was obtained at the 0.10 mg/g dose with an average AMK metabolite concentration of 2.2 ng/g. For kinetics, the highest concentration of the AMK metabolite was found to be 32.0 ng/g at 0.03 mg/g dose in 3-d sample. Further elimination of the metabolite showed kinetics with a half-life estimated to be 2 d, assuming first-order kinetics. The metabolite was not detected in the control samples, non-hydrolyzed Hb, and reagent blank extracts. The detection limit for AMK in the Hb was approximately 0.30 (g/L, based on a signal to noise ratio of 3 (S/N = 3).

  10. Effect of statistical fluctuation in Monte Carlo based photon beam dose calculation on gamma index evaluation.

    Science.gov (United States)

    Graves, Yan Jiang; Jia, Xun; Jiang, Steve B

    2013-03-21

    The γ-index test has been commonly adopted to quantify the degree of agreement between a reference dose distribution and an evaluation dose distribution. Monte Carlo (MC) simulation has been widely used for the radiotherapy dose calculation for both clinical and research purposes. The goal of this work is to investigate both theoretically and experimentally the impact of the MC statistical fluctuation on the γ-index test when the fluctuation exists in the reference, the evaluation, or both dose distributions. To the first order approximation, we theoretically demonstrated in a simplified model that the statistical fluctuation tends to overestimate γ-index values when existing in the reference dose distribution and underestimate γ-index values when existing in the evaluation dose distribution given the original γ-index is relatively large for the statistical fluctuation. Our numerical experiments using realistic clinical photon radiation therapy cases have shown that (1) when performing a γ-index test between an MC reference dose and a non-MC evaluation dose, the average γ-index is overestimated and the gamma passing rate decreases with the increase of the statistical noise level in the reference dose; (2) when performing a γ-index test between a non-MC reference dose and an MC evaluation dose, the average γ-index is underestimated when they are within the clinically relevant range and the gamma passing rate increases with the increase of the statistical noise level in the evaluation dose; (3) when performing a γ-index test between an MC reference dose and an MC evaluation dose, the gamma passing rate is overestimated due to the statistical noise in the evaluation dose and underestimated due to the statistical noise in the reference dose. We conclude that the γ-index test should be used with caution when comparing dose distributions computed with MC simulation.

  11. The effect of 18F-florbetapir dose reduction on region-based classification of cortical amyloid deposition

    Energy Technology Data Exchange (ETDEWEB)

    Herholz, K.; Evans, R.; Anton-Rodriguez, J.; Hinz, R.; Matthews, J.C. [University of Manchester, Wolfson Molecular Imaging Centre and Manchester Academic Health Science Centre, Manchester, England (United Kingdom)

    2014-11-15

    There are specific dose recommendations for diagnostic amyloid PET imaging with 18F-florbetapir, but they may not apply to research studies using regional quantitative analysis. We, therefore, studied the effect of tracer dose reduction on the discriminative power of regional analysis. Using bootstrap resampling of list-mode data from 18F-florbetapir scans, a total of 800 images were reconstructed for four different dosage levels: 100, 50, 20, and 10 %. The effect of the injected dose on the variation of measured radiotracer uptake was determined in large cortical regions defined on co-registered and segmented magnetic resonance images. The impact of the observed variation on the discrimination between normal controls and patients with AD was then assessed using data in a cohort study described by Fleisher et al. (Arch Neurol 68(11):1404-1411, 2011). The coefficient of variance for the cortex to cerebellum uptake ratio increased from 0.9 % at full dose of 300 MBq to 2.5 % at 10 % of this dose, but was still small compared to biological variation. It, therefore, had very little impact on discrimination between AD and elderly controls. The original area under the ROC curve was 0.881, decreasing to 0.878 at 10 % of full dose. Original sensitivity for discrimination between AD and controls was 82.0 %, while specificity was 77.3 %; these decreased to 81.8 and 77.1 %, respectively, at the reduced dose. However, the number of subjects within the classification border zone between proven amyloid pathology and young healthy controls increased substantially by 7 to 14 %. A substantial reduction of tracer dose increases uncertainty at the classification border zone while still providing good discrimination between AD patients and controls when using activity data from cortical regions defined on co-registered and segmented MR scans. (orig.)

  12. Biologically based strategies to augment rotator cuff tears

    Directory of Open Access Journals (Sweden)

    M Schaer

    2012-01-01

    Full Text Available Lesions of the rotator cuff (RC are among the most frequent tendon injuries. In spite of the developments in both open and arthroscopic surgery, RC repair still very often fails. In order to reduce the failure rate after surgery, several experimental in vitro and in vivo therapy methods have been developed for biological improvement of the reinsertion. This article provides an overview of the current evidence for augmentation of RC reconstruction with growth factors. Furthermore, potential future therapeutic approaches are discussed. We performed a comprehensive search of the PubMed database using various combinations of the keywords "tendon," "rotator cuff," "augmentation," "growth factor," "platelet-rich fibrin," and "platelet-rich plasma" for publications up to 2011. Given the linguistic capabilities of the research team, we considered publications in English, German, French, and Spanish. We excluded literature reviews, case reports, and letters to the editor.

  13. Stem cell-based biological tooth repair and regeneration.

    Science.gov (United States)

    Volponi, Ana Angelova; Pang, Yvonne; Sharpe, Paul T

    2010-12-01

    Teeth exhibit limited repair in response to damage, and dental pulp stem cells probably provide a source of cells to replace those damaged and to facilitate repair. Stem cells in other parts of the tooth, such as the periodontal ligament and growing roots, play more dynamic roles in tooth function and development. Dental stem cells can be obtained with ease, making them an attractive source of autologous stem cells for use in restoring vital pulp tissue removed because of infection, in regeneration of periodontal ligament lost in periodontal disease, and for generation of complete or partial tooth structures to form biological implants. As dental stem cells share properties with mesenchymal stem cells, there is also considerable interest in their wider potential to treat disorders involving mesenchymal (or indeed non-mesenchymal) cell derivatives, such as in Parkinson's disease.

  14. Antibacterial bioagents based on principles of bacteriophage biology: an overview.

    Science.gov (United States)

    Knoll, Bettina M; Mylonakis, Eleftherios

    2014-02-01

    Bacteriophages were discovered almost a century ago. With the advent of antibiotics, the use of bacteriophages for treatment of infections fell out of favor in Western medicine. In light of the rise of antibiotic resistance, phages and their products (lysins) are rediscovered as antibacterial bioagents. This overview summarizes principles of phage biology and their translation for therapeutic and preventive applications. Examples are presented to highlight their therapeutic promise for prophylaxis and treatment of bacterial infections including multidrug-resistant organisms in humans and animals, and their use as decontaminants of food supplies and environments. Besides research on the in vivo behavior of phages and lysins, dialogues between researchers and regulatory agencies are necessary to publish guidelines for bacteriophage manufacturing and formulation for human use. Only well-designed, double-blind randomized controlled trials will determine if phages and lysins are safe and effective adjuncts or alternatives to antibiotic therapy for infections with multidrug-resistant organisms.

  15. Automated telecommunication-based reminders and adherence with once-daily glaucoma medication dosing: the automated dosing reminder study.

    Science.gov (United States)

    Boland, Michael V; Chang, Dolly S; Frazier, Travis; Plyler, Ryan; Jefferys, Joan L; Friedman, David S

    2014-07-01

    Topical glaucoma medications lower intraocular pressure and alter the course of the disease. Because adherence with glaucoma medications is a known problem, interventions are needed to help those patients who do not take their medications as prescribed. To assess the ability of an automated telecommunication-based intervention to improve adherence with glaucoma medications. We performed a prospective cohort study of medication adherence, followed by a randomized intervention for those found to be nonadherent, of individuals recruited from a university-based glaucoma subspecialty clinic. A total of 491 participants were enrolled in the initial assessment of adherence. Of those, 70 were nonadherent with their medications after 3 months of electronic monitoring and randomized to intervention and control groups. A personal health record was used to store the list of patient medications and reminder preferences. On the basis of those data, participants randomized to the intervention received daily messages, either text or voice, reminding them to take their medication. Participants randomized to the control group received usual care. Difference in adherence before and after initiation of the intervention. Using an intent-to-treat analysis, we found that the median adherence rate in the 38 participants randomized to the intervention increased from 53% to 64% (P telecommunication-based reminders linked to data in a personal health record improved adherence with once-daily glaucoma medications. This is an effective method to improve adherence that could realistically be implemented in ophthalmology practices with a minimum amount of effort on the part of the practice or the patient.

  16. Comparison of hybridization-based and sequencing-based gene expression technologies on biological replicates

    Directory of Open Access Journals (Sweden)

    Cepko Connie L

    2007-06-01

    Full Text Available Abstract Background High-throughput systems for gene expression profiling have been developed and have matured rapidly through the past decade. Broadly, these can be divided into two categories: hybridization-based and sequencing-based approaches. With data from different technologies being accumulated, concerns and challenges are raised about the level of agreement across technologies. As part of an ongoing large-scale cross-platform data comparison framework, we report here a comparison based on identical samples between one-dye DNA microarray platforms and MPSS (Massively Parallel Signature Sequencing. Results The DNA microarray platforms generally provided highly correlated data, while moderate correlations between microarrays and MPSS were obtained. Disagreements between the two types of technologies can be attributed to limitations inherent to both technologies. The variation found between pooled biological replicates underlines the importance of exercising caution in identification of differential expression, especially for the purposes of biomarker discovery. Conclusion Based on different principles, hybridization-based and sequencing-based technologies should be considered complementary to each other, rather than competitive alternatives for measuring gene expression, and currently, both are important tools for transcriptome profiling.

  17. Which Is the Optimal Biologically Effective Dose of Stereotactic Body Radiotherapy for Stage I Non-Small-Cell Lung Cancer? A Meta-Analysis

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Jian; Yang Fujun [Department of Radiation Oncology, Cancer Hospital, Tianjin Medical University, Tianjin (China); Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Shandong' s Key Laboratory of Radiation Oncology, Jinan (China); Li Baosheng, E-mail: baoshli@yahoo.com [Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Shandong' s Key Laboratory of Radiation Oncology, Jinan (China); Li Hongsheng [Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Shandong' s Key Laboratory of Radiation Oncology, Jinan (China); Liu Jing [School of Public Health, Shandong University, Jinan (China); Huang Wei; Wang Dongqing; Yi Yan; Wang Juan [Department of Radiation Oncology, Shandong Cancer Hospital, Shandong Academy of Medical Sciences, Jinan (China); Shandong' s Key Laboratory of Radiation Oncology, Jinan (China)

    2011-11-15

    Purpose: To assess the relationship between biologically effective dose (BED) and efficacy of stereotactic body radiation therapy (SBRT) and to explore the optimal BED range for Stage I non-small-cell lung cancer (NSCLC). Methods and Materials: Eligible studies were identified on Medline, Embase, the Cochrane Library, and the proceedings of annual meetings through June 2010. According to the quartile of included studies, BED was divided into four dose groups: low (<83.2 Gy), medium (83.2-106 Gy), medium to high (106-146 Gy), high (>146 Gy). To obtain pooled estimates of overall survival (OS), cancer-specific survival (CSS), and local control rate (LCR), data were combined in a random effect model. Pooled estimates were corrected for the percentage of small tumors (<3 cm). Results: Thirty-four observational studies with a total of 2,587 patients were included in the meta-analysis. Corrected pooled estimates of 2- or 3-year OS in the medium BED (76.1%, 63.5%) or the medium to high BED (68.3%, 63.2%) groups were higher than in the low (62.3%, 51.9%) or high groups (55.9%, 49.5%), respectively (p {<=} 0.004). Corrected 3-year CSS in the medium (79.5%), medium to high (80.6%), and high groups (90.0%) were higher than in the low group (70.1%, p = 0.016, 0.018, 0.001, respectively). Conclusion: The OS for the medium or medium to high BED groups were higher than those for the low or high BED group for SBRT in Stage I NSCLC. The medium or medium to high BED (range, 83.2-146 Gy) for SBRT may currently be more beneficial and reasonable in Stage I NSCLC.

  18. Patient-specific Monte Carlo-based dose-kernel approach for inverse planning in afterloading brachytherapy.

    Science.gov (United States)

    D'Amours, Michel; Pouliot, Jean; Dagnault, Anne; Verhaegen, Frank; Beaulieu, Luc

    2011-12-01

    Brachytherapy planning software relies on the Task Group report 43 dosimetry formalism. This formalism, based on a water approximation, neglects various heterogeneous materials present during treatment. Various studies have suggested that these heterogeneities should be taken into account to improve the treatment quality. The present study sought to demonstrate the feasibility of incorporating Monte Carlo (MC) dosimetry within an inverse planning algorithm to improve the dose conformity and increase the treatment quality. The method was based on precalculated dose kernels in full patient geometries, representing the dose distribution of a brachytherapy source at a single dwell position using MC simulations and the Geant4 toolkit. These dose kernels are used by the inverse planning by simulated annealing tool to produce a fast MC-based plan. A test was performed for an interstitial brachytherapy breast treatment using two different high-dose-rate brachytherapy sources: the microSelectron iridium-192 source and the electronic brachytherapy source Axxent operating at 50 kVp. A research version of the inverse planning by simulated annealing algorithm was combined with MC to provide a method to fully account for the heterogeneities in dose optimization, using the MC method. The effect of the water approximation was found to depend on photon energy, with greater dose attenuation for the lower energies of the Axxent source compared with iridium-192. For the latter, an underdosage of 5.1% for the dose received by 90% of the clinical target volume was found. A new method to optimize afterloading brachytherapy plans that uses MC dosimetric information was developed. Including computed tomography-based information in MC dosimetry in the inverse planning process was shown to take into account the full range of scatter and heterogeneity conditions. This led to significant dose differences compared with the Task Group report 43 approach for the Axxent source. Copyright © 2011

  19. Patient-Specific Monte Carlo-Based Dose-Kernel Approach for Inverse Planning in Afterloading Brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    D' Amours, Michel [Departement de Radio-Oncologie et Centre de Recherche en Cancerologie de l' Universite Laval, Hotel-Dieu de Quebec, Quebec, QC (Canada); Department of Physics, Physics Engineering, and Optics, Universite Laval, Quebec, QC (Canada); Pouliot, Jean [Department of Radiation Oncology, University of California, San Francisco, School of Medicine, San Francisco, CA (United States); Dagnault, Anne [Departement de Radio-Oncologie et Centre de Recherche en Cancerologie de l' Universite Laval, Hotel-Dieu de Quebec, Quebec, QC (Canada); Verhaegen, Frank [Department of Radiation Oncology, Maastro Clinic, GROW Research Institute, Maastricht University Medical Centre, Maastricht (Netherlands); Department of Oncology, McGill University, Montreal, QC (Canada); Beaulieu, Luc, E-mail: beaulieu@phy.ulaval.ca [Departement de Radio-Oncologie et Centre de Recherche en Cancerologie de l' Universite Laval, Hotel-Dieu de Quebec, Quebec, QC (Canada); Department of Physics, Physics Engineering, and Optics, Universite Laval, Quebec, QC (Canada)

    2011-12-01

    Purpose: Brachytherapy planning software relies on the Task Group report 43 dosimetry formalism. This formalism, based on a water approximation, neglects various heterogeneous materials present during treatment. Various studies have suggested that these heterogeneities should be taken into account to improve the treatment quality. The present study sought to demonstrate the feasibility of incorporating Monte Carlo (MC) dosimetry within an inverse planning algorithm to improve the dose conformity and increase the treatment quality. Methods and Materials: The method was based on precalculated dose kernels in full patient geometries, representing the dose distribution of a brachytherapy source at a single dwell position using MC simulations and the Geant4 toolkit. These dose kernels are used by the inverse planning by simulated annealing tool to produce a fast MC-based plan. A test was performed for an interstitial brachytherapy breast treatment using two different high-dose-rate brachytherapy sources: the microSelectron iridium-192 source and the electronic brachytherapy source Axxent operating at 50 kVp. Results: A research version of the inverse planning by simulated annealing algorithm was combined with MC to provide a method to fully account for the heterogeneities in dose optimization, using the MC method. The effect of the water approximation was found to depend on photon energy, with greater dose attenuation for the lower energies of the Axxent source compared with iridium-192. For the latter, an underdosage of 5.1% for the dose received by 90% of the clinical target volume was found. Conclusion: A new method to optimize afterloading brachytherapy plans that uses MC dosimetric information was developed. Including computed tomography-based information in MC dosimetry in the inverse planning process was shown to take into account the full range of scatter and heterogeneity conditions. This led to significant dose differences compared with the Task Group report

  20. Predictive Modeling of Tacrolimus Dose Requirement Based on High-Throughput Genetic Screening.

    Science.gov (United States)

    Damon, C; Luck, M; Toullec, L; Etienne, I; Buchler, M; Hurault de Ligny, B; Choukroun, G; Thierry, A; Vigneau, C; Moulin, B; Heng, A-E; Subra, J-F; Legendre, C; Monnot, A; Yartseva, A; Bateson, M; Laurent-Puig, P; Anglicheau, D; Beaune, P; Loriot, M A; Thervet, E; Pallet, N

    2017-04-01

    Any biochemical reaction underlying drug metabolism depends on individual gene-drug interactions and on groups of genes interacting together. Based on a high-throughput genetic approach, we sought to identify a set of covariant single-nucleotide polymorphisms predictive of interindividual tacrolimus (Tac) dose requirement variability. Tac blood concentrations (Tac C0 ) of 229 kidney transplant recipients were repeatedly monitored after transplantation over 3 mo. Given the high dimension of the genomic data in comparison to the low number of observations and the high multicolinearity among the variables (gene variants), we developed an original predictive approach that integrates an ensemble variable-selection strategy to reinforce the stability of the variable-selection process and multivariate modeling. Our predictive models explained up to 70% of total variability in Tac C0 per dose with a maximum of 44 gene variants (p-value <0.001 with a permutation test). These models included molecular networks of drug metabolism with oxidoreductase activities and the multidrug-resistant ABCC8 transporter, which was found in the most stringent model. Finally, we identified an intronic variant of the gene encoding SLC28A3, a drug transporter, as a key gene involved in Tac metabolism, and we confirmed it in an independent validation cohort. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. Visualization of energy: light dose indicator based on electrochromic gyroid nano-materials

    Science.gov (United States)

    Wei, Di; Scherer, Maik R. J.; Astley, Michael; Steiner, Ullrich

    2015-06-01

    The typical applications of electrochromic devices do not make use of the charge-dependent, gradual optical response due to their slow voltage-sensitive coloration. However, in this paper we present a design for a reusable, self-powered light dose indicator consisting of a solar cell and a gyroid-structured nickel oxide (NiO) electrochromic display that measures the cumulative charge per se, making use of the efficient voltage-sensitive coloration of gyroid materials. To circumvent the stability issues associated with the standard aqueous electrolyte that is typically accompanied by water splitting and gas evolution, we investigate a novel nano-gyroid NiO electrochromic device based on organic solvents of 1,1,1,3,3,3-hexafluoropropan-2-ol, and room temperature ionic liquid (RTIL) triethylsulfonium bis(trifluoromethylsulfonyl) imide ([SET3][TFSI]) containing lithium bis(trifluoromethylsulfonyl) imide. We show that an effective light dose indicator can be enabled by nano-gyroid NiO with RTIL; this proves to be a reliable device since it does not involve solvent degradation or gas generation.

  2. GMC: a GPU implementation of a Monte Carlo dose calculation based on Geant4.

    Science.gov (United States)

    Jahnke, Lennart; Fleckenstein, Jens; Wenz, Frederik; Hesser, Jürgen

    2012-03-07

    We present a GPU implementation called GMC (GPU Monte Carlo) of the low energy (CUDA programming interface. The classes for electron and photon interactions as well as a new parallel particle transport engine were implemented. The way a particle is processed is not in a history by history manner but rather by an interaction by interaction method. Every history is divided into steps that are then calculated in parallel by different kernels. The geometry package is currently limited to voxelized geometries. A modified parallel Mersenne twister was used to generate random numbers and a random number repetition method on the GPU was introduced. All phantom results showed a very good agreement between GPU and CPU simulation with gamma indices of >97.5% for a 2%/2 mm gamma criteria. The mean acceleration on one GTX 580 for all cases compared to Geant4 on one CPU core was 4860. The mean number of histories per millisecond on the GPU for all cases was 658 leading to a total simulation time for one intensity-modulated radiation therapy dose distribution of 349 s. In conclusion, Geant4-based Monte Carlo dose calculations were significantly accelerated on the GPU.

  3. Monte Carlo modeling in CT-based geometries: dosimetry for biological modeling experiments with particle beam radiation.

    Science.gov (United States)

    Diffenderfer, Eric S; Dolney, Derek; Schaettler, Maximilian; Sanzari, Jenine K; McDonough, James; Cengel, Keith A

    2014-03-01

    The space radiation environment imposes increased dangers of exposure to ionizing radiation, particularly during a solar particle event (SPE). These events consist primarily of low energy protons that produce a highly inhomogeneous dose distribution. Due to this inherent dose heterogeneity, experiments designed to investigate the radiobiological effects of SPE radiation present difficulties in evaluating and interpreting dose to sensitive organs. To address this challenge, we used the Geant4 Monte Carlo simulation framework to develop dosimetry software that uses computed tomography (CT) images and provides radiation transport simulations incorporating all relevant physical interaction processes. We found that this simulation accurately predicts measured data in phantoms and can be applied to model dose in radiobiological experiments with animal models exposed to charged particle (electron and proton) beams. This study clearly demonstrates the value of Monte Carlo radiation transport methods for two critically interrelated uses: (i) determining the overall dose distribution and dose levels to specific organ systems for animal experiments with SPE-like radiation, and (ii) interpreting the effect of random and systematic variations in experimental variables (e.g. animal movement during long exposures) on the dose distributions and consequent biological effects from SPE-like radiation exposure. The software developed and validated in this study represents a critically important new tool that allows integration of computational and biological modeling for evaluating the biological outcomes of exposures to inhomogeneous SPE-like radiation dose distributions, and has potential applications for other environmental and therapeutic exposure simulations.

  4. Clustering and rule-based classifications of chemical structures evaluated in the biological activity space.

    Science.gov (United States)

    Schuffenhauer, Ansgar; Brown, Nathan; Ertl, Peter; Jenkins, Jeremy L; Selzer, Paul; Hamon, Jacques

    2007-01-01

    Classification methods for data sets of molecules according to their chemical structure were evaluated for their biological relevance, including rule-based, scaffold-oriented classification methods and clustering based on molecular descriptors. Three data sets resulting from uniformly determined in vitro biological profiling experiments were classified according to their chemical structures, and the results were compared in a Pareto analysis with the number of classes and their average spread in the profile space as two concurrent objectives which were to be minimized. It has been found that no classification method is overall superior to all other studied methods, but there is a general trend that rule-based, scaffold-oriented methods are the better choice if classes with homogeneous biological activity are required, but a large number of clusters can be tolerated. On the other hand, clustering based on chemical fingerprints is superior if fewer and larger classes are required, and some loss of homogeneity in biological activity can be accepted.

  5. Robotic, MEMS-based Multi Utility Sample Preparation Instrument for ISS Biological Workstation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — This project will develop a multi-functional, automated sample preparation instrument for biological wet-lab workstations on the ISS. The instrument is based on a...

  6. Development and validation of a fast voxel-based dose evaluation system in nuclear medicine

    Science.gov (United States)

    Lu, Cheng-Chang; Lin, Hsin-Hon; Chuang, Keh-Shih; Dong, Shang-Lung; Wu, Jay; Ni, Yu-Ching; Jan, Meei-Ling

    2014-11-01

    PET imaging has been widely used in the detection and staging of malignancies and the evaluation of patient-specific dosimetry for PET scans is important in nuclear medicine. However, patient-specific dosimetry can be estimated only by Monte Carlo methods which are usually time-consuming. The purpose of this study is to develop a fast dose evaluation system namely SimDOSE. SimDOSE is a Monte Carlo code embedded in SimSET with a dose scoring routine to record the deposited energy of the photons and electrons. Fluorine-18 is one of the most commonly used radionuclides that decay predominantly by positron emission. Only a 635 keV (Emax) positron and two annihilation photons should be concerned in F-18 radiation dosimetry, hence simulation is relatively simple. To evaluate the effects of resolution, an F-18 point source placed in a 20 cm diameter sphere filled with water was simulated by SimDOSE and GATE v6.1. Grid sizes of 1 mm, 3 mm, and 5 mm were tested and each was simulated with a total of 107 decays. The resultant dose distribution functions were compared. Dose evaluation on ORNL phantom was also performed to validate the accuracy of SimDOSE. The grid size of phantom was set as 3 mm and the number of decays was 107. The S-values of liver computed by SimDOSE were compared with GATE and OLINDA (Organ Level INternal Dose Assessment) for 11C, 15O, and 18F.Finally, the CPU time of simulations was compared between SimDOSE and GATE. The dose profiles show the absorption doses located 3 mm outside the center are similar between SimDOSE and GATE. However, 71% (19%) difference of the center dose between SimDOSE and GATE are observed for 1 mm (3 mm) grid. The differences of the profile lie in the assumption in SimDOSE that all kinetic energies of electrons are locally absorbed. The ratios of S values of (SimDOSE/OLINDA) range from 0.95 to 1.11 with a mean value of 1.02±0.043. To compare simulation time from SimDOSE to GATE for calculation of 1 mm, 3 mm, 5 mm gird point

  7. Amyloid beta: structure, biology and structure-based therapeutic development.

    Science.gov (United States)

    Chen, Guo-Fang; Xu, Ting-Hai; Yan, Yan; Zhou, Yu-Ren; Jiang, Yi; Melcher, Karsten; Xu, H Eric

    2017-09-01

    Amyloid beta peptide (Aβ) is produced through the proteolytic processing of a transmembrane protein, amyloid precursor protein (APP), by β- and γ-secretases. Aβ accumulation in the brain is proposed to be an early toxic event in the pathogenesis of Alzheimer's disease, which is the most common form of dementia associated with plaques and tangles in the brain. Currently, it is unclear what the physiological and pathological forms of Aβ are and by what mechanism Aβ causes dementia. Moreover, there are no efficient drugs to stop or reverse the progression of Alzheimer's disease. In this paper, we review the structures, biological functions, and neurotoxicity role of Aβ. We also discuss the potential receptors that interact with Aβ and mediate Aβ intake, clearance, and metabolism. Additionally, we summarize the therapeutic developments and recent advances of different strategies for treating Alzheimer's disease. Finally, we will report on the progress in searching for novel, potentially effective agents as well as selected promising strategies for the treatment of Alzheimer's disease. These prospects include agents acting on Aβ, its receptors and tau protein, such as small molecules, vaccines and antibodies against Aβ; inhibitors or modulators of β- and γ-secretase; Aβ-degrading proteases; tau protein inhibitors and vaccines; amyloid dyes and microRNAs.

  8. Calibrating passive sampling and passive dosing techniques to lipid based concentrations

    DEFF Research Database (Denmark)

    Mayer, Philipp; Schmidt, Stine Nørgaard; Annika, A.

    2011-01-01

    external partitioning standards in vegetable or fish oil for the complete calibration of equilibrium sampling techniques without additional steps. Equilibrium in tissue sampling in three different fish yielded lipid based PCB concentrations in good agreement with those determined using total extraction...... and lipid normalization. These results support the validity of the in tissue sampling technique, while at the same time confirming that the fugacity capacity of these lipid-rich fish tissues for PCBs was dominated by the lipid fraction. Equilibrium sampling of PCB contaminated lake sediments with PDMS......Equilibrium sampling into various formats of the silicone polydimethylsiloxane (PDMS) is increasingly used to measure the exposure of hydrophobic organic chemicals in environmental matrices, and passive dosing from silicone is increasingly used to control and maintain their exposure in laboratory...

  9. Radiations from GSM Base Stations and its Biological Effects on ...

    African Journals Online (AJOL)

    Michael Horsfall

    The levels of radiofrequency (RF) radiations around the base stations were found .... of Turk's solution (Glacial Acetic Acid tinted with ... dissolved in distilled, 40% formaldehyde) is balanced .... agencies in different countries have come up with.

  10. A GPU OpenCL based cross-platform Monte Carlo dose calculation engine (goMC)

    Science.gov (United States)

    Tian, Zhen; Shi, Feng; Folkerts, Michael; Qin, Nan; Jiang, Steve B.; Jia, Xun

    2015-09-01

    Monte Carlo (MC) simulation has been recognized as the most accurate dose calculation method for radiotherapy. However, the extremely long computation time impedes its clinical application. Recently, a lot of effort has been made to realize fast MC dose calculation on graphic processing units (GPUs). However, most of the GPU-based MC dose engines have been developed under NVidia’s CUDA environment. This limits the code portability to other platforms, hindering the introduction of GPU-based MC simulations to clinical practice. The objective of this paper is to develop a GPU OpenCL based cross-platform MC dose engine named goMC with coupled photon-electron simulation for external photon and electron radiotherapy in the MeV energy range. Compared to our previously developed GPU-based MC code named gDPM (Jia et al 2012 Phys. Med. Biol. 57 7783-97), goMC has two major differences. First, it was developed under the OpenCL environment for high code portability and hence could be run not only on different GPU cards but also on CPU platforms. Second, we adopted the electron transport model used in EGSnrc MC package and PENELOPE’s random hinge method in our new dose engine, instead of the dose planning method employed in gDPM. Dose distributions were calculated for a 15 MeV electron beam and a 6 MV photon beam in a homogenous water phantom, a water-bone-lung-water slab phantom and a half-slab phantom. Satisfactory agreement between the two MC dose engines goMC and gDPM was observed in all cases. The average dose differences in the regions that received a dose higher than 10% of the maximum dose were 0.48-0.53% for the electron beam cases and 0.15-0.17% for the photon beam cases. In terms of efficiency, goMC was ~4-16% slower than gDPM when running on the same NVidia TITAN card for all the cases we tested, due to both the different electron transport models and the different development environments. The code portability of our new dose engine goMC was validated by

  11. A GPU OpenCL based cross-platform Monte Carlo dose calculation engine (goMC).

    Science.gov (United States)

    Tian, Zhen; Shi, Feng; Folkerts, Michael; Qin, Nan; Jiang, Steve B; Jia, Xun

    2015-10-07

    Monte Carlo (MC) simulation has been recognized as the most accurate dose calculation method for radiotherapy. However, the extremely long computation time impedes its clinical application. Recently, a lot of effort has been made to realize fast MC dose calculation on graphic processing units (GPUs). However, most of the GPU-based MC dose engines have been developed under NVidia's CUDA environment. This limits the code portability to other platforms, hindering the introduction of GPU-based MC simulations to clinical practice. The objective of this paper is to develop a GPU OpenCL based cross-platform MC dose engine named goMC with coupled photon-electron simulation for external photon and electron radiotherapy in the MeV energy range. Compared to our previously developed GPU-based MC code named gDPM (Jia et al 2012 Phys. Med. Biol. 57 7783-97), goMC has two major differences. First, it was developed under the OpenCL environment for high code portability and hence could be run not only on different GPU cards but also on CPU platforms. Second, we adopted the electron transport model used in EGSnrc MC package and PENELOPE's random hinge method in our new dose engine, instead of the dose planning method employed in gDPM. Dose distributions were calculated for a 15 MeV electron beam and a 6 MV photon beam in a homogenous water phantom, a water-bone-lung-water slab phantom and a half-slab phantom. Satisfactory agreement between the two MC dose engines goMC and gDPM was observed in all cases. The average dose differences in the regions that received a dose higher than 10% of the maximum dose were 0.48-0.53% for the electron beam cases and 0.15-0.17% for the photon beam cases. In terms of efficiency, goMC was ~4-16% slower than gDPM when running on the same NVidia TITAN card for all the cases we tested, due to both the different electron transport models and the different development environments. The code portability of our new dose engine goMC was validated by

  12. Modes-of-Action Related to Repeated Dose Toxicity: Tissue-Specific Biological Roles of PPARγ Ligand-Dependent Dysregulation in Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Merilin Al Sharif

    2014-01-01

    Full Text Available Comprehensive understanding of the precise mode of action/adverse outcome pathway (MoA/AOP of chemicals becomes a key step towards superseding the current repeated dose toxicity testing methodology with new generation predictive toxicology tools. The description and characterization of the toxicological MoA leading to non-alcoholic fatty liver disease (NAFLD are of specific interest, due to its increasing incidence in the modern society. Growing evidence stresses on the PPARγ ligand-dependent dysregulation as a key molecular initiating event (MIE for this adverse effect. The aim of this work was to analyze and systematize the numerous scientific data about the steatogenic role of PPARγ. Over 300 papers were ranked according to preliminary defined criteria and used as reliable and significant sources of data about the PPARγ-dependent prosteatotic MoA. A detailed analysis was performed regarding proteins which PPARγ-mediated expression changes had been confirmed to be prosteatotic by most experimental evidence. Two probable toxicological MoAs from PPARγ ligand binding to NAFLD were described according to the Organisation for Economic Cooperation and Development (OECD concepts: (i PPARγ activation in hepatocytes and (ii PPARγ inhibition in adipocytes. The possible events at different levels of biological organization starting from the MIE to the organ response and the connections between them were described in details.

  13. Carbon Nanostructure-Based Field-Effect Transistors for Label-Free Chemical/Biological Sensors

    Directory of Open Access Journals (Sweden)

    PingAn Hu

    2010-05-01

    Full Text Available Over the past decade, electrical detection of chemical and biological species using novel nanostructure-based devices has attracted significant attention for chemical, genomics, biomedical diagnostics, and drug discovery applications. The use of nanostructured devices in chemical/biological sensors in place of conventional sensing technologies has advantages of high sensitivity, low decreased energy consumption and potentially highly miniaturized integration. Owing to their particular structure, excellent electrical properties and high chemical stability, carbon nanotube and graphene based electrical devices have been widely developed for high performance label-free chemical/biological sensors. Here, we review the latest developments of carbon nanostructure-based transistor sensors in ultrasensitive detection of chemical/biological entities, such as poisonous gases, nucleic acids, proteins and cells.

  14. Ultra-low dose abdominal MDCT: Using a knowledge-based Iterative Model Reconstruction technique for substantial dose reduction in a prospective clinical study

    Energy Technology Data Exchange (ETDEWEB)

    Khawaja, Ranish Deedar Ali, E-mail: rkhawaja@mgh.harvard.edu [MGH Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Singh, Sarabjeet; Blake, Michael; Harisinghani, Mukesh; Choy, Gary; Karosmangulu, Ali; Padole, Atul; Do, Synho [MGH Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Brown, Kevin; Thompson, Richard; Morton, Thomas; Raihani, Nilgoun [CT Research and Advanced Development, Philips Healthcare, Cleveland, OH (United States); Koehler, Thomas [Philips Technologie GmbH, Innovative Technologies, Hamburg (Germany); Kalra, Mannudeep K. [MGH Imaging, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

    2015-01-15

    Highlights: • Limited abdominal CT indications can be performed at a size specific dose estimate of (SSDE) 1.5 mGy (∼0.9 mSv) in smaller patients (BMI less than or equal to 25 kg/m{sup 2}) using a knowledge based Iterative Model Reconstruction (IMR) technique. • Evaluation of liver tumors and pathologies is unacceptable at this reduced dose with IMR technique especially in patients with a BMI greater than 25 kg/m{sup 2}. • IMR body soft tissue and routine settings perform substantially better than IMR sharp plus setting in reduced dose CT images. • At SSDE of 1.5 mGy, objective image noise in reduced dose IMR images is 8–56% less than compared to standard dose FBP images, with lowest image noise in IMR body-soft tissue images. - Abstract: Purpose: To assess lesion detection and image quality parameters of a knowledge-based Iterative Model Reconstruction (IMR) in reduced dose (RD) abdominal CT examinations. Materials and methods: This IRB-approved prospective study included 82 abdominal CT examinations performed for 41 consecutive patients (mean age, 62 ± 12 years; F:M 28:13) who underwent a RD CT (SSDE, 1.5 mGy ± 0.4 [∼0.9 mSv] at 120 kV with 17–20 mAs/slice) immediately after their standard dose (SD) CT exam (10 mGy ± 3 [∼6 mSv] at 120 kV with automatic exposure control) on 256 MDCT (iCT, Philips Healthcare). SD data were reconstructed using filtered back projection (FBP). RD data were reconstructed with FBP and IMR. Four radiologists used a five-point scale (1 = image quality better than SD CT to 5 = image quality unacceptable) to assess both subjective image quality and artifacts. Lesions were first detected on RD FBP images. RD IMR and RD FBP images were then compared side-by-side to SD-FBP images in an independent, randomized and blinded fashion. Friedman's test and intraclass correlation coefficient were used for data analysis. Objective measurements included image noise and attenuation as well as noise spectral density (NSD) curves

  15. Synthesis, Characterization, and Biological Evaluation of Gelatin-based Scaffolds

    CERN Document Server

    Tronci, G

    2011-01-01

    This thesis presents the development of entropy-elastic gelatin based networks in the form of films or scaffolds. The materials have good prospects for biomedical applications, especially in the context of bone regeneration. Entropy-elastic gelatin based hydrogel films with varying crosslinking densities were prepared with tailored mechanical properties. Gelatin was covalently crosslinked in water above its sol gel transition, which suppressed the gelatin chain helicity. Amorphous films were prepared with tailorable degrees of swelling and wet state Young's modulus. The knowledge gained with this bulk material was transferred to the integrated process of foaming and crosslinking to obtain porous gelatin-based scaffolds. A gelatin solution was foamed in the presence of saponin and the resulting foam was fixed by chemical crosslinking with a diisocyanate. The scaffolds were analyzed in the dry state by micro computed tomography (\\mu CT, porosity: 65\\pm 11-73\\pm 14 vol.-%), and scanning electron microscopy (SEM,...

  16. Paper-based chemical and biological sensors: Engineering aspects.

    Science.gov (United States)

    Ahmed, Snober; Bui, Minh-Phuong Ngoc; Abbas, Abdennour

    2016-03-15

    Remarkable efforts have been dedicated to paper-based chemosensors and biosensors over the last few years, mainly driven by the promise of reaching the best trade-off between performance, affordability and simplicity. Because of the low-cost and rapid prototyping of these sensors, recent research has been focused on providing affordable diagnostic devices to the developing world. The recent progress in sensitivity, multi-functionality and integration of microfluidic paper-based analytical devices (µPADs), increasingly suggests that this technology is not only attractive in resource-limited environments but it also represents a serious challenger to silicon, glass and polymer-based biosensors. This review discusses the design, chemistry and engineering aspects of these developments, with a focus on the past few years.

  17. Mesh-Based Fourier Imaging for Biological and Security Applications

    Science.gov (United States)

    Hayden, Danielle

    Traditional x-ray imaging provides only low contrast from low atomic number materials, like soft tissue, due to the small attenuation variations producing very small intensity changes. Higher contrast can be achieved through phase information. The phase change is obtained from the x-ray refracting in a sample, or phase object, due to the difference in refractive indexes. This causes a small angular deviation from the original path. Phase contrast imaging has not been realized in everyday practice due to the requirement for large spatial coherence width of the x-ray beam which typically requires sources on the order of 10-50 m, the use of a grating technique or synchrotron sources. The grating-based phase imaging method depends upon multiple fine-pitched, expensive gratings and extremely precise alignment. An alternative procedure based on a technique recently demonstrated by Bennett is mesh-based phase imaging that utilizes a single, inexpensive mesh with a coarse pitch. This considerably eases the small spot size source requirement, allowing the use of a 150 micron, micro-focus, tungsten anode source. The mesh-based phase imaging set up used to study biomedical and security screening applications consisted of a 123x123 m stainless steel mesh and a 1200x1600 CCD detector with a pixel size of 22 microns. This mesh based approach allows for near-real-time phase extraction of the first harmonics in the Fourier domain. With the phase information and absorption information (collected at the zeroth harmonic), edge enhanced images of a mouse's skull were optimized and several potentially dangerous liquids and powders were discriminated from water. The mesh-based phase set up resulted in high contrasts, signal-to-noise ratios and good resolution verifying the potential utility of this technique for future biomedical imaging and airport security screening.

  18. Estimation of breast dose saving potential using a breast positioning technique for organ-based tube current modulated CT

    Science.gov (United States)

    Fu, Wanyi; Tian, Xiaoyu; Sturgeon, Gregory; Agasthya, Greeshma; Segars, William Paul; Goodsitt, Mitchell M.; Kazerooni, Ella A.; Samei, Ehsan

    2016-04-01

    In thoracic CT, organ-based tube current modulation (OTCM) reduces breast dose by lowering the tube current in the 120° anterior dose reduction zone of patients. However, in practice the breasts usually expand to an angle larger than the dose reduction zone. This work aims to simulate a breast positioning technique (BPT) to constrain the breast tissue to within the dose reduction zone for OTCM and to evaluate the corresponding potential reduction in breast dose. Thirteen female anthropomorphic computational phantoms were studied (age range: 27-65 y.o., weight range: 52-105.8 kg). Each phantom was modeled in the supine position with and without application of the BPT. Attenuation-based tube current (ATCM, reference mA) was generated by a ray-tracing program, taking into account the patient attenuation change in the longitudinal and angular plane (CAREDose4D, Siemens Healthcare). OTCM was generated by reducing the mA to 20% between +/- 60° anterior of the patient and increasing the mA in the remaining projections correspondingly (X-CARE, Siemens Healthcare) to maintain the mean tube current. Breast tissue dose was estimated using a validated Monte Carlo program for a commercial scanner (SOMATOM Definition Flash, Siemens Healthcare). Compared to standard tube current modulation, breast dose was significantly reduced using OTCM by 19.8+/-4.7%. With the BPT, breast dose was reduced by an additional 20.4+/-6.5% to 37.1+/-6.9%, using the same CTDIvol. BPT was more effective for phantoms simulating women with larger breasts with the average breast dose reduction of 30.2%, 39.2%, and 49.2% from OTCMBP to ATCM, using the same CTDIvol for phantoms with 0.5, 1.5, and 2.5 kg breasts, respectively. This study shows that a specially designed BPT improves the effectiveness of OTCM.

  19. National Biological Monitoring Inventory. [Data base for information on biological monitoring of power plant impacts on environment

    Energy Technology Data Exchange (ETDEWEB)

    Burgess, R. L.

    1979-01-01

    The National Biological Monitoring Inventory, initiated in 1975, currently consists of four computerized data bases and voluminous manual files. MAIN BIOMON contains detailed information on 1,021 projects, while MINI BIOMON provides skeletal data for over 3,000 projects in the 50 states, Puerto Rico, the Virgin Islands, plus a few in Canada and Mexico. BIBLIO BIOMON and DIRECTORY BIOMON complete the computerized data bases. The structure of the system provides for on-line search capabilities to generate details of agency sponsorship, indications of funding levels, taxonomic and geographic coverage, length of program life, managerial focus or emphasis, and condition of the data. Examples of each of these are discussed and illustrated, and potential use of the Inventory in a variety of situations is emphasized.

  20. Inquiry-based Science Instruction in High School Biology Courses: A Multiple Case Study

    Science.gov (United States)

    Aso, Eze

    A lack of research exists about how secondary school science teachers use inquiry-based instruction to improve student learning. The purpose of this qualitative study was to explore how science teachers used inquiry-based instruction to improve student learning in high school biology courses. The conceptual framework was based on Banchi and Bell's model of increasing levels of complexity for inquiry-based instruction. A multiple case study research design was conducted of biology programs at 3 high schools in an urban school district in the northeastern region of the United States. Participants included 2 biology teachers from each of the 3 high schools. Data were collected from individual interviews with biology teachers, observations of lessons in biology, and documents related to state standards, assessments, and professional development. The first level of data analysis involved coding and categorizing the interview and observation data. A content analysis was used for the documents. The second level of data analysis involved examining data across all sources and all cases for themes and discrepancies. According to study findings, biology teachers used confirmation, structure, and guided inquiry to improve student learning. However, they found open inquiry challenging and frustrating to implement because professional development about scaffolding of instruction over time was needed, and students' reading and writing skills needed to improve. This study contributes to positive social change by providing educators and researchers with a deeper understanding about how to scaffold levels of inquiry-based science instruction in order to help students become scientifically literate citizens.

  1. SU-E-J-228: MRI-Based Planning: Dosimetric Feasibility of Dose Painting for ADCDefined Intra-Prostatic Tumor

    Energy Technology Data Exchange (ETDEWEB)

    Chen, X; Dalah, E; Prior, P; Lawton, C; Li, X [Medical College of Wisconsin, Milwaukee, WI (United States)

    2015-06-15

    Purpose: Apparent diffusion coefficient (ADC) map may help to delineate the gross tumor volume (GTV) in prostate gland. Dose painting with external beam radiotherapy for GTV might increase the local tumor control. The purpose of this study is to explore the maximum boosting dose on GTV using VMAT without sacrificing sparing of organs at risk (OARs) in MRI based planning. Methods: VMAT plans for 5 prostate patients were generated following the commonly used dose volume (DV) criteria based on structures contoured on T2 weighted MRI with bulk electron density assignment using electron densities derived from ICRU46. GTV for each patient was manually delineated based on ADC maps and fused to T2-weighted image set for planning study. A research planning system with Monte Carlo dose engine (Monaco, Elekta) was used to generate the VMAT plans with boosting dose on GTV gradually increased from 85Gy to 100Gy. DV parameters, including V(boosting-dose) (volume covered by boosting dose) for GTV, V75.6Gy for PTV, V45Gy, V70Gy, V72Gy and D1cc (Maximum dose to 1cc volume) for rectum and bladder, were used to measure plan quality. Results: All cases achieve at least 99.0% coverage of V(boosting-dose) on GTV and 95% coverage of V75.6Gy to the PTV. All the DV criteria, V45Gy≤50% and V70Gy≤15% for bladder and rectum, D1cc ≤77Gy (Rectum) and ≤80Gy (Bladder), V72Gy≤5% (rectum and bladder) were maintained when boosting GTV to 95Gy for all cases studied. Except for two patients, all the criteria were also met when the boosting dose goes to 100Gy. Conclusion: It is dosimetrically feasible safe to boost the dose to at least 95Gy to ADC defined GTV in prostate cancer using MRI guided VMAT delivery. Conclusion: It is dosimetrically feasible safe to boost the dose to at least 95Gy to ADC defined GTV in prostate cancer using MRI guided VMAT delivery. This research is partially supported by Elekta Inc.

  2. An OpenCL-based Monte Carlo dose calculation engine (oclMC) for coupled photon-electron transport

    CERN Document Server

    Tian, Zhen; Folkerts, Michael; Qin, Nan; Jiang, Steve B; Jia, Xun

    2015-01-01

    Monte Carlo (MC) method has been recognized the most accurate dose calculation method for radiotherapy. However, its extremely long computation time impedes clinical applications. Recently, a lot of efforts have been made to realize fast MC dose calculation on GPUs. Nonetheless, most of the GPU-based MC dose engines were developed in NVidia CUDA environment. This limits the code portability to other platforms, hindering the introduction of GPU-based MC simulations to clinical practice. The objective of this paper is to develop a fast cross-platform MC dose engine oclMC using OpenCL environment for external beam photon and electron radiotherapy in MeV energy range. Coupled photon-electron MC simulation was implemented with analogue simulations for photon transports and a Class II condensed history scheme for electron transports. To test the accuracy and efficiency of our dose engine oclMC, we compared dose calculation results of oclMC and gDPM, our previously developed GPU-based MC code, for a 15 MeV electron ...

  3. Effective dose evaluation for BNCT brain tumor treatment based on voxel phantoms.

    Science.gov (United States)

    Wang, Jeng-Ning; Lee, Kuo-Wei; Jiang, Shiang-Huei

    2014-06-01

    For BNCT treatments, in addition to tumor target doses, non-negligible doses will result in all the remaining organs of the body. This work aims to evaluate the effective dose as well as the average absorbed doses of each of organs of patients with brain tumor treated in the BNCT epithermal neutron beam at THOR. The effective doses were evaluated according to the definitions of ICRP Publications 60 and 103 for the reference male and female computational phantoms developed in ICRP Publication 110 by using the MCNP5 Monte Carlo code with the THOR-Y09 beam source. The effective dose acquired in this work was compared with the results of our previous work calculated for an adult hermaphrodite mathematical phantom. It was found that the effective dose for the female voxel phantom is larger than that for the male voxel phantom by a factor of 1.2-1.5 and the effective dose for the voxel phantom is larger than that for the mathematical phantom by a factor of 1.3-1.6. For a typical brain tumor BNCT, the effective dose was calculated to be 1.51Sv and the average absorbed dose for eye lenses was 1.07Gy.

  4. Promoting Conceptual Coherence Within Context-Based Biology Education

    NARCIS (Netherlands)

    Ummels, Micha H J; Kamp, Marcel J A; De Kroon, Hans; Boersma, Kerst Th

    2015-01-01

    In secondary science education, the learning and teaching of coherent conceptual understanding are often problematic. Context-based education has been proposed as a partial solution to this problem. This study aims to gain insight into the development of conceptual coherence and how context-embedded

  5. Synthesis and Biological Activities of Substituted Triazolethione Schiff Base

    Institute of Scientific and Technical Information of China (English)

    SUN, Xiao-Hong; TAO, Yan; LIU, Yuan-Fa; CHEN, Bang

    2007-01-01

    Six novel Schiff bases have been synthesized by the condensation reaction of 4-amino-5-(4-pyridyl)-2,4-dihydro-1,2,4-triazole-3-thione with various benzaldehydes. The structures of the compounds have been confirmed by 1H NMR, IR and elemental analysis. The preliminary bioassay indicated that the title compounds possessed good fungicidal activities to several vegetable pathogens.

  6. Determination of the dose of gamma radiation sterilization for assessment of biological parameters of male Ceratitis capitada (Diptera: Tephritidae), tsl - Vienna 8 strain; Determinacao da dose de radiacao gama esterilizante pela avaliacao dos parametros biologicos de machos de Ceratitis capitata (Diptera: Tephritidae), linhagem tsl - Vienna 8

    Energy Technology Data Exchange (ETDEWEB)

    Rocha, Aline Cristina Pereira da

    2011-07-01

    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 - {sup 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

  7. A Taxonomy of Causality-Based Biological Properties

    CERN Document Server

    Bodei, Chiara; Chiarugi, Davide; Gori, Roberta; 10.4204/EPTCS.19.8

    2010-01-01

    We formally characterize a set of causality-based properties of metabolic networks. This set of properties aims at making precise several notions on the production of metabolites, which are familiar in the biologists' terminology. From a theoretical point of view, biochemical reactions are abstractly represented as causal implications and the produced metabolites as causal consequences of the implication representing the corresponding reaction. The fact that a reactant is produced is represented by means of the chain of reactions that have made it exist. Such representation abstracts away from quantities, stoichiometric and thermodynamic parameters and constitutes the basis for the characterization of our properties. Moreover, we propose an effective method for verifying our properties based on an abstract model of system dynamics. This consists of a new abstract semantics for the system seen as a concurrent network and expressed using the Chemical Ground Form calculus. We illustrate an application of this fr...

  8. A Taxonomy of Causality-Based Biological Properties

    Directory of Open Access Journals (Sweden)

    Chiara Bodei

    2010-02-01

    Full Text Available We formally characterize a set of causality-based properties of metabolic networks. This set of properties aims at making precise several notions on the production of metabolites, which are familiar in the biologists' terminology. From a theoretical point of view, biochemical reactions are abstractly represented as causal implications and the produced metabolites as causal consequences of the implication representing the corresponding reaction. The fact that a reactant is produced is represented by means of the chain of reactions that have made it exist. Such representation abstracts away from quantities, stoichiometric and thermodynamic parameters and constitutes the basis for the characterization of our properties. Moreover, we propose an effective method for verifying our properties based on an abstract model of system dynamics. This consists of a new abstract semantics for the system seen as a concurrent network and expressed using the Chemical Ground Form calculus. We illustrate an application of this framework to a portion of a real metabolic pathway.

  9. Chitosan improves the biological performance of soy-based biomaterials

    OpenAIRE

    Santos, T. C.; MARQUES, A.P.; SILVA, S. S.; Oliveira, Joaquim M.; Mano, J. F.; Castro, António G.; van Griensven, Martijn; Reis, R. L.

    2010-01-01

    Soybean protein has been proposed for distinct applications within nutritional, pharmaceutical, and cosmetic industries among others. More recently, soy-based biomaterials have also demonstrated promising properties for biomedical applications.However, althoughmany reports within other fields exist, the inflammatory/immunogenic potential of those materials is still poorly understood and therefore can hardly be controlled. On the contrary, chitosan (Cht) has been well explored in t...

  10. Prospective evaluation of potential toxicity of repeated doses of Thymus vulgaris L. extracts in rats by means of clinical chemistry, histopathology and NMR-based metabonomic approach.

    Science.gov (United States)

    Benourad, Fouzia; Kahvecioglu, Zehra; Youcef-Benkada, Mokhtar; Colet, Jean-Marie

    2014-10-01

    In the field of natural extracts, research generally focuses on the study of their biological activities for food, cosmetic, or pharmacological purposes. The evaluation of their adverse effects is often overlooked. In this study, the extracts of Thymus vulgaris L. were obtained by two different extraction methods. Intraperitoneal injections of both extracts were given daily for four days to male Wistar Han rats, at two different doses for each extract. The evaluation of the potential toxic effects included histopathological examination of liver, kidney, and lung tissues, as well as serum biochemistry of liver and kidney parameters, and (1)H-NMR-based metabonomic profiles of urine. The results showed that no histopathological changes were observed in the liver and kidney in rats treated with both extracts of thyme. Serum biochemical investigations revealed significant increases in blood urea nitrogen, creatinine, and uric acid in animals treated with polyphenolic extract at both doses. In these latter groups, metabonomic analysis revealed alterations in a number of urine metabolites involved in the energy metabolism in liver mitochondria. Indeed, the results showed alterations of glycolysis, Krebs cycle, and β-oxidative pathways as evidenced by increases in lactate and ketone bodies, and decreases in citrate, α-ketoglutarate, creatinine, hippurate, dimethylglycine, and dimethyalanine. In conclusion, this work showed that i.p. injection of repeated doses of thyme extracts causes some disturbances of intermediary metabolism in rats. The metabonomic study revealed interesting data which could be further used to determine the cellular pathways affected by such treatments.

  11. Parameter-based estimation of CT dose index and image quality using an in-house android™-based software

    Science.gov (United States)

    Mubarok, S.; Lubis, L. E.; Pawiro, S. A.

    2016-03-01

    Compromise between radiation dose and image quality is essential in the use of CT imaging. CT dose index (CTDI) is currently the primary dosimetric formalisms in CT scan, while the low and high contrast resolutions are aspects indicating the image quality. This study was aimed to estimate CTDIvol and image quality measures through a range of exposure parameters variation. CTDI measurements were performed using PMMA (polymethyl methacrylate) phantom of 16 cm diameter, while the image quality test was conducted by using catphan ® 600. CTDI measurements were carried out according to IAEA TRS 457 protocol using axial scan mode, under varied parameters of tube voltage, collimation or slice thickness, and tube current. Image quality test was conducted accordingly under the same exposure parameters with CTDI measurements. An Android™ based software was also result of this study. The software was designed to estimate the value of CTDIvol with maximum difference compared to actual CTDIvol measurement of 8.97%. Image quality can also be estimated through CNR parameter with maximum difference to actual CNR measurement of 21.65%.

  12. SU-E-J-181: Effect of Prostate Motion On Combined Brachytherapy and External Beam Dose Based On Daily Motion of the Prostate

    Energy Technology Data Exchange (ETDEWEB)

    Narayana, V; McLaughlin, P [Providence Cancer Center, Southfield, MI (United States); University of Michigan, Ann Arbor, MI (United States); Ealbaj, J [University of Michigan, Ann Arbor, MI (United States)

    2015-06-15

    Purpose: In this study, the adequacy of target expansions on the combined external beam and implant dose was examined based on the measured daily motion of the prostate. Methods: Thirty patients received an I–125 prostate implant prescribed to dose of 90Gy. This was followed by external beam to deliver a dose of 90Gyeq (external beam equivalent) to the prostate over 25 to 30 fractions. An ideal IMRT plan was developed by optimizing the external beam dose based on the delivered implant dose. The implant dose was converted to an equivalent external beam dose using the linear quadratic model. Patients were set up on the treatment table by daily orthogonal imaging and aligning the marker seeds in the prostate. Orthogonal images were obtained at the end of treatment to assess prostate intrafraction motion. Based on the observed motion of the markers between the initial and final images, 5 individual plans showing the actual dose delivered to the patient were calculated. A final true dose distribution was established based on summing the implant dose and the 5 external beam plans. Dose to the prostate, seminal vesicles, lymphnodes and normal tissues, rectal wall, urethra and lower sphincter were calculated and compared to ideal. On 18 patients who were sexually active, dose to the corpus cavernosum and internal pudendal artery was also calculated. Results: The average prostate motion in 3 orthogonal directions was less than 1 mm with a standard deviation of less than +2 mm. Dose and volume parameters showed that there was no decrease in dose to the targets and a marginal decrease in dose to in normal tissues. Conclusion: Dose delivered by seed implant moves with the prostate, decreasing the impact of intrafractions dose movement on actual dose delivered. Combined brachytherapy and external beam dose delivered to the prostate was not sensitive to prostate motion.

  13. A practical and transferable methodology for dose estimation in irradiated spices, based on thermoluminescence dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    D' Oca, M.C. [Dipartimento Farmacochimico, Tossicologico e Biologico, Universita di Palermo, Via M.Cipolla 74d, 90123 Palermo (Italy)], E-mail: cristinadoca@libero.it; Bartolotta, A.; Cammilleri, C.; Giuffrida, S. [Dipartimento Farmacochimico, Tossicologico e Biologico, Universita di Palermo, Via M.Cipolla 74d, 90123 Palermo (Italy); Parlato, A. [Dipartimento di Ingegneria Nucleare, Universita di Palermo, Viale delle Scienze, Edificio 6, 90100 Palermo (Italy); Di Stefano, V. [Dipartimento di Chimica e Tecnologie Farmaceutiche, Universita di Palermo, Via Archirafi 32, 90123 Palermo (Italy)

    2010-04-15

    The thermoluminescence technique is recommended by the European Committee for Standardization for the detection of irradiated food containing silicates as contaminants. In this work, the applicability of the thermoluminescence technique as a quantitative method to assess the original dose in irradiated oregano was studied; the additive-dose method was used, with reirradiation doses up to 600 Gy. The proposed new procedure allows to clearly discriminate irradiated from unirradiated samples, even after one year storage, and it gives an acceptable estimation of the original dose; the overall modified procedure requires only one day to be completed.

  14. Synthesize of biological active substances on base carbom oxides

    Directory of Open Access Journals (Sweden)

    Kh. Suerbaev

    2012-03-01

    Full Text Available New effective method of obtaining of drugs on basice hydroxybenzoic acids and esters of isovaleric acid (drug substances «Ethylic ether of α-bromisovaleric acid», «Salycilic acid», «p-Hydroxybenzoic acid» and drugs «Validolum», «Korvalolum», «p-Aminosalycilic acid» had been worked out. The methods based on catalytical isobutylene hydroalkoxycarbonylation reaction with carbon monoxide and alcohols and phenol carboxylation reaction with alkaline salts of ethylcarbonic acid, easily obtained from carbon dioxide.

  15. Enhancing Higher Order Thinking Skills In A Marine Biology Class Through Problem-Based Learning

    Directory of Open Access Journals (Sweden)

    Richard M. Magsino

    2014-10-01

    Full Text Available The purpose of this research was to examine students' perspectives of their learning in marine biology in the collaborative group context of Problem-based Learning (PBL. Students’ higher order thinking skills (HOTS using PBL involves the development of their logical thinking and reasoning abilities which stimulates their curiosity and associative thinking. This study aimed to investigate how critical thinking skills, particularly analysis, synthesis and evaluation were enhanced in a marine biology class through PBL. Qualitative research approach was used to examine student responses in a questionnaire involving 10 open-ended questions that target students’ HOTS on a problem presented in a marine biology class for BS Biology students. Using axial coding as a qualitative data analysis technique by which grounded theory can be performed, the study was able to determine how students manifest their higher reasoning abilities when confronted with a marine biology situation. Results show student responses yielding affirmative remarks on the 10 questions intended to know their level of analysis (e.g., analyzing, classifying, inferring, discriminating and relating or connecting, synthesis (e.g., synthesizing and collaborating, and evaluation (e.g., comparing, criticizing, and convincing of information from the presented marine biology problem. Consequently, students were able to effectively design experiments to address the presented issue through problem-based learning. Results of the study show that PBL is an efficient instructional strategy embedded within a conventional curriculum used to develop or enhance critical thinking in marine biology.

  16. Bacteriophage-based synthetic biology for the study of infectious diseases

    Science.gov (United States)

    Lu, Timothy K.

    2014-01-01

    Since their discovery, bacteriophages have contributed enormously to our understanding of molecular biology as model systems. Furthermore, bacteriophages have provided many tools that have advanced the fields of genetic engineering and synthetic biology. Here, we discuss bacteriophage-based technologies and their application to the study of infectious diseases. New strategies for engineering genomes have the potential to accelerate the design of novel phages as therapies, diagnostics, and tools. Though almost a century has elapsed since their discovery, bacteriophages continue to have a major impact on modern biological sciences, especially with the growth of multidrug-resistant bacteria and interest in the microbiome. PMID:24997401

  17. Tissue decomposition from dual energy CT data for MC based dose calculation in particle therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hünemohr, Nora, E-mail: n.huenemohr@dkfz.de; Greilich, Steffen [Medical Physics in Radiation Oncology, German Cancer Research Center, 69120 Heidelberg (Germany); Paganetti, Harald; Seco, Joao [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114 (United States); Jäkel, Oliver [Medical Physics in Radiation Oncology, German Cancer Research Center, 69120 Heidelberg, Germany and Department of Radiation Oncology and Radiation Therapy, University Hospital of Heidelberg, 69120 Heidelberg (Germany)

    2014-06-15

    Purpose: The authors describe a novel method of predicting mass density and elemental mass fractions of tissues from dual energy CT (DECT) data for Monte Carlo (MC) based dose planning. Methods: The relative electron density ϱ{sub e} and effective atomic number Z{sub eff} are calculated for 71 tabulated tissue compositions. For MC simulations, the mass density is derived via one linear fit in the ϱ{sub e} that covers the entire range of tissue compositions (except lung tissue). Elemental mass fractions are predicted from the ϱ{sub e} and the Z{sub eff} in combination. Since particle therapy dose planning and verification is especially sensitive to accurate material assignment, differences to the ground truth are further analyzed for mass density, I-value predictions, and stopping power ratios (SPR) for ions. Dose studies with monoenergetic proton and carbon ions in 12 tissues which showed the largest differences of single energy CT (SECT) to DECT are presented with respect to range uncertainties. The standard approach (SECT) and the new DECT approach are compared to reference Bragg peak positions. Results: Mean deviations to ground truth in mass density predictions could be reduced for soft tissue from (0.5±0.6)% (SECT) to (0.2±0.2)% with the DECT method. Maximum SPR deviations could be reduced significantly for soft tissue from 3.1% (SECT) to 0.7% (DECT) and for bone tissue from 0.8% to 0.1%. MeanI-value deviations could be reduced for soft tissue from (1.1±1.4%, SECT) to (0.4±0.3%) with the presented method. Predictions of elemental composition were improved for every element. Mean and maximum deviations from ground truth of all elemental mass fractions could be reduced by at least a half with DECT compared to SECT (except soft tissue hydrogen and nitrogen where the reduction was slightly smaller). The carbon and oxygen mass fraction predictions profit especially from the DECT information. Dose studies showed that most of the 12 selected tissues would

  18. Feasibility of voxel-based Dose Painting for recurrent Glioblastoma guided by ADC values of Diffusion-Weighted MR imaging.

    Science.gov (United States)

    Orlandi, M; Botti, A; Sghedoni, R; Cagni, E; Ciammella, P; Iotti, C; Iori, M

    2016-12-01

    Glioblastoma Multiforme (GBM) is the most common malignant brain tumor and frequently recurs in the same location after radiotherapy. Intensive treatment targeting localized lesion is required to improve GBM outcome, but dose escalation using conventional methods is limited by healthy tissue tolerance. Helical Tomotherapy (HT) Dose Painting (DP) treatments were simulated to safely deliver high doses in the recurrent regions. Apparent Diffusion Coefficient (ADC) data from five recurrent GBM were retrospectively considered for planning. Hypo-fractionated (25-50Gy, 5 fractions) voxel-based prescriptions were opportunely converted to personalized structured-based dose maps to create DP plans with a commercial Treatment Planning System. Optimized plans were generated and analyzed in terms of plan conformity to dose prescription (Q0.90-1.10), tolerance of the healthy tissues (DMAX), and dosimetry accuracy of the deliverable plans (γ-index). Only three of the five cases could receive a safe retreatment without violating the maximum critical organs dose constraints. The conformity of the simulated plans was between 40.9% and 79.9% (Q0.90-1.10), their delivery time was in the range of 38.3-63.6min, while the dosimetry showed γ-index of 82.4-92.4%. This study proved the ability of our method to simulate personalized, deliverable and dosimetrically accurate DPBN plans. HT hypo-fractionated treatments guided by ADC maps can be realized and applied to deliver high doses in the GBM recurrent regions, although there are some critical issues related to low Q0.90-1.10 values, to exceeding of healthy-tissue dose constraints for some patients and long delivery times. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  19. Use of model-based iterative reconstruction (MBIR) in reduced-dose CT for routine follow-up of patients with malignant lymphoma: dose savings, image quality and phantom study

    Energy Technology Data Exchange (ETDEWEB)

    Herin, Edouard; Chiaradia, Melanie; Cavet, Madeleine; Deux, Jean-Francois; Rahmouni, Alain [AP-HP, Hopitaux Universitaires Henri Mondor, Imagerie Medicale, Creteil (France); Universite Paris Est Creteil, Faculte de Medecine, Creteil (France); Gardavaud, Francois; Beaussart, Pauline [AP-HP, Hopitaux Universitaires Henri Mondor, Imagerie Medicale, Creteil (France); Richard, Philippe [GE Healthcare France, Buc (France); Haioun, Corinne [Universite Paris Est Creteil, Faculte de Medecine, Creteil (France); AP-HP, Hopitaux Universitaires Henri Mondor, Hemopathies Lymphoides, Creteil (France); Itti, Emmanuel [Universite Paris Est Creteil, Faculte de Medecine, Creteil (France); AP-HP, Hopitaux Universitaires Henri Mondor, Medecine Nucleaire, Creteil (France); Luciani, Alain [AP-HP, Hopitaux Universitaires Henri Mondor, Imagerie Medicale, Creteil (France); Universite Paris Est Creteil, Faculte de Medecine, Creteil (France); INSERM Unite U 955, Creteil (France); AP-HP, Groupe Henri Mondor Albert Chenevier, Imagerie Medicale, CHU Henri Mondor, Creteil Cedex (France)

    2015-08-15

    To evaluate both in vivo and in phantom studies, dose reduction, and image quality of body CT reconstructed with model-based iterative reconstruction (MBIR), performed during patient follow-ups for lymphoma. This study included 40 patients (mean age 49 years) with lymphoma. All underwent reduced-dose CT during follow-up, reconstructed using MBIR or 50 % advanced statistical iterative reconstruction (ASIR). All had previously undergone a standard dose CT with filtered back projection (FBP) reconstruction. The volume CT dose index (CTDIvol), the density measures in liver, spleen, fat, air, and muscle, and the image quality (noise and signal to noise ratio, SNR) (ANOVA) observed using standard or reduced-dose CT were compared both in patients and a phantom study (Catphan 600) (Kruskal Wallis). The CTDIvol was decreased on reduced-dose body CT (4.06 mGy vs. 15.64 mGy p < 0.0001). SNR was higher in reduced-dose CT reconstructed with MBIR than in 50 % ASIR or than standard dose CT with FBP (patients, p ≤ 0.01; phantoms, p = 0.003). Low contrast detectability and spatial resolution in phantoms were not altered on MBIR-reconstructed CT (p ≥ 0.11). Reduced-dose CT with MBIR reconstruction can decrease radiation dose delivered to patients with lymphoma, while keeping an image quality similar to that obtained on standard-dose CT. (orig.)

  20. Biological assay of chromatin dispersal simplified for determining absorbed dose of ionizing radiation; Ensayo biologico simplificado de dispersion de cromatina para la determinacion de dosis de radiacion ionizante

    Energy Technology Data Exchange (ETDEWEB)

    Galaz, S.; Perez, G.; Stockert, J. C.; Blazquez-Castro, A.

    2011-07-01

    Currently, the production of nuclear halos chromatin dispersion methods is a good procedure for nuclear analysis by in situ hybridization (Wiegant et al., 1992, Gerdes et al. 1994), to detect apoptosis, DNA fragmentation and cell death rates in cell cultures (Fernandez et al., 2005, Enciso et al. 2006). It is customary to display the nuclear halos by fluorescence microscopy using propidium iodide, ethidium bromide or DAPI (Gerdes et al., 1994, Sestili et al. 2006). Using this technique based on a modified protocol of fast halo assay [FHA],(Sestili et al. 2006), has developed a simplified method to quantify the cytogenetic damage induced by ionizing radiation (dispersion test chromatin in agarose thin smear), which allows visualization of halos after staining for light microscopy or fluorescence and correlating the ratio: total area occuped by the halo nucleus / nucleus (halo-core index [IHN] ) with radiation dose.

  1. The contribution of 'omic'-based approaches to the study of enhanced biological phosphorus removal microbiology.

    Science.gov (United States)

    Forbes, Christina M; O'Leary, Niall D; Dobson, Alan D; Marchesi, Julian R

    2009-07-01

    The role that microorganisms play in the biological removal of phosphate from wastewater streams has received sustained interest since its initial observation over 30 years ago. Recent advances in 'omic'-based approaches have greatly advanced our knowledge in this field and facilitated a refinement of existing enhanced biological phosphate removal (EBPR) models, which were primarily based on culture-dependent approaches that had predominantly been used to investigate the process. This minireview will focus on the recent advances made in our overall understanding of the EBPR process resulting from the use of 'omic'-based methodologies.

  2. SU-E-I-41: Dictionary Learning Based Quantitative Reconstruction for Low-Dose Dual-Energy CT (DECT)

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Q [School of Electronic and Information Engineering, Xi’an Jiaotong University, Xi’an, Shaanxi 710049 (China); Department of Radiation Oncology, Stanford University, Stanford, CA 94305 (United States); Xing, L [Department of Radiation Oncology, Stanford University, Stanford, CA 94305 (United States); Xiong, G; Elmore, K; Min, J [Dalio Institute of Cardiovascular Imaging, New York-Presbyterian Hospital and Weill Cornell Medical College, New York, NY (United States)

    2015-06-15

    Purpose: DECT collects two sets of projection data under higher and lower energies. With appropriates composition methods on linear attenuation coefficients, quantitative information about the object, such as density, can be obtained. In reality, one of the important problems in DECT is the radiation dose due to doubled scans. This work is aimed at establishing a dictionary learning based reconstruction framework for DECT for improved image quality while reducing the imaging dose. Methods: In our method, two dictionaries were learned respectively from the high-energy and lowenergy image datasets of similar objects under normal dose in advance. The linear attenuation coefficient was decomposed into two basis components with material based composition method. An iterative reconstruction framework was employed. Two basis components were alternately updated with DECT datasets and dictionary learning based sparse constraints. After one updating step under the dataset fidelity constraints, both high-energy and low-energy images can be obtained from the two basis components. Sparse constraints based on the learned dictionaries were applied to the high- and low-energy images to update the two basis components. The iterative calculation continues until a pre-set number of iteration was reached. Results: We evaluated the proposed dictionary learning method with dual energy images collected using a DECT scanner. We re-projected the projection data with added Poisson noise to reflect the low-dose situation. The results obtained by the proposed method were compared with that obtained using FBP based method and TV based method. It was found that the proposed approach yield better results than other methods with higher resolution and less noise. Conclusion: The use of dictionary learned from DECT images under normal dose is valuable and leads to improved results with much lower imaging dose.

  3. Acute biological effects of simulating the whole-body radiation dose distribution from a solar particle event using a porcine model.

    Science.gov (United States)

    Wilson, Jolaine M; Sanzari, Jenine K; Diffenderfer, Eric S; Yee, Stephanie S; Seykora, John T; Maks, Casey; Ware, Jeffrey H; Litt, Harold I; Reetz, Jennifer A; McDonough, James; Weissman, Drew; Kennedy, Ann R; Cengel, Keith A

    2011-11-01

    In a solar particle event (SPE), an unshielded astronaut would receive proton radiation with an energy profile that produces a highly inhomogeneous dose distribution (skin receiving a greater dose than internal organs). The novel concept of using megavoltage electron-beam radiation to more accurately reproduce both the total dose and the dose distribution of SPE protons and make meaningful RBE comparisons between protons and conventional radiation has been described previously. Here, Yucatan minipigs were used to determine the effects of a superficial, SPE-like proton dose distribution using megavoltage electrons. In these experiments, dose-dependent increases in skin pigmentation, ulceration, keratinocyte necrosis and pigment incontinence were observed. Five of 18 animals (one each exposed to 7.5 Gy and 12.5 Gy radiation and three exposed to 25 Gy radiation) developed symptomatic, radiation-associated pneumonopathy approximately 90 days postirradiation. The three animals from the highest dose group showed evidence of mycoplasmal pneumonia along with radiation pneumonitis. Moreover, delayed-type hypersensitivity was found to be altered, suggesting that superficial irradiation of the skin with ionizing radiation might cause immune dysfunction or dysregulation. In conclusion, using total doses, patterns of dose distribution, and dose rates that are compatible with potential astronaut exposure to SPE radiation, animals experienced significant toxicities that were qualitatively different from toxicities previously reported in pigs for homogeneously delivered radiation at similar doses.

  4. Novel model-based dosing guidelines for gentamicin and tobramycin in preterm and term neonates

    NARCIS (Netherlands)

    P.A.J. Välitalo (Pyry A. J.); J.N. van den Anker (John); K. Allegaert (Karel); R.F.W. de Cock (Roosmarijn); M. de Hoog (Matthijs); S.H. Simons (Sinno); J.W. Mouton (Johan); C.A.J. Knibbe (Catherijne)

    2015-01-01

    textabstractObjectives: In the heterogeneous group of preterm and term neonates, gentamicin and tobramycin are mainly dosed according to empirical guidelines, after which therapeutic drug monitoring and subsequent dose adaptation are applied. In view of the variety of neonatal guidelines available,

  5. Immunotoxicity of perfluorinated alkylates: calculation of benchmark doses based on serum concentrations in children

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Budtz-Joergensen, Esben

    2013-01-01

    acid and 0.3 ng/mL serum for perfluorooctanoic acid at a benchmark dose response of 5%. These results are below average serum concentrations reported in recent population studies. Even lower results were obtained using logarithmic dose--response curves. Assumption of no effect below the lowest observed...

  6. Modeling low-dose-rate effects in irradiated bipolar-base oxides

    Energy Technology Data Exchange (ETDEWEB)

    Graves, R.J.; Cirba, C.R.; Schrimpf, R.D.; Milanowski, R.J.; Saigne, F. [Vanderbilt Univ., Nashville, TN (United States); Michez, A. [Univ. Montpellier 2 (France); Fleetwood, D.M. [Sandia National Labs., Albuquerque, NM (United States); Witczak, S.C. [Aerospace Corp., Los Angeles, CA (United States)

    1997-02-01

    A physical model is developed to quantify the contribution of oxide-trapped charge to enhanced low-dose-rate gain degradation in BJTs. Simulations show that space charge limited transport is partially responsible for the low-dose-rate enhancement.

  7. Impedance based sensor technology to monitor stiffness of biological structures

    Science.gov (United States)

    Annamdas, Venu Gopal Madhav; Annamdas, Kiran Kishore Kumar

    2010-04-01

    In countries like USA or Japan it is not so uncommon to have wooden structures in their homes. However, metals and its alloys are the most widely used engineering materials in construction of any military or civil structure. Revisiting natural disasters like the recent Haiti earthquake (12 Jan 2010) or Katrina (cyclones) reminds the necessity to have better housing infrastructure with robust monitoring systems. Traditionally wood is accepted as excellent rehabilitation material, after any disaster. The recycling materials extracted from in-organic, biodegradable wastes, also can be used for rehabilitation. The key issue which dampens the life of these rehabilitated structure including green materials (like wood) is unnecessary deposits (nails, screws, bolts etc)/damages due to insect attack. Thus, a few health monitoring techniques have emerged in the recent past. Electromechanical Impedance technique is one such technique, which is simple but robust to detect variations in the integrity of structures. In this paper, impedance based piezoceramic sensor was bonded on wooden sample, which was used to study changes due to metallic (steel nails) deposits at various locations. A study of weight deposits on aluminum plate was used for comparisons.

  8. Determination of radiation dose to patient by biological dosimetry in interventional radiological procedures; Estimacion de la dosis de radiacion a paciente mediante dosimetria biologica en exploraciones complejas de radiodiagnostico

    Energy Technology Data Exchange (ETDEWEB)

    Serna Berna, A.; Alcaraz, M.; Armero, D.; Navarro, J. L.; Morant, J. J.; Canteras, M.

    2006-07-01

    Interventional radiology is substituting complex surgical procedures. The requirements of high quality images and long fluoroscopy exposure times gives rise to high levels of radiation doses to patients. This topic is increasingly becoming of high concern. The purpose of this work was to evaluate the micronucleus assay (MN) in lymphocytes for the determination of the dose delivered to 15 patients who underwent interventional radiological procedures. The determination of a dose to patients supposing uniform irradiation was done with a dose-effect calibration curve previously determined for 120 keV X-rays. due to the low level of MN rate compared with background we used a bayesian approach to obtain the net MN counting rate, resulting and average counting rate of 3,2{+-}2,5 MN/500 bi nucleated cell. The group of coronariography patients resulted in higher MN rate 5,1 MN/500 BC vs 2,6 for the rest of patients. Average equivalent uniform dose for the total group of patients was 6,5{+-}2,6 cGy, while for the coronariography group was 8,8 {+-} 4,6 cGy. In conclusion, interventional radiology procedures deliver significant doses to patients and the MN assay as biological dosimeter is a good too to evaluate this range to doses. (Author)

  9. WormBase: network access to the genome and biology of Caenorhabditis elegans.

    Science.gov (United States)

    Stein, L; Sternberg, P; Durbin, R; Thierry-Mieg, J; Spieth, J

    2001-01-01

    WormBase (http://www.wormbase.org) is a web-based resource for the Caenorhabditis elegans genome and its biology. It builds upon the existing ACeDB database of the C.elegans genome by providing data curation services, a significantly expanded range of subject areas and a user-friendly front end.

  10. [Amikacin pharmacokinetics in adults: a variability that question the dose calculation based on weight].

    Science.gov (United States)

    Bourguignon, Laurent; Goutelle, Sylvain; Gérard, Cécile; Guillermet, Anne; Burdin de Saint Martin, Julie; Maire, Pascal; Ducher, Michel

    2009-01-01

    The use of amikacin is difficult because of its toxicity and its pharmacokinetic variability. This variability is almost ignored in adult standard dosage regimens since only the weight is used in the dose calculation. Our objective is to test if the pharmacokinetic of amikacin can be regarded as homogenous, and if the method for calculating the dose according to patients' weight is appropriate. From a cohort of 580 patients, five groups of patients were created by statistical data partitioning. A population pharmacokinetic analysis was performed in each group. The adult population is not homogeneous in term of pharmacokinetics. The doses required to achieve a maximum concentration of 60 mg/L are strongly different (585 to 1507 mg) between groups. The exclusive use of the weight to calculate the dose of amikacine appears inappropriate for 80% of the patients, showing the limits of the formulae for calculating doses of aminoglycosides.

  11. Polycarbonate-based benzo-δ-sultam films for high-dose dosimetry in radiation processing

    Energy Technology Data Exchange (ETDEWEB)

    Feizi, Shazad [University of Tehran, Tehran (India). School of Chemistry; Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Application Research School; Ziaie, Farhood [Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of). Radiation Application Research School; Ghandi, Mehdi [University of Tehran, Tehran (India). School of Chemistry

    2015-05-01

    In this work characteristics of the polycarbonate films with 20 μm in thickness containing different weight percentage of Benzo-δ-sultam were studied for use as a high dose dosimetry system in radiation processing facilities. The sensitivity of the dosimeters and the linearity of dose-response curves were investigated under {sup 60}Co γ-rays in a dose range of 0-100 kGy, and obtained results were compared with the commercial CTA and FWT film dosimeters. The results show that the absorbance at 348 nm depends linearly on the dose in the investigated dose range. The effects of pre-irradiation (shelf-life) and post-irradiation storage in dark and in indirect sunlight are also discussed. The results show that the dosimeters characteristics are stable within 1% at 25 C, 3 months after the irradiation.

  12. Dosage and Dose Schedule Screening of Drug Combinations in Agent-Based Models Reveals Hidden Synergies.

    Science.gov (United States)

    Barros de Andrade E Sousa, Lisa C; Kühn, Clemens; Tyc, Katarzyna M; Klipp, Edda

    2015-01-01

    The fungus Candida albicans is the most common causative agent of human fungal infections and better drugs or drug combination strategies are urgently needed. Here, we present an agent-based model of the interplay of C. albicans with the host immune system and with the microflora of the host. We took into account the morphological change of C. albicans from the yeast to hyphae form and its dynamics during infection. The model allowed us to follow the dynamics of fungal growth and morphology, of the immune cells and of microflora in different perturbing situations. We specifically focused on the consequences of microflora reduction following antibiotic treatment. Using the agent-based model, different drug types have been tested for their effectiveness, namely drugs that inhibit cell division and drugs that constrain the yeast-to-hyphae transition. Applied individually, the division drug turned out to successfully decrease hyphae while the transition drug leads to a burst in hyphae after the end of the treatment. To evaluate the effect of different drug combinations, doses, and schedules, we introduced a measure for the return to a healthy state, the infection score. Using this measure, we found that the addition of a transition drug to a division drug treatment can improve the treatment reliability while minimizing treatment duration and drug dosage. In this work we present a theoretical study. Although our model has not been calibrated to quantitative experimental data, the technique of computationally identifying synergistic treatment combinations in an agent based model exemplifies the importance of computational techniques in translational research.

  13. Dosage and dose schedule screening of drug combinations in agent-based models reveals hidden synergies

    Directory of Open Access Journals (Sweden)

    Lisa Corina Barros de Andrade e Sousa1

    2016-01-01

    Full Text Available The fungus Candida albicans is the most common causative agent of human fungal infections and better drugs or drug combination strategies are urgently needed. Here, we present an agent-based model of the interplay of C. albicans with the host immune system and with the microflora of the host. We took into account the morphological change of C. albicans from the yeast to hyphae form and its dynamics during infection. The model allowed us to follow the dynamics of fungal growth and morphology, of the immune cells and of microflora in different perturbing situations. We specifically focused on the consequences of microflora reduction following antibiotic treatment. Using the agent-based model, different drug types have been tested for their effectiveness, namely drugs that inhibit cell division and drugs that constrain the yeast-to-hyphae transition. Applied individually, the division drug turned out to successfully decrease hyphae while the transition drug leads to a burst in hyphae after the end of the treatment. To evaluate the effect of different drug combinations, doses, and schedules, we introduced a measure for the return to a healthy state, the infection score. Using this measure, we found that the addition of a transition drug to a division drug treatment can improve the treatment reliability while minimizing treatment duration and drug dosage. In this work we present a theoretical study. Although our model has not been calibrated to quantitative experimental data, the technique of computationally identifying synergistic treatment combinations in an agent based model exemplifies the importance of computational techniques in translational research.

  14. Synthesis, structural, spectroscopic and biological studies of Schiff base complexes

    Science.gov (United States)

    Diab, M. A.; El-Sonbati, A. Z.; Shoair, A. F.; Eldesoky, A. M.; El-Far, N. M.

    2017-08-01

    Schiff base ligand 4-((pyridin-2- yl)methyleneamino)-1,2-dihydro-2,3-dimethyl-1-phenylpyrazol-5-one (PDMP) and its complexes were prepared and characterized on the basis of elemental analysis, IR, mass spectra and thermogravimetric analysis. All results confirm that the complexes have 1:1 (M: PMDP) stoichiometric formula [M(PMDP)Cl2H2O ] (M = Cu(II), Co(II), Ni(II) and Mn(II)), [Cd(PMDP)Cl2] and the ligand behaves as a bi/tridentate forming five-membered chelating ring towards the metal ions, bonding through azomethine nitrogen/exocyclic carbonyl oxygen, azomethine pyridine nitrogen and exocyclic carbonyl oxygen. The shift in the band positions of the groups involved in coordination has been utilized to estimate the metal-nitrogen and/or oxygen bond lengths. The complexes of Co(II), Ni(II) and Cu(II) are paramagnetic and the magnetic as well as spectral data suggest octahedral geometry, whereas the Cd(II) complex is tetrahedral. The XRD studies show that both the ligand and its metal complexes (1 and 3) show polycrystalline with crystal structure. Molecular docking was used to predict the binding between PMDP ligand and the receptors. The corrosion inhibition of mild steel in 2 M HCl solution by PDMP was explored utilizing potentiodynamic polarization, electrochemical impedance spectroscopy (EIS) and (EFM) electrochemical frequency modulation method. Potentiodynamic polarization demonstrated that PDMP compound is mixed-type inhibitor. EIS spectra exhibit one capacitive loop and confirm the protective ability. The percentage of inhibition efficiency was found to increase with increasing the inhibitor concentration.

  15. Role of the parameters involved in the plan optimization based on the generalized equivalent uniform dose and radiobiological implications

    Science.gov (United States)

    Widesott, L.; Strigari, L.; Pressello, M. C.; Benassi, M.; Landoni, V.

    2008-03-01

    We investigated the role and the weight of the parameters involved in the intensity modulated radiation therapy (IMRT) optimization based on the generalized equivalent uniform dose (gEUD) method, for prostate and head-and-neck plans. We systematically varied the parameters (gEUDmax and weight) involved in the gEUD-based optimization of rectal wall and parotid glands. We found that the proper value of weight factor, still guaranteeing planning treatment volumes coverage, produced similar organs at risks dose-volume (DV) histograms for different gEUDmax with fixed a = 1. Most of all, we formulated a simple relation that links the reference gEUDmax and the associated weight factor. As secondary objective, we evaluated plans obtained with the gEUD-based optimization and ones based on DV criteria, using the normal tissue complication probability (NTCP) models. gEUD criteria seemed to improve sparing of rectum and parotid glands with respect to DV-based optimization: the mean dose, the V40 and V50 values to the rectal wall were decreased of about 10%, the mean dose to parotids decreased of about 20-30%. But more than the OARs sparing, we underlined the halving of the OARs optimization time with the implementation of the gEUD-based cost function. Using NTCP models we enhanced differences between the two optimization criteria for parotid glands, but no for rectum wall.

  16. Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico

    Science.gov (United States)

    Luevano-Gurrola, Sergio; Perez-Tapia, Angelica; Pinedo-Alvarez, Carmelo; Carrillo-Flores, Jorge; Montero-Cabrera, Maria Elena; Renteria-Villalobos, Marusia

    2015-01-01

    Determining ionizing radiation in a geographic area serves to assess its effects on a population’s health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h−1. At the same sites, 48 soil samples were taken to obtain the activity concentrations of 226Ra, 232Th and 40K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h−1. Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg−1, for 226Ra, 232Th and 40K, respectively. From the analysis, the spatial distribution of 232Th, 226Ra and 40K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize. PMID:26437425

  17. Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico.

    Science.gov (United States)

    Luevano-Gurrola, Sergio; Perez-Tapia, Angelica; Pinedo-Alvarez, Carmelo; Carrillo-Flores, Jorge; Montero-Cabrera, Maria Elena; Renteria-Villalobos, Marusia

    2015-09-30

    Determining ionizing radiation in a geographic area serves to assess its effects on a population's health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h(-1). At the same sites, 48 soil samples were taken to obtain the activity concentrations of (226)Ra, (232)Th and (40)K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h(-1). Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg(-1), for (226)Ra, (232)Th and (40)K, respectively. From the analysis, the spatial distribution of (232)Th, (226)Ra and (40)K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize.

  18. Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico

    Directory of Open Access Journals (Sweden)

    Sergio Luevano-Gurrola

    2015-09-01

    Full Text Available Determining ionizing radiation in a geographic area serves to assess its effects on a population’s health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h−1. At the same sites, 48 soil samples were taken to obtain the activity concentrations of 226Ra, 232Th and 40K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h−1. Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg−1, for 226Ra, 232Th and 40K, respectively. From the analysis, the spatial distribution of 232Th, 226Ra and 40K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize.

  19. SU-E-T-107: Development of a GPU-Based Dose Delivery System for Adaptive Pencil Beam Scanning

    Energy Technology Data Exchange (ETDEWEB)

    Giordanengo, S; Russo, G; Marchetto, F; Attili, A [Istituto Nazionale di Fisica Nucleare, Section of Torino, Torino (Italy); Monaco, V; Varasteh, M [University of Torino, Torino (Italy); Pella, A [Centro Nazionale di Adroterapia Oncologica, Pavia (Italy)

    2014-06-01

    Purpose: A description of a GPU-based dose delivery system (G-DDS) to integrate a fast forward planning implementing in real-time the prescribed sequence of pencil beams. The system, which is under development, is designed to evaluate the dose distribution deviations due to range variations and interplay effects affecting mobile tumors treatments. Methods: The Dose Delivery System (DDS) in use at the Italian Centro Nazionale di Adroterapia Oncologica (CNAO), is the starting point for the presented system. A fast and partial forward planning (FP) tool has been developed to evaluate in few seconds the delivered dose distributions using the DDS data (on-line measurements of spot properties, i.e. number of particles and positions). The computation is performed during the intervals between synchrotron spills and, made available at t