Sample records for critical dose values

  1. Geometric parameter analysis to predetermine optimal radiosurgery technique for the treatment of arteriovenous malformation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mestrovic, Ante; Clark, Brenda G.; Department of Medical Physics, British Columbia Cancer Agency, Vancouver, British Columbia

    2005-11-01

    Purpose: To develop a method of predicting the values of dose distribution parameters of different radiosurgery techniques for treatment of arteriovenous malformation (AVM) based on internal geometric parameters. Methods and Materials: For each of 18 previously treated AVM patients, four treatment plans were created: circular collimator arcs, dynamic conformal arcs, fixed conformal fields, and intensity-modulated radiosurgery. An algorithm was developed to characterize the target and critical structure shape complexity and the position of the critical structures with respect to the target. Multiple regression was employed to establish the correlation between the internal geometric parameters and the dose distribution for differentmore » treatment techniques. The results from the model were applied to predict the dosimetric outcomes of different radiosurgery techniques and select the optimal radiosurgery technique for a number of AVM patients. Results: Several internal geometric parameters showing statistically significant correlation (p < 0.05) with the treatment planning results for each technique were identified. The target volume and the average minimum distance between the target and the critical structures were the most effective predictors for normal tissue dose distribution. The structure overlap volume with the target and the mean distance between the target and the critical structure were the most effective predictors for critical structure dose distribution. The predicted values of dose distribution parameters of different radiosurgery techniques were in close agreement with the original data. Conclusions: A statistical model has been described that successfully predicts the values of dose distribution parameters of different radiosurgery techniques and may be used to predetermine the optimal technique on a patient-to-patient basis.« less

  2. A Probabilistic Approach to Uncertainty Analysis in NTPR Radiation Dose Assessments

    DTIC Science & Technology

    2009-11-01

    Zeman, members of the Subcommittee on Dose Reconstruction of the Veterans’ Advisory Board on Dose Reconstruction (VBDR) for their critical review of...production and decay of fission products, activation products, and actinides . (It is generally assumed in these calculations that no 30 Time...histories”), and on each history selecting random values from each of the pdf’s, they were able to conduct “numerical experiments” and derive critical

  3. SU-F-T-659: Nanoparticle-Aided Eye Plaque Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chin, J; Ngwa, W

    Purpose: Eye plaque brachytherapy is one of the approaches for radiotherapy treatment for ocular cancers: retinoblastoma and choroidal melanoma. This study, investigates the potential benefits of using gold nanoparticles to enhance therapeutic efficacy during eye plaque brachytherapy. Methods: The EYE PHYSICS Inc. Plaque Simulator program distributed by IsoAid, LLC, Port Richey, Florida was used. It is based on the superposition of dose contributions from individual seeds following the TG–43 formalism. Dose enhancement factor (DEF) values for feasible nanoparticle concentrations from previous studies was used to investigate the benefit of using nanoparticles to enhance dose to tumour or reduce dose tomore » healthy tissue. The dose enhancement factor (DEF) represents the ratio of the dose deposited in tumour with nanoparticles divided by dose deposited in the tumour without nanoparticles. The investigation was done for I–125 and Pd–103 typical sources employed for eye plaque brachytherapy. The prescription dose used is 85 Gy. Results: Lower dose enhancement values were obtained for Pd–103. With DEF of 2 due to gold nanoparticles, critical structure doses reduce by a factor of 2. Optic disc dose is 6.69 Gy and 4.571 Gy, opposite retina dose is 4.064 and 2.484 Gy, lens dose is 12.66 Gy and 9.870 Gy, and fovea dose is 9.85 Gy and 7.275 Gy. With DEF of 3 due to gold nanoparticles, critical structure doses reduce by a factor of 3. Optic disc dose is 4.352 Gy and 2.975 Gy, opposite retina dose is 2.644 Gy and 1.618 Gy, lens dose is 8.322 Gy and 6.427 Gy, and fovea dose is 4.815 Gy and 4.737 Gy. Conclusion: The results of this research predict that using gold nanoparticles will lead to major sparing of dose to critical structures. The finding provides more impetus for the development of nanoparticle–aided brachytherapy.« less

  4. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Botas, Pablo; Faculty of Physics, Ruprecht-Karls-Universität Heidelberg, Heidelberg

    Purpose: We describe a treatment plan optimization method for intensity modulated proton therapy (IMPT) that avoids high values of linear energy transfer (LET) in critical structures located within or near the target volume while limiting degradation of the best possible physical dose distribution. Methods and Materials: To allow fast optimization based on dose and LET, a GPU-based Monte Carlo code was extended to provide dose-averaged LET in addition to dose for all pencil beams. After optimizing an initial IMPT plan based on physical dose, a prioritized optimization scheme is used to modify the LET distribution while constraining the physical dosemore » objectives to values close to the initial plan. The LET optimization step is performed based on objective functions evaluated for the product of LET and physical dose (LET×D). To first approximation, LET×D represents a measure of the additional biological dose that is caused by high LET. Results: The method is effective for treatments where serial critical structures with maximum dose constraints are located within or near the target. We report on 5 patients with intracranial tumors (high-grade meningiomas, base-of-skull chordomas, ependymomas) in whom the target volume overlaps with the brainstem and optic structures. In all cases, high LET×D in critical structures could be avoided while minimally compromising physical dose planning objectives. Conclusion: LET-based reoptimization of IMPT plans represents a pragmatic approach to bridge the gap between purely physical dose-based and relative biological effectiveness (RBE)-based planning. The method makes IMPT treatments safer by mitigating a potentially increased risk of side effects resulting from elevated RBE of proton beams near the end of range.« less

  5. Dose impact in radiographic lung injury following lung SBRT: Statistical analysis and geometric interpretation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yu, Victoria; Kishan, Amar U.; Cao, Minsong

    2014-03-15

    Purpose: To demonstrate a new method of evaluating dose response of treatment-induced lung radiographic injury post-SBRT (stereotactic body radiotherapy) treatment and the discovery of bimodal dose behavior within clinically identified injury volumes. Methods: Follow-up CT scans at 3, 6, and 12 months were acquired from 24 patients treated with SBRT for stage-1 primary lung cancers or oligometastic lesions. Injury regions in these scans were propagated to the planning CT coordinates by performing deformable registration of the follow-ups to the planning CTs. A bimodal behavior was repeatedly observed from the probability distribution for dose values within the deformed injury regions. Basedmore » on a mixture-Gaussian assumption, an Expectation-Maximization (EM) algorithm was used to obtain characteristic parameters for such distribution. Geometric analysis was performed to interpret such parameters and infer the critical dose level that is potentially inductive of post-SBRT lung injury. Results: The Gaussian mixture obtained from the EM algorithm closely approximates the empirical dose histogram within the injury volume with good consistency. The average Kullback-Leibler divergence values between the empirical differential dose volume histogram and the EM-obtained Gaussian mixture distribution were calculated to be 0.069, 0.063, and 0.092 for the 3, 6, and 12 month follow-up groups, respectively. The lower Gaussian component was located at approximately 70% prescription dose (35 Gy) for all three follow-up time points. The higher Gaussian component, contributed by the dose received by planning target volume, was located at around 107% of the prescription dose. Geometrical analysis suggests the mean of the lower Gaussian component, located at 35 Gy, as a possible indicator for a critical dose that induces lung injury after SBRT. Conclusions: An innovative and improved method for analyzing the correspondence between lung radiographic injury and SBRT treatment dose has been demonstrated. Bimodal behavior was observed in the dose distribution of lung injury after SBRT. Novel statistical and geometrical analysis has shown that the systematically quantified low-dose peak at approximately 35 Gy, or 70% prescription dose, is a good indication of a critical dose for injury. The determined critical dose of 35 Gy resembles the critical dose volume limit of 30 Gy for ipsilateral bronchus in RTOG 0618 and results from previous studies. The authors seek to further extend this improved analysis method to a larger cohort to better understand the interpatient variation in radiographic lung injury dose response post-SBRT.« less

  6. Role of renal function in risk assessment of target non-attainment after standard dosing of meropenem in critically ill patients: a prospective observational study.

    PubMed

    Ehmann, Lisa; Zoller, Michael; Minichmayr, Iris K; Scharf, Christina; Maier, Barbara; Schmitt, Maximilian V; Hartung, Niklas; Huisinga, Wilhelm; Vogeser, Michael; Frey, Lorenz; Zander, Johannes; Kloft, Charlotte

    2017-10-21

    Severe bacterial infections remain a major challenge in intensive care units because of their high prevalence and mortality. Adequate antibiotic exposure has been associated with clinical success in critically ill patients. The objective of this study was to investigate the target attainment of standard meropenem dosing in a heterogeneous critically ill population, to quantify the impact of the full renal function spectrum on meropenem exposure and target attainment, and ultimately to translate the findings into a tool for practical application. A prospective observational single-centre study was performed with critically ill patients with severe infections receiving standard dosing of meropenem. Serial blood samples were drawn over 4 study days to determine meropenem serum concentrations. Renal function was assessed by creatinine clearance according to the Cockcroft and Gault equation (CLCR CG ). Variability in meropenem serum concentrations was quantified at the middle and end of each monitored dosing interval. The attainment of two pharmacokinetic/pharmacodynamic targets (100%T >MIC , 50%T >4×MIC ) was evaluated for minimum inhibitory concentration (MIC) values of 2 mg/L and 8 mg/L and standard meropenem dosing (1000 mg, 30-minute infusion, every 8 h). Furthermore, we assessed the impact of CLCR CG on meropenem concentrations and target attainment and developed a tool for risk assessment of target non-attainment. Large inter- and intra-patient variability in meropenem concentrations was observed in the critically ill population (n = 48). Attainment of the target 100%T >MIC was merely 48.4% and 20.6%, given MIC values of 2 mg/L and 8 mg/L, respectively, and similar for the target 50%T >4×MIC . A hyperbolic relationship between CLCR CG (25-255 ml/minute) and meropenem serum concentrations at the end of the dosing interval (C 8h ) was derived. For infections with pathogens of MIC 2 mg/L, mild renal impairment up to augmented renal function was identified as a risk factor for target non-attainment (for MIC 8 mg/L, additionally, moderate renal impairment). The investigated standard meropenem dosing regimen appeared to result in insufficient meropenem exposure in a considerable fraction of critically ill patients. An easy- and free-to-use tool (the MeroRisk Calculator) for assessing the risk of target non-attainment for a given renal function and MIC value was developed. Clinicaltrials.gov, NCT01793012 . Registered on 24 January 2013.

  7. Are standard doses of piperacillin sufficient for critically ill patients with augmented creatinine clearance?

    PubMed

    Udy, Andrew A; Lipman, Jeffrey; Jarrett, Paul; Klein, Kerenaftali; Wallis, Steven C; Patel, Kashyap; Kirkpatrick, Carl M J; Kruger, Peter S; Paterson, David L; Roberts, Michael S; Roberts, Jason A

    2015-01-30

    The aim of this study was to explore the impact of augmented creatinine clearance and differing minimum inhibitory concentrations (MIC) on piperacillin pharmacokinetic/pharmacodynamic (PK/PD) target attainment (time above MIC (fT>MIC)) in critically ill patients with sepsis receiving intermittent dosing. To be eligible for enrolment, critically ill patients with sepsis had to be receiving piperacillin-tazobactam 4.5 g intravenously (IV) by intermittent infusion every 6 hours for presumed or confirmed nosocomial infection without significant renal impairment (defined by a plasma creatinine concentration greater than 171 μmol/L or the need for renal replacement therapy). Over a single dosing interval, blood samples were drawn to determine unbound plasma piperacillin concentrations. Renal function was assessed by measuring creatinine clearance (CLCR). A population PK model was constructed, and the probability of target attainment (PTA) for 50% and 100% fT>MIC was calculated for varying MIC and CLCR values. In total, 48 patients provided data. Increasing CLCR values were associated with lower trough plasma piperacillin concentrations (P < 0.01), such that with an MIC of 16 mg/L, 100% fT>MIC would be achieved in only one-third (n = 16) of patients. Mean piperacillin clearance was approximately 1.5-fold higher than in healthy volunteers and correlated with CLCR (r = 0.58, P < 0.01). A reduced PTA for all MIC values, when targeting either 50% or 100% fT>MIC, was noted with increasing CLCR measures. Standard intermittent piperacillin-tazobactam dosing is unlikely to achieve optimal piperacillin exposures in a significant proportion of critically ill patients with sepsis, owing to elevated drug clearance. These data suggest that CLCR can be employed as a useful tool to determine whether piperacillin PK/PD target attainment is likely with a range of MIC values.

  8. Dosimetric comparison between 10MV-FFF and 6MV-FFF for lung SBRT

    NASA Astrophysics Data System (ADS)

    Durmus, I. F.; Atalay, E. D.

    2017-02-01

    Plans were prepared by using same non-coplanar fields and physical parameters in 6MV-FFF and 10MV-FFF energies for fourteen lung Stereotactic Body Radio Therapy (SBRT) patients. In two plans which have different energies, critic organ doses, PTV doses, quality of plans (Gradient Index (GI), Homogeneity Index (HI), Conformity Index (CI)) and Monitor Unit (MU) values were compared. Quality controls were performed with 2D-Array Iba MatriXX Evolution® dosimetry system for each plans. As a results, plan with 6MV-FFF energy give better results in terms of CI and GI values. In this way, when more conformal dose distributions were provided, there was a rapid dose decrease at out of target volume. Lower MU values were obtained in plans which was prepared with 10MV-FFF energy. In plan with 10MV-FFF energy lower MU values are obtained. Lower values in heart and spinal cord doses are founded and better results are obtained in Body and Ipsa-Lung V5, V10, V20 values with 6MV-FFF energies. When differences were very small in volume which were taken low dose (V5), these differences increased in volume which were taken high dose (V20). High dose rates can be reached by both two unfiltered energies and can be used in lung SBRT.

  9. Improving the Accuracy of a Heliocentric Potential (HCP) Prediction Model for the Aviation Radiation Dose

    NASA Astrophysics Data System (ADS)

    Hwang, Junga; Yoon, Kyoung-Won; Jo, Gyeongbok; Noh, Sung-Jun

    2016-12-01

    The space radiation dose over air routes including polar routes should be carefully considered, especially when space weather shows sudden disturbances such as coronal mass ejections (CMEs), flares, and accompanying solar energetic particle events. We recently established a heliocentric potential (HCP) prediction model for real-time operation of the CARI-6 and CARI-6M programs. Specifically, the HCP value is used as a critical input value in the CARI-6/6M programs, which estimate the aviation route dose based on the effective dose rate. The CARI-6/6M approach is the most widely used technique, and the programs can be obtained from the U.S. Federal Aviation Administration (FAA). However, HCP values are given at a one month delay on the FAA official webpage, which makes it difficult to obtain real-time information on the aviation route dose. In order to overcome this critical limitation regarding the time delay for space weather customers, we developed a HCP prediction model based on sunspot number variations (Hwang et al. 2015). In this paper, we focus on improvements to our HCP prediction model and update it with neutron monitoring data. We found that the most accurate method to derive the HCP value involves (1) real-time daily sunspot assessments, (2) predictions of the daily HCP by our prediction algorithm, and (3) calculations of the resultant daily effective dose rate. Additionally, we also derived the HCP prediction algorithm in this paper by using ground neutron counts. With the compensation stemming from the use of ground neutron count data, the newly developed HCP prediction model was improved.

  10. Evaluation of variations in absorbed dose and image noise according to patient forms in X-ray computed tomography.

    PubMed

    Matsubara, Kosuke; Koshida, Kichiro; Suzuki, Masayuki; Hayakawa, Mayumi; Tsujii, Hideo; Yamamoto, Tomoyuki

    2005-12-20

    Excessive radiation exposure in pediatric computed tomography (CT) scanning has become a serious problem, and it is difficult to select scan parameters for the scanning of small patients such as children. We investigated differences in absorbed dose and standard deviation (SD) in Hounsfield unit (HU) caused by differences in the form of the subject using a body-type phantom with removable body parts. Using four X-ray CT scanners, measurements were made with values from 50 mAs to 300 mAs, with slices of 50 mAs, using scan protocols that were assumed to perform thorough examinations. The results showed that the mAs values and absorbed doses were almost proportional, and the absorbed doses in the phantom without body parts were about 1.1-2.2-fold higher than those of the phantom with body parts at the same points. The SD values obtained indicated that the absorbed doses in the phantom with body parts were 0.3-0.6 times those of the phantom without body parts when the mAs values used were adjusted so that both SD values were the same. The absorbed doses in various patient forms can be estimated from these results, and they will become critical data for the selection of appropriate scan protocols.

  11. Combined Effects of Supersaturation Rates and Doses on the Kinetic-Solubility Profiles of Amorphous Solid Dispersions Based on Water-Insoluble Poly(2-hydroxyethyl methacrylate) Hydrogels.

    PubMed

    Schver, Giovanna C R M; Lee, Ping I

    2018-05-07

    Under nonsink dissolution conditions, the kinetic-solubility profiles of amorphous solid dispersions (ASDs) based on soluble carriers typically exhibit so-called "spring-and-parachute" concentration-time behaviors. However, the kinetic-solubility profiles of ASDs based on insoluble carriers (including hydrogels) are known to show sustained supersaturation during nonsink dissolution through a matrix-regulated diffusion mechanism by which the supersaturation of the drug is built up gradually and sustained over an extended period without any dissolved polymers acting as crystallization inhibitors. Despite previous findings demonstrating the interplay between supersaturation rates and total doses on the kinetic-solubility profiles of soluble amorphous systems (including ASDs based on dissolution-regulated releases from soluble polymer carriers), the combined effects of supersaturation rates and doses on the kinetic-solubility profiles of ASDs based on diffusion-regulated releases from water-insoluble carriers have not been investigated previously. Thus, the objective of this study is to examine the impacts of total doses and supersaturation-generation rates on the resulting kinetic-solubility profiles of ASDs based on insoluble hydrogel carriers. We employed a previously established ASD-carrier system based on water-insoluble-cross-linked-poly(2-hydroxyethyl methacrylate) (PHEMA)-hydrogel beads and two poorly water soluble model drugs: the weakly acidic indomethacin (IND) and the weakly basic posaconazole (PCZ). Our results show clearly for the first time that by using the smallest-particle-size fraction and a high dose (i.e., above the critical dose), it is indeed possible to significantly shorten the duration of sustained supersaturation in the kinetic-solubility profile of an ASD based on a water-insoluble hydrogel carrier, such that it resembles the spring-and-parachute dissolution profiles normally associated with ASDs based on soluble carriers. This generates sufficiently rapid initial supersaturation buildup above the critical supersaturation, resulting in more rapid precipitation. Above this smallest-particle-size range, the matrix-diffusion-regulated nonlinear rate of drug release gets slower, which results in a more modest rate of supersaturation buildup, leading to a maximum supersaturation below the critical-supersaturation level without appreciable precipitation. The area-under-the-curve (AUC) values of the in vitro kinetic-solubility concentration-time profiles were used to correlate the corresponding trends in dissolution enhancement. There are observed monotonic increases in AUC values with increasing particle sizes for high-dose ASDs based on water-insoluble hydrogel matrixes, as opposed to the previously reported AUC maxima at some intermediate supersaturation rates or doses in soluble amorphous systems, whereas in the case of low-dose ASDs (i.e., below the critical dose levels), crystallization would be negligible, leading to sustained supersaturation with all particle sizes (i.e., eventually reaching the same maximum supersaturation) and the smallest particle size reaching the maximum supersaturation the fastest. As a result, the smallest particle sizes yield the largest AUC values in the case of low-dose ASDs based on water-insoluble hydrogel matrixes. In addition to probing the interplay between the supersaturation-generation rates and total doses in ASDs based on insoluble hydrogel carriers, our results further support the fact that through either increasing the hydrogel-particle size or lowering the total dose to achieve maximum supersaturation still below the critical-supersaturation level, it is possible to avoid drug precipitation so as to maintain sustained supersaturation.

  12. Doses to organs and tissues from concomitant imaging in radiotherapy: a suggested framework for clinical justification.

    PubMed

    Harrison, R M

    2008-12-01

    The increasing use of imaging for localization and verification in radiotherapy has raised issues concerning the justifiable doses to critical organs and tissues from concomitant exposures, particularly when extensive image-guided radiotherapy is indicated. Doses at positions remote from the target volume include components from high-energy leakage and scatter, as well as from concomitant imaging. In this paper, simulated prostate, breast and larynx treatments are used to compare doses from both high-energy and concomitant exposures as a function of distance from the target volume. It is suggested that the fraction, R, of the total dose at any point within the patient that is attributable to concomitant exposures may be a useful aid in their justification. R is small within the target volume and at large distances from it. However, there is a critical region immediately adjacent to the planning target volume where the dose from concomitant imaging combines with leakage and scatter to give values of R that approach 0.5 in the examples given here. This is noteworthy because the regions just outside the target volume will receive total doses in the order of 1 Gy, where commensurately high risk factors may not be substantially reduced because of cell kill. Other studies have identified these regions as sites of second cancers. The justification of an imaging regimen might therefore usefully take into account the maximum value of R encountered from the combination of imaging and radiotherapy for particular treatment sites.

  13. Linear energy transfer incorporated intensity modulated proton therapy optimization

    NASA Astrophysics Data System (ADS)

    Cao, Wenhua; Khabazian, Azin; Yepes, Pablo P.; Lim, Gino; Poenisch, Falk; Grosshans, David R.; Mohan, Radhe

    2018-01-01

    The purpose of this study was to investigate the feasibility of incorporating linear energy transfer (LET) into the optimization of intensity modulated proton therapy (IMPT) plans. Because increased LET correlates with increased biological effectiveness of protons, high LETs in target volumes and low LETs in critical structures and normal tissues are preferred in an IMPT plan. However, if not explicitly incorporated into the optimization criteria, different IMPT plans may yield similar physical dose distributions but greatly different LET, specifically dose-averaged LET, distributions. Conventionally, the IMPT optimization criteria (or cost function) only includes dose-based objectives in which the relative biological effectiveness (RBE) is assumed to have a constant value of 1.1. In this study, we added LET-based objectives for maximizing LET in target volumes and minimizing LET in critical structures and normal tissues. Due to the fractional programming nature of the resulting model, we used a variable reformulation approach so that the optimization process is computationally equivalent to conventional IMPT optimization. In this study, five brain tumor patients who had been treated with proton therapy at our institution were selected. Two plans were created for each patient based on the proposed LET-incorporated optimization (LETOpt) and the conventional dose-based optimization (DoseOpt). The optimized plans were compared in terms of both dose (assuming a constant RBE of 1.1 as adopted in clinical practice) and LET. Both optimization approaches were able to generate comparable dose distributions. The LET-incorporated optimization achieved not only pronounced reduction of LET values in critical organs, such as brainstem and optic chiasm, but also increased LET in target volumes, compared to the conventional dose-based optimization. However, on occasion, there was a need to tradeoff the acceptability of dose and LET distributions. Our conclusion is that the inclusion of LET-dependent criteria in the IMPT optimization could lead to similar dose distributions as the conventional optimization but superior LET distributions in target volumes and normal tissues. This may have substantial advantages in improving tumor control and reducing normal tissue toxicities.

  14. Chemical dosimetry system for criticality accidents.

    PubMed

    Miljanić, Saveta; Ilijas, Boris

    2004-01-01

    Ruder Bosković Institute (RBI) criticality dosimetry system consists of a chemical dosimetry system for measuring the total (neutron + gamma) dose, and a thermoluminescent (TL) dosimetry system for a separate determination of the gamma ray component. The use of the chemical dosemeter solution chlorobenzene-ethanol-trimethylpentane (CET) is based on the radiolytic formation of hydrochloric acid, which protonates a pH indicator, thymolsulphonphthalein. The high molar absorptivity of its red form at 552 nm is responsible for a high sensitivity of the system: doses in the range 0.2-15 Gy can be measured. The dosemeter has been designed as a glass ampoule filled with the CET solution and inserted into a pen-shaped plastic holder. For dose determinations, a newly constructed optoelectronic reader has been used. The RBI team took part in the International Intercomparison of Criticality Accident Dosimetry Systems at the SILENE Reactor, Valduc, June 2002, with the CET dosimetry system. For gamma ray dose determination TLD-700 TL detectors were used. The results obtained with CET dosemeter show very good agreement with the reference values.

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

    PubMed

    Klingenberg, B

    2009-01-30

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

  16. Radiation exposure and risk assessment for critical female body organs

    NASA Technical Reports Server (NTRS)

    Atwell, William; Weyland, Mark D.; Hardy, Alva C.

    1991-01-01

    Space radiation exposure limits for astronauts are based on recommendations of the National Council on Radiation Protection and Measurements. These limits now include the age at exposure and sex of the astronaut. A recently-developed computerized anatomical female (CAF) model is discussed in detail. Computer-generated, cross-sectional data are presented to illustrate the completeness of the CAF model. By applying ray-tracing techniques, shield distribution functions have been computed to calculate absorbed dose and dose equivalent values for a variety of critical body organs (e.g., breasts, lungs, thyroid gland, etc.) and mission scenarios. Specific risk assessments, i.e., cancer induction and mortality, are reviewed.

  17. SU-E-T-375: Passive Scattering to Pencil-Beam-Scanning Comparison for Medulloblastoma Proton Therapy: LET Distributions and Radiobiological Implications

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Giantsoudi, D; MacDonald, S; Paganetti, H

    2014-06-01

    Purpose: To compare the linear energy transfer (LET) distributions between passive scattering and pencil beam scanning proton radiation therapy techniques for medulloblastoma patients and study the potential radiobiological implications. Methods: A group of medulloblastoma patients, previously treated with passive scattering (PS) proton craniospinal irradiation followed by prosterior fossa or involved field boost, were selected from the patient database of our institution. Using the beam geometry and planning computed tomography (CT) image sets of the original treatment plans, pencil beam scanning (PBS) treatment plans were generated for the cranial treatment for each patient, with average beam spot size of 8mm (sigmamore » in air at isocenter). 3-dimensional dose and LET distributions were calculated by Monte Carlo methods (TOPAS) both for the original passive scattering and new pencil beam scanning treatment plans. LET volume histograms were calculated for the target and OARs and compared for the two delivery methods. Variable RBE weighted dose distributions and volume histograms were also calculated using a variable dose and LET-based model. Results: Better dose conformity was achieved with PBS planning compared to PS, leading to increased dose coverage for the boost target area and decreased average dose to the structures adjacent to it and critical structures outside the whole brain treatment field. LET values for the target were lower for PBS plans. Elevated LET values for OARs close to the boosted target areas were noticed, due to end of range of proton beams falling inside these structures, resulting in higher RBE weighted dose for these structures compared to the clinical RBE value of 1.1. Conclusion: Transitioning from passive scattering to pencil beam scanning proton radiation treatment can be dosimetrically beneficial for medulloblastoma patients. LET–guided treatment planning could contribute to better decision making for these cases, especially for critical structures at close proximity to the boosted target area.« less

  18. Radiation doses to members of the public near to Sellafield, Cumbria, from liquid discharges 1952-98.

    PubMed

    Jackson, D; Lambers, B; Gray, J

    2000-06-01

    Liquid wastes containing low levels of radioactivity have been discharged to the Irish Sea from the nuclear fuel reprocessing site at Sellafield since operations began in the early 1950s, and monitoring of radioactivity in foodstuffs has been undertaken over many years. Based on the best available monitoring data, supplemented by modelled values where necessary, doses to local critical groups have been reassessed using the most recent dosimetry. Contemporary habits data have been used where available, again supplemented by assumed habits where necessary. During the 1950s and 1960s the highest doses were received by individuals consuming Cumbrian Porphyra as laverbread, and peak doses around 0.8 to 1.0 mSv year(-1) have been estimated. During the 1970s and 1980s the critical exposure group switched to consumers of local fish and shellfish, with peak doses possibly reaching 2.5 to 3.0 mSv year(-1). Latterly, doses to all marine-related groups have declined to less than 150 to 200 microSv year(-1). At all times, doses have been within the appropriate limits set for members of the public.

  19. Methamphetamine blood concentrations in human abusers: application to pharmacokinetic modeling.

    PubMed

    Melega, William P; Cho, Arthur K; Harvey, Dennis; Laćan, Goran

    2007-04-01

    Characterization of methamphetamine's (METH) dose-dependent effects on brain neurochemistry may represent a critical component for better understanding the range of resultant behavioral pathologies. Most human studies, however, have assessed only the effects of long term, high dose METH abuse (e.g., greater than 1000 mg/day) in individuals meeting DSM-IV criteria for METH dependence. Yet, for the majority of METH abusers, their patterns of METH exposure that consist of lower doses remain less well-characterized. In this study, blood samples were obtained from 105 individuals detained by police for possible criminal activity and testing positive for stimulants by EMIT assay. METH blood concentrations were subsequently quantified by GC-MS and were predominantly in the low micromolar range (0.1-11.1 microM), with median and mean values of 1.3 microM (0.19 mg/l) and 2 microM (0.3 mg/l), respectively. Pharmacokinetic calculations based on these measured values were used to estimate initial METH body burdens, the median value being 52 mg. Modeling a 52 mg dose for a 4 day-METH maintenance exposure pattern of 4 doses/day at 4 h intervals showed that blood concentrations remained between 1 and 4 microM during this period. Collectively, these data present evidence for a METH exposure pattern distinct from high dose-METH abuse and provide the rationale for assessing potential brain pathology associated with such lower dose-METH exposure.

  20. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gorissen, BL; Giantsoudi, D; Unkelbach, J

    Purpose: Cell survival experiments suggest that the relative biological effectiveness (RBE) of proton beams depends on linear energy transfer (LET), leading to higher RBE near the end of range. With intensity-modulated proton therapy (IMPT), multiple treatment plans that differ in the dose contribution per field may yield a similar physical dose distribution, but the RBE-weighted dose distribution may be disparate. RBE models currently do not have the required predictive power to be included in an optimization model due to the variations in experimental data. We propose an LET-based planning method that guides IMPT optimization models towards plans with reduced RBE-weightedmore » dose in surrounding organs at risk (OARs) compared to inverse planning based on physical dose alone. Methods: Optimization models for physical dose are extended with a term for dose times LET (doseLET). Monte Carlo code is used to generate the physical dose and doseLET distribution of each individual pencil beam. The method is demonstrated for an atypical meningioma patient where the target volume abuts the brainstem and partially overlaps with the optic nerve. Results: A reference plan optimized based on physical dose alone yields high doseLET values in parts of the brainstem and optic nerve. Minimizing doseLET in these critical structures as an additional planning goal reduces the risk of high RBE-weighted dose. The resulting treatment plan avoids the distal fall-off of the Bragg peaks for shaping the dose distribution in front of critical stuctures. The maximum dose in the OARs evaluated with RBE models from literature is reduced by 8–14\\% with our method compared to conventional planning. Conclusion: LET-based inverse planning for IMPT offers the ability to reduce the RBE-weighted dose in OARs without sacrificing target dose. This project was in part supported by NCI - U19 CA 21239.« less

  1. Nuclear accident dosimetry intercomparison studies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sims, C.S.

    1989-09-01

    Twenty-two nuclear accident dosimetry intercomparison studies utilizing the fast-pulse Health Physics Research Reactor at the Oak Ridge National Laboratory have been conducted since 1965. These studies have provided a total of 62 different organizations a forum for discussion of criticality accident dosimetry, an opportunity to test their neutron and gamma-ray dosimetry systems under a variety of simulated criticality accident conditions, and the experience of comparing results with reference dose values as well as with the measured results obtained by others making measurements under identical conditions. Sixty-nine nuclear accidents (27 with unmoderated neutron energy spectra and 42 with eight different shieldedmore » spectra) have been simulated in the studies. Neutron doses were in the 0.2-8.5 Gy range and gamma doses in the 0.1-2.0 Gy range. A total of 2,289 dose measurements (1,311 neutron, 978 gamma) were made during the intercomparisons. The primary methods of neutron dosimetry were activation foils, thermoluminescent dosimeters, and blood sodium activation. The main methods of gamma dose measurement were thermoluminescent dosimeters, radiophotoluminescent glass, and film. About 68% of the neutron measurements met the accuracy guidelines (+/- 25%) and about 52% of the gamma measurements met the accuracy criterion (+/- 20%) for accident dosimetry.« less

  2. New stomatal flux-based critical levels for ozone effects on vegetation

    NASA Astrophysics Data System (ADS)

    Mills, Gina; Pleijel, Håkan; Braun, Sabine; Büker, Patrick; Bermejo, Victoria; Calvo, Esperanza; Danielsson, Helena; Emberson, Lisa; Fernández, Ignacio González; Grünhage, Ludger; Harmens, Harry; Hayes, Felicity; Karlsson, Per-Erik; Simpson, David

    2011-09-01

    The critical levels for ozone effects on vegetation have been reviewed and revised by the LRTAP Convention. Eight new or revised critical levels based on the accumulated stomatal flux of ozone (POD Y, the Phytotoxic Ozone Dose above a threshold flux of Y nmol m -2 PLA s -1, where PLA is the projected leaf area) have been agreed. For each receptor, data were combined from experiments conducted under naturally fluctuating environmental conditions in 2-4 countries, resulting in linear dose-response relationships with response variables specific to each receptor ( r2 = 0.49-0.87, p < 0.001 for all). For crops, critical levels were derived for effects on wheat (grain yield, grain mass, and protein yield), potato (tuber yield) and tomato (fruit yield). For forest trees, critical levels were derived for effects on changes in annual increment in whole tree biomass for beech and birch, and Norway spruce. For (semi-)natural vegetation, the critical level for effects on productive and high conservation value perennial grasslands was based on effects on important component species of the genus Trifolium (clover species). These critical levels can be used to assess protection against the damaging effects of ozone on food security, important ecosystem services provided by forest trees (roundwood production, C sequestration, soil stability and flood prevention) and the vitality of pasture.

  3. TL detectors for gamma ray dose measurements in criticality accidents.

    PubMed

    Miljanić, Saveta; Zorko, Benjamin; Gregori, Beatriz; Knezević, Zeljka

    2007-01-01

    Determination of gamma ray dose in mixed neutron+gamma ray fields is still a demanding task. Dosemeters used for gamma ray dosimetry are usually in some extent sensitive to neutrons and their response variations depend on neutron energy i.e., on neutron spectra. Besides, it is necessary to take into account the energy dependence of dosemeter responses to gamma rays. In this work, several types of thermoluminescent detectors (TLD) placed in different holders used for gamma ray dose determination in the mixed fields were examined. Dosemeters were from three different institutions: Ruder Bosković Institute (RBI), Croatia, JoZef Stefan Institute (JSI), Slovenia and Autoridad Regulatoria Nuclear (ARN), Argentina. All dosemeters were irradiated during the International Intercomparison of Criticality Accident Dosimetry Systems at the SILENE Reactor, Valduc, June 2002. Three accidental scenarios were reproduced and in each irradiation the dosemeters were exposed placed on the front of phantom and 'free in air'. Following types of TLDs were used: 7LiF (TLD-700), CaF2:Mn and Al2O3:Mg,Y-all from RBI; CaF2:Mn from JSI and 7LiF (TLD-700) from ARN. Reported doses were compared with the reference values as well as with the values obtained from the results of all participants. The results show satisfactory agreement with other dosimetry systems used in the Intercomparison. The influence of different types of holders and applied corrections of dosemeters' readings are discussed.

  4. Generation of uniformly distributed dose points for anatomy-based three-dimensional dose optimization methods in brachytherapy.

    PubMed

    Lahanas, M; Baltas, D; Giannouli, S; Milickovic, N; Zamboglou, N

    2000-05-01

    We have studied the accuracy of statistical parameters of dose distributions in brachytherapy using actual clinical implants. These include the mean, minimum and maximum dose values and the variance of the dose distribution inside the PTV (planning target volume), and on the surface of the PTV. These properties have been studied as a function of the number of uniformly distributed sampling points. These parameters, or the variants of these parameters, are used directly or indirectly in optimization procedures or for a description of the dose distribution. The accurate determination of these parameters depends on the sampling point distribution from which they have been obtained. Some optimization methods ignore catheters and critical structures surrounded by the PTV or alternatively consider as surface dose points only those on the contour lines of the PTV. D(min) and D(max) are extreme dose values which are either on the PTV surface or within the PTV. They must be avoided for specification and optimization purposes in brachytherapy. Using D(mean) and the variance of D which we have shown to be stable parameters, achieves a more reliable description of the dose distribution on the PTV surface and within the PTV volume than does D(min) and D(max). Generation of dose points on the real surface of the PTV is obligatory and the consideration of catheter volumes results in a realistic description of anatomical dose distributions.

  5. Blister formation at subcritical doses in tungsten irradiated by MeV protons

    NASA Astrophysics Data System (ADS)

    Gavish Segev, I.; Yahel, E.; Silverman, I.; Makov, G.

    2017-12-01

    The material response of tungsten to irradiation by MeV protons has been studied experimentally, in particular with respect to bubble and blister formation. Tungsten samples were irradiated by 2.2 MeV protons at the Soreq Applied Research Accelerator Facility (SARAF) to doses of the order of 1017 protons/cm2 which are below the reported critical threshold for blister formation derived from keV range irradiation studies. Large, well-developed blisters are observed indicating that for MeV range protons the critical threshold is at least an order of magnitude lower than the lowest value reported previously. The effects of fluence, flux, and corresponding temperature on the distribution and characteristics of the obtained blisters were studied. FIB cross sections of several blisters exposed their depth and structure.

  6. SU-F-P-19: Fetal Dose Estimate for a High-Dose Fluoroscopy Guided Intervention Using Modern Data Tools

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moirano, J

    Purpose: An accurate dose estimate is necessary for effective patient management after a fetal exposure. In the case of a high-dose exposure, it is critical to use all resources available in order to make the most accurate assessment of the fetal dose. This work will demonstrate a methodology for accurate fetal dose estimation using tools that have recently become available in many clinics, and show examples of best practices for collecting data and performing the fetal dose calculation. Methods: A fetal dose estimate calculation was performed using modern data collection tools to determine parameters for the calculation. The reference pointmore » air kerma as displayed by the fluoroscopic system was checked for accuracy. A cumulative dose incidence map and DICOM header mining were used to determine the displayed reference point air kerma. Corrections for attenuation caused by the patient table and pad were measured and applied in order to determine the peak skin dose. The position and depth of the fetus was determined by ultrasound imaging and consultation with a radiologist. The data collected was used to determine a normalized uterus dose from Monte Carlo simulation data. Fetal dose values from this process were compared to other accepted calculation methods. Results: An accurate high-dose fetal dose estimate was made. Comparison to accepted legacy methods were were within 35% of estimated values. Conclusion: Modern data collection and reporting methods ease the process for estimation of fetal dose from interventional fluoroscopy exposures. Many aspects of the calculation can now be quantified rather than estimated, which should allow for a more accurate estimation of fetal dose.« less

  7. Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of Quantitative Pharmacology Towards First Registration and Expanding Therapeutic Use

    PubMed Central

    Nayak, Satyaprakash; Sander, Oliver; Al‐Huniti, Nidal; de Alwis, Dinesh; Chain, Anne; Chenel, Marylore; Sunkaraneni, Soujanya; Agrawal, Shruti; Gupta, Neeraj

    2018-01-01

    Quantitative pharmacology (QP) applications in translational medicine, drug‐development, and therapeutic use were crowd‐sourced by the ASCPT Impact and Influence initiative. Highlighted QP case studies demonstrated faster access to innovative therapies for patients through 1) rational dose selection for pivotal trials; 2) reduced trial‐burden for vulnerable populations; or 3) simplified posology. Critical success factors were proactive stakeholder engagement, alignment on the value of model‐informed approaches, and utilizing foundational clinical pharmacology understanding of the therapy. PMID:29330855

  8. Conversion of ICRP male reference phantom to polygon-surface phantom

    NASA Astrophysics Data System (ADS)

    Yeom, Yeon Soo; Han, Min Cheol; Kim, Chan Hyeong; Jeong, Jong Hwi

    2013-10-01

    The International Commission on Radiological Protection (ICRP) reference phantoms, developed based on computed tomography images of human bodies, provide much more realism of human anatomy than the previously used MIRD5 (Medical Internal Radiation Dose) mathematical phantoms. It has been, however, realized that the ICRP reference phantoms have some critical limitations showing a considerable amount of holes for the skin and wall organs mainly due to the nature of voxels of which the phantoms are made, especially due to their low voxel resolutions. To address this problem, we are planning to develop the polygon-surface version of ICRP reference phantoms by directly converting the ICRP reference phantoms (voxel phantoms) to polygon-surface phantoms. The objective of this preliminary study is to see if it is indeed possible to construct the high-quality polygon-surface phantoms based on the ICRP reference phantoms maintaining identical organ morphology and also to identify any potential issues, and technologies to address these issues, in advance. For this purpose, in the present study, the ICRP reference male phantom was roughly converted to a polygon-surface phantom. Then, the constructed phantom was implemented in Geant4, Monte Carlo particle transport code, for dose calculations, and the calculated dose values were compared with those of the original ICRP reference phantom to see how much the calculated dose values are sensitive to the accuracy of the conversion process. The results of the present study show that it is certainly possible to convert the ICRP reference phantoms to surface phantoms with enough accuracy. In spite of using relatively less resources (<2 man-months), we were able to construct the polygon-surface phantom with the organ masses perfectly matching the ICRP reference values. The analysis of the calculated dose values also implies that the dose values are indeed not very sensitive to the detailed morphology of the organ models in the phantom for highly penetrating radiations such as photons and neutrons. The results of the electron beams, on the other hand, show that the dose values of the polygon-surface phantom are higher by a factor of 2-5 times than those of the ICRP reference phantom for the skin and wall organs which have large holes due to low voxel resolution. The results demonstrate that the ICRP reference phantom could provide significantly unreasonable dose values to thin or wall organs especially for weakly penetrating radiations. Therefore, when compared to the original ICRP reference phantoms, it is believed that the polygon-surface version of ICRP reference phantoms properly developed will not only provide the same or similar dose values (say, difference <5 or 10%) for highly penetrating radiations, but also provide correct dose values for the weakly penetrating radiations such as electrons and other charged particles.

  9. Beam Attenuators and the Risk of Unrecognized Large-Fraction Irradiation of Critical Tissues

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Luka, S.; Marks, J.E.

    2015-01-15

    The use of radiation beam attenuators led to radiation injury of the spinal cord in one patient and of the peripheral nerve in another due to unsuspected large-fraction irradiation. The anatomic distribution of radiation dose was reconstructed in the sagittal plane for the patient who developed radiation myelopathy and in the axial plane for the patient who developed peripheral neuropathy. The actual dose delivered to the injured structure in each patient was taken from the dose distribution and recorded along with the time, number of fractions, and dose per fraction. The patient who developed radiation myelopathy received a total ofmore » 46.5 Gy in twenty-three 2.1 Gy fractions in 31 days to the upper cervical spinal cord where the thickness of the neck was less than the central axis thickness due to cervical lordosis and absence of a posterior compensating filter. The patient who developed peripheral neuropathy received 55 Gy in twenty-five 2.2 Gy fractions in 50 days to the femoral nerve using bolus over the groins and an anterior one-half value layer Cerrobend pelvic block to bias the dose anteriorly. Compensating filters and other beam attenuators should be used with caution because they may result in unsuspected large-fraction irradiation and total doses of radiation that exceed the tolerance of critical structures.« less

  10. Structural analysis of ion-implanted chemical-vapor-deposited diamond by transmission electron microscope

    NASA Astrophysics Data System (ADS)

    Jiang, N.; Deguchi, M.; Wang, C. L.; Won, J. H.; Jeon, H. M.; Mori, Y.; Hatta, A.; Kitabatake, M.; Ito, T.; Hirao, T.; Sasaki, T.; Hiraki, A.

    1997-04-01

    A transmission electron microscope (TEM) study of ion-implanted chemical-vapor-deposited (CVD) diamond is presented. CVD diamond used for transmission electron microscope observation was directly deposited onto Mo TEM grids. As-deposited specimens were irradiated by C (100 keV) ions at room temperature with a wide range of implantation doses (10 12-10 17/cm 2). Transmission electron diffraction (TED) patterns indicate that there exists a critical dose ( Dc) for the onset of amorphization of CVD diamond as a result of ion induced damage and the value of critical dose is confirmed to be about 3 × 10 15/cm 2. The ion-induced transformation process is clearly revealed by high resolution electron microscope (HREM) images. For a higher dose implantation (7 × 10 15/cm 2) a large amount of diamond phase is transformed into amorphous carbon and many tiny misoriented diamond blocks are found to be left in the amorphous solid. The average size of these misoriented diamond blocks is only about 1-2 nm. Further bombardment (10 17/cm 2) almost kills all of the diamond phase within the irradiated volume and moreover leads to local formation of micropolycrystalline graphite.

  11. The changing face of nanomaterials: Risk assessment challenges along the value chain.

    PubMed

    Mattsson, Mats-Olof; Simkó, Myrtill

    2017-03-01

    Risk assessment (RA) of manufactured nanomaterials (MNM) is essential for regulatory purposes and risk management activities. Similar to RA of "classical" chemicals, MNM RA requires knowledge about exposure as well as of hazard potential and dose response relationships. What makes MNM RA especially challenging is the multitude of materials (which is expected to increase substantially in the future), the complexity of MNM value chains and life cycles, the accompanying possible changes in material properties over time and in contact with various environmental and organismal milieus, and the difficulties to obtain proper exposure data and to consider the proper dose metric. This article discusses these challenges and also critically overviews the current state of the art regarding MNM RA approaches. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. SU-E-T-272: Direct Verification of a Treatment Planning System Megavoltage Linac Beam Photon Spectra Models, and Analysis of the Effects On Patient Plans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Leheta, D; Shvydka, D; Parsai, E

    2015-06-15

    Purpose: For the photon dose calculation Philips Pinnacle Treatment Planning System (TPS) uses collapsed cone convolution algorithm, which relies on energy spectrum of the beam in computing the scatter component. The spectrum is modeled based on Linac’s standard commissioning data and typically is not independently verified. We explored a methodology of using transmission measurements in combination with regularization data processing to unfold Linac spectra. The measured spectra were compared to those modeled by the TPS, and the effect on patient plans was evaluated. Methods: Transmission measurements were conducted in narrow-beam geometry using a standard Farmer ionization chamber. Two attenuating materialsmore » and two build -up caps, having different atomic numbers, served to enhance discrimination between absorption of low and high-energy portions of the spectra, thus improving the accuracy of the results. The data was analyzed using a regularization technique implemented through spreadsheet-based calculations. Results: The unfolded spectra were found to deviate from the TPS beam models. The effect of such deviations on treatment planning was evaluated for patient plans through dose distribution calculations with either TPS modeled or measured energy spectra. The differences were reviewed through comparison of isodose distributions, and quantified based on maximum dose values for critical structures. While in most cases no drastic differences in the calculated doses were observed, plans with deviations of 4 to 8% in the maximum dose values for critical structures were discovered. The anatomical sites with large scatter contributions are the most vulnerable to inaccuracies in the modeled spectrum. Conclusion: An independent check of the TPS model spectrum is highly desirable and should be included as part of commissioning of a new Linac. The effect is particularly important for dose calculations in high heterogeneity regions. The developed approach makes acquisition of megavoltage Linac beam spectra achievable in a typical radiation oncology clinic.« less

  13. Phenytoin pharmacokinetics in critically ill trauma patients.

    PubMed

    Boucher, B A; Rodman, J H; Jaresko, G S; Rasmussen, S N; Watridge, C B; Fabian, T C

    1988-12-01

    Preliminary data have suggested that phenytoin systemic clearance may increase during initial therapy in critically ill patients. The objectives for this study were to model the time-variant phenytoin clearance and evaluate concomitant changes in protein binding and urinary metabolite elimination. Phenytoin was given as an intravenous loading dose of 15 mg/kg followed by an initial maintenance dose of 6 mg/kg/day in 10 adult critically ill trauma patients. Phenytoin bound and unbound plasma concentrations were determined in 10 patients and urinary excretion of the metabolite p-hydroxyphenyl phenylhydantoin (p-HPPH) was measured in seven patients for 7 to 14 days. A Michaelis-Menten one-compartment model incorporating a time-variant maximal velocity (Vmax) was sufficient to describe the data and superior to a conventional time-invariant Michaelis-Menten model. Vmax for the time-variant model was defined as V'max + Vmax delta (1 - e(-kindt)). Vmax infinity is the value for Vmax when t is large. The median values (ranges) for the parameters were Km = 4.8 (2.6 to 20) mg/L, Vmax infinity = 1348 (372 to 4741) mg/day, and kind = 0.0115 (0.0045 to 0.132) hr-1. Phenytoin free fraction increased in a majority of patients during the study period, with a binding ratio inversely related to albumin. Measured urinary p-HPPH data were consistent with the proposed model. A loading and constant maintenance dose of phenytoin frequently yielded a substantial, clinically significant fall in plasma concentrations with a pattern of apparently increasing clearance that may be a consequence of changes in protein binding, induction of metabolism, or the influence of stress on hepatic metabolic capacity.

  14. Tolerability and outcomes of kinetically guided therapy with gentamicin in critically ill neonates during the first week of life: an open-label, prospective study.

    PubMed

    Martínková, Jirina; Pokorná, Pavla; Záhora, Jiri; Chládek, Jaroslav; Vobruba, Václav; Selke-Krulichová, Iva; Chládková, Jirina

    2010-12-01

    Aminoglycosides are bactericidal antibiotics used worldwide for the treatment of serious infections in critically ill patients, including neonates. Critically ill neonates constitute a unique challenge in dosing owing to the pathologic alterations that accompany severe illness and the rapidly changing conditions of these patients. The main objective of this study was to analyze the kinetically guided dosage adjustment of gentamicin in neonates critically ill during the first week of life based on plasma concentrations after the first dose and to identify the impact of covariates (eg, fluid intake, body fluid retention) with respect to gestational age (GA). Tolerability of therapy was also assessed. This 10-day, open-label, prospective study included neonates critically ill during the first week of life admitted to the neonatal intensive care unit of a children's hospital between January 2006 and July 2009. Hearing and renal assessments were conducted over a 24-month follow-up period. The patients were treated with gentamicin for suspected sepsis, proven sepsis, or pneumonia as an early sign of sepsis. The first and second doses of gentamicin 4 mg/kg were adjusted according to birth weight and GA: group 1 (GA < 34 weeks), 48-hour interdose intervals; group 2 (GA 34-38 weeks), 36 hours; and group 3 (GA > 38 weeks), 24 or 48 hours. Individual pharmacokinetic parameters were estimated after the first dose (given in 30-minute intravenous infusions) using 4 concentrations. Individual pharmacokinetic parameters were estimated by fitting the parameters of a 2-compartment model into 4 concentrations. The last 2 blood samples were taken 30 minutes before the fourth infusion (C(trough,3)) and 1 hour after its start (C(max,4)). Dosing was individualized to reach target ranges for the C(trough,3) (0.5-2.0 mg/L) and C(max,4) (6-10 mg/L) values. If needed, initial dosing was changed after the second dose by adjusting (reducing or increasing) the third and subsequent doses, or by adjusting (prolonging or shortening) the interdose intervals. C(trough,3) and C(max,4) were assessed to determine differences between predicted and assayed values. Fluid retention was registered as the difference between fluid intake and urine output at different intervals related to the first dose per kilogram of birth weight, and from the start of the first infusion (0 hour) to the day of the fourth infusion. The C(max)/minimum inhibitory concentration (MIC) ratio was determined for assessment of optimal response. Tolerability was evaluated during the 24-month follow-up period using renal sonography to screen for nephrocalcinosis and transient evoked otoacoustic emission recordings to evaluate hearing abnormalities. A total of 84 neonates (all white; 53 males, 31 females; birth weight range, 0.8-4.56 kg; GA range, 24-42 weeks) were enrolled in 3 groups: group 1, GA < 34 weeks, n = 27; group 2, GA 34-38 weeks, n = 22; and group 3, GA > 38 weeks, n = 35. The C(max) value detected 1 hour after the start of the first infusion (C(max,1)) reached the target range of 6-10 mg/L in 66 of the 84 neonates (79%). After the initial dose, C(max,1) was variable (%CV, 29%); the failure rate to reach 6 mg/L was 13%. V(d) decreased with GA (r = -0.30, P < 0.01) and achieved mean (SD) rates of 0.51 (0.10), 0.48 (0.13), and 0.40 (0.15) L/kg in groups 1, 2, and 3, respectively. Neither C(max) nor V(d) was correlated with fluid intake relative to the first infusion. Mean gentamicin clearance measured after dose 1 (0.47 [0.23], 0.66 [0.26], and 0.76 [0.32] mL/min/kg) increased with GA (r = 0.45, P < 0.001). The interdose interval was prolonged after the second and subsequent infusions in 8 of 84 neonates (10%) or by decreasing the third dose and subsequent doses in 51 neonates (61%). The target C(max,4) and C(trough,3) values occurred in 63% (22 of 35) and 83% (29 of 35) of full-term patients (GA >38 weeks), respectively. In preterm neonates, the target range for C(max,4) was reached in 11 of 27 patients (41%) in group 1 and 11 of 22 patients (50%) in group 2; for C(trough,3), the target range was reached in 25 patients (93%) in group 1 and in 16 (73%) in group 2. C(trough,3) >2 mg/L was detected in 1 full-term neonate, and gentamicin was withdrawn. Suspected fluid retention within the time period of 0 hour to the day of the fourth infusion was well correlated with actual body weight (r = 0.58, P < 0.001), but it was negatively correlated with C(max,4) (r = -0.25, P = 0.02). Thirteen of the 84 neonates (15%) had confirmed sepsis. C(max)/MIC was >12 except for 2 resistant staphylococcal infections (C(max)/MIC = 0.4); amikacin and vancomycin were substituted for gentamicin in these cases. Clinical signs and laboratory data indicative of suspected sepsis disappeared in 5 to 10 days in 68 of 71 neonates. In 1 neonate, gentamicin was withdrawn after dose 4 because of a high C(trough,3) value. In the 3 remaining neonates, C-reactive protein was decreased >10 days without changing therapy. Two neonates died, 1 of severe hypoxic-ischemic encephalopathy as a consequence of perinatal asphyxia and another of stage IV intraventricular hemorrhage. Transient renal dysfunction attributable to gentamicin was detected in 1 case. No signs of late toxicity (nephrocalcinosis) were found during the second year of follow-up. Two neonates were diagnosed with unilateral hearing loss, a secondary phenomenon of hypoxic-ischemic encephalopathy thought to be related to the severe perinatal asphyxia. The initial dose of gentamicin 4 mg/kg for these critically ill premature and mature neonates with sepsis during the first week of life was high enough to reach bactericidal C(max,1) within 6-10 mg/L. C(max,1) <6 mg/L occurred in 13% of neonates. The interdose interval modified according to the recommendation resulted in C(trough) values within the target range of 0.5-2.0 mg/L in all but 2 neonates. The kinetically guided maintenance dosing of gentamicin based on plasma concentrations after the first dose should be optimized, taking into account actual body weight. (EudraCT number: 2005-002723-13). Copyright © 2010 Elsevier HS Journals, Inc. All rights reserved.

  15. Dosimetric verification of lung cancer treatment using the CBCTs estimated from limited-angle on-board projections.

    PubMed

    Zhang, You; Yin, Fang-Fang; Ren, Lei

    2015-08-01

    Lung cancer treatment is susceptible to treatment errors caused by interfractional anatomical and respirational variations of the patient. On-board treatment dose verification is especially critical for the lung stereotactic body radiation therapy due to its high fractional dose. This study investigates the feasibility of using cone-beam (CB)CT images estimated by a motion modeling and free-form deformation (MM-FD) technique for on-board dose verification. Both digital and physical phantom studies were performed. Various interfractional variations featuring patient motion pattern change, tumor size change, and tumor average position change were simulated from planning CT to on-board images. The doses calculated on the planning CT (planned doses), the on-board CBCT estimated by MM-FD (MM-FD doses), and the on-board CBCT reconstructed by the conventional Feldkamp-Davis-Kress (FDK) algorithm (FDK doses) were compared to the on-board dose calculated on the "gold-standard" on-board images (gold-standard doses). The absolute deviations of minimum dose (ΔDmin), maximum dose (ΔDmax), and mean dose (ΔDmean), and the absolute deviations of prescription dose coverage (ΔV100%) were evaluated for the planning target volume (PTV). In addition, 4D on-board treatment dose accumulations were performed using 4D-CBCT images estimated by MM-FD in the physical phantom study. The accumulated doses were compared to those measured using optically stimulated luminescence (OSL) detectors and radiochromic films. Compared with the planned doses and the FDK doses, the MM-FD doses matched much better with the gold-standard doses. For the digital phantom study, the average (± standard deviation) ΔDmin, ΔDmax, ΔDmean, and ΔV100% (values normalized by the prescription dose or the total PTV) between the planned and the gold-standard PTV doses were 32.9% (±28.6%), 3.0% (±2.9%), 3.8% (±4.0%), and 15.4% (±12.4%), respectively. The corresponding values of FDK PTV doses were 1.6% (±1.9%), 1.2% (±0.6%), 2.2% (±0.8%), and 17.4% (±15.3%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.3% (±0.2%), 0.9% (±0.6%), 0.6% (±0.4%), and 1.0% (±0.8%), respectively. Similarly, for the physical phantom study, the average ΔDmin, ΔDmax, ΔDmean, and ΔV100% of planned PTV doses were 38.1% (±30.8%), 3.5% (±5.1%), 3.0% (±2.6%), and 8.8% (±8.0%), respectively. The corresponding values of FDK PTV doses were 5.8% (±4.5%), 1.6% (±1.6%), 2.0% (±0.9%), and 9.3% (±10.5%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.4% (±0.8%), 0.8% (±1.0%), 0.5% (±0.4%), and 0.8% (±0.8%), respectively. For the 4D dose accumulation study, the average (± standard deviation) absolute dose deviation (normalized by local doses) between the accumulated doses and the OSL measured doses was 3.3% (±2.7%). The average gamma index (3%/3 mm) between the accumulated doses and the radiochromic film measured doses was 94.5% (±2.5%). MM-FD estimated 4D-CBCT enables accurate on-board dose calculation and accumulation for lung radiation therapy. It can potentially be valuable for treatment quality assessment and adaptive radiation therapy.

  16. A neutron dosemeter for nuclear criticality accidents.

    PubMed

    d'Errico, F; Curzio, G; Ciolini, R; Del Gratta, A; Nath, R

    2004-01-01

    A neutron dosemeter which offers instant read-out has been developed for nuclear criticality accidents. The system is based on gels containing emulsions of superheated dichlorodifluoromethane droplets, which vaporise into bubbles upon neutron irradiation. The expansion of these bubbles displaces an equivalent volume of gel into a graduated pipette, providing an immediate measure of the dose. Instant read-out is achieved using an array of transmissive optical sensors which consist of coupled LED emitters and phototransistor receivers. When the gel displaced in the pipette crosses the sensing region of the photomicrosensors, it generates a signal collected on a computer through a dedicated acquisition board. The performance of the device was tested during the 2002 International Accident Dosimetry Intercomparison in Valduc, France. The dosemeter was able to follow the initial dose gradient of a simulated accident, providing accurate values of neutron kerma; however, the emulsion was rapidly depleted of all its drops. A model of the depletion effects was developed and it indicates that an adequate dynamic range of the dose response can be achieved by using emulsions of smaller droplets.

  17. Cumulative total effective whole-body radiation dose in critically ill patients.

    PubMed

    Rohner, Deborah J; Bennett, Suzanne; Samaratunga, Chandrasiri; Jewell, Elizabeth S; Smith, Jeffrey P; Gaskill-Shipley, Mary; Lisco, Steven J

    2013-11-01

    Uncertainty exists about a safe dose limit to minimize radiation-induced cancer. Maximum occupational exposure is 20 mSv/y averaged over 5 years with no more than 50 mSv in any single year. Radiation exposure to the general population is less, but the average dose in the United States has doubled in the past 30 years, largely from medical radiation exposure. We hypothesized that patients in a mixed-use surgical ICU (SICU) approach or exceed this limit and that trauma patients were more likely to exceed 50 mSv because of frequent diagnostic imaging. Patients admitted into 15 predesignated SICU beds in a level I trauma center during a 30-day consecutive period were prospectively observed. Effective dose was determined using Huda's method for all radiography, CT imaging, and fluoroscopic examinations. Univariate and multivariable linear regressions were used to analyze the relationships between observed values and outcomes. Five of 74 patients (6.8%) exceeded exposures of 50 mSv. Univariate analysis showed trauma designation, length of stay, number of CT scans, fluoroscopy minutes, and number of general radiographs were all associated with increased doses, leading to exceeding occupational exposure limits. In a multivariable analysis, only the number of CT scans and fluoroscopy minutes remained significantly associated with increased whole-body radiation dose. Radiation levels frequently exceeded occupational exposure standards. CT imaging contributed the most exposure. Health-care providers must practice efficient stewardship of radiologic imaging in all critically ill and injured patients. Diagnostic benefit must always be weighed against the risk of cumulative radiation dose.

  18. Reliability of Current Biokinetic and Dosimetric Models for Radionuclides: A Pilot Study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Leggett, Richard Wayne; Eckerman, Keith F; Meck, Robert A.

    2008-10-01

    This report describes the results of a pilot study of the reliability of the biokinetic and dosimetric models currently used by the U.S. Nuclear Regulatory Commission (NRC) as predictors of dose per unit internal or external exposure to radionuclides. The study examines the feasibility of critically evaluating the accuracy of these models for a comprehensive set of radionuclides of concern to the NRC. Each critical evaluation would include: identification of discrepancies between the models and current databases; characterization of uncertainties in model predictions of dose per unit intake or unit external exposure; characterization of variability in dose per unit intakemore » or unit external exposure; and evaluation of prospects for development of more accurate models. Uncertainty refers here to the level of knowledge of a central value for a population, and variability refers to quantitative differences between different members of a population. This pilot study provides a critical assessment of models for selected radionuclides representing different levels of knowledge of dose per unit exposure. The main conclusions of this study are as follows: (1) To optimize the use of available NRC resources, the full study should focus on radionuclides most frequently encountered in the workplace or environment. A list of 50 radionuclides is proposed. (2) The reliability of a dose coefficient for inhalation or ingestion of a radionuclide (i.e., an estimate of dose per unit intake) may depend strongly on the specific application. Multiple characterizations of the uncertainty in a dose coefficient for inhalation or ingestion of a radionuclide may be needed for different forms of the radionuclide and different levels of information of that form available to the dose analyst. (3) A meaningful characterization of variability in dose per unit intake of a radionuclide requires detailed information on the biokinetics of the radionuclide and hence is not feasible for many infrequently studied radionuclides. (4) The biokinetics of a radionuclide in the human body typically represents the greatest source of uncertainty or variability in dose per unit intake. (5) Characterization of uncertainty in dose per unit exposure is generally a more straightforward problem for external exposure than for intake of a radionuclide. (6) For many radionuclides the most important outcome of a large-scale critical evaluation of databases and biokinetic models for radionuclides is expected to be the improvement of current models. Many of the current models do not fully or accurately reflect available radiobiological or physiological information, either because the models are outdated or because they were based on selective or uncritical use of data or inadequate model structures. In such cases the models should be replaced with physiologically realistic models that incorporate a wider spectrum of information.« less

  19. SU-E-T-346: Effect of Jaw Position On Dose to Critical Structures in 3-D Conformal Radiotherapy Treatment of Pancreatic Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Paudel, N; Han, E; Liang, X

    Purpose: Three-dimensional conformal therapy remains a valid and widely used modality for pancreatic radiotherapy treatment. It usually meets dose constraints on critical structures. However, careful positioning of collimation jaws can reduce dose to the critical structures. Here we investigate the dosimetric effect of jaw position in MLC-based 3-D conformal treatment planning on critical structures. Methods: We retrospectively selected seven pancreatic cancer patients treated with 3-D conformal radiotherapy. We started with treatment plans (Varian Truebeam LINAC, Eclipse TPS, AAA, 18MV) having both x and y jaws aligned with the farthest extent of the block outline (8mm around PTV). Then we subsequentlymore » moved either both x-jaws or all x and y jaws outwards upto 3 cm in 1 cm increments and investigated their effect on average and maximum dose to neighboring critical structures keeping the same coverage to treatment volume. Results: Lateral displacement of both x-jaws by 1cm each increased kidney and spleen mean dose by as much as 1.7% and 1.3% respectively and superior inferior displacement increased liver, right kidney, stomach and spleen dose by as much as 2.1%, 2%, 5.2% and 1.6% respectively. Displacement of all x and y-jaws away by 1cm increased the mean dose to liver, right kidney, left kidney, bowels, cord, stomach and spleen by as much as 4.9%, 5.9%, 2.1%, 2.8%, 7.4%, 10.4% and 4.2% respectively. Percentage increase in mean dose due to 2 and 3cm jaw displacement increased almost linearly with the displaced distance. Changes in maximum dose were much smaller (mostly negligible) than the changes in mean dose. Conclusion: Collimation jaw position affects dose mostly to critical structures adjacent to it. Though treatment plans with MLCs conforming the block margin usually meet dose constraints to critical structures, keeping jaws all the way in, to the edge of the block reduces dose to the critical structures during radiation treatment.« less

  20. Evaluation of dose coverage to target volume and normal tissue sparing in the adjuvant radiotherapy of gastric cancers: 3D-CRT compared with dynamic IMRT.

    PubMed

    Murthy, Kk; Shukeili, Ka; Kumar, Ss; Davis, Ca; Chandran, Rr; Namrata, S

    2010-01-01

    To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over 3D-conformal radiotherapy (3D-CRT) planning in postoperative adjuvant radiotherapy for patients with gastric carcinoma. In a retrospective study, for plan comparison, dose distribution was recalculated in 15 patients treated with 3D-CRT on the contoured structures of same CT images using an IMRT technique. 3D-conformal plans with three fields and four-fields were compared with seven-field dynamic IMRT plans. The different plans were compared by analyzing the dose coverage of planning target volume using TV(95), D(mean), uniformity index, conformity index and homogeneity index parameters. To assess critical organ sparing, D(mean), D(max), dose to one-third and two-third volumes of the OARs and percentage of volumes receiving more than their tolerance doses were compared. The average dose coverage values of PTV with 3F-CRT and 4F-CRT plans were comparable, where as IMRT plans achieved better target coverage(p<0.001) with higher conformity index value of 0.81±0.07 compared to both the 3D-CRT plans. The doses to the liver and bowel reduced significantly (p<0.001) with IMRT plans compared to other 3D-CRT plans. For all OARs the percentage of volumes receiving more than their tolerance doses were reduced with the IMRT plans. This study showed that a better target coverage and significant dose reduction to OARs could be achieved with the IMRT plans. The IMRT can be preferred with caution for organ motion. The authors are currently studying organ motion in the upper abdomen to use IMRT for patient treatment.

  1. SU-F-T-198: Dosimetric Comparison of Carbon and Proton Radiotherapy for Recurrent Nasopharynx Carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sheng, Y; Zhao, J; Wang, W

    2016-06-15

    Purpose: Various radiotherapy planning methods for locally recurrent nasopharynx carcinoma (R-NPC) have been proposed. The purpose of this study was to compare carbon and proton therapy for the treatment of R-NPC in terms of dose coverage for target volume and sparing for organs at risk (OARs). Methods: Six patients who were suffering from R-NPC and treated using carbon therapy were selected for this study. Treatment plans with a total dose of 57.5Gy (RBE) in 23 fractions were made using SIEMENS Syngo V11. An intensity-modulated radiotherapy optimization method was chosen for carbon plans (IMCT) while for proton plans both intensity-modulated radiotherapymore » (IMPT) and single beam optimization (proton-SBO) methods were chosen. Dose distributions, dose volume parameters, and selected dosimetric indices for target volumes and OARs were compared for all treatment plans. Results: All plans provided comparable PTV coverage. The volume covered by 95% of the prescribed dose was comparable for all three plans. The average values were 96.11%, 96.24% and 96.11% for IMCT, IMPT, and proton-SBO respectively. A significant reduction of the 80% and 50% dose volumes were observed for the IMCT plans compared to the IMPT and proton-SBO plans. Critical organs lateral to the target such as brain stem and spinal cord were better spared by IMPT than by proton-SBO, while IMCT spared those organs best. For organs in the beam path, such as parotid glands, the mean dose results were similar for all three plans. Conclusion: Carbon plans yielded better dose conformity than proton plans. They provided similar or better target coverage while significantly lowering the dose for normal tissues. Dose sparing for critical organs in IMPT plans was better than proton-SBO, however, IMPT is known to be more sensitive to range uncertainties. For proton plans it is essential to find a balance between the two optimization methods.« less

  2. Conditions for critical effects in the mass action kinetics equations for water radiolysis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wittman, Richard S.; Buck, Edgar C.; Mausolf, Edward J.

    We report on a subtle global feature of the mass action kinetics equations for water radiolysis that results in predictions of a critical behavior in H2O2 and associated radical concentrations. While radiolysis kinetics has been studied extensively in the past, it is only in recent years that high speed computing has allowed the rapid exploration of the solution over widely varying dose and compositional conditions. We explore the radiolytic production of H2O2 under various externally fixed conditions of molecular H2 and O2 that have been regarded as problematic in the literature – specifically, “jumps” in predicted concentrations, and inconsistencies betweenmore » predictions and experiments have been reported for alpha radiolysis. We computationally map-out a critical concentration behavior for alpha radiolysis kinetics using a comprehensive set of reactions. We then show that all features of interest are accurately reproduced with 15 reactions. An analytical solution for steady-state concentrations of the 15 reactions reveals regions in [H2] and [O2] where the H2O2 concentration is not unique – both stable and unstable concentrations exist. The boundary of this region can be characterized analytically as a function of G-values and rate constants independent of dose rate. Physically, the boundary can be understood as separating a region where a steady-state H2O2 concentration exists, from one where it does not exist without a direct decomposition reaction. We show that this behavior is consistent with reported alpha radiolysis data and that no such behavior should occur for gamma radiolysis. We suggest experiments that could verify or discredit a critical concentration behavior for alpha radiolysis and could place more restrictive ranges on G-values from derived relationships between them.« less

  3. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Badkul, R; Nicolai, W; Pokhrel, D

    Purpose: To compare the impact of Pencil Beam(PB) and Anisotropic Analytic Algorithm(AAA) dose calculation algorithms on OARs and planning target volume (PTV) in thoracic spine stereotactic body radiation therapy (SBRT). Methods: Ten Spine SBRT patients were planned on Brainlab iPlan system using hybrid plan consisting of 1–2 non-coplanar conformal-dynamic arcs and few IMRT beams treated on NovalisTx with 6MV photon. Dose prescription varied from 20Gy to 30Gy in 5 fractions depending on the situation of the patient. PB plans were retrospectively recalculated using the Varian Eclipse with AAA algorithm using same MUs, MLC pattern and grid size(3mm).Differences in dose volumemore » parameters for PTV, spinal cord, lung, and esophagus were analyzed and compared for PB and AAA algorithms. OAR constrains were followed per RTOG-0631. Results: Since patients were treated using PB calculation, we compared all the AAA DVH values with respect to PB plan values as standard, although AAA predicts the dose more accurately than PB. PTV(min), PTV(Max), PTV(mean), PTV(D99%), PTV(D90%) were overestimated with AAA calculation on average by 3.5%, 1.84%, 0.95%, 3.98% and 1.55% respectively as compared to PB. All lung DVH parameters were underestimated with AAA algorithm mean deviation of lung V20, V10, V5, and 1000cc were 42.81%,19.83%, 18.79%, and 18.35% respectively. AAA overestimated Cord(0.35cc) by mean of 17.3%; cord (0.03cc) by 12.19% and cord(max) by 10.5% as compared to PB. Esophagus max dose were overestimated by 4.4% and 5cc by 3.26% for AAA algorithm as compared to PB. Conclusion: AAA overestimated the PTV dose values by up to 4%.The lung DVH had the greatest underestimation of dose by AAA versus PB. Spinal cord dose was overestimated by AAA versus PB. Given the critical importance of accuracy of OAR and PTV dose calculation for SBRT spine, more accurate algorithms and validation of calculated doses in phantom models are indicated.« less

  4. Comparison of reference doses (RfDs) developed for the protection of wildlife species in contrast to humans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Valoppi, L.; Carlisle, J.; Polisini, J.

    1995-12-31

    A component of both human health and ecological risk assessments is the evaluation of toxicity values. A comparison between the methodology for the development of Reference Doses (RfDs) to be protective of humans, and that developed for vertebrate wildlife species is presented. For all species, a chronic No Observable Adverse Effect Level (NOAEL) is developed by applying uncertainty factors (UFs) to literature-based toxicity values. Uncertainty factors are used to compensate for the length of exposure, sensitivity of endpoints, and cross-species extrapolations between the test species and the species being assessed. Differences between human and wildlife species could include the toxicologicalmore » endpoint, the critical study, and the magnitude of the cross-species extrapolation factor. Case studies for select chemicals are presented which contrast RfDs developed for humans and those developed for avian and mammalian wildlife.« less

  5. Sanitation of chicken eggs by ionizing radiation: HACCP and inactivation studies

    NASA Astrophysics Data System (ADS)

    Verde, S. Cabo; Tenreiro, R.; Botelho, M. L.

    2004-09-01

    The aim of this study is to develop the application of irradiation technology to chicken eggs in order to get a product free of pathogenic microorganisms. Bioburden values of eggs from chickens of different ages ( n=150) were found to not be significantly different ( p<0.05) and an average value of (2.0±0.3). 10 5 cfu/egg was obtained for the shell. Two major microbial groups were characterized in the egg's natural microbiota, no Salmonella or Campylobacter were detected. HACCP studies indicated the feed as a critical point. Dosimetry studies were carried out in a γ facility to find the best geometry and dose rate for irradiation. Whole eggs were artificially contaminated with reference strains of Salmonella typhimurium, Salmonella enteritidis, Campylobacter coli and Campylobacter jejuni and irradiated in the γ facility at sub-lethal doses (0.2-1 kGy) with a dose rate of 1.0 kGy/h. Dvalue varied between 0.31-0.26 kGy and 0.20-0.19 kGy in S. typhimurium and S. enteritidis, and between 0.21-0.18 kGy and 0.07-0.09 in C. coli and C. jejuni, for shell and yolk+white. Using sub-lethal doses up to 5 kGy, the Dvalue of natural microbiota in whole eggs was 1.29 kGy. Results show that low irradiation doses could guarantee egg sanitation.

  6. SU-D-206-05: A Critical Look at CBCT-Based Dose Calculation Accuracy as It Is Applied to Adaptive Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bejarano Buele, A; Sperling, N; Parsai, E

    2016-06-15

    Purpose: Cone-beam CTs (CBCT) obtained from On-Board Imaging Devices (OBI) are increasingly being used for dose calculation purposes in adaptive radiotherapy. Patient and target morphology are monitored and the treatment plan is updated using CBCT. Due to the difference in image acquisition parameters, dose calculated in a CBCT can differ from planned dose. We evaluate the difference between dose calculation in kV CBCT and simulation CT, and the effect of HU-density tables in dose discrepancies Methods: HU values for various materials were obtained using a Catphan 504 phantom for a simulator CT (CTSIM) and two different OBI systems using threemore » imaging protocols: Head, Thorax and Pelvis. HU-density tables were created in the TPS for each OBI image protocol. Treatment plans were made on each Catphan 504 dataset and on the head, thorax and pelvis sections of an anthropomorphic phantom, with and without the respective HU-density table. DVH information was compared among OBI systems and planning CT. Results: Dose calculations carried on the Catphan 504 CBCTs, with and without the respective CT-density table, had a maximum difference of −0.65% from the values on the planning CT. The use of the respective HU-density table decreased the percent differences from planned values by half in most of the protocols. For the anthropomorphic phantom datasets, the use of the correct HU-density table reduced differences by 0.89% on OBI1 and 0.59% on OBI2 for the head, 0.49% on OBI1 for the thorax, and 0.25% on OBI2 for the pelvis. Differences from planned values without HU-density correction ranged from 3.13% (OBI1, thorax) to 0.30% (OBI2, thorax). Conclusion: CT-density tables in the TPS yield acceptable differences when used in partly homogeneous medium. Further corrections are needed when the medium contains pronounced density differences for accurate CBCT calculation. Current difference range (1–3%) can be clinically acceptable.« less

  7. Dosimetric verification of lung cancer treatment using the CBCTs estimated from limited-angle on-board projections

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, You; Yin, Fang-Fang; Ren, Lei, E-mail: lei.ren@duke.edu

    2015-08-15

    Purpose: Lung cancer treatment is susceptible to treatment errors caused by interfractional anatomical and respirational variations of the patient. On-board treatment dose verification is especially critical for the lung stereotactic body radiation therapy due to its high fractional dose. This study investigates the feasibility of using cone-beam (CB)CT images estimated by a motion modeling and free-form deformation (MM-FD) technique for on-board dose verification. Methods: Both digital and physical phantom studies were performed. Various interfractional variations featuring patient motion pattern change, tumor size change, and tumor average position change were simulated from planning CT to on-board images. The doses calculated onmore » the planning CT (planned doses), the on-board CBCT estimated by MM-FD (MM-FD doses), and the on-board CBCT reconstructed by the conventional Feldkamp-Davis-Kress (FDK) algorithm (FDK doses) were compared to the on-board dose calculated on the “gold-standard” on-board images (gold-standard doses). The absolute deviations of minimum dose (ΔD{sub min}), maximum dose (ΔD{sub max}), and mean dose (ΔD{sub mean}), and the absolute deviations of prescription dose coverage (ΔV{sub 100%}) were evaluated for the planning target volume (PTV). In addition, 4D on-board treatment dose accumulations were performed using 4D-CBCT images estimated by MM-FD in the physical phantom study. The accumulated doses were compared to those measured using optically stimulated luminescence (OSL) detectors and radiochromic films. Results: Compared with the planned doses and the FDK doses, the MM-FD doses matched much better with the gold-standard doses. For the digital phantom study, the average (± standard deviation) ΔD{sub min}, ΔD{sub max}, ΔD{sub mean}, and ΔV{sub 100%} (values normalized by the prescription dose or the total PTV) between the planned and the gold-standard PTV doses were 32.9% (±28.6%), 3.0% (±2.9%), 3.8% (±4.0%), and 15.4% (±12.4%), respectively. The corresponding values of FDK PTV doses were 1.6% (±1.9%), 1.2% (±0.6%), 2.2% (±0.8%), and 17.4% (±15.3%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.3% (±0.2%), 0.9% (±0.6%), 0.6% (±0.4%), and 1.0% (±0.8%), respectively. Similarly, for the physical phantom study, the average ΔD{sub min}, ΔD{sub max}, ΔD{sub mean}, and ΔV{sub 100%} of planned PTV doses were 38.1% (±30.8%), 3.5% (±5.1%), 3.0% (±2.6%), and 8.8% (±8.0%), respectively. The corresponding values of FDK PTV doses were 5.8% (±4.5%), 1.6% (±1.6%), 2.0% (±0.9%), and 9.3% (±10.5%), respectively. In contrast, the corresponding values of MM-FD PTV doses were 0.4% (±0.8%), 0.8% (±1.0%), 0.5% (±0.4%), and 0.8% (±0.8%), respectively. For the 4D dose accumulation study, the average (± standard deviation) absolute dose deviation (normalized by local doses) between the accumulated doses and the OSL measured doses was 3.3% (±2.7%). The average gamma index (3%/3 mm) between the accumulated doses and the radiochromic film measured doses was 94.5% (±2.5%). Conclusions: MM-FD estimated 4D-CBCT enables accurate on-board dose calculation and accumulation for lung radiation therapy. It can potentially be valuable for treatment quality assessment and adaptive radiation therapy.« less

  8. The Efficacy of Denaturing Actinide Elements as a Means of Decreasing Materials Attractiveness

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hase, Kevin R.; Ebbinghaus, Bartley B.; Sleaford, Brad W.

    2013-07-01

    This paper is an extension to earlier studies that examined the attractiveness of materials mixtures containing special nuclear materials (SNM) and alternate nuclear materials (ANM). This study considers the concept of denaturing as applied to the actinide elements present in spent fuel as a means to reduce materials attractiveness. Highly attractive materials generally have low values of bare critical mass, heat content, and dose.

  9. Dose distribution and mapping with 3D imaging presentation in intraoral and panoramic examinations

    NASA Astrophysics Data System (ADS)

    Chen, Hsiu-Ling; Huang, Yung-Hui; Wu, Tung-Hsin; Wang, Shih-Yuan; Lee, Jason J. S.

    2011-10-01

    In current medical imaging applications, high quality images not only provide more diagnostic value for anatomic delineation but also offer functional information for treatment direction. However, this approach would potentially subscribe higher radiation dose in dental radiographies, which has been putatively associated with low-birth-weight during pregnancy, which affects the hypothalamus-pituitary-thyroid axis or thereby directly affects the reproductive organs. The aim of this study was to apply the high resolution 3-D image mapping technique to evaluate radiation doses from the following aspects: (1) verifying operating parameters of dental X-ray units, (2) measuring the leakage radiations and (3) mapping dose with 3-D radiographic imaging to evaluate dose distribution in head and neck regions. From the study results, we found that (1) leakage radiation from X-ray units was about 21.31±15.24 mR/h (<100 mR/h), (2) error of actual tube voltage for 60 kVp setting was from 0.2% to 6.5%, with an average of 2.5% (<7%) and (3) the error of exposure time for a 0.5-1.5 s setting was within 0.7-8.5%, with an average of 7.3% (<10%) error as well. Our 3-D dose mapping demonstrated that dose values were relatively lower in soft tissues and higher in bone surfaces compared with other investigations. Multiple causes could contribute to these variations, including irradiation geometry, image equipment and type of technique applied, etc. From the results, we also observed that larger accumulated doses were presented in certain critical organs, such as salivary gland, thyroid gland and bone marrow. Potential biological affects associated with these findings warrant further investigation.

  10. Spray dried amikacin powder for inhalation in cystic fibrosis patients: a quality by design approach for product construction.

    PubMed

    Belotti, Silvia; Rossi, Alessandra; Colombo, Paolo; Bettini, Ruggero; Rekkas, Dimitrios; Politis, Stavros; Colombo, Gaia; Balducci, Anna Giulia; Buttini, Francesca

    2014-08-25

    An amikacin product for convenient and compliant inhalation in cystic fibrosis patients was constructed by spray-drying in order to produce powders of pure drug having high respirability and flowability. An experimental design was applied as a statistical tool for the characterization of amikacin spray drying process, through the establishment of mathematical relationships between six Critical Quality Attributes (CQAs) of the finished product and five Critical Process Parameters (CPPs). The surface-active excipient, PEG-32 stearate, studied for particle engineering, in general did not benefit the CQAs of the spray dried powders for inhalation. The spray drying feed solution required the inclusion of 10% (v/v) ethanol in order to reach the desired aerodynamic performance of powders. All desirable function solutions indicated that the favourable concentration of amikacin in the feed solution had to be kept at 1% w/v level. It was found that when the feed rate of the sprayed solution was raised, an increase in the drying temperature to the maximum value (160 °C) was required to maintain good powder respirability. Finally, the increase in drying temperature always led to an evident increase in emitted dose (ED) without affecting the desirable fine particle dose (FPD) values. The application of the experimental design enabled us to obtain amikacin powders with both ED and FPD, well above the regulatory and scientific references. The finished product contained only the active ingredient, which keeps low the mass to inhale for dose requirement. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Phantom torso experiment on the international space station; flight measurements and calculations

    NASA Astrophysics Data System (ADS)

    Atwell, W.; Semones, E.; Cucinotta, F.

    The Phantom Torso Experiment (PTE) first flew on the 10-day Space Shuttle mission STS-91 in June 1998 during a period near solar minimum. The PTE was re- f l o w n on the I ternational Space Station (ISS) Increment 2 mission from April-n A u g u s t 2001 during a period near solar maximum. The experiment was located with a suite of other radiation experiments in the US Lab module Human Research Facility (HRF) rack. The objective of the experiment was to measure space radiation exposures at several radiosensitive critical body organs (brain, thyroid, heart/lung, stomach and colon) and two locations on the surface (skin) of a modified RandoTM phantom. Prior to flight, active solid -state silicon dosimeters were located at the RandoTM critical body organ locations and passive dosimeters were placed at the two surface locations. Using a mathematically modified Computerized Anatomical Male (CAM) model, shielding distributions were generated for the five critical body organ and two skin locations. These shielding distributions were then combined with the ISS HRF rack shielding distribution to account for the total shielding "seen" by the PTE. Using the trapped proton and galactic cosmic radiation environment models and high -energy particle transport codes, absorbed dose, dose equivalent, and LET (linear energy transfer) values were computed for the seven dose point locations of interest. The results of these computations are compared with the actual flight measurements.

  12. Getting Innovative Therapies Faster to Patients at the Right Dose: Impact of Quantitative Pharmacology Towards First Registration and Expanding Therapeutic Use.

    PubMed

    Nayak, Satyaprakash; Sander, Oliver; Al-Huniti, Nidal; de Alwis, Dinesh; Chain, Anne; Chenel, Marylore; Sunkaraneni, Soujanya; Agrawal, Shruti; Gupta, Neeraj; Visser, Sandra A G

    2018-03-01

    Quantitative pharmacology (QP) applications in translational medicine, drug-development, and therapeutic use were crowd-sourced by the ASCPT Impact and Influence initiative. Highlighted QP case studies demonstrated faster access to innovative therapies for patients through 1) rational dose selection for pivotal trials; 2) reduced trial-burden for vulnerable populations; or 3) simplified posology. Critical success factors were proactive stakeholder engagement, alignment on the value of model-informed approaches, and utilizing foundational clinical pharmacology understanding of the therapy. © 2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  13. Augmented renal clearance implies a need for increased amoxicillin-clavulanic acid dosing in critically ill children.

    PubMed

    De Cock, Pieter A J G; Standing, Joseph F; Barker, Charlotte I S; de Jaeger, Annick; Dhont, Evelyn; Carlier, Mieke; Verstraete, Alain G; Delanghe, Joris R; Robays, Hugo; De Paepe, Peter

    2015-11-01

    There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study [NCT02456974].). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  14. Response of rat skin to boron neutron capture therapy with p-boronophenylalanine or borocaptate sodium.

    PubMed

    Morris, G M; Coderre, J A; Hopewell, J W; Micca, P L; Rezvani, M

    1994-08-01

    The effects of boron neutron capture irradiation employing either BPA or BSH as neutron capture agents has been assessed using the dorsal skin of Fischer 344 rats. Pharmacokinetic studies, using prompt gamma spectrometry, revealed comparable levels of boron-10 (10B) in blood and skin after the intravenous infusion of BSH (100 mg/kg body wt.). The 10B content of blood (12.0 +/- 0.5 micrograms/g) was slightly higher than that of skin (10.0 +/- 0.5 micrograms/g) after oral dosing with BPA. Biphasic skin reactions were observed after irradiation with the thermal neutron beam alone or in combination with BPA or BSH. The time of onset of the first phase of the skin reaction, moist desquamation, was approximately 2 weeks. The time at which the second-wave skin reaction, dermal necrosis, became evident was dose-related and occurred after a latent interval of > or = 24 weeks, well after the acute epithelial reaction had healed. The incidence of both phases of skin damage was also dose-related. The radiation doses required to produce skin damage in 50% of skin sites (ED50 values) were calculated from dose-effect curves and these values were used to determine relative biological effectiveness (RBE) and compound biological effectiveness (CBE) factors for both moist desquamation and dermal necrosis. It was concluded on the basis of these calculations that the microdistribution of the two neutron capture agents had a critical bearing on the overall biological effect after thermal neutron activation. BSH, which was possibly excluded from the cytoplasm of epidermal cells, had a low CBE factor value (0.56 +/- 0.06) while BPA, which may be selectively accumulated in epidermal cells had a very high CBE factor (3.74 +/- 0.7). For the dermal reaction, where vascular endothelial cells represent the likely target cell population, the CBE factor values were comparable, at 0.73 +/- 0.42 and 0.86 +/- 0.08 for BPA ad BSH, respectively.

  15. Biodistribution and radiation dosimetry of the hypoxia marker 18F-HX4 in monkeys and humans determined by using whole-body PET/CT.

    PubMed

    Doss, Mohan; Zhang, James J; Bélanger, Marie-José; Stubbs, James B; Hostetler, Eric D; Alpaugh, Katherine; Kolb, Hartmuth C; Yu, Jian Q

    2010-12-01

    F-HX4 is a novel positron emission tomography (PET) tracer for imaging hypoxia. The purpose of this study was to determine the biodistribution and estimate the radiation dose of F-HX4 using whole-body PET/computed tomography (CT) scans in monkeys and humans. Successive whole-body PET/CT scans were done after the injection of F-HX4 in four healthy humans (422±142 MBq) and in three rhesus monkeys (189±3 MBq). Biodistribution was determined from PET images and organ doses were estimated using OLINDA/EXM software. The bladder, liver, and kidneys showed the highest percentage of the injected radioactivity for humans and monkeys. For humans, approximately 45% of the activity is eliminated by bladder voiding in 3.6 h, and for monkeys 60% is in the bladder content after 3 h. The critical organ is the urinary bladder wall with the highest absorbed radiation dose of 415±18 (monkeys) and 299±38 μGy/MBq (humans), in the 4.8-h bladder voiding interval model. The average value of effective dose for the adult male was estimated at 42±4.2 μSv/MBq from monkey data and 27±2 μSv/MBq from human data. Bladder, kidneys, and liver have the highest uptake of injected F-HX4 activity for both monkeys and humans. The urinary bladder wall receives the highest dose of F-HX4 and is the critical organ. Thus, patients should be encouraged to maintain adequate hydration and void frequently. The effective dose of F-HX4 is comparable with that of other F-based imaging agents.

  16. Evaluation of the radiation dose in the thyroid gland using different protective collars in panoramic imaging.

    PubMed

    Hafezi, Ladan; Arianezhad, S Marjan; Hosseini Pooya, Seyed Mahdi

    2018-04-25

    The value for the use of thyroid shield is one of the issues in radiation protection of patients in dental panoramic imaging. The objective of this research is to investigate the attenuation characteristics of some models of thyroid shielding in dental panoramic examinations. The effects of five different types of lead and lead-free (Pb-equivalent) shields on dose reduction of thyroid gland were investigated using implanted Thermoluminescence Dosemeters (TLDs) in head-neck parts of a Rando phantom. The results show that frontal lead and Pb-equivalent shields can reduce the thyroid dose around 50% and 19%, respectively. It can be concluded that the effective shielding area is an important parameter in thyroid gland dose reduction. Lead frontal collars with large effective shielding areas (>~300 cm 2 but not necessarily very large) are appropriate for an optimized thyroid gland dose reduction particularly for the critical patients in dental panoramic imaging. Regardless of the shape and thickness, using the Pb-equivalent shields is not justifiable in dental panoramic imaging.

  17. Correlation of Noncancer Benchmark Doses in Short- and Long-Term Rodent Bioassays.

    PubMed

    Kratchman, Jessica; Wang, Bing; Fox, John; Gray, George

    2018-05-01

    This study investigated whether, in the absence of chronic noncancer toxicity data, short-term noncancer toxicity data can be used to predict chronic toxicity effect levels by focusing on the dose-response relationship instead of a critical effect. Data from National Toxicology Program (NTP) technical reports have been extracted and modeled using the Environmental Protection Agency's Benchmark Dose Software. Best-fit, minimum benchmark dose (BMD), and benchmark dose lower limits (BMDLs) have been modeled for all NTP pathologist identified significant nonneoplastic lesions, final mean body weight, and mean organ weight of 41 chemicals tested by NTP between 2000 and 2012. Models were then developed at the chemical level using orthogonal regression techniques to predict chronic (two years) noncancer health effect levels using the results of the short-term (three months) toxicity data. The findings indicate that short-term animal studies may reasonably provide a quantitative estimate of a chronic BMD or BMDL. This can allow for faster development of human health toxicity values for risk assessment for chemicals that lack chronic toxicity data. © 2017 Society for Risk Analysis.

  18. Personalized Assessment of kV Cone Beam Computed Tomography Doses in Image-guided Radiotherapy of Pediatric Cancer Patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang Yibao; Yan Yulong; Nath, Ravinder

    2012-08-01

    Purpose: To develop a quantitative method for the estimation of kV cone beam computed tomography (kVCBCT) doses in pediatric patients undergoing image-guided radiotherapy. Methods and Materials: Forty-two children were retrospectively analyzed in subgroups of different scanned regions: one group in the head-and-neck and the other group in the pelvis. Critical structures in planning CT images were delineated on an Eclipse treatment planning system before being converted into CT phantoms for Monte Carlo simulations. A benchmarked EGS4 Monte Carlo code was used to calculate three-dimensional dose distributions of kVCBCT scans with full-fan high-quality head or half-fan pelvis protocols predefined by themore » manufacturer. Based on planning CT images and structures exported in DICOM RT format, occipital-frontal circumferences (OFC) were calculated for head-and-neck patients using DICOMan software. Similarly, hip circumferences (HIP) were acquired for the pelvic group. Correlations between mean organ doses and age, weight, OFC, and HIP values were analyzed with SigmaPlot software suite, where regression performances were analyzed with relative dose differences (RDD) and coefficients of determination (R{sup 2}). Results: kVCBCT-contributed mean doses to all critical structures decreased monotonically with studied parameters, with a steeper decrease in the pelvis than in the head. Empirical functions have been developed for a dose estimation of the major organs at risk in the head and pelvis, respectively. If evaluated with physical parameters other than age, a mean RDD of up to 7.9% was observed for all the structures in our population of 42 patients. Conclusions: kVCBCT doses are highly correlated with patient size. According to this study, weight can be used as a primary index for dose assessment in both head and pelvis scans, while OFC and HIP may serve as secondary indices for dose estimation in corresponding regions. With the proposed empirical functions, it is possible to perform an individualized quantitative dose assessment of kVCBCT scans.« less

  19. Normal tissue complication probability modeling of radiation-induced hypothyroidism after head-and-neck radiation therapy.

    PubMed

    Bakhshandeh, Mohsen; Hashemi, Bijan; Mahdavi, Seied Rabi Mehdi; Nikoofar, Alireza; Vasheghani, Maryam; Kazemnejad, Anoshirvan

    2013-02-01

    To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-based treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with α/β = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D(50) estimated from the models was approximately 44 Gy. The implemented normal tissue complication probability models showed a parallel architecture for the thyroid. The mean dose model can be used as the best model to describe the dose-response relationship for hypothyroidism complication. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. A new approach using coagulation rate constant for evaluation of turbidity removal

    NASA Astrophysics Data System (ADS)

    Al-Sameraiy, Mukheled

    2017-06-01

    Coagulation-flocculation-sedimentation processes for treating three levels of bentonite synthetic turbid water using date seeds (DS) and alum (A) coagulants were investigated in the previous research work. In the current research, the same experimental results were used to adopt a new approach on a basis of using coagulation rate constant as an investigating parameter to identify optimum doses of these coagulants. Moreover, the performance of these coagulants to meet (WHO) turbidity standard was assessed by introducing a new evaluating criterion in terms of critical coagulation rate constant (kc). Coagulation rate constants (k2) were mathematically calculated in second order form of coagulation process for each coagulant. The maximum (k2) values corresponded to doses, which were obviously to be considered as optimum doses. The proposed criterion to assess the performance of coagulation process of these coagulants was based on the mathematical representation of (WHO) turbidity guidelines in second order form of coagulation process stated that (k2) for each coagulant should be ≥ (kc) for each level of synthetic turbid water. For all tested turbid water, DS coagulant could not satisfy it. While, A coagulant could satisfy it. The results obtained in the present research are exactly in agreement with the previous published results in terms of finding optimum doses for each coagulant and assessing their performances. On the whole, it is recommended considering coagulation rate constant to be a new approach as an indicator for investigating optimum doses and critical coagulation rate constant to be a new evaluating criterion to assess coagulants' performance.

  1. Consensus on Insulin Dose and Titration Algorithms in Ambulatory Care of Type 2 Diabetes in India.

    PubMed

    Kovil, Rajiv; Chawla, Manoj; Rajput, Rajesh; Singh, A K; Sinha, Binayak; Ghosal, Samit; Ballani, Piya; Gupta, Sunil; Tanna, Snehal; Bandukwala, S M; Shah, Tejas; Negalur, Vijay; Bhoraskar, Anil; Aravind, S R; Zargar, Abdul H; Kesavadev, Jothydev; Das, Ashok Kumar

    2017-02-01

    Insulin is the oldest of the currently available treatment options in Type 2 diabetes mellitus (T2DM) and is considered as the most effective glucose lowering agent. Despite this, decision on starting insulin therapy is often delayed in India as well as worldwide due to various barriers at both patient and physician levels. Appropriate insulin dosing and titration is also critical to the successful achievement of tight glycaemic control. To provide simple and easily implementable guidelines to primary care physicians on appropriate insulin dosing and titration of various insulin regimens for both initiation and intensification. Each insulin regimen (once daily [OD] basal, OD, twice daily and thrice daily premixed, basal-plus and basal-bolus) was presented and evaluated for dosing and titration based on established guidelines, data from approved pack inserts, and published scientific literature. These evaluations were then factored into the national context based on the expert committee representatives patient-physician experience in their clinical practice and common therapeutic practices followed in India. Recommendations for dosing and titration of basal, basal-plus, premixed and basal-bolus insulins were developed. The key recommendations are that insulin doses can be adjusted once or twice weekly; adjustment can be based on lowest/mean of three recent self-monitoring of plasma glucose pre-meal/fasting plasma glucose (FPG) values. The titration should be based on FPG or pre-meal value of 80-130 mg/dL and the dose should be reduced by 10-20% for patients reporting hypoglycaemia(<70mg/dL). The consensus based recommendations mentioned in this paper will be a useful reference tool for health care practitioners, to initiate, optimise and intensify insulin therapy and to successfully achieve optimal glucose control.

  2. Absorbed Dose Rate Due to Intake of Natural Radionuclides by Tilapia Fish (Tilapia nilotica,Linnaeus, 1758) Estimated Near Uranium Mining at Caetité, Bahia, Brazil

    NASA Astrophysics Data System (ADS)

    Pereira, Wagner de S.; Kelecom, Alphonse; Py Júnior, Delcy de Azevedo

    2008-08-01

    The uranium mining at Caetité (Uranium Concentrate Unit—URA) is in its operational phase. Aiming to estimate the radiological environmental impact of the URA, a monitoring program is underway. In order to preserve the biota of the deleterious effects from radiation and to act in a pro-active way as expected from a licensing body, the present work aims to use an environmental protection methodology based on the calculation of absorbed dose rate in biota. Thus, selected target organism was the Tilapia fish (Tilapia nilotica, Linnaeus, 1758) and the radionuclides were: uranium (U-238), thorium (Th-232), radium (Ra-226 and Ra-228) and lead (Pb-210). As, in Brazil there are no radiation exposure limits adopted for biota the value proposed by the Department of Energy (DOE) of the United States of 3.5×103 μGy y-1 has been used. The derived absorbed dose rate calculated for Tilapia was 2.51×100 μGy y-1, that is less than 0.1% of the dose limit established by DOE. The critical radionuclide was Ra-226, with 56% of the absorbed dose rate, followed by U-238 with 34% and Th-232 with 9%. This value of 0.1% of the limit allows to state that, in the operational conditions analyzed, natural radionuclides do not represent a radiological problem to biota.

  3. Absorbed Dose Rate Due to Intake of Natural Radionuclides by Tilapia Fish (Tilapia nilotica,Linnaeus, 1758) Estimated Near Uranium Mining at Caetite, Bahia, Brazil

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pereira, Wagner de S; Universidade Federal Fluminense, Programa de Pos-graduacao em Biologia Marinha; Kelecom, Alphonse

    2008-08-07

    The uranium mining at Caetite (Uranium Concentrate Unit--URA) is in its operational phase. Aiming to estimate the radiological environmental impact of the URA, a monitoring program is underway. In order to preserve the biota of the deleterious effects from radiation and to act in a pro-active way as expected from a licensing body, the present work aims to use an environmental protection methodology based on the calculation of absorbed dose rate in biota. Thus, selected target organism was the Tilapia fish (Tilapia nilotica, Linnaeus, 1758) and the radionuclides were: uranium (U-238), thorium (Th-232), radium (Ra-226 and Ra-228) and lead (Pb-210).more » As, in Brazil there are no radiation exposure limits adopted for biota the value proposed by the Department of Energy (DOE) of the United States of 3.5x10{sup 3} {mu}Gy y{sup -1} has been used. The derived absorbed dose rate calculated for Tilapia was 2.51x10{sup 0} {mu}Gy y{sup -1}, that is less than 0.1% of the dose limit established by DOE. The critical radionuclide was Ra-226, with 56% of the absorbed dose rate, followed by U-238 with 34% and Th-232 with 9%. This value of 0.1% of the limit allows to state that, in the operational conditions analyzed, natural radionuclides do not represent a radiological problem to biota.« less

  4. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Li, K; John R Marsh Cancer Center

    Purpose: To evaluate the clinical rationale for Truebeam and Trilogy Linac machines from Varian Medical System as exchangeable treatment modalities in the same radiation oncology department. Methods: Intensity Modulated Radiotherapy (IMRT) plans for different diseases were selected for this study. These disease sites included brain, head and neck, breast, lung, and prostate. The parameters selected for this study were the energy amount, Monitor Unit (MU); dose coverage of target reflected by prescription isodose volume(PIV); dose spillage described by the volume of 50% isodoseline of the prescription; and dose homogeneities represented by the maximum dose (MaxD) and the minimum dose (MinD)more » of target volume (TV) and critical structure (CS). Each percentage difference between the values of these parameters formed an element of a matrix, which was called Similarity Comparison Matrix(SCM). The elements of the SCM were then simplified by dimensional conversion algorithm, which was used to determine clinical similarity between two machines through a single value. Results: For the selected clinical cases in this study, the average percentage differences between Trilogy and Truebeam in MU was 0.28% with standard deviation(SD) 0.66%, PIV was 0.23% with SD 0.20%, Volume at 50% prescription dose was 0.31% with SD at 0.78%, MaxD at TV is 0.26% with SD 0.35%, MinD at TV is −0.04% with SD 0.51%, MaxD in CS is −0.53% with SD 0.92%, and MinD in CS 3.31%, with SD at 2.89%. The sum, product, geometric and harmonic mean for the matrix elements were 19.0%, 0.00%, 0.19%, and 0.00%. Conclusion: A method to compare two machines in clinical level was developed and some reference values were calculated for decision-making in clinical practice, and this strategy could be expanded to different clinical applications.« less

  5. Estimation of Risk of Normal-tissue Toxicity Following Gastric Cancer Radiotherapy with Photon- or Scanned Proton-beams.

    PubMed

    Mondlane, Gracinda; Ureba, Ana; Gubanski, Michael; Lind, Pehr A; Siegbahn, Albert

    2018-05-01

    Gastric cancer (GC) radiotherapy involves irradiation of large tumour volumes located in the proximities of critical structures. The advantageous dose distributions produced by scanned-proton beams could reduce the irradiated volumes of the organs at risk (OARs). However, treatment-induced side-effects may still appear. The aim of this study was to estimate the normal tissue complication probability (NTCP) following proton therapy of GC, compared to photon radiotherapy. Eight GC patients, previously treated with volumetric-modulated arc therapy (VMAT), were retrospectively planned with scanned proton beams carried out with the single-field uniform-dose (SFUD) method. A beam-specific planning target volume was used for spot positioning and a clinical target volume (CTV) based robust optimisation was performed considering setup- and range-uncertainties. The dosimetric and NTCP values obtained with the VMAT and SFUD plans were compared. With SFUD, lower or similar dose-volume values were obtained for OARs, compared to VMAT. NTCP values of 0% were determined with the VMAT and SFUD plans for all OARs (p>0.05), except for the left kidney (p<0.05), for which lower toxicity was estimated with SFUD. The NTCP reduction, determined for the left kidney with SFUD, can be of clinical relevance for preserving renal function after radiotherapy of GC. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  6. Americium-241 Decorporation Model

    DTIC Science & Technology

    2014-10-01

    doses compared Radiation Dose Convert mass to activity if needed Calculate critical organ doses/ effective whole body dose (Christy and Eckerman...compartments over time with and without treatment, excretion rates, and radiation doses to critical organs. Calculations from the model may be used to...268 x E + 2 newton-meter (N/m) pound-force/foot2 4.788 026 x E – 2 kilo pascal (kPa) pound-force/inch2 (psi) 6.894 757 kilo pascal (kPa) pound- mass

  7. Critical Combinations of Radiation Dose and Volume Predict Intelligence Quotient and Academic Achievement Scores After Craniospinal Irradiation in Children With Medulloblastoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Merchant, Thomas E., E-mail: thomas.merchant@stjude.org; Schreiber, Jane E.; Wu, Shengjie

    Purpose: To prospectively follow children treated with craniospinal irradiation to determine critical combinations of radiation dose and volume that would predict for cognitive effects. Methods and Materials: Between 1996 and 2003, 58 patients (median age 8.14 years, range 3.99-20.11 years) with medulloblastoma received risk-adapted craniospinal irradiation followed by dose-intense chemotherapy and were followed longitudinally with multiple cognitive evaluations (through 5 years after treatment) that included intelligence quotient (estimated intelligence quotient, full-scale, verbal, and performance) and academic achievement (math, reading, spelling) tests. Craniospinal irradiation consisted of 23.4 Gy for average-risk patients (nonmetastatic) and 36-39.6 Gy for high-risk patients (metastatic or residual disease >1.5 cm{sup 2}). The primary sitemore » was treated using conformal or intensity modulated radiation therapy using a 2-cm clinical target volume margin. The effect of clinical variables and radiation dose to different brain volumes were modeled to estimate cognitive scores after treatment. Results: A decline with time for all test scores was observed for the entire cohort. Sex, race, and cerebrospinal fluid shunt status had a significant impact on baseline scores. Age and mean radiation dose to specific brain volumes, including the temporal lobes and hippocampi, had a significant impact on longitudinal scores. Dichotomized dose distributions at 25 Gy, 35 Gy, 45 Gy, and 55 Gy were modeled to show the impact of the high-dose volume on longitudinal test scores. The 50% risk of a below-normal cognitive test score was calculated according to mean dose and dose intervals between 25 Gy and 55 Gy at 10-Gy increments according to brain volume and age. Conclusions: The ability to predict cognitive outcomes in children with medulloblastoma using dose-effects models for different brain subvolumes will improve treatment planning, guide intervention, and help estimate the value of newer methods of irradiation.« less

  8. The path of least resistance: paying for antibiotics in non-human uses.

    PubMed

    Hollis, Aidan; Ahmed, Ziana

    2014-11-01

    Antibiotic resistance is a critical threat to human and animal health. Despite the importance of antibiotics, regulators continue to allow antibiotics to be used in low-value applications--subtherapeutic dosing in animals, and spraying tobacco plants for blue mold, for example--where the benefits are unlikely to outweigh the costs in terms of increased resistance. We explore the application of a user fee in non-human uses of antibiotics. Such a fee would efficiently deter low value uses while also providing funding to support the development of the urgently needed new antibiotics. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. Radiation induced leakage due to stochastic charge trapping in isolation layers of nanoscale MOSFETs

    NASA Astrophysics Data System (ADS)

    Zebrev, G. I.; Gorbunov, M. S.; Pershenkov, V. S.

    2008-03-01

    The sensitivity of sub-100 nm devices to microdose effects, which can be considered as intermediate case between cumulative total dose and single event errors, is investigated. A detailed study of radiation-induced leakage due to stochastic charge trapping in irradiated planar and nonplanar devices is developed. The influence of High-K insulators on nanoscale ICs reliability is discussed. Low critical values of trapped charge demonstrate a high sensitivity to single event effect.

  10. Accelerated heavy particles and the lens. VII: The cataractogenic potential of 450 MeV/amu iron ions

    NASA Technical Reports Server (NTRS)

    Worgul, B. V.; Brenner, D. J.; Medvedovsky, C.; Merriam, G. R. Jr; Huang, Y.

    1993-01-01

    PURPOSE. To determine the cataractogenic potential dose of high velocity iron ions as a fixation of dose administered singly or fractionated. The dose is critical to risk assessment and to theories of radiation action and cataractogenesis. METHODS. Twenty-eight-day-old rats were examined by slit-lamp biomicroscopy on a weekly-bi-weekly basis for more than 2 yr after radiation exposure. For the acute exposure study doses of 1, 2, 5, 25, and 50 cGy were evaluated. The fractionated regimens involved total doses of 2, 25, and 50 cGy. The reference radiation consisted of 50, 100, 200, or 700 cGy of 250 kilovolt (peak) x-rays. RESULTS. In accordance with previous findings in the rat using 570 MeV/amu 40Ar ions, the relative biologic effectiveness increased rapidly with decreasing dose, reaching values as high as 100. Unlike 40Ar ions, fractionation of the 56Fe doses did not produce a consistent enhancement at any of the doses examined. CONCLUSIONS. The data support the previous findings of a high cataractogenic potential for high linear energy transfer (LET) radiation. The effectiveness for the production of cataracts increases with decreasing dose relative to x-rays and is independent of dose protraction. Although the present study did not reveal a consistent enhancement of effect when the ions were applied in fractions, the results are consistent with at least one theory of the inverse dose-rate effect observed for high-LET radiation.

  11. Critical analysis of adsorption data statistically

    NASA Astrophysics Data System (ADS)

    Kaushal, Achla; Singh, S. K.

    2017-10-01

    Experimental data can be presented, computed, and critically analysed in a different way using statistics. A variety of statistical tests are used to make decisions about the significance and validity of the experimental data. In the present study, adsorption was carried out to remove zinc ions from contaminated aqueous solution using mango leaf powder. The experimental data was analysed statistically by hypothesis testing applying t test, paired t test and Chi-square test to (a) test the optimum value of the process pH, (b) verify the success of experiment and (c) study the effect of adsorbent dose in zinc ion removal from aqueous solutions. Comparison of calculated and tabulated values of t and χ 2 showed the results in favour of the data collected from the experiment and this has been shown on probability charts. K value for Langmuir isotherm was 0.8582 and m value for Freundlich adsorption isotherm obtained was 0.725, both are <1, indicating favourable isotherms. Karl Pearson's correlation coefficient values for Langmuir and Freundlich adsorption isotherms were obtained as 0.99 and 0.95 respectively, which show higher degree of correlation between the variables. This validates the data obtained for adsorption of zinc ions from the contaminated aqueous solution with the help of mango leaf powder.

  12. Continuing education: online monitoring of haemodialysis dose.

    PubMed

    Vartia, Aarne

    2018-01-25

    Kt/V urea reflects the efficacy of haemodialysis scaled to patient size (urea distribution volume). The guidelines recommend monthly Kt/V measurements based on blood samples. Modern haemodialysis machines are equipped with accessories monitoring the dose online at every session without extra costs, blood samples and computers. To describe the principles, devices, benefits and shortcomings of online monitoring of haemodialysis dose. A critical literature overview and discussion. UV absorbance methods measure Kt/V, ionic dialysance Kt (product of clearance and treatment time; cleared volume without scaling). Both are easy and useful methods, but comparison is difficult due to problems in scaling of the dialysis dose to the patient's size. The best dose estimation method is the one which predicts the quality of life and survival most accurately. There is some evidence on the predictive value of ionic dialysance Kt, but more documentation is required on the UV method. Online monitoring is a useful tool in everyday quality assurance, but blood samples are still required for more accurate kinetic modelling. After reading this article the reader should be able to: Understand the elements of the Kt/V equation for dialysis dose. Compare and contrast different methods of measurement of dialysis dose. Reflect on the importance of adequate dialysis dose for patient survival and life quality. © 2018 European Dialysis and Transplant Nurses Association/European Renal Care Association.

  13. Thermoluminescence dosimetry applied to in vivo dose measurements for total body irradiation techniques.

    PubMed

    Duch, M A; Ginjaume, M; Chakkor, H; Ortega, X; Jornet, N; Ribas, M

    1998-06-01

    In total body irradiation (TBI) treatments in vivo dosimetry is recommended because it makes it possible to ensure the accuracy and quality control of dose delivery. The aim of this work is to set up an in vivo thermoluminescence dosimetry (TLD) system to measure the dose distribution during the TBI technique used prior to bone marrow transplant. Some technical problems due to the presence of lung shielding blocks are discussed. Irradiations were performed in the Hospital de la Santa Creu i Sant Pau by means of a Varian Clinac-1800 linear accelerator with 18 MV X-ray beams. Different TLD calibration experiments were set up to optimize in vivo dose assessment and to analyze the influence on dose measurement of shielding blocks. An algorithm to estimate midplane doses from entrance and exit doses is proposed and the estimated dose in critical organs is compared to internal dose measurements performed in an Alderson anthropomorphic phantom. The predictions of the dose algorithm, even in heterogeneous zones of the body such as the lungs, are in good agreement with the experimental results obtained with and without shielding blocks. The differences between measured and predicted values are in all cases lower than 2%. The TLD system described in this work has been proven to be appropriate for in vivo dosimetry in TBI irradiations. The described calibration experiments point out the difficulty of calibrating an in vivo dosimetry system when lung shielding blocks are used.

  14. Right dose, right now: using big data to optimize antibiotic dosing in the critically ill.

    PubMed

    Elbers, Paul W G; Girbes, Armand; Malbrain, Manu L N G; Bosman, Rob

    2015-01-01

    Antibiotics save lives and are essential for the practice of intensive care medicine. Adequate antibiotic treatment is closely related to outcome. However this is challenging in the critically ill, as their pharmacokinetic profile is markedly altered. Therefore, it is surprising that critical care physicians continue to rely on standard dosing regimens for every patient, regardless of the actual clinical situation. This review outlines the pharmacokinetic and pharmacodynamic principles that underlie the need for individualized and personalized drug dosing. At present, therapeutic drug monitoring may be of help, but has major disadvantages, remains unavailable for most antibiotics and has produced mixed results. We therefore propose the AutoKinetics concept, taking decision support for antibiotic dosing back to the bedside. By direct interaction with electronic patient records, this opens the way for the use of big data for providing the right dose at the right time in each patient.

  15. Estimation of Rectal Dose Using Daily Megavoltage Cone-Beam Computed Tomography and Deformable Image Registration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Akino, Yuichi, E-mail: akino@radonc.med.osaka-u.ac.jp; Department of Radiology, Osaka University Hospital, Suita, Osaka; Yoshioka, Yasuo

    2013-11-01

    Purpose: The actual dose delivered to critical organs will differ from the simulated dose because of interfractional organ motion and deformation. Here, we developed a method to estimate the rectal dose in prostate intensity modulated radiation therapy with consideration to interfractional organ motion using daily megavoltage cone-beam computed tomography (MVCBCT). Methods and Materials: Under exemption status from our institutional review board, we retrospectively reviewed 231 series of MVCBCT of 8 patients with prostate cancer. On both planning CT (pCT) and MVCBCT images, the rectal contours were delineated and the CT value within the contours was replaced by the mean CTmore » value within the pelvis, with the addition of 100 Hounsfield units. MVCBCT images were rigidly registered to pCT and then nonrigidly registered using B-Spline deformable image registration (DIR) with Velocity AI software. The concordance between the rectal contours on MVCBCT and pCT was evaluated using the Dice similarity coefficient (DSC). The dose distributions normalized for 1 fraction were also deformed and summed to estimate the actual total dose. Results: The DSC of all treatment fractions of 8 patients was improved from 0.75±0.04 (mean ±SD) to 0.90 ±0.02 by DIR. Six patients showed a decrease of the generalized equivalent uniform dose (gEUD) from total dose compared with treatment plans. Although the rectal volume of each treatment fraction did not show any correlation with the change in gEUD (R{sup 2}=0.18±0.13), the displacement of the center of gravity of rectal contours in the anterior-posterior (AP) direction showed an intermediate relationship (R{sup 2}=0.61±0.16). Conclusion: We developed a method for evaluation of rectal dose using DIR and MVCBCT images and showed the necessity of DIR for the evaluation of total dose. Displacement of the rectum in the AP direction showed a greater effect on the change in rectal dose compared with the rectal volume.« less

  16. Intracellular accumulation dynamics and fate of zinc ions in alveolar epithelial cells exposed to airborne ZnO nanoparticles at the air–liquid interface

    DOE PAGES

    Mihai, Cosmin; Chrisler, William B.; Xie, Yumei; ...

    2013-12-02

    Airborne nanoparticles (NPs) that enter the respiratory tract are likely to reach the alveolar region. Accumulating observations support a role for zinc oxide (ZnO) NP dissolution in toxicity, but the majority of in vitro studies were conducted in cells exposed to NPs in growth media, where large doses of dissolved ions are shed into the exposure solution. To determine the precise intracellular accumulation dynamics and fate of zinc ions (Zn 2+) shed by airborne NPs in the cellular environment, we exposed alveolar epithelial cells to aerosolized NPs at the air-liquid interface (ALI). Using a fluorescent indicator for Zn 2+, togethermore » with organelle-specific fluorescent proteins, we quantified Zn 2+ in single cells and organelles over time. We found that at the ALI, intracellular Zn 2+ values peaked 3 h post exposure and decayed to normal values by 12 h, while in submersed cultures, intracellular Zn 2+ values continued to increase over time. The lowest toxic NP dose at the ALI generated peak intracellular Zn 2+ values that were nearly 3 folds lower than the peak values generated by the lowest toxic dose of NPs in submersed cultures, and 8 folds lower than the peak values generated by the lowest toxic dose of ZnSO4 or Zn 2+. At the ALI, the majority of intracellular Zn 2+ was found in endosomes and lysosomes as early as 1 h post exposure. In contrast, the majority of intracellular Zn 2+ following exposures to ZnSO 4 was found in other larger vesicles, with less than 10% in endosomes and lysosomes. In conclusion, together, our observations indicate that low but critical levels of intracellular Zn 2+ have to be reached, concentrated specifically in endosomes and lysosomes, for toxicity to occur, and point to the focal dissolution of the NPs in the cellular environment and the accumulation of the ions specifically in endosomes and lysosomes as the processes underlying the potent toxicity of airborne ZnO NPs.« less

  17. Intracellular accumulation dynamics and fate of zinc ions in alveolar epithelial cells exposed to airborne ZnO nanoparticles at the air–liquid interface

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mihai, Cosmin; Chrisler, William B.; Xie, Yumei

    Airborne nanoparticles (NPs) that enter the respiratory tract are likely to reach the alveolar region. Accumulating observations support a role for zinc oxide (ZnO) NP dissolution in toxicity, but the majority of in vitro studies were conducted in cells exposed to NPs in growth media, where large doses of dissolved ions are shed into the exposure solution. To determine the precise intracellular accumulation dynamics and fate of zinc ions (Zn 2+) shed by airborne NPs in the cellular environment, we exposed alveolar epithelial cells to aerosolized NPs at the air-liquid interface (ALI). Using a fluorescent indicator for Zn 2+, togethermore » with organelle-specific fluorescent proteins, we quantified Zn 2+ in single cells and organelles over time. We found that at the ALI, intracellular Zn 2+ values peaked 3 h post exposure and decayed to normal values by 12 h, while in submersed cultures, intracellular Zn 2+ values continued to increase over time. The lowest toxic NP dose at the ALI generated peak intracellular Zn 2+ values that were nearly 3 folds lower than the peak values generated by the lowest toxic dose of NPs in submersed cultures, and 8 folds lower than the peak values generated by the lowest toxic dose of ZnSO4 or Zn 2+. At the ALI, the majority of intracellular Zn 2+ was found in endosomes and lysosomes as early as 1 h post exposure. In contrast, the majority of intracellular Zn 2+ following exposures to ZnSO 4 was found in other larger vesicles, with less than 10% in endosomes and lysosomes. In conclusion, together, our observations indicate that low but critical levels of intracellular Zn 2+ have to be reached, concentrated specifically in endosomes and lysosomes, for toxicity to occur, and point to the focal dissolution of the NPs in the cellular environment and the accumulation of the ions specifically in endosomes and lysosomes as the processes underlying the potent toxicity of airborne ZnO NPs.« less

  18. Intracellular accumulation dynamics and fate of zinc ions in alveolar epithelial cells exposed to airborne ZnO nanoparticles at the air–liquid interface

    PubMed Central

    Mihai, Cosmin; Chrisler, William B.; Xie, Yumei; Hu, Dehong; Szymanski, Craig J.; Tolic, Ana; Klein, Jessica A.; Smith, Jordan N.; Tarasevich, Barbara J.; Orr, Galya

    2015-01-01

    Airborne nanoparticles (NPs) that enter the respiratory tract are likely to reach the alveolar region. Accumulating observations support a role for zinc oxide (ZnO) NP dissolution in toxicity, but the majority of in-vitro studies were conducted in cells exposed to NPs in growth media, where large doses of dissolved ions are shed into the exposure solution. To determine the precise intracellular accumulation dynamics and fate of zinc ions (Zn2+) shed by airborne NPs in the cellular environment, we exposed alveolar epithelial cells to aerosolized NPs at the air–liquid interface (ALI). Using a fluorescent indicator for Zn2+, together with organelle-specific fluorescent proteins, we quantified Zn2+ in single cells and organelles over time. We found that at the ALI, intracellular Zn2+ values peaked 3 h post exposure and decayed to normal values by 12 h, while in submerged cultures, intracellular Zn2+ values continued to increase over time. The lowest toxic NP dose at the ALI generated peak intracellular Zn2+ values that were nearly three-folds lower than the peak values generated by the lowest toxic dose of NPs in submerged cultures, and eight-folds lower than the peak values generated by the lowest toxic dose of ZnSO4 or Zn2+. At the ALI, the majority of intracellular Zn2+ was found in endosomes and lysosomes as early as 1 h post exposure. In contrast, the majority of intracellular Zn2+ following exposures to ZnSO4 was found in other larger vesicles, with less than 10% in endosomes and lysosomes. Together, our observations indicate that low but critical levels of intracellular Zn2+ have to be reached, concentrated specifically in endosomes and lysosomes, for toxicity to occur, and point to the focal dissolution of the NPs in the cellular environment and the accumulation of the ions specifically in endosomes and lysosomes as the processes underlying the potent toxicity of airborne ZnO NPs. PMID:24289294

  19. Intracellular accumulation dynamics and fate of zinc ions in alveolar epithelial cells exposed to airborne ZnO nanoparticles at the air-liquid interface.

    PubMed

    Mihai, Cosmin; Chrisler, William B; Xie, Yumei; Hu, Dehong; Szymanski, Craig J; Tolic, Ana; Klein, Jessica A; Smith, Jordan N; Tarasevich, Barbara J; Orr, Galya

    2015-02-01

    Airborne nanoparticles (NPs) that enter the respiratory tract are likely to reach the alveolar region. Accumulating observations support a role for zinc oxide (ZnO) NP dissolution in toxicity, but the majority of in-vitro studies were conducted in cells exposed to NPs in growth media, where large doses of dissolved ions are shed into the exposure solution. To determine the precise intracellular accumulation dynamics and fate of zinc ions (Zn(2+)) shed by airborne NPs in the cellular environment, we exposed alveolar epithelial cells to aerosolized NPs at the air-liquid interface (ALI). Using a fluorescent indicator for Zn(2+), together with organelle-specific fluorescent proteins, we quantified Zn(2+) in single cells and organelles over time. We found that at the ALI, intracellular Zn(2+) values peaked 3 h post exposure and decayed to normal values by 12 h, while in submerged cultures, intracellular Zn(2+) values continued to increase over time. The lowest toxic NP dose at the ALI generated peak intracellular Zn(2+) values that were nearly three-folds lower than the peak values generated by the lowest toxic dose of NPs in submerged cultures, and eight-folds lower than the peak values generated by the lowest toxic dose of ZnSO4 or Zn(2+). At the ALI, the majority of intracellular Zn(2+) was found in endosomes and lysosomes as early as 1 h post exposure. In contrast, the majority of intracellular Zn(2+) following exposures to ZnSO4 was found in other larger vesicles, with less than 10% in endosomes and lysosomes. Together, our observations indicate that low but critical levels of intracellular Zn(2+) have to be reached, concentrated specifically in endosomes and lysosomes, for toxicity to occur, and point to the focal dissolution of the NPs in the cellular environment and the accumulation of the ions specifically in endosomes and lysosomes as the processes underlying the potent toxicity of airborne ZnO NPs.

  20. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pirlepesov, F.; Shin, J.; Moskvin, V. P.

    Purpose: Dose weighted Linear Energy Transfer (LETd) analysis of critical structures may be useful in understanding the side effects of the proton therapy. The objective is to analyze the differences between LETd and dose distributions in brain tumor patients receiving double scattering proton therapy, to quantify LETd variation in critical organs, and to identify beam arrangements contributing to high LETd in critical organs. Methods: Monte Carlo simulations of 9 pediatric brain tumor patients were performed. The treatment plans were reconstructed with the TOPAS Monte Carlo code to calculate LETd and dose. The beam data were reconstructed proximal to the aperturemore » of the double scattering nozzle. The dose and LETd to target and critical organs including brain stem, optic chiasm, lens, optic nerve, pituitary gland, and hypothalamus were computed for each beam. Results: Greater variability in LETd compared to dose was observed in the brainstem for patients with a variety of tumor types including 5 patients with tumors located in the posterior fossa. Approximately 20%–44% brainstem volume received LETd of 5kev/µm or greater from beams within gantry angles 180°±30° for 5 patients treated with a 3 beam arrangement. Critical organs received higher LETd when located in the vicinity of the beam distal edge. Conclusion: This study presents a novel strategy in the evaluation of the proton treatment impact on critical organs. While the dose to critical organs is confined below the required limits, the LETd may have significant variation. Critical organs in the vicinity of beam distal edge receive higher LETd and depended on beam arrangement, e.g. in posterior fossa tumor treatment, brainstem receive higher LETd from posterior-anterior beams. This study shows importance of the LETd analysis of the radiation impact on the critical organs in proton therapy and may be used to explain clinical imaging observations after therapy.« less

  1. Radon and Thoron Measured in Petrol and Gas-oil Exhaust Fumes by Using CR-39 and LR-115 II Nuclear Track Detectors: Radiation Doses to the Respiratory Tract of Mechanic Workers.

    PubMed

    Misdaq, M A; Chaouqi, A; Ouguidi, J; Touti, R; Mortassim, A

    2015-06-01

    Mechanic workers are exposed to exhaust fumes when controlling vehicle engines in motion inside repair shops. To assess radiation doses due to radon short-lived progeny from the inhalation of exhaust fumes by mechanic workers, concentrations of these radionuclides were measured in petrol (gasoline) and gas-oil exhaust fumes by evaluating mean critical angles of etching of the CR-39 and LR-115 type II SSNTDs for alpha particles emitted by the radon and thoron decay series. Committed effective doses due to ²¹⁸Po and ²¹⁴Po short-lived radon decay products from the inhalation of petrol and gas-oil exhaust fumes by workers were evaluated. A maximum value of 1.35 mSv y⁻¹ due to radon short-lived decay products from the inhalation of gas-oil exhaust fumes by mechanic workers was found, which is lower than the (3-10 mSv y⁻¹) dose limit interval for workers.

  2. Comparative analysis of dosimetry parameters for nuclear medicine

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Toohey, R.E.; Stabin, M.G.

    For years many have employed the concept of ``total-body dose`` or ``whole-body dose,`` i.e., the total energy deposited in the body divided by the mass of the body, when evaluating the risks of different nuclear medicine procedures. The effective dose equivalent (H{sub E}), first described in ICRP Publication 26, has been accepted by some as a better quantity to use in evaluating the total risk of a procedure, but its use has been criticized by others primarily because the tissue weighting factors were intended for use in the radiation worker, rather than the nuclear medicine patient population. Nevertheless, in ICRPmore » Publication 52, the ICRP has suggested that the H{sub E} may be used in nuclear medicine. The ICRP also has published a compendium of dose estimates, including H{sub E} values, for various nuclear medicine procedures at various ages in ICRP Publication 53. The effective dose (E) of ICRP Publication 60 is perhaps more suitable for use in nuclear medicine, with tissue weighting factors based on the entire population. Other comparisons of H{sub E} and E have been published. The authors have used the program MIRDOSE 3.1 to compute total-body dose, H{sub E}, and E for 62 radiopharmaceutical procedures, based on the best current biokinetic data available.« less

  3. Challenges and Potential Solutions – Individualised Antibiotic Dosing at the Bedside for Critically Ill Patients: a structured review

    PubMed Central

    Roberts, Jason A.; Aziz, Mohd Hafiz Abdul; Lipman, Jeffrey; Mouton, Johan W.; Vinks, Alexander A.; Felton, Timothy W.; Hope, William W.; Farkas, Andras; Neely, Michael N.; Schentag, Jerome J.; Drusano, George; Frey, Otto R.; Theuretzbacher, Ursula; Kuti, Joseph L.

    2014-01-01

    Summary Infections in critically ill patients are associated with persistently poor clinical outcomes. These patients have severely altered and variable antibiotic pharmacokinetics and are infected by less susceptible pathogens. Antibiotic dosing that does not account for these features is likely to result in sub-optimal outcomes. In this paper, we review the patient- and pathogen-related challenges that contribute to inadequate antibiotic dosing and discuss how a process for individualised antibiotic therapy, that increases the accuracy of dosing, can be implemented to further optimise care for the critically ill patient. The process for optimised antibiotic dosing firstly requires determination of the physiological derangements in the patient that can alter antibiotic concentrations including altered fluid status, microvascular failure, serum albumin concentrations as well as altered renal and hepatic function. Secondly, knowledge of the susceptibility of the infecting pathogen should be determined through liaison with the microbiology laboratory. The patient and pathogen challenges can then be solved by combining susceptibility data with measured antibiotic concentration data (where possible) into a clinical dosing software. Such software uses pharmacokinetic-pharmacodynamic (PK/PD) models from critically ill patients to accurately predict the dosing requirements for the individual patient with the aim of optimising antibiotic exposure and maximising effectiveness. PMID:24768475

  4. Optimizing 18F-FDG PET/CT Imaging of Vessel Wall Inflammation –The Impact of 18F-FDG Circulation Time, Injected Dose, Uptake Parameters, and Fasting Blood Glucose Levels

    PubMed Central

    Bucerius, Jan; Mani, Venkatesh; Moncrieff, Colin; Machac, Josef; Fuster, Valentin; Farkouh, Michael E.; Tawakol, Ahmed; Rudd, James H. F.; Fayad, Zahi A.

    2014-01-01

    Purpose 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is increasingly used for imaging of vessel wall inflammation. However, limited data is available regarding the impact of methodological variables, i. e. patient’s pre-scan fasting glucose, the FDG circulation time, the injected FDG dose, and of different FDG uptake parameters, in vascular FDG-PET imaging. Methods 195 patients underwent vascular FDG-PET/CT of the aorta and the carotids. Arterial standard uptake values (meanSUVmax) as well as target-to-background-ratios (meanTBRmax) and the FDG blood pool activity in the superior vein cava (SVC) and the jugular veins (JV) were quantified. Vascular FDG uptake classified according to tertiles of patient’s pre-scan fasting glucose levels, the FDG circulation time, and the injected FDG dose was compared using ANOVA. Multivariate regression analyses were performed to identify the potential impact of all variables described on the arterial and blood pool FDG uptake. Results Tertile analyses revealed FDG circulation times of about 2.5 h and prescan glucose levels of less than 7.0 mmol/l showing favorable relations between the arterial and blood pool FDG uptake. FDG circulation times showed negative associations with the aortic meanSUVmax values as well as SVC- and JV FDG blood pool activity but a positive correlation with the aortic- and carotid meanTBRmax values. Pre-scan glucose was negatively associated with aortic- and carotid meanTBRmax and carotid meanSUVmax values, but correlated positively with the SVC blood pool uptake. Injected FDG dose failed to show any significant association with the vascular FDG uptake. Conclusion FDG circulation times and pre-scan blood glucose levels significantly impact FDG uptake within the aortic and carotid wall and may bias the results of image interpretation in patients undergoing vascular FDG-PET/CT. FDG dose injected was less critical. Therefore, circulation times of about 2.5 h and pre-scan glucose levels less than 7.0 mmol/l should be preferred in this setting. PMID:24271038

  5. Biological optimization of simultaneous boost on intra-prostatic lesions (DILs): sensitivity to TCP parameters.

    PubMed

    Azzeroni, R; Maggio, A; Fiorino, C; Mangili, P; Cozzarini, C; De Cobelli, F; Di Muzio, N G; Calandrino, R

    2013-11-01

    The aim of this investigation was to explore the potential of biological optimization in the case of simultaneous integrated boost on intra-prostatic dominant lesions (DIL) and evaluating the impact of TCP parameters uncertainty. Different combination of TCP parameters (TD50 and γ50 in the Poisson-like model), were considered for DILs and the prostate outside DILs (CTV) for 7 intermediate/high-risk prostate patients. The aim was to maximize TCP while constraining NTCPs below 5% for all organs at risk. TCP values were highly depending on the parameters used and ranged between 38.4% and 99.9%; the optimized median physical doses were in the range 94-116 Gy and 69-77 Gy for DIL and CTV respectively. TCP values were correlated with the overlap PTV-rectum and the minimum distance between rectum and DIL. In conclusion, biological optimization for selective dose escalation is feasible and suggests prescribed dose around 90-120 Gy to the DILs. The obtained result is critically depending on the assumptions concerning the higher radioresistence in the DILs. In case of very resistant clonogens into the DIL, it may be difficult to maximize TCP to acceptable levels without violating NTCP constraints. Copyright © 2012 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  6. A Comparison of Dose-Response Models for the Parotid Gland in a Large Group of Head-and-Neck Cancer Patients

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Houweling, Antonetta C., E-mail: A.Houweling@umcutrecht.n; Philippens, Marielle E.P.; Dijkema, Tim

    2010-03-15

    Purpose: The dose-response relationship of the parotid gland has been described most frequently using the Lyman-Kutcher-Burman model. However, various other normal tissue complication probability (NTCP) models exist. We evaluated in a large group of patients the value of six NTCP models that describe the parotid gland dose response 1 year after radiotherapy. Methods and Materials: A total of 347 patients with head-and-neck tumors were included in this prospective parotid gland dose-response study. The patients were treated with either conventional radiotherapy or intensity-modulated radiotherapy. Dose-volume histograms for the parotid glands were derived from three-dimensional dose calculations using computed tomography scans. Stimulatedmore » salivary flow rates were measured before and 1 year after radiotherapy. A threshold of 25% of the pretreatment flow rate was used to define a complication. The evaluated models included the Lyman-Kutcher-Burman model, the mean dose model, the relative seriality model, the critical volume model, the parallel functional subunit model, and the dose-threshold model. The goodness of fit (GOF) was determined by the deviance and a Monte Carlo hypothesis test. Ranking of the models was based on Akaike's information criterion (AIC). Results: None of the models was rejected based on the evaluation of the GOF. The mean dose model was ranked as the best model based on the AIC. The TD{sub 50} in these models was approximately 39 Gy. Conclusions: The mean dose model was preferred for describing the dose-response relationship of the parotid gland.« less

  7. Normal Tissue Complication Probability Modeling of Radiation-Induced Hypothyroidism After Head-and-Neck Radiation Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bakhshandeh, Mohsen; Hashemi, Bijan, E-mail: bhashemi@modares.ac.ir; Mahdavi, Seied Rabi Mehdi

    Purpose: To determine the dose-response relationship of the thyroid for radiation-induced hypothyroidism in head-and-neck radiation therapy, according to 6 normal tissue complication probability models, and to find the best-fit parameters of the models. Methods and Materials: Sixty-five patients treated with primary or postoperative radiation therapy for various cancers in the head-and-neck region were prospectively evaluated. Patient serum samples (tri-iodothyronine, thyroxine, thyroid-stimulating hormone [TSH], free tri-iodothyronine, and free thyroxine) were measured before and at regular time intervals until 1 year after the completion of radiation therapy. Dose-volume histograms (DVHs) of the patients' thyroid gland were derived from their computed tomography (CT)-basedmore » treatment planning data. Hypothyroidism was defined as increased TSH (subclinical hypothyroidism) or increased TSH in combination with decreased free thyroxine and thyroxine (clinical hypothyroidism). Thyroid DVHs were converted to 2 Gy/fraction equivalent doses using the linear-quadratic formula with {alpha}/{beta} = 3 Gy. The evaluated models included the following: Lyman with the DVH reduced to the equivalent uniform dose (EUD), known as LEUD; Logit-EUD; mean dose; relative seriality; individual critical volume; and population critical volume models. The parameters of the models were obtained by fitting the patients' data using a maximum likelihood analysis method. The goodness of fit of the models was determined by the 2-sample Kolmogorov-Smirnov test. Ranking of the models was made according to Akaike's information criterion. Results: Twenty-nine patients (44.6%) experienced hypothyroidism. None of the models was rejected according to the evaluation of the goodness of fit. The mean dose model was ranked as the best model on the basis of its Akaike's information criterion value. The D{sub 50} estimated from the models was approximately 44 Gy. Conclusions: The implemented normal tissue complication probability models showed a parallel architecture for the thyroid. The mean dose model can be used as the best model to describe the dose-response relationship for hypothyroidism complication.« less

  8. Radiation exposure in interventional radiology

    NASA Astrophysics Data System (ADS)

    Pinto, N. G. V.; Braz, D.; Vallim, M. A.; Filho, L. G. P.; Azevedo, F. S.; Barroso, R. C.; Lopes, R. T.

    2007-09-01

    The aim of this study is to evaluate dose values in patients and staff involved in some interventional radiology procedures. Doses have been measured using thermoluminescent dosemeters for single procedures (such as renal and cerebral arteriography, transjungular intrahepatic portasystemic shunt (TIPS) and chemoembolization). The magnitude of doses through the hands of interventional radiologists has been studied. Dose levels were evaluated in three points for patients (eye, thyroid and gonads). The dose-area product (DAP) was also investigated using a Diamentor (PTW-M2). The dose in extremities was estimated for a professional who generally performed one TIPS, two chemoembolizations, two cerebral arteriographies and two renal arteriographies in a week. The estimated annual radiation dose was converted to effective dose as suggested by the 453-MS/Brazil norm The annual dose values were 137.25 mSv for doctors, 40.27 mSv for nurses and 51.95 mSv for auxiliary doctors, and all these annual dose values are below the limit established. The maximum values of the dose obtained for patients were 6.91, 10.92 and 15.34 mGy close to eye, thyroid and gonads, respectively. The DAP values were evaluated for patients in the same interventional radiology procedures. The dose and DAP values obtained are in agreement with values encountered in the literature.

  9. The Relationship Between Vitamin E Plasma and BAL Concentrations, SOD Activity and Ventilatory Support Measures in Critically Ill Patients

    PubMed Central

    Ziaie, Shadi; Jamaati, Hamidreza; Hajimahmoodi, Mannan; Hashemian, Seyyed Mohammadreza; Fahimi, Fanak; Farzanegan, Behrooz; Moghaddam, Ghazaleh; Radmand, Golnar; Vahdani, Behzad; Nadji, Seyed Alireza; Mousavi, Sarah; Hamishehkar, Hadi; Mojtahedzadeh, Mojtaba

    2011-01-01

    Vitamin E is a potent reactive oxygen metabolites (ROM) scavenger. It is a lipid-soluble vitamin and its main function is to protect polyunsaturated fatty acids against oxidative stress. Twenty-five mechanically ventilated Intensive Care Unit (ICU) adult patients participated in a prospective randomized clinical trial receiving either placebo (10 patients) or 3 IM doses (1000 IU each) of vitamin E (15 patients). We determined plasma and bronchoalveolar lavage (BAL) fluid concentrations of vitamin E and superoxide dismutase (SOD). Among these 25 patients, there were 14 men and 11 women, aged 63.16 ±15.48 years (mean ± SD; range = 33 to 87 years). Vitamin E supplementation resulted in significant differences in plasma and BAL vitamin E concentrations between the two groups (p-value = 0.01, 0.01), decrease in SOD activities (not differ significantly in plasma (p-value = 0.23)), but with significant differences in BAL (p-value = 0.016) and progressive reduction in Acute Physiology and Chronic Health Evaluation II (APACHE II) (p-value = 0.52) and Sequential Organ Failure Assessment (SOFA) (p-value = 0.008) score in vitamin E group. From the results of this study, it seems that supplementation of vitamin E as a potent antioxidant, along with other supportive measures, can be beneficial in decreasing SOD total activity, ROM production and risk of organ failure in critically ill patients. PMID:24250434

  10. Pharmacologic Treatment Reduces Pressure Times Time Dose and Relative Duration of Intracranial Hypertension.

    PubMed

    Colton, Katharine; Yang, S; Hu, P F; Chen, H H; Bonds, B; Stansbury, L G; Scalea, T M; Stein, D M

    2016-05-01

    Past work has shown the importance of the "pressure times time dose" (PTD) of intracranial hypertension (intracranial pressure [ICP] > 19 mm Hg) in predicting outcome after severe traumatic brain injury. We used automated data collection to measure the effect of common medications on the duration and dose of intracranial hypertension. Patients >17 years old, admitted and requiring ICP monitoring between 2008 and 2010 at a single, large urban tertiary care facility, were retrospectively enrolled. Timing and dose of ICP-directed therapy were recorded from paper and electronic medical records. The ICP data were collected automatically at 6-second intervals and averaged over 5 minutes. The percentage of time of intracranial hypertension (PTI) and PTD (mm Hg h) were calculated. A total of 98 patients with 664 treatment instances were identified. Baseline PTD ranged from 27 (before administration of propofol and fentanyl) to 150 mm Hg h (before mannitol). A "small" dose of hypertonic saline (HTS; ≤250 mL 3%) reduced PTD by 38% in the first hour and 37% in the second hour and reduced the time with ICP >19 by 38% and 39% after 1 and 2 hours, respectively. A "large" dose of HTS reduced PTD by 40% in the first hour and 63% in the second (PTI reduction of 36% and 50%, respectively). An increased dose of propofol or fentanyl infusion failed to decrease PTD but reduced PTI between 14% (propofol alone) and 30% (combined increase in propofol and fentanyl, after 2 hours). Barbiturates failed to decrease PTD but decreased PTI by 30% up to 2 hours after administration. All reductions reported are significantly changed from baseline, P < .05. Baseline PTD values before drug administration reflects varied patient criticality, with much higher values seen before the use of mannitol or barbiturates. Treatment with HTS reduced PTD and PTI burden significantly more than escalation of sedation or pain management, and this effect remained significant at 2 hours after administration. © The Author(s) 2014.

  11. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Siauw, Timmy; Cunha, Adam; Berenson, Dmitry

    Purpose: In this study, the authors introduce skew line needle configurations for high dose rate (HDR) brachytherapy and needle planning by integer program (NPIP), a computational method for generating these configurations. NPIP generates needle configurations that are specific to the anatomy of the patient, avoid critical structures near the penile bulb and other healthy structures, and avoid needle collisions inside the body. Methods: NPIP consisted of three major components: a method for generating a set of candidate needles, a needle selection component that chose a candidate needle subset to be inserted, and a dose planner for verifying that the finalmore » needle configuration could meet dose objectives. NPIP was used to compute needle configurations for prostate cancer data sets from patients previously treated at our clinic. NPIP took two user-parameters: a number of candidate needles, and needle coverage radius, {delta}. The candidate needle set consisted of 5000 needles, and a range of {delta} values was used to compute different needle configurations for each patient. Dose plans were computed for each needle configuration. The number of needles generated and dosimetry were analyzed and compared to the physician implant. Results: NPIP computed at least one needle configuration for every patient that met dose objectives, avoided healthy structures and needle collisions, and used as many or fewer needles than standard practice. These needle configurations corresponded to a narrow range of {delta} values, which could be used as default values if this system is used in practice. The average end-to-end runtime for this implementation of NPIP was 286 s, but there was a wide variation from case to case. Conclusions: The authors have shown that NPIP can automatically generate skew line needle configurations with the aforementioned properties, and that given the correct input parameters, NPIP can generate needle configurations which meet dose objectives and use as many or fewer needles than the current HDR brachytherapy workflow. Combined with robot assisted brachytherapy, this system has the potential to reduce side effects associated with treatment. A physical trial should be done to test the implant feasibility of NPIP needle configurations.« less

  12. Dose determinants in continuous renal replacement therapy.

    PubMed

    Clark, William R; Turk, Joseph E; Kraus, Michael A; Gao, Dayong

    2003-09-01

    Increasing attention is being paid to quantifying the dose of dialysis prescribed and delivered to critically ill patients with acute renal failure (ARF). Recent trials in both the intermittent hemodialysis (IHD) and continuous renal replacement therapy (CRRT) realms have suggested that a direct relationship between dose and survival exists for both of these therapies. The purpose of this review, first, is to analyze critically the above-mentioned dose/outcome studies in acute dialysis. Subsequently, the factors influencing dose prescription and delivery are discussed, with the focus on continuous venovenous hemofiltration (CVVH). Specifically, differences between postdilution and predilution CVVH will be highlighted, and the importance of blood flow rate in dose delivery for these therapies will be discussed.

  13. Radiation Dose Optimization For Critical Organs

    NASA Astrophysics Data System (ADS)

    Khodadadegan, Yasaman

    Ionizing radiation used in the patient diagnosis or therapy has negative effects on the patient body in short term and long term depending on the amount of exposure. More than 700,000 examinations are everyday performed on Interventional Radiology modalities, however; there is no patient-centric information available to the patient or the Quality Assurance for the amount of organ dose received. In this study, we are exploring the methodologies to systematically reduce the absorbed radiation dose in the Fluoroscopically Guided Interventional Radiology procedures. In the first part of this study, we developed a mathematical model which determines a set of geometry settings for the equipment and a level for the energy during a patient exam. The goal is to minimize the amount of absorbed dose in the critical organs while maintaining image quality required for the diagnosis. The model is a large-scale mixed integer program. We performed polyhedral analysis and derived several sets of strong inequalities to improve the computational speed and quality of the solution. Results present the amount of absorbed dose in the critical organ can be reduced up to 99% for a specific set of angles. In the second part, we apply an approximate gradient method to simultaneously optimize angle and table location while minimizing dose in the critical organs with respect to the image quality. In each iteration, we solve a sub-problem as a MIP to determine the radiation field size and corresponding X-ray tube energy. In the computational experiments, results show further reduction (up to 80%) of the absorbed dose in compare with previous method. Last, there are uncertainties in the medical procedures resulting imprecision of the absorbed dose. We propose a robust formulation to hedge from the worst case absorbed dose while ensuring feasibility. In this part, we investigate a robust approach for the organ motions within a radiology procedure. We minimize the absorbed dose for the critical organs across all input data scenarios which are corresponding to the positioning and size of the organs. The computational results indicate up to 26% increase in the absorbed dose calculated for the robust approach which ensures the feasibility across scenarios.

  14. Incorporating deliverable monitor unit constraints into spot intensity optimization in intensity modulated proton therapy treatment planning

    PubMed Central

    Cao, Wenhua; Lim, Gino; Li, Xiaoqiang; Li, Yupeng; Zhu, X. Ronald; Zhang, Xiaodong

    2014-01-01

    The purpose of this study is to investigate the feasibility and impact of incorporating deliverable monitor unit (MU) constraints into spot intensity optimization in intensity modulated proton therapy (IMPT) treatment planning. The current treatment planning system (TPS) for IMPT disregards deliverable MU constraints in the spot intensity optimization (SIO) routine. It performs a post-processing procedure on an optimized plan to enforce deliverable MU values that are required by the spot scanning proton delivery system. This procedure can create a significant dose distribution deviation between the optimized and post-processed deliverable plans, especially when small spot spacings are used. In this study, we introduce a two-stage linear programming (LP) approach to optimize spot intensities and constrain deliverable MU values simultaneously, i.e., a deliverable spot intensity optimization (DSIO) model. Thus, the post-processing procedure is eliminated and the associated optimized plan deterioration can be avoided. Four prostate cancer cases at our institution were selected for study and two parallel opposed beam angles were planned for all cases. A quadratic programming (QP) based model without MU constraints, i.e., a conventional spot intensity optimization (CSIO) model, was also implemented to emulate the commercial TPS. Plans optimized by both the DSIO and CSIO models were evaluated for five different settings of spot spacing from 3 mm to 7 mm. For all spot spacings, the DSIO-optimized plans yielded better uniformity for the target dose coverage and critical structure sparing than did the CSIO-optimized plans. With reduced spot spacings, more significant improvements in target dose uniformity and critical structure sparing were observed in the DSIO- than in the CSIO-optimized plans. Additionally, better sparing of the rectum and bladder was achieved when reduced spacings were used for the DSIO-optimized plans. The proposed DSIO approach ensures the deliverability of optimized IMPT plans that take into account MU constraints. This eliminates the post-processing procedure required by the TPS as well as the resultant deteriorating effect on ultimate dose distributions. This approach therefore allows IMPT plans to adopt all possible spot spacings optimally. Moreover, dosimetric benefits can be achieved using smaller spot spacings. PMID:23835656

  15. Ozone dose-response relationships for spring oilseed rape and broccoli

    NASA Astrophysics Data System (ADS)

    De Bock, Maarten; Op de Beeck, Maarten; De Temmerman, Ludwig; Guisez, Yves; Ceulemans, Reinhart; Vandermeiren, Karine

    2011-03-01

    Tropospheric ozone is an important air pollutant with known detrimental effects for several crops. Ozone effects on seed yield, oil percentage, oil yield and 1000 seed weight were examined for spring oilseed rape ( Brassica napus cv. Ability). For broccoli ( Brassica oleracea L. cv. Italica cv. Monaco) the effects on fresh marketable weight and total dry weight were studied. Current ozone levels were compared with an increase of 20 and 40 ppb during 8 h per day, over the entire growing season. Oilseed rape seed yield was negatively correlated with ozone dose indices calculated from emergence until harvest. This resulted in an R2 of 0.24 and 0.26 ( p < 0.001) for the accumulated hourly O 3 exposure over a threshold of 40 ppb (AOT40) and the phytotoxic ozone dose above a threshold of 6 nmol m -2 s -1 (POD 6) respectively. Estimated critical levels, above which 5% yield reduction is expected, were 3.7 ppm h and 4.4 mmol m -2 respectively. Our results also confirm that a threshold value of 6 nmol s -1 m -2 projected leaf area, as recommended for agricultural crops (UNECE, Mills, 2004), can indeed be applied for spring oilseed rape. The reduction of oilseed rape yield showed the highest correlation with the ozone uptake during the vegetative growth stage: when only the first 47 days after emergence were used to calculate POD 6, R2 values increased up to 0.476 or even 0.545 when the first 23 days were excluded. The highest ozone treatments, corresponding to the future ambient level by 2100 (IPCC, Meehl et al., 2007), led to a reduction of approximately 30% in oilseed rape seed yield in comparison to the current ozone concentrations. Oil percentage was also significantly reduced in response to ozone ( p < 0.001). As a consequence oil yield was even more severely affected by elevated ozone exposure compared to seed yield: critical levels for oil yield dropped to 3.2 ppm h and 3.9 mmol m -2. For broccoli the applied ozone doses had no effect on yield.

  16. Comparison of internal dose estimates obtained using organ-level, voxel S value, and Monte Carlo techniques

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grimes, Joshua, E-mail: grimes.joshua@mayo.edu; Celler, Anna

    2014-09-15

    Purpose: The authors’ objective was to compare internal dose estimates obtained using the Organ Level Dose Assessment with Exponential Modeling (OLINDA/EXM) software, the voxel S value technique, and Monte Carlo simulation. Monte Carlo dose estimates were used as the reference standard to assess the impact of patient-specific anatomy on the final dose estimate. Methods: Six patients injected with{sup 99m}Tc-hydrazinonicotinamide-Tyr{sup 3}-octreotide were included in this study. A hybrid planar/SPECT imaging protocol was used to estimate {sup 99m}Tc time-integrated activity coefficients (TIACs) for kidneys, liver, spleen, and tumors. Additionally, TIACs were predicted for {sup 131}I, {sup 177}Lu, and {sup 90}Y assuming themore » same biological half-lives as the {sup 99m}Tc labeled tracer. The TIACs were used as input for OLINDA/EXM for organ-level dose calculation and voxel level dosimetry was performed using the voxel S value method and Monte Carlo simulation. Dose estimates for {sup 99m}Tc, {sup 131}I, {sup 177}Lu, and {sup 90}Y distributions were evaluated by comparing (i) organ-level S values corresponding to each method, (ii) total tumor and organ doses, (iii) differences in right and left kidney doses, and (iv) voxelized dose distributions calculated by Monte Carlo and the voxel S value technique. Results: The S values for all investigated radionuclides used by OLINDA/EXM and the corresponding patient-specific S values calculated by Monte Carlo agreed within 2.3% on average for self-irradiation, and differed by as much as 105% for cross-organ irradiation. Total organ doses calculated by OLINDA/EXM and the voxel S value technique agreed with Monte Carlo results within approximately ±7%. Differences between right and left kidney doses determined by Monte Carlo were as high as 73%. Comparison of the Monte Carlo and voxel S value dose distributions showed that each method produced similar dose volume histograms with a minimum dose covering 90% of the volume (D90) agreeing within ±3%, on average. Conclusions: Several aspects of OLINDA/EXM dose calculation were compared with patient-specific dose estimates obtained using Monte Carlo. Differences in patient anatomy led to large differences in cross-organ doses. However, total organ doses were still in good agreement since most of the deposited dose is due to self-irradiation. Comparison of voxelized doses calculated by Monte Carlo and the voxel S value technique showed that the 3D dose distributions produced by the respective methods are nearly identical.« less

  17. AREA RADIATION MONITOR

    DOEpatents

    Manning, F.W.; Groothuis, S.E.; Lykins, J.H.; Papke, D.M.

    1962-06-12

    S>An improved area radiation dose monitor is designed which is adapted to compensate continuously for background radiation below a threshold dose rate and to give warning when the dose integral of the dose rate of an above-threshold radiation excursion exceeds a selected value. This is accomplished by providing means for continuously charging an ionization chamber. The chamber provides a first current proportional to the incident radiation dose rate. Means are provided for generating a second current including means for nulling out the first current with the second current at all values of the first current corresponding to dose rates below a selected threshold dose rate value. The second current has a maximum value corresponding to that of the first current at the threshold dose rate. The excess of the first current over the second current, which occurs above the threshold, is integrated and an alarm is given at a selected integrated value of the excess corresponding to a selected radiation dose. (AEC)

  18. SaMpling Antibiotics in Renal Replacement Therapy (SMARRT): an observational pharmacokinetic study in critically ill patients.

    PubMed

    Roberts, Jason A; Choi, Gordon Y S; Joynt, Gavin M; Paul, Sanjoy K; Deans, Renae; Peake, Sandra; Cole, Louise; Stephens, Dianne; Bellomo, Rinaldo; Turnidge, John; Wallis, Steven C; Roberts, Michael S; Roberts, Darren M; Lassig-Smith, Melissa; Starr, Therese; Lipman, Jeffrey

    2016-03-01

    Optimal antibiotic dosing is key to maximising patient survival, and minimising the emergence of bacterial resistance. Evidence-based antibiotic dosing guidelines for critically ill patients receiving RRT are currently not available, as RRT techniques and settings vary greatly between ICUs and even individual patients. We aim to develop a robust, evidence-based antibiotic dosing guideline for critically ill patients receiving various forms of RRT. We further aim to observe whether therapeutic antibiotic concentrations are associated with reduced 28-day mortality. We designed a multi-national, observational pharmacokinetic study in critically ill patients requiring RRT. The study antibiotics will be vancomycin, linezolid, piperacillin/tazobactam and meropenem. Pharmacokinetic sampling of each patient's blood, RRT effluent and urine will take place during two separate dosing intervals. In addition, a comprehensive data set, which includes the patients' demographic and clinical parameters, as well as modality, technique and settings of RRT, will be collected. Pharmacokinetic data will be analysed using a population pharmacokinetic approach to identify covariates associated with changes in pharmacokinetic parameters in critically ill patients with AKI who are undergoing RRT for the five commonly prescribed antibiotics. Using the comprehensive data set collected, the pharmacokinetic profile of the five antibiotics will be constructed, including identification of RRT and other factors indicative of the need for altered antibiotic dosing requirements. This will enable us to develop a dosing guideline for each individual antibiotic that is likely to be relevant to any critically ill patient with acute kidney injury receiving any of the included forms of RRT. Australian New Zealand Clinical Trial Registry ( ACTRN12613000241730 ) registered 28 February 2013.

  19. SU-F-T-441: Dose Calculation Accuracy in CT Images Reconstructed with Artifact Reduction Algorithm

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ng, C; Chan, S; Lee, F

    Purpose: Accuracy of radiotherapy dose calculation in patients with surgical implants is complicated by two factors. First is the accuracy of CT number, second is the dose calculation accuracy. We compared measured dose with dose calculated on CT images reconstructed with FBP and an artifact reduction algorithm (OMAR, Philips) for a phantom with high density inserts. Dose calculation were done with Varian AAA and AcurosXB. Methods: A phantom was constructed with solid water in which 2 titanium or stainless steel rods could be inserted. The phantom was scanned with the Philips Brillance Big Bore CT. Image reconstruction was done withmore » FBP and OMAR. Two 6 MV single field photon plans were constructed for each phantom. Radiochromic films were placed at different locations to measure the dose deposited. One plan has normal incidence on the titanium/steel rods. In the second plan, the beam is at almost glancing incidence on the metal rods. Measurements were then compared with dose calculated with AAA and AcurosXB. Results: The use of OMAR images slightly improved the dose calculation accuracy. The agreement between measured and calculated dose was best with AXB and image reconstructed with OMAR. Dose calculated on titanium phantom has better agreement with measurement. Large discrepancies were seen at points directly above and below the high density inserts. Both AAA and AXB underestimated the dose directly above the metal surface, while overestimated the dose below the metal surface. Doses measured downstream of metal were all within 3% of calculated values. Conclusion: When doing treatment planning for patients with metal implants, care must be taken to acquire correct CT images to improve dose calculation accuracy. Moreover, great discrepancies in measured and calculated dose were observed at metal/tissue interface. Care must be taken in estimating the dose in critical structures that come into contact with metals.« less

  20. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang Hua; Department of Radiation Oncology, Cancer Hospital of Jiangxi Province, Jiangxi Province; Li Yexiong, E-mail: yexiong@yahoo.com

    Purpose: The value of intensity-modulated radiotherapy (IMRT) for early-stage nasal NK/T-cell lymphoma has not been previously reported. The aim of the present study was to assess the dosimetric parameters, toxicity, and treatment outcomes of patients with nasal NK/T-cell lymphoma. Methods and Materials: Between 2003 and 2008, 42 patients with early-stage nasal NK/T-cell lymphoma underwent definitive high-dose and extended involved-field IMRT with or without combination chemotherapy. The median radiation dose to the primary tumor was 50 Gy. The dose-volume histograms of the target volume and critical normal structures were evaluated in all patients. The locoregional control, overall survival, and progression-free survivalmore » were calculated using the Kaplan-Meier method. Results: The average mean dose delivered to the planning target volume was 55.5 Gy. Only 1.3% and 2.5% of the planning target volume received <90% and 95% of the prescribed dose, respectively, indicating excellent planning target volume coverage. The mean dose and average dose to the parotid glands was 15 Gy and 14 Gy, respectively. With a median follow-up time of 27 months, the 2-year locoregional control, overall survival, and progression-free survivalrate was 93%, 78%, and 74%, respectively. No Grade 4 or 5 acute or late toxicity was reported. Conclusions: High-dose and extended involved-field IMRT for patients with early-stage nasal NK/T-cell lymphoma showed favorable locoregional control, overall survival, and progression-free survival, with mild toxicity. The dose constraints of IMRT for the parotid glands can be limited to <20 Gy in these patients.« less

  1. Standard dosing of amikacin and gentamicin in critically ill patients results in variable and subtherapeutic concentrations.

    PubMed

    Roger, Claire; Nucci, Bastian; Molinari, Nicolas; Bastide, Sophie; Saissi, Gilbert; Pradel, Gael; Barbar, Saber; Aubert, Clément; Lloret, Sophie; Elotmani, Loubna; Polge, Anne; Lefrant, Jean-Yves; Roberts, Jason A; Muller, Laurent

    2015-07-01

    Low peak plasma concentrations (Cmax) of amikacin and gentamicin are reported in intensive care unit (ICU) patients after administration of the first dose. The present study aimed to describe the proportion of ICU patients in whom an adequate Cmax was achieved throughout the course of therapy. Septic ICU patients with an indication for intravenous amikacin or gentamicin were eligible for inclusion in this single-centre observational study. The first and subsequent doses and the corresponding Cmax values were recorded. The target Cmax was ≥60mg/L for amikacin and ≥30mg/L for gentamicin. Amikacin and gentamicin plasma concentrations were available in 66 and 24 patients, respectively (59±17 years; 79±19kg; height 169±12cm; SAPS II score 46±19). Pulmonary, abdominal and urinary tract infections were diagnosed in 64 patients. Culture-positive infection was confirmed in 65 patients (72%). A target first Cmax was achieved in 17/90 patients (19%). For amikacin, the target Cmax was achieved in 16/66 patients (24%) after the initial dose. In the 50 remaining patients, a change in dosing was performed in 14 patients, leading adequate peak plasma level in 2 patients. For gentamicin, the targeted Cmax was achieved in only 1/24 patient (4%) after the initial dose and was never achieved after the third dose. In conclusion, standard dosing of amikacin or gentamicin led to adequate Cmax in only 19% of patients. Subtherapeutic Cmax were not significantly corrected after subsequent doses. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  2. Criticality accident dosimetry systems: an international intercomparison at the SILENE reactor in 2002.

    PubMed

    Médioni, R; Asselineau, B; Verrey, B; Trompier, F; Itié, C; Texier, C; Muller, H; Pelcot, G; Clairand, I; Jacquet, X; Pochat, J L

    2004-01-01

    In criticality accident dosimetry and more generally for high dose measurements, special techniques are used to measure separately the gamma ray and neutron components of the dose. To improve these techniques and to check their dosimetry systems (physical and/or biological), a total of 60 laboratories from 29 countries (America, Europe, Asia) participated in an international intercomparaison, which took place in France from 9 to 21 June 2002, at the SILENE reactor in Valduc and at a pure gamma source in Fontenay-aux-Roses. This intercomparison was jointly organised by the IRSN and the CEA with the help of the NEA/OCDE and was partly supported by the European Communities. This paper describes the aim of this intercomparison, the techniques used by the participants and the two radiation sources and their characteristics. The experimental arrangements of the dosemeters for the irradiations in free air or on phantoms are given. Then the dosimetric quantities measured and reported by the participants are summarised, analysed and compared with the reference values. The present paper concerns only the physical dosimetry and essentially experiments performed on the SILENE facility. The results obtained with the biological dosimetry are published in two other papers of this issue.

  3. 1983 international intercomparison of nuclear accident dosimetry systems at Oak Ridge National Laboratory

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Swaja, R.E.; Greene, R.T.; Sims, C.S.

    1985-04-01

    An international intercomparison of nuclear accident dosimetry systems was conducted during September 12-16, 1983, at Oak Ridge National Laboratory (ORNL) using the Health Physics Research Reactor operated in the pulse mode to simulate criticality accidents. This study marked the twentieth in a series of annual accident dosimetry intercomparisons conducted at ORNL. Participants from ten organizations attended this intercomparison and measured neutron and gamma doses at area monitoring stations and on phantoms for three different shield conditions. Results of this study indicate that foil activation techniques are the most popular and accurate method of determining accident-level neutron doses at area monitoringmore » stations. For personnel monitoring, foil activation, blood sodium activation, and thermoluminescent (TL) methods are all capable of providing accurate dose estimates in a variety of radiation fields. All participants in this study used TLD's to determine gamma doses with very good results on the average. Chemical dosemeters were also shown to be capable of yielding accurate estimates of total neutron plus gamma doses in a variety of radiation fields. While 83% of all neutron measurements satisfied regulatory standards relative to reference values, only 39% of all gamma results satisfied corresponding guidelines for gamma measurements. These results indicate that continued improvement in accident dosimetry evaluation and measurement techniques is needed.« less

  4. Influence of γ-irradiation and temperature on the mechanical properties of EPDM cable insulation

    NASA Astrophysics Data System (ADS)

    Šarac, T.; Quiévy, N.; Gusarov, A.; Konstantinović, M. J.

    2016-08-01

    The mechanical properties of EPDM polymers, degraded as a result of extensive thermal and radiochemical aging treatment, are studied. The focus is given to dose rate effects in polymer insulation materials extracted from industrial cables in use in Belgian nuclear power plants. All studied mechanical characteristics such as the ultimate tensile stress, the Young's modulus, and the total elongation (or elongation at break) are found to be strongly affected by the irradiation dose. The ultimate tensile stress and Young's modulus are clearly exhibiting the dose rate effect, which originated from oxidation mediated interplay of polymer cross-linking and chain scission processes. The change of crossover between these two processes is found to be gradual, without critical dose rate or temperature values. On the contrary, the total elongation is observed not to be sensitive neither to irradiation temperature nor to the dose rate. Both cross-linking and chain scission seem to affect the total elongation in a similar way by reducing the average polymers chain length. This idea is confirmed by the model which shows that all total elongation data as a function of irradiation time can be reproduced by varying a single parameter, the pre-exponential factor of the irradiation rate constant.

  5. SU-E-T-86: A Systematic Method for GammaKnife SRS Fetal Dose Estimation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Geneser, S; Paulsson, A; Sneed, P

    Purpose: Estimating fetal dose is critical to the decision-making process when radiation treatment is indicated during pregnancy. Fetal doses less than 5cGy confer no measurable non-cancer developmental risks but can produce a threefold increase in developing childhood cancer. In this study, we estimate fetal dose for a patient receiving Gamma Knife stereotactic radiosurgery (GKSRS) treatment and develop a method to estimate dose directly from plan details. Methods: A patient underwent GKSRS on a Perfexion unit for eight brain metastases (two infratentorial and one brainstem). Dose measurements were performed using a CC13, head phantom, and solid water. Superficial doses to themore » thyroid, sternum, and pelvis were measured using MOSFETs during treatment. Because the fetal dose was too low to accurately measure, we obtained measurements proximally to the isocenter, fitted to an exponential function, and extrapolated dose to the fundus of the uterus, uterine midpoint, and pubic synthesis for both the preliminary and delivered plans. Results: The R-squared fit for the delivered doses was 0.995. The estimated fetal doses for the 72 minute preliminary and 138 minute delivered plans range from 0.0014 to 0.028cGy and 0.07 to 0.38cGy, respectively. MOSFET readings during treatment were just above background for the thyroid and negligible for all inferior positions. The method for estimating fetal dose from plan shot information was within 0.2cGy of the measured values at 14cm cranial to the fetal location. Conclusion: Estimated fetal doses for both the preliminary and delivered plan were well below the 5cGy recommended limit. Due to Pefexion shielding, internal dose is primarily governed by attenuation and drops off exponentially. This is the first work that reports fetal dose for a GK Perfexion unit. Although multiple lesions were treated and the duration of treatment was long, the estimated fetal dose remained very low.« less

  6. Dose-dependent analysis of acute medical effects of mixed neutron-gamma radiation from selected severe 235U or 239Pu criticality accidents in USSR, United States, and Argentina.

    PubMed

    Barabanova, Tatyana; Wiley, Albert L; Bushmanov, Andrey

    2012-04-01

    Eight of the most severe cases of acute radiation disease (ARS) known to have occurred in humans (as the result of criticality accidents) had survival times less than 120 h (herein defined as "early death"). These accidents were analyzed and are discussed with respect to the specific accident scenarios and the resulting accident-specific, mixed neutron-gamma radiation clinical dose distributions. This analysis concludes that the cardiovascular system appears to be the most critical organ system failure for causing "early death" following approximate total body, mixed gamma-neutron radiation doses greater than 40-50 Gy. The clinical data also suggest that there was definite chest dose dependence in the resulting survival times for these eight workers, who unfortunately suffered profound radiation injury and unusual clinical effects from such high dose radiation exposures. In addition, "toxemic syndrome" is correlated with the irradiation of large volumes of soft tissues. Doses to the hands or legs greater than 80-100 Gy or radiation lung injury also play significant but secondary roles in causing "early death" in accidents delivering chest doses greater than 50 Gy.

  7. [Critical level of radiation damage of root apical meristem and mechanisms for its recovery in Pisum sativum L].

    PubMed

    Kravets, E A; Mikheev, A N; Ovsiannikova, L G; Grodzinskiĭ, D M

    2011-01-01

    The dose dependencies of growth and cytogenetical values have been built to determine the critical level of root apical meristem damage induced by cute irradiation in the range from 2 to 20 Gr. We have analyzed the frequencies of aberrant anaphases and the aberration distribution per cell, on the one hand, and the growth of biomass, the survival and regeneration of the root meristem, on the other hand. The critical level of damage to the stem apical meristem and root of seedlings was defined as 44-48% of aberrant anaphase. Exceeding of this level leads to the launch of suicidal program through induction of multiaberrant damages and interphase cell death. It appears that competition of clones of non-aberrant cells, the cells bearing 1 and 2 damages and multiaberrant cells plays the primary role in the mechanisms of recovery. The regeneration provides full or partial restoration of the main root apical meristem. However these local processes are insufficient to restore morphogenesis and survival of seedlings in excess of the critical level damage.

  8. Beta- and gamma-dose measurements of the Godiva IV critical assembly.

    PubMed

    Hankins, D E

    1984-03-01

    To aid in the re-evaluation of an exposure that occurred in 1963, information was required on the response of film badges to the beta- and gamma-ray doses from a critical assembly. Of particular interest was the beta spectra from the assembly. The techniques used and the results obtained in this study are of interest to health physicists at facilities where exposures to betas occur. The dose rates from the Los Alamos National Laboratory Godiva IV Critical Assembly were measured at numerous distances from the assembly four and 12 days following a burst. Information was obtained on the beta-particle spectra using absorption curve studies. The beta/gamma dose-rate ratio as a function of distance from the assembly was determined. Shielding provided by various metals, gloves and clothing was measured. The beta- and gamma-ray doses measured were compared with a film packet used in the past at the Nevada Test Site with two types of current TLD personnel badges. Measurements made with a commercial thin-window ion chamber instrument are compared with the dose rates obtained using other dosimeters.

  9. Influence of dose calculation algorithms on the predicted dose distribution and NTCP values for NSCLC patients.

    PubMed

    Nielsen, Tine B; Wieslander, Elinore; Fogliata, Antonella; Nielsen, Morten; Hansen, Olfred; Brink, Carsten

    2011-05-01

    To investigate differences in calculated doses and normal tissue complication probability (NTCP) values between different dose algorithms. Six dose algorithms from four different treatment planning systems were investigated: Eclipse AAA, Oncentra MasterPlan Collapsed Cone and Pencil Beam, Pinnacle Collapsed Cone and XiO Multigrid Superposition, and Fast Fourier Transform Convolution. Twenty NSCLC patients treated in the period 2001-2006 at the same accelerator were included and the accelerator used for treatments were modeled in the different systems. The treatment plans were recalculated with the same number of monitor units and beam arrangements across the dose algorithms. Dose volume histograms of the GTV, PTV, combined lungs (excluding the GTV), and heart were exported and evaluated. NTCP values for heart and lungs were calculated using the relative seriality model and the LKB model, respectively. Furthermore, NTCP for the lungs were calculated from two different model parameter sets. Calculations and evaluations were performed both including and excluding density corrections. There are found statistical significant differences between the calculated dose to heart, lung, and targets across the algorithms. Mean lung dose and V20 are not very sensitive to change between the investigated dose calculation algorithms. However, the different dose levels for the PTV averaged over the patient population are varying up to 11%. The predicted NTCP values for pneumonitis vary between 0.20 and 0.24 or 0.35 and 0.48 across the investigated dose algorithms depending on the chosen model parameter set. The influence of the use of density correction in the dose calculation on the predicted NTCP values depends on the specific dose calculation algorithm and the model parameter set. For fixed values of these, the changes in NTCP can be up to 45%. Calculated NTCP values for pneumonitis are more sensitive to the choice of algorithm than mean lung dose and V20 which are also commonly used for plan evaluation. The NTCP values for heart complication are, in this study, not very sensitive to the choice of algorithm. Dose calculations based on density corrections result in quite different NTCP values than calculations without density corrections. It is therefore important when working with NTCP planning to use NTCP parameter values based on calculations and treatments similar to those for which the NTCP is of interest.

  10. Solar particle dose rate buildup and distribution in critical body organs

    NASA Technical Reports Server (NTRS)

    Atwell, William; Weyland, Mark D.; Simonsen, Lisa C.

    1993-01-01

    Human body organs have varying degrees of radiosensitivity as evidenced by radioepidemiologic tables. The major critical organs for both the male and female that have been identified include the lung, thyroid, stomach, and breast (female). Using computerized anatomical models of the 50th percentile United States Air Force male and female, we present the self-shielding effects of these various body organs and how the shielding effects change as the location (dose point) in the body varies. Several major solar proton events from previous solar cycles and several events from the current 22nd solar cycle have been analyzed. The solar particle event rise time, peak intensity, and decay time vary considerably from event to event. Absorbed dose and dose equivalent rate calculations and organ risk assessment data are presented for each critical body organ. These data are compared with the current NASA astronaut dose limits as recommended by the National Council on Radiation Protection and Measurements.

  11. Radiobiological Impact of Reduced Margins and Treatment Technique for Prostate Cancer in Terms of Tumor Control Probability (TCP) and Normal Tissue Complication Probability (NTCP)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jensen, Ingelise, E-mail: inje@rn.d; Carl, Jesper; Lund, Bente

    2011-07-01

    Dose escalation in prostate radiotherapy is limited by normal tissue toxicities. The aim of this study was to assess the impact of margin size on tumor control and side effects for intensity-modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3DCRT) treatment plans with increased dose. Eighteen patients with localized prostate cancer were enrolled. 3DCRT and IMRT plans were compared for a variety of margin sizes. A marker detectable on daily portal images was presupposed for narrow margins. Prescribed dose was 82 Gy within 41 fractions to the prostate clinical target volume (CTV). Tumor control probability (TCP) calculations based on themore » Poisson model including the linear quadratic approach were performed. Normal tissue complication probability (NTCP) was calculated for bladder, rectum and femoral heads according to the Lyman-Kutcher-Burman method. All plan types presented essentially identical TCP values and very low NTCP for bladder and femoral heads. Mean doses for these critical structures reached a minimum for IMRT with reduced margins. Two endpoints for rectal complications were analyzed. A marked decrease in NTCP for IMRT plans with narrow margins was seen for mild RTOG grade 2/3 as well as for proctitis/necrosis/stenosis/fistula, for which NTCP <7% was obtained. For equivalent TCP values, sparing of normal tissue was demonstrated with the narrow margin approach. The effect was more pronounced for IMRT than 3DCRT, with respect to NTCP for mild, as well as severe, rectal complications.« less

  12. Plutonium 238/239 Decorporation Model

    DTIC Science & Technology

    2014-10-01

    distribution in tissue compartments over time with and without treatment, excretion rates, and radiation doses to critical organs. Calculations from...kPa) pound- mass -foot2 (moment of inertia) 4.214 011 x E – 2 kilogram-meter2 (kg*m2) pound- mass /foot3 1.601 846 x E + 1 kilogram/m3 (kg/m3) rad...45 Figure 21. Acute Doses to Critical Organs from Pu-238 and Pu-239 Over 90 Days ................... 46 Figure 22. Doses

  13. Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant.

    PubMed

    Minhas, Anum S; Jiang, Qingmei; Gu, Xiaokui; Haymart, Brian; Kline-Rogers, Eva; Almany, Steve; Kozlowski, Jay; Krol, Gregory D; Kaatz, Scott; Froehlich, James B; Barnes, Geoffrey D

    2016-11-01

    All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0 %) had a baseline creatinine clearance <50 mL/min and 23 (12.2 %) experienced important fluctuations in renal function. Of these 23 patients, 6 (26.1 %) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9 %) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.

  14. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vostrotin, Vadim; Birchall, Alan; Zhdanov, Alexey

    The distribution of calculated internal doses was determined for 8043 Mayak Production Associate (Mayak PA) workers according to the epidemiological cohorts and groups of raw data used as well as the type of industrial compounds of inhaled aerosols. Statistical characteristics of point estimates of accumulated doses to 17 different tissues and organs and the uncertainty ranges were calculated. Under the MWDS-2013 dosimetry system, the mean accumulated lung dose was 185585 mGy, with a median value of 31 mGy and a maximum of 8980 mGy maximum. The ranges of relative standard uncertainty were: from 40 to 2200% for accumulated lung dose,more » from 25-90% to 2600-3000% for accumulated dose to different regions of respiratory tract, from 13-18% to 2300-2500% for systemic organs and tissues. The Mayak PA workers accumulated internal plutonium lung dose is shown to be close to lognormal. The accumulated internal plutonium dose to systemic organs was close to a log-triangle. The dependency of uncertainty of accumulated absorbed lung and liver doses on the dose estimates itself is also shown. The accumulated absorbed doses to lung, alveolar-interstitial region, liver, bone surface cells and red bone marrow, calculated both with MWDS-2013 and MWDS-2008 have been compared. In general, the accumulated lung doses increased by a factor of 1.8 in median value, while the accumulated doses to systemic organs decreased by factor of 1.3-1.4 in median value. For the cases with identical initial data, accumulated lung doses increased by a factor of 2.1 in median value, while accumulated doses to systemic organs decreased by 8-13% in median value. For the cases with both identical initial data and all of plutonium activity in urine measurements above the decision threshold, accumulated lung doses increased by a factor of 2.8 in median value, while accumulated doses to systemic organs increased by 6-12% in median value.« less

  15. Critical values in hematology of 862 institutions in China.

    PubMed

    Ye, Y Y; Zhao, H J; Fei, Y; Wang, W; He, F L; Zhong, K; Yuan, S; Wang, Z G

    2017-10-01

    A national survey on critical values in hematology of China laboratories was conducted to determine the current practice and assess the quality indicators so as to obtain a quality improvement. Laboratories participating were asked to submit the general information, the practice of critical value reporting, and the status of timeliness of critical value reporting. A total of 862 laboratories submitted the results. The majority of participants have included white blood cell count, blood platelet count, hemoglobin, prothrombin time, and activated partial thromboplastin time in their critical value lists. Many sources are used for establishing a critical value policy, and some of the laboratories consult with clinicians. The unreported critical value rate, late critical value reporting rate, and clinically unacknowledged rate in China are relatively low, and the median of critical value reporting time is 8-9 minutes. There exists a wide variety for critical value reporting in hematology in China. Laboratories should establish a policy of critical value reporting suited for their own situations and consult with clinicians to set critical value lists. Critical values are generally reported in a timely manner in China, but some measures should be taken to further improve the timeliness of critical value reporting. © 2017 John Wiley & Sons Ltd.

  16. Auger-electron cascades, charge potential and microdosimetry of iodine-125.

    PubMed

    Booz, J; Paretzke, H G; Pomplun, E; Olko, P

    1987-01-01

    This paper is a contribution to the microdosimetry of I-125. It shows microdosimetric spectra of individual and average disintegrations of I-125 for various target sizes and gives evidence for the relative contributions of energy-deposition events of low and high LET. It further presents information on the relative efficiencies of Auger-electrons and multiple charges in terms of local energy deposition, e.g. to model targets of DNA, and discusses their radiobiological implications, e.g. the microdosimetric understanding of the different efficiencies of specific and random incorporations of I-125. When I-125 is specifically incorporated into DNA, most of the energy deposition events are very large, e.g. above 40 keV/micron for a simulated target volume of 20 nm diameter, regardless of the number and energy of Auger electrons emitted. Therefore it is not necessary, for the discussion of the radiobiological implications, to distinguish between different classes of disintegrations. For unspecific, homogeneous incorporation of I-125 somewhere into tissue, about 20% of the dose to critical targets of 25 nm diameter is made up by disintegrations that happen to occur within these targets. When assuming that other critical targets and target structures can be neglected, this part of the dose will be equally effective as in the case of specific incorporation of I-125 into such target models. In addition, there are the normal, low-LET radiation effects from the other, 80% large fraction of the dose. With this information, for the biological systems and end points for which a short section of the elemental chromatine fiber can be taken as the relevant critical target, it is shown that the expected D37 value for homogeneous unspecific incorporation of I-125 can be estimated when the D37 for specific incorporation in DNA is known. For an example calculation, the estimated D37-value for nonspecific, homogeneous incorporation of I-125 would be about half as effective as specifically incorporated I-125. Thus, the microdosimetric data of the present work show that a high efficiency of homogeneous incorporation of I-125 into the cell nucleus is not necessarily in contradiction with the idea of I-125 disintegrations inside the DNA being the main cause of radiation action.

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

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

  18. SU-F-T-650: The Comparison of Robotic Partial Breast Stereotactic Irradiation Using MLC Vs. Iris Cone

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ding, C; Timmerman, R; Jiang, S

    Purpose: To evaluate the dosimetric impact on treatment planning for partial breast stereotactic irradiation using Cyberknife with MLC versus Iris Cone. Methods: Ten patients whom underwent lumpectomy for DCIS or stage I invasive non-lobular epithelial breast cancer were included in this study. All patients were previously treated on the Cyberknife using Iris cone with the prescription dose of 37.5Gy in 5 fractions covering at least 95% of PTV on our phase I SBRT 5 fraction partial breast irradiation trial. Retrospectively, treatment planning was performed and compared using the new Cyberknife M6 MLC system for each patient. Using the same contoursmore » and critical organ constraints for both MLC and Iris cone plans, the dose on target and critical organs were analyzed accordingly. Results: Dose to critical organs such as ipsilateral lung, contralateral lung, heart, skin, ipsilateral breast, and rib were analyzed, as well as conformity index and high dose spillage of the target area. In 9 of 10 patients, the MLC plans had less total ipsilateral breast volume encompassing the 50% prescription isodose (mean:22.3±8.2% MLC vs. 31.6±8.0 Iris, p=0.00014) .The MLC plans mean estimated treatment delivery time was significantly less than the Iris plans (51±3.9min vs. 56.2±9min, p=0.03) Both MLC and Iris cone plans were able to meet all dose constraints and there was no statistical difference between those dose constraints. Conclusion: Both MLC and Iris Cone can deliver conformal dose to a partial breast target and satisfy the dose constraints of critical organs. The new Cyberknife with MLC can deliver a more conformal dose in the lower dose region and spare more ipsilateral breast tissue to the 50% prescription isodose. The treatment time for partial breast SBRT plans was also reduced using MLC. Project receives research support from Accuray Inc.« less

  19. Determinants of amikacin first peak concentration in critically ill patients.

    PubMed

    Boidin, Clément; Jenck, Sophie; Bourguignon, Laurent; Torkmani, Sejad; Roussey-Jean, Aurore; Ledochowski, Stanislas; Marry, Lucie; Ammenouche, Nacim; Dupont, Hervé; Marçon, Frédéric; Allaouchiche, Bernard; Bohé, Julien; Lepape, Alain; Goutelle, Sylvain; Friggeri, Arnaud

    2018-04-16

    Amikacin antimicrobial effect has been correlated with the ratio of the peak concentration (C max ) to the minimum inhibitory concentration. A target C max ≥ 60-80 mg/L has been suggested. It has been shown that such target is not achieved in a large proportion of critically ill patients in intensive care units. A retrospective analysis was performed to examine the determinants of C max ≥ 80 mg/L on the first peak in 339 critically ill patients treated by amikacin. The influence of available variables on C max target attainment was analyzed using a classification and regression tree (CART) and logistic regression. Mean C max in the 339 patients was 73.0 ± 23.9 mg/L, with a target attainment rate (TAR, C max ≥ 80 mg/L) of 37.5%. In CART analysis, the strongest predictor of amikacin target peak attainment was dose per kilogram of lean body weight (dose/LBW). TAR was 60.1% in patients with dose/LBW ≥ 37.8 vs. 19.9% in patients with lower dose/LBW (OR = 6.0 (95% CI: 3.6-10.2)). Renal function was a secondary predictor of C max . Logistic regression analysis identified dose per kilogram of ideal body weight (OR = 1.13 (95% CI: 1.09-1.17)) and creatinine clearance (OR = 0.993 (95% CI: 0.988-0.998)) as predictors of target peak achievement. Based on our results, an amikacin dose ≥ 37.8 mg/kg of LBW should be used to optimize the attainment of C max ≥ 80 mg/L after the first dose in critically ill patients. An even higher dose may be necessary in patients with normal renal function. © 2018 Société Française de Pharmacologie et de Thérapeutique.

  20. Color-coded prefilled medication syringes decrease time to delivery and dosing errors in simulated prehospital pediatric resuscitations: A randomized crossover trial☆, ☆

    PubMed Central

    Stevens, Allen D.; Hernandez, Caleb; Jones, Seth; Moreira, Maria E.; Blumen, Jason R.; Hopkins, Emily; Sande, Margaret; Bakes, Katherine; Haukoos, Jason S.

    2016-01-01

    Background Medication dosing errors remain commonplace and may result in potentially life-threatening outcomes, particularly for pediatric patients where dosing often requires weight-based calculations. Novel medication delivery systems that may reduce dosing errors resonate with national healthcare priorities. Our goal was to evaluate novel, prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape, compared to conventional medication administration, in simulated prehospital pediatric resuscitation scenarios. Methods We performed a prospective, block-randomized, cross-over study, where 10 full-time paramedics each managed two simulated pediatric arrests in situ using either prefilled, color-coded-syringes (intervention) or their own medication kits stocked with conventional ampoules (control). Each paramedic was paired with two emergency medical technicians to provide ventilations and compressions as directed. The ambulance patient compartment and the intravenous medication port were video recorded. Data were extracted from video review by blinded, independent reviewers. Results Median time to delivery of all doses for the intervention and control groups was 34 (95% CI: 28–39) seconds and 42 (95% CI: 36–51) seconds, respectively (difference = 9 [95% CI: 4–14] seconds). Using the conventional method, 62 doses were administered with 24 (39%) critical dosing errors; using the prefilled, color-coded syringe method, 59 doses were administered with 0 (0%) critical dosing errors (difference = 39%, 95% CI: 13–61%). Conclusions A novel color-coded, prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by paramedics during simulated prehospital pediatric resuscitations. PMID:26247145

  1. Color-coded prefilled medication syringes decrease time to delivery and dosing errors in simulated prehospital pediatric resuscitations: A randomized crossover trial.

    PubMed

    Stevens, Allen D; Hernandez, Caleb; Jones, Seth; Moreira, Maria E; Blumen, Jason R; Hopkins, Emily; Sande, Margaret; Bakes, Katherine; Haukoos, Jason S

    2015-11-01

    Medication dosing errors remain commonplace and may result in potentially life-threatening outcomes, particularly for pediatric patients where dosing often requires weight-based calculations. Novel medication delivery systems that may reduce dosing errors resonate with national healthcare priorities. Our goal was to evaluate novel, prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape, compared to conventional medication administration, in simulated prehospital pediatric resuscitation scenarios. We performed a prospective, block-randomized, cross-over study, where 10 full-time paramedics each managed two simulated pediatric arrests in situ using either prefilled, color-coded syringes (intervention) or their own medication kits stocked with conventional ampoules (control). Each paramedic was paired with two emergency medical technicians to provide ventilations and compressions as directed. The ambulance patient compartment and the intravenous medication port were video recorded. Data were extracted from video review by blinded, independent reviewers. Median time to delivery of all doses for the intervention and control groups was 34 (95% CI: 28-39) seconds and 42 (95% CI: 36-51) seconds, respectively (difference=9 [95% CI: 4-14] seconds). Using the conventional method, 62 doses were administered with 24 (39%) critical dosing errors; using the prefilled, color-coded syringe method, 59 doses were administered with 0 (0%) critical dosing errors (difference=39%, 95% CI: 13-61%). A novel color-coded, prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by paramedics during simulated prehospital pediatric resuscitations. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. A dose-response relationship for marketable yield reduction of two lettuce (Lactuca sativa L.) cultivars exposed to tropospheric ozone in Southern Europe.

    PubMed

    Marzuoli, Riccardo; Finco, Angelo; Chiesa, Maria; Gerosa, Giacomo

    2017-12-01

    The present study investigated the response to ozone (O 3 ) of two cultivars (cv.'Romana' and cv. 'Canasta') of irrigated lettuce grown in an open-top chamber (OTC) experiment in Mediterranean conditions. Two different levels of O 3 were applied, ambient O 3 in non-filtered OTCs (NF-OTCs) and -40% of ambient O 3 in charcoal-filtered OTCs (CF-OTCs), during four consecutive growing cycles. At the end of each growing cycle, the marketable yield (fresh biomass) was assessed while during the growing periods, measurements of the stomatal conductance at leaf level were performed and used to define a stomatal conductance model for calculation of the phytotoxic ozone dose (POD) absorbed by the plants.Results showed that O 3 caused statistically significant yield reductions in the first and in the last growing cycle. In general, the marketable yield of the NF-OTC plants was always lower than the CF-OTC plants for both cultivars, with mean reductions of -18.5 and -14.5% for 'Romana' and 'Canasta', respectively. On the contrary, there was no statistically significant difference in marketable yield due to the cultivar factor or to the interaction between O 3 and cultivar in any of the growing cycle performed.Dose-response relationships for the marketable relative yield based on the POD values were calculated according to different flux threshold values (Y). The best regression fit was obtained using an instantaneous flux threshold of 6 nmol O 3 m -2  s -1 (POD 6 ); the same value was obtained also for other crops. According to the generic lettuce dose-response relationship, an O 3 critical level of 1 mmol O 3 m -2 of POD 6 for a 15% of marketable yield loss was found.

  3. A critical appraisal of the clinical utility of proton therapy in oncology

    PubMed Central

    Wang, Dongxu

    2015-01-01

    Proton therapy is an emerging technology for providing radiation therapy to cancer patients. The depth dose distribution of a proton beam makes it a preferable radiation modality as it reduces radiation to the healthy tissue outside the tumor, compared with conventional photon therapy. While theoretically beneficial, its clinical values are still being demonstrated from the increasing number of patients treated with proton therapy, from several dozen proton therapy centers around the world. High equipment and facility costs are often the major obstacle for its wider adoption. Because of the high cost and lack of definite clinical evidence of its superiority, proton therapy treatment faces criticism on its cost-effectiveness. Technological development is causing a gradual lowering of costs, and research and clinical studies are providing further evidence on its clinical utility. PMID:26604838

  4. Whole-body vibration exposure in sport: four relevant cases.

    PubMed

    Tarabini, Marco; Saggin, Bortolino; Scaccabarozzi, Diego

    2015-01-01

    This study investigates the whole-body vibration exposure in kite surfing, alpine skiing, snowboarding and cycling. The vibration exposure was experimentally evaluated following the ISO 2631 guidelines. Results evidenced that the most critical axis is the vertical one. The weighted vibration levels are always larger than 2.5 m/s(2) and the vibration dose values are larger than 25 m/s(1.75). The exposure limit values of the EU directive are reached after 8-37 min depending on the sport. The vibration magnitude is influenced by the athletes' speed, by their skill level and sometimes by the equipment. The large vibration values suggest that the practice of sport activities may be a confounding factor in the aetiology of vibration-related diseases. The vibration exposure in some sports is expected to be large, but has never been quantified in the literature. Results of experiments performed in cycling, alpine and water sports outlined vibration levels exceeding the EU standard limit values.

  5. Strategies to assess systemic exposure of chemicals in subchronic/chronic diet and drinking water studies.

    PubMed

    Saghir, Shakil A; Mendrala, Alan L; Bartels, Michael J; Day, Sue J; Hansen, Steve C; Sushynski, Jacob M; Bus, James S

    2006-03-15

    Strategies were developed for the estimation of systemically available daily doses of chemicals, diurnal variations in blood levels, and rough elimination rates in subchronic feeding/drinking water studies, utilizing a minimal number of blood samples. Systemic bioavailability of chemicals was determined by calculating area under the plasma concentration curve over 24 h (AUC-24 h) using complete sets of data (> or =5 data points) and also three, two, and one selected time points. The best predictions of AUC-24 h were made when three time points were used, corresponding to Cmax, a mid-morning sample, and C(min). These values were found to be 103 +/- 10% of the original AUC-24 h, with 13 out of 17 values ranging between 96 and 105% of the original. Calculation of AUC-24 h from two samples (Cmax and Cmin) or one mid-morning sample afforded slightly larger variations in the calculated AUC-24 h (69-136% of the actual). Following drinking water exposure, prediction of AUC-24 h using 3 time points (Cmax, mid-morning, and Cmin) was very close to actual values (80-100%) among mice, while values for rats were only 63% of the original due to less frequent drinking behavior of rats during the light cycle. Collection and analysis of 1-3 blood samples per dose may provide insight into dose-proportional or non-dose-proportional differences in systemic bioavailability, pointing towards saturation of absorption or elimination or some other phenomenon warranting further investigation. In addition, collection of the terminal blood samples from rats, which is usually conducted after 18 h of fasting, will be helpful in rough estimation of blood/plasma half-life of the compound. The amount of chemical(s) and/or metabolite(s) in excreta and their possible use as biomarkers in predicting the daily systemic exposure levels are also discussed. Determining these parameters in the early stages of testing will provide critical information to improve the appropriate design of other longer-term toxicity studies.

  6. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Saghir, Shakil A.; Mendrala, Alan L.; Bartels, Michael J.

    Strategies were developed for the estimation of systemically available daily doses of chemicals, diurnal variations in blood levels, and rough elimination rates in subchronic feeding/drinking water studies, utilizing a minimal number of blood samples. Systemic bioavailability of chemicals was determined by calculating area under the plasma concentration curve over 24 h (AUC-24 h) using complete sets of data ({>=}5 data points) and also three, two, and one selected time points. The best predictions of AUC-24 h were made when three time points were used, corresponding to C {sub max}, a mid-morning sample, and C {sub min}. These values were foundmore » to be 103 {+-} 10% of the original AUC-24 h, with 13 out of 17 values ranging between 96 and 105% of the original. Calculation of AUC-24 h from two samples (C {sub max} and C {sub min}) or one mid-morning sample afforded slightly larger variations in the calculated AUC-24 h (69-136% of the actual). Following drinking water exposure, prediction of AUC-24 h using 3 time points (C {sub max}, mid-morning, and C {sub min}) was very close to actual values (80-100%) among mice, while values for rats were only 63% of the original due to less frequent drinking behavior of rats during the light cycle. Collection and analysis of 1-3 blood samples per dose may provide insight into dose-proportional or non-dose-proportional differences in systemic bioavailability, pointing towards saturation of absorption or elimination or some other phenomenon warranting further investigation. In addition, collection of the terminal blood samples from rats, which is usually conducted after 18 h of fasting, will be helpful in rough estimation of blood/plasma half-life of the compound. The amount of chemical(s) and/or metabolite(s) in excreta and their possible use as biomarkers in predicting the daily systemic exposure levels are also discussed. Determining these parameters in the early stages of testing will provide critical information to improve the appropriate design of other longer-term toxicity studies.« less

  7. The radiological exposure of man from radioactivity in the Baltic Sea.

    PubMed

    Nielsen, S P; Bengtson, P; Bojanowsky, R; Hagel, P; Herrmann, J; Ilus, E; Jakobson, E; Motiejunas, S; Panteleev, Y; Skujina, A; Suplinska, M

    1999-09-30

    A radiological assessment has been carried out considering discharges of radioactivity to the Baltic Sea marine environment since 1950. The sources of radioactivity that have been evaluated are atmospheric nuclear-weapons fallout, fallout from the Chernobyl accident in 1986, discharges of radionuclides from Sellafield and La Hague transported into the Baltic Sea, and discharges of radionuclides from nuclear installations located in the Baltic Sea area. Dose rates from man-made radioactivity to individual members of the public (critical groups) have been calculated based on annual intake of seafood and beach occupancy time. The dose rates to individuals from the regions of the Bothnian Sea and Gulf of Finland are predicted to be larger than from any other area in the Baltic Sea due to the pattern of Chernobyl fallout. The dose rates are predicted to have peaked in 1986 at a value of 0.2 mSv year-1. Collective committed doses to members of the public have been calculated based on fishery statistics and predicted concentrations of radionuclides in biota and coastal sediments. The total collective dose from man-made radioactivity in the Baltic Sea is estimated at 2600 manSv, of which approximately two-thirds originate from Chernobyl fallout, approximately one-quarter from atmospheric nuclear-weapons fallout, approximately 8% from European reprocessing facilities, and approximately 0.04% from nuclear installations bordering the Baltic Sea area. An assessment of small-scale dumping of low-level radioactive waste in the Baltic Sea in the 1960s by Sweden and the Soviet Union has showed that doses to man from these activities are negligible. Dose rates and doses from natural radioactivity dominate except for the year 1986 where dose rates to individuals from Chernobyl fallout in some regions of the Baltic Sea approached those from natural radioactivity.

  8. [Decision process of Notification Value by the Dose Index Registry system in X-ray computed tomography].

    PubMed

    Shinozaki, Masafumi; Muramatsu, Yoshihisa; Sasaki, Toru

    2014-01-01

    A new technical standard for X-ray computed tomography (CT) has been published by the National Electrical Manufacturers Association (NEMA) that allows the Alert Value and Notification Value for cumulative dose to be configurable by CT systems operators in conjunction with the XR-25 (Dose check) standard. In this study, a decision method of the Notification Values for reducing the radiation dose was examined using the dose index registry (DIR) system, during 122 continuous days from August 1, 2012 to November 30, 2012. CT images were obtained using the Discovery CT 750HD (GE Healthcare) and the dose index was calculated using the DoseWatch DIR system. The CT dose index-volume (CTDIvol) and dose-length product (DLP) were output from the DIR system in comma-separated value (CSV) file format for each examination protocol. All data were shown as a schematic boxplot using statistical processing software. The CTDIvol of a routine chest examination showed the following values (maximum: 23.84 mGy; minimum: 2.55 mGy; median: 7.60 mGy; 75% tile: 10.01 mGy; 25% tile: 6.54 mGy). DLP showed the following values (maximum: 944.56 mGy·cm; minimum: 97.25 mGy·cm; median: 307.35 mGy·cm; 75% tile: 406.87 mGy·cm; 25% tile: 255.75 mGy·cm). These results indicate that the 75% tile of CTDIvol and DLP as an initial value proved to be safe and efficient for CT examination and operation. We have thus established one way of determining the Notification Value from the output of the DIR system. Transfer back to the protocol of the CT and automated processing each numeric value in the DIR system is desired.

  9. Measures for curtailment of iatrogenic exposure. Guide to correct x-ray examinations (in Japanese)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Misonoo, K.

    1973-08-01

    Of the coposure dose for humans from various radiation sources, introgenic exposure amounts to 1/2 to twice the natural radiation source. Although the mechanism of induction of malignant tumor by radiation is not clanified, it is evident that it is induced after receiving a dose above 100 rads. However, the presence of a threshold, under which it does not develop, is unknown. Tabulated were ICRP's calculations on the degree of risk of injury and the estimated values of genetic injury due to 1 rad. In order to estimate the harmful effect of exposure in x-ray diagnosis, the dose in themore » critical tissue of the human body and the types and the frequency of radiation examinations are important. The judgment of genetic injury is expressed by the genetically significant dose, which is calculated from the dose in the genital gland received by individuals. The impcrtant criterion for the judgment of physical injury is the mean annual dose per person in the marrow (mean dose in the red marrow). The dose in the genital organ is important as the dose related to the evaluation of the degree of genetic risk. The characteristics of iatrogenic exposure are partial and acute exposure and a high dose rate. Tabulated individually were the frequency of x-ray examinations, the mean dose in the genital organ according urce. The radiation dose during x-ray pelvimetry to 51 patients was estimated, and the cytogenetic response of peripheral lymphocytes was determined in 25 of their newborn babies. The calculations resulted in an average midline fetal dose of 1,035 and 1,860 mrads for the patients receiving 2 projections and more than 2 projections, respectively. There was no evidence of radioinduced chromosomal darnage in the newborn infants following x-ray exposure in utero. (auth)« less

  10. An analytical dose-averaged LET calculation algorithm considering the off-axis LET enhancement by secondary protons for spot-scanning proton therapy.

    PubMed

    Hirayama, Shusuke; Matsuura, Taeko; Ueda, Hideaki; Fujii, Yusuke; Fujii, Takaaki; Takao, Seishin; Miyamoto, Naoki; Shimizu, Shinichi; Fujimoto, Rintaro; Umegaki, Kikuo; Shirato, Hiroki

    2018-05-22

    To evaluate the biological effects of proton beams as part of daily clinical routine, fast and accurate calculation of dose-averaged linear energy transfer (LET d ) is required. In this study, we have developed the analytical LET d calculation method based on the pencil-beam algorithm (PBA) considering the off-axis enhancement by secondary protons. This algorithm (PBA-dLET) was then validated using Monte Carlo simulation (MCS) results. In PBA-dLET, LET values were assigned separately for each individual dose kernel based on the PBA. For the dose kernel, we employed a triple Gaussian model which consists of the primary component (protons that undergo the multiple Coulomb scattering) and the halo component (protons that undergo inelastic, nonelastic and elastic nuclear reaction); the primary and halo components were represented by a single Gaussian and the sum of two Gaussian distributions, respectively. Although the previous analytical approaches assumed a constant LET d value for the lateral distribution of a pencil beam, the actual LET d increases away from the beam axis, because there are more scattered and therefore lower energy protons with higher stopping powers. To reflect this LET d behavior, we have assumed that the LETs of primary and halo components can take different values (LET p and LET halo ), which vary only along the depth direction. The values of dual-LET kernels were determined such that the PBA-dLET reproduced the MCS-generated LET d distribution in both small and large fields. These values were generated at intervals of 1 mm in depth for 96 energies from 70.2 to 220 MeV and collected in the look-up table. Finally, we compared the LET d distributions and mean LET d (LET d,mean ) values of targets and organs at risk between PBA-dLET and MCS. Both homogeneous phantom and patient geometries (prostate, liver, and lung cases) were used to validate the present method. In the homogeneous phantom, the LET d profiles obtained by the dual-LET kernels agree well with the MCS results except for the low-dose region in the lateral penumbra, where the actual dose was below 10% of the maximum dose. In the patient geometry, the LET d profiles calculated with the developed method reproduces MCS with the similar accuracy as in the homogeneous phantom. The maximum differences in LET d,mean for each structure between the PBA-dLET and the MCS were 0.06 keV/μm in homogeneous phantoms and 0.08 keV/μm in patient geometries under all tested conditions, respectively. We confirmed that the dual-LET-kernel model well reproduced the MCS, not only in the homogeneous phantom but also in complex patient geometries. The accuracy of the LET d was largely improved from the single-LET-kernel model, especially at the lateral penumbra. The model is expected to be useful, especially for proper recognition of the risk of side effects when the target is next to critical organs. © 2018 American Association of Physicists in Medicine.

  11. Dosimetric Evaluation of Intensity Modulated Radiotherapy and 4-Field 3-D Conformal Radiotherapy in Prostate Cancer Treatment

    PubMed Central

    Uysal, Bora; Beyzadeoğlu, Murat; Sager, Ömer; Dinçoğlan, Ferrat; Demiral, Selçuk; Gamsız, Hakan; Sürenkök, Serdar; Oysul, Kaan

    2013-01-01

    Objective: The purpose of this dosimetric study is the targeted dose homogeneity and critical organ dose comparison of 7-field Intensity Modulated Radiotherapy (IMRT) and 3-D 4-field conformal radiotherapy. Study Design: Cross sectional study. Material and Methods: Twenty patients with low and moderate risk prostate cancer treated at Gülhane Military Medical School Radiation Oncology Department between January 2009 and December 2009 are included in this study. Two seperate dosimetric plans both for 7-field IMRT and 3D-CRT have been generated for each patient to comparatively evaluate the dosimetric status of both techniques and all the patients received 7-field IMRT. Results: Dose-comparative evaluation of two techniques revealed the superiority of IMRT technique with statistically significantly lower femoral head doses along with reduced critical organ dose-volume parameters of bladder V60 (the volume receiving 60 Gy) and rectal V40 (the volume receiving 40 Gy) and V60. Conclusion: It can be concluded that IMRT is an effective definitive management tool for prostate cancer with improved critical organ sparing and excellent dose homogenization in target organs of prostate and seminal vesicles. PMID:25207069

  12. High- to low-dose extrapolation: critical determinants involved in the dose response of carcinogenic substances.

    PubMed

    Swenberg, J A; Richardson, F C; Boucheron, J A; Deal, F H; Belinsky, S A; Charbonneau, M; Short, B G

    1987-12-01

    Recent investigations on mechanism of carcinogenesis have demonstrated important quantitative relationships between the induction of neoplasia, the molecular dose of promutagenic DNA adducts and their efficiency for causing base-pair mismatch, and the extent of cell proliferation in target organ. These factors are involved in the multistage process of carcinogenesis, including initiation, promotion, and progression. The molecular dose of DNA adducts can exhibit supralinear, linear, or sublinear relationships to external dose due to differences in absorption, biotransformation, and DNA repair at high versus low doses. In contrast, increased cell proliferation is a common phenomena that is associated with exposures to relatively high doses of toxic chemicals. As such, it enhances the carcinogenic response at high doses, but has little effect at low doses. Since data on cell proliferation can be obtained for any exposure scenario and molecular dosimetry studies are beginning to emerge on selected chemical carcinogens, methods are needed so that these critical factors can be utilized in extrapolation from high to low doses and across species. The use of such information may provide a scientific basis for quantitative risk assessment.

  13. High- to low-dose extrapolation: critical determinants involved in the dose response of carcinogenic substances.

    PubMed Central

    Swenberg, J A; Richardson, F C; Boucheron, J A; Deal, F H; Belinsky, S A; Charbonneau, M; Short, B G

    1987-01-01

    Recent investigations on mechanism of carcinogenesis have demonstrated important quantitative relationships between the induction of neoplasia, the molecular dose of promutagenic DNA adducts and their efficiency for causing base-pair mismatch, and the extent of cell proliferation in target organ. These factors are involved in the multistage process of carcinogenesis, including initiation, promotion, and progression. The molecular dose of DNA adducts can exhibit supralinear, linear, or sublinear relationships to external dose due to differences in absorption, biotransformation, and DNA repair at high versus low doses. In contrast, increased cell proliferation is a common phenomena that is associated with exposures to relatively high doses of toxic chemicals. As such, it enhances the carcinogenic response at high doses, but has little effect at low doses. Since data on cell proliferation can be obtained for any exposure scenario and molecular dosimetry studies are beginning to emerge on selected chemical carcinogens, methods are needed so that these critical factors can be utilized in extrapolation from high to low doses and across species. The use of such information may provide a scientific basis for quantitative risk assessment. PMID:3447904

  14. Cell-based dose responses from open-well microchambers.

    PubMed

    Hamon, Morgan; Jambovane, Sachin; Bradley, Lauren; Khademhosseini, Ali; Hong, Jong Wook

    2013-05-21

    Cell-based assays play a critical role in discovery of new drugs and facilitating research in cancer, immunology, and stem cells. Conventionally, they are performed in Petri dishes, tubes, or well plates, using milliliters of reagents and thousands of cells to obtain one data point. Here, we are introducing a new platform to realize cell-based assay capable of increased throughput and greater sensitivity with a limited number of cells. We integrated an array of open-well microchambers into a gradient generation system. Consequently, cell-based dose responses were examined with a single device. We measured IC50 values of three cytotoxic chemicals, Triton X-100, H2O2, and cadmium chloride, as model compounds. The present system is highly suitable for the discovery of new drugs and studying the effect of chemicals on cell viability or mortality with limited samples and cells.

  15. Pharmacokinetic Study of Intravenous Acetaminophen Administered to Critically Ill Multiple-Trauma Patients at the Usual Dosage and a New Proposal for Administration.

    PubMed

    Fuster-Lluch, Oscar; Zapater-Hernández, Pedro; Gerónimo-Pardo, Manuel

    2017-10-01

    The pharmacokinetic profile of intravenous acetaminophen administered to critically ill multiple-trauma patients was studied after 4 consecutive doses of 1 g every 6 hours. Eleven blood samples were taken (predose and 15, 30, 45, 60, 90, 120, 180, 240, 300, and 360 minutes postdose), and urine was collected (during 6-hour intervals between doses) to determine serum and urine acetaminophen concentrations. These were used to calculate the following pharmacokinetic parameters: maximum and minimum concentrations, terminal half-life, area under serum concentration-time curve from 0 to 6 hours, mean residence time, volume of distribution, and serum and renal clearance of acetaminophen. Daily doses of acetaminophen required to obtain steady-state minimum (bolus dosing) and average plasma concentrations (continuous infusion) of 10 μg/mL were calculated (10 μg/mL is the presumed lower limit of the analgesic range). Data are expressed as median [interquartile range]. Twenty-two patients were studied, mostly young (age 44 [34-64] years) males (68%), not obese (weight 78 [70-84] kg). Acetaminophen concentrations and pharmacokinetic parameters were these: maximum concentration 33.6 [25.7-38.7] μg/mL and minimum concentration 0.5 [0.2-2.3] μg/mL, all values below 10 μg/mL and 8 below the detection limit; half-life 1.2 [1.0-1.9] hours; area under the curve for 6 hours 34.7 [29.7-52.7] μg·h/mL; mean residence time 1.8 [1.3-2.6] hours; steady-state volume of distribution 50.8 [42.5-66.5] L; and serum and renal clearance 28.8 [18.9-33.7] L/h and 15 [11-19] mL/min, respectively. Theoretically, daily doses for a steady-state minimum concentration of 10 μg/mL would be 12.2 [7.8-16.4] g/day (166 [112-202] mg/[kg·day]); for an average steady-state concentration of 10 μg/mL, they would be 6.9 [4.5-8.1] g/day (91 [59-111] mg/[kg·day]). In conclusion, administration of acetaminophen at the recommended dosage of 1 g per 6 hours to critically ill multiple-trauma patients yields serum concentrations below 10 μg/mL due to increased elimination. To reach the 10 μg/mL target, and from a strictly pharmacokinetic point of view, continuous infusion may be more feasible than bolus dosing. Such a change in dosing strategy requires appropriate, pharmacokinetic-pharmacodynamic and specific safety study. © 2017, The American College of Clinical Pharmacology.

  16. Pulmonary deposition modeling with airborne fiber exposure data: a study of workers manufacturing refractory ceramic fibers.

    PubMed

    Lentz, Thomas J; Rice, Carol H; Succop, Paul A; Lockey, James E; Dement, John M; LeMasters, Grace K

    2003-04-01

    Increasing production of refractory ceramic fiber (RCF), a synthetic vitreous material with industrial applications (e.g., kiln insulation), has created interest in potential respiratory effects of exposure to airborne fibers during manufacturing. An ongoing study of RCF manufacturing workers in the United States has indicated an association between cumulative fiber exposure and pleural plaques. Fiber sizing data, obtained from electron microscopy analyses of 118 air samples collected in three independent studies over a 20-year period (1976-1995), were used with a computer deposition model to estimate pulmonary dose of fibers of specified dimensions for 652 former and current RCF production workers. Separate dose correction factors reflecting differences in fiber dimensions in six uniform job title groups were used with data on airborne fiber concentration and employment duration to calculate cumulative dose estimates for each worker. From review of the literature, critical dimensions (diameter <0.4 microm, length <10 microm) were defined for fibers that may translocate to the parietal pleura. Each of three continuous exposure/dose metrics analyzed in separate logistic regression models was significantly related to plaques, even after adjusting for possible past asbestos exposure: cumulative fiber exposure, chi(2) = 15.2 (p < 0.01); cumulative pulmonary dose (all fibers), chi(2) = 14.6 (p < 0.01); cumulative pulmonary dose (critical dimension fibers), chi(2) = 12.4 (p < 0.01). Odds ratios (ORs) were calculated for levels of each metric. Increasing ORs were statistically significant for the two highest dose levels of critical dimension fibers (level three, OR = 11, 95%CI = [1.4, 98]; level four, OR = 25, 95%CI = [3.2, 190]). Similar associations existed for all metrics after adjustment for possible asbestos exposure. It was concluded that development of pleural plaques follows exposure- and dose-response patterns, and that airborne fibers in RCF manufacturing facilities include those with critical dimensions associated with pleural plaque formation. Analysis of additional air samples may improve estimates of the dose-response relationship.

  17. National survey on current situation of critical value reporting in 973 laboratories in China.

    PubMed

    Fei, Yang; Zhao, Haijian; Wang, Wei; He, Falin; Zhong, Kun; Yuan, Shuai; Wang, Zhiguo

    2017-10-15

    The aim of the study was to investigate the state-of-the-art of the performance of critical value reporting and provide recommendations for laboratories setting critical value reporting time frames. The National Centre for Clinical Laboratories in China initiated a critical value reporting investigation in 2015. A questionnaire related to critical value reporting policy was sent to 1589 clinical laboratories in China online. The questionnaire consisted of a set of questions related to critical value reporting policy and a set of questions related to timeliness of critical value reporting. The survey data were collected between March and April 2015. A total survey response rate was 61.2%. The critical value unreported rate, unreported timely rate, and clinical unacknowledged rate of more than half of participants were all 0.0%. More than 75.0% of participants could report half of critical values to clinicians within 20 minutes and could report 90.0% of critical values to clinicians within 25 minutes (from result validation to result communication to the clinician). The median of target critical value reporting time was 15 minutes. "Reporting omission caused by laboratory staff", "communications equipment failure to connect", and "uncompleted application form without contact information of clinician" were the three major reasons for unreported critical value. The majority of laboratories can report critical values to responsible clinical staff within 25 minutes. Thus, this value could be recommended as suitable critical value reporting time frame for biochemistry laboratories in China. However, careful monitoring of the complete reporting process and improvement of information systems should ensure further improvement of critical value reporting timeliness.

  18. In Vivo Absorption and Disposition of Cefadroxil after Escalating Oral Doses in Wild-Type and PepT1 Knockout Mice

    PubMed Central

    Posada, Maria M.; Smith, David E.

    2013-01-01

    Purpose To determine the effect of PepT1 on the absorption and disposition of cefadroxil, including the potential for saturable intestinal uptake, after escalating oral doses of drug. Methods The absorption and disposition kinetics of [3H]cefadroxil was determined in wild-type and PepT1 knockout mice after 44.5, 89.1, 178, and 356 nmol/g oral doses of drug. The pharmacokinetics of [3H]cefadroxil was also determined in both genotypes after 44.5 nmol/g intravenous bolus doses. Results PepT1 deletion reduced the area under the plasma concentration-time profile (AUC0-120) of cefadroxil by 10-fold, the maximum plasma concentration (Cmax) by 17.5-fold, and increased the time to reach a maximum plasma concentration (Tmax) by 3-fold. There was no evidence of nonlinear intestinal absorption since AUC0-120 and Cmax values changed in a dose-proportional manner. Moreover, the pharmacokinetics of cefadroxil was not different between genotypes after intravenous bolus doses, indicating that PepT1 did not affect drug disposition. Finally, no differences were observed in the peripheral tissue distribution of cefadroxil (i.e., outside gastrointestinal tract) once these tissues were corrected for differences in perfusing blood concentrations. Conclusions The findings demonstrate convincingly the critical role of intestinal PepT1 in both the rate and extent of oral administration for cefadroxil and potentially other aminocephalosporin drugs. PMID:23959853

  19. The protective effects of ascorbic acid, cimetidine, and nifedipine on diethyldithiocarbamate-induced hepatic toxicity in albino rats.

    PubMed

    Gaafa, Khadiga Mohammed; Badawy, Mohammed M; Hamza, Alaaeldin A

    2011-10-01

    The aim of the present work was to clarify the involvement of free radicals, cytochrome P450 toxic metabolites, and deregulation of calcium homeostasis in the mechanism of diethyldithiocarbamate (DDC) hepatotoxicity. This was elucidated through the preadministration of ascorbic acid (a free radical scavenger), cimetidine (an inhibitor of cytochrome P450 enzymes), or nifedipine (a calcium-blocking agent) before DDC treatment to male albino rats. DDC was administered either as a single dose [800 mg/kg body weight (b.w.), subcutaneously, s.c.] or daily repeated doses for 30 days (400 mg/kg b.w., s.c.). Oxidative stress indicators [e.g., malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase enzyme (SOD)] showed that single or repeated DDC doses induce an increase in MDA level and a decrease in SOD activity in the liver, whereas it causes depletion in hepatic GSH after a single dose and an elevation in its value after repeated doses. Severe histopathological changes were also observed in the livers of rats treated with single or repeated DDC doses. Ascorbic acid, cimetidine, and nifedipine pretreatments were found to induce highly protective effects against the evinced DDC hepatotoxicity, manifesting that free radical, cytochrome P450, and calcium-dependent processes contribute to DDC liver toxicity. Finally, although multiple mechanisms may be involved in the hepatotoxic changes induced by DDC, calcium disarrangement and free radical formation play a more critical role than cytochrome P450 in metabolic events leading to toxic effects of DDC.

  20. Three-dimensional radiotherapy of head and neck and esophageal carcinomas: a monoisocentric treatment technique to achieve improved dose distributions.

    PubMed

    Ahmad, M; Nath, R

    2001-02-20

    The specific aim of three-dimensional conformal radiotherapy is to deliver adequate therapeutic radiation dose to the target volume while concomitantly keeping the dose to surrounding and intervening normal tissues to a minimum. The objective of this study is to examine dose distributions produced by various radiotherapy techniques used in managing head and neck tumors when the upper part of the esophagus is also involved. Treatment planning was performed with a three-dimensional (3-D) treatment planning system. Computerized tomographic (CT) scans used by this system to generate isodose distributions and dose-volume histograms were obtained directly from the CT scanner, which is connected via ethernet cabling to the 3-D planning system. These are useful clinical tools for evaluating the dose distribution to the treatment volume, clinical target volume, gross tumor volume, and certain critical organs. Using 6 and 18 MV photon beams, different configurations of standard treatment techniques for head and neck and esophageal carcinoma were studied and the resulting dose distributions were analyzed. Film validation dosimetry in solid-water phantom was performed to assess the magnitude of dose inhomogeneity at the field junction. Real-time dose measurements on patients using diode dosimetry were made and compared with computed dose values. With regard to minimizing radiation dose to surrounding structures (i.e., lung, spinal cord, etc.), the monoisocentric technique gave the best isodose distributions in terms of dose uniformity. The mini-mantle anterior-posterior/posterior-anterior (AP/PA) technique produced grossly non-uniform dose distribution with excessive hot spots. The dose measured on the patient during the treatment agrees to within +/- 5 % with the computed dose. The protocols presented in this work for simulation, immobilization and treatment planning of patients with head and neck and esophageal tumors provide the optimum dose distributions in the target volume with reduced irradiation of surrounding non-target tissues, and can be routinely implemented in a radiation oncology department. The presence of a real-time dose-measuring system plays an important role in verifying the actual delivery of radiation dose.

  1. Analysis of uncertainties in Monte Carlo simulated organ dose for chest CT

    NASA Astrophysics Data System (ADS)

    Muryn, John S.; Morgan, Ashraf G.; Segars, W. P.; Liptak, Chris L.; Dong, Frank F.; Primak, Andrew N.; Li, Xiang

    2015-03-01

    In Monte Carlo simulation of organ dose for a chest CT scan, many input parameters are required (e.g., half-value layer of the x-ray energy spectrum, effective beam width, and anatomical coverage of the scan). The input parameter values are provided by the manufacturer, measured experimentally, or determined based on typical clinical practices. The goal of this study was to assess the uncertainties in Monte Carlo simulated organ dose as a result of using input parameter values that deviate from the truth (clinical reality). Organ dose from a chest CT scan was simulated for a standard-size female phantom using a set of reference input parameter values (treated as the truth). To emulate the situation in which the input parameter values used by the researcher may deviate from the truth, additional simulations were performed in which errors were purposefully introduced into the input parameter values, the effects of which on organ dose per CTDIvol were analyzed. Our study showed that when errors in half value layer were within ± 0.5 mm Al, the errors in organ dose per CTDIvol were less than 6%. Errors in effective beam width of up to 3 mm had negligible effect (< 2.5%) on organ dose. In contrast, when the assumed anatomical center of the patient deviated from the true anatomical center by 5 cm, organ dose errors of up to 20% were introduced. Lastly, when the assumed extra scan length was longer by 4 cm than the true value, dose errors of up to 160% were found. The results answer the important question: to what level of accuracy each input parameter needs to be determined in order to obtain accurate organ dose results.

  2. Main Sources and Doses of Space Radiation during Mars Missions and Total Radiation Risk for Cosmonauts

    NASA Astrophysics Data System (ADS)

    Mitrikas, Victor; Aleksandr, Shafirkin; Shurshakov, Vyacheslav

    This work contains calculation data of generalized doses and dose equivalents in critical organs and tissues of cosmonauts produces by galactic cosmic rays (GCR), solar cosmic rays (SCR) and the Earth’s radiation belts (ERB) that will impact crewmembers during a flight to Mars, while staying in the landing module and on the Martian surface, and during the return to Earth. Also calculated total radiation risk values during whole life of cosmonauts after the flight are presented. Radiation risk (RR) calculations are performed on the basis of a radiobiological model of radiation damage to living organisms, while taking into account reparation processes acting during continuous long-term exposure at various dose rates and under acute recurrent radiation impact. The calculations of RR are performed for crewmembers of various ages implementing a flight to Mars over 2 - 3 years in maximum and minimum of the solar cycle. The total carcinogenic and non-carcinogenic RR and possible life-span shortening are estimated on the basis of a model of the radiation death probability for mammals. This model takes into account the decrease in compensatory reserve of an organism as well as the increase in mortality rate and descent of the subsequent lifetime of the cosmonaut. The analyzed dose distributions in the shielding and body areas are applied to making model calculations of tissue equivalent spherical and anthropomorphic phantoms.

  3. Electron beam initiated modification of acrylic elastomer in presence of polyfunctional monomers

    NASA Astrophysics Data System (ADS)

    Vijayabaskar, V.; Bhattacharya, S.; Tikku, V. K.; Bhowmick, Anil K.

    2004-12-01

    The structural changes of an acrylic rubber (ACM) in presence and absence of polyfunctional monomers like trimethylolpropane triacrylate, tripropyleneglycol diacrylate, trimethylolmethane tetraacrylate and trimethylolpropane trimethacrylate at different doses of electron beam (EB) irradiations were investigated with the help of FTIR spectroscopy (in the attenuated total reflectance mode) and sol-gel analysis. As the radiation dose increases, the concentration of carbonyl group increases in the ACM rubber due to aerial oxidation. This is corroborated from the increase in the absorbance values at 1734 and 1160 cm -1, which are due to carbonyl and C-O-C stretching frequencies, respectively. The increase in crosslinking is revealed by the increase in percentage gel content with radiation dose. The lifetime of spurs formed and the critical dose, an important criterion for overlapping of spurs have been determined for both grafted and ungrafted ACM rubber using a mathematical model. The predominance of crosslinking by electronic stopping with energetic EB projectile and the increase in effective radius of crosslinking have also been verified by this model. The doses at which the synergistic occurrence of both dislinking and endlinking steps originate have been calculated using linear energy transfer of EB. The ratio of scissioning to crosslinking for ACM rubber has been determined by using Charlesby-Pinner equation. The mechanical properties have been studied for different modified and unmodified systems and the tensile strength is found to increase with grafting of polyfunctional monomers.

  4. The cellular distribution of fluorescently labeled arrestins provides a robust, sensitive, and universal assay for screening G protein-coupled receptors.

    PubMed

    Oakley, Robert H; Hudson, Christine C; Cruickshank, Rachael D; Meyers, Diane M; Payne, Richard E; Rhem, Shay M; Loomis, Carson R

    2002-11-01

    G protein-coupled receptors (GPCRs) have proven to be a rich source of therapeutic targets; therefore, finding compounds that regulate these receptors is a critical goal in drug discovery. The Transfluor technology utilizes the redistribution of fluorescently labeled arrestins from the cytoplasm to agonist-occupied receptors at the plasma membrane to monitor quantitatively the activation or inactivation of GPCRs. Here, we show that the Transfluor technology can be quantitated on the INCell Analyzer system (INCAS) using the vasopressin V(2) receptor (V(2)R), which binds arrestin with high affinity, and the beta(2)-adrenergic receptor (beta(2)AR), which binds arrestin with low affinity. U2OS cells stably expressing an arrestin-green fluorescent protein conjugate and either the V(2)R or the beta(2)AR were plated in 96-well plastic plates and analyzed by the INCAS at a screening rate of 5 min per plate. Agonist dose-response and antagonist dose-inhibition curves revealed signal-to-background ratios of approximately 25:1 and 8:1 for the V(2)R and beta(2)AR, respectively. EC(50) values agreed closely with K(d) values reported in the literature for the different receptor agonists. In addition, small amounts of arrestin translocation induced by sub-EC(50) doses of agonist were distinguished from the background noise of untreated cells. Furthermore, differences in the magnitude of arrestin translocation distinguished partial agonists from full agonists, and Z' values for these ligands were >0.5. These data show that the Transfluor technology, combined with an automated image analysis system, provides a direct, robust, and universal assay for high throughput screening of known and orphan GPCRs.

  5. SU-E-T-577: Obliquity Factor and Surface Dose in Proton Beam Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Das, I; Andersen, A; Coutinho, L

    2015-06-15

    Purpose: The advantage of lower skin dose in proton beam may be diminished creating radiation related sequalae usually seen with photon and electron beams. This study evaluates the surface dose as a complex function of beam parameters but more importantly the effect of beam angle. Methods: Surface dose in proton beam depends on the beam energy, source to surface distance, the air gap between snout and surface, field size, material thickness in front of surface, atomic number of the medium, beam angle and type of nozzle (ie double scattering, (DS), uniform scanning (US) or pencil beam scanning (PBS). Obliquity factormore » (OF) is defined as ratio of surface dose in 0° to beam angle Θ. Measurements were made in water phantom at various beam angles using very small microdiamond that has shown favorable beam characteristics for high, medium and low proton energy. Depth dose measurements were performed in the central axis of the beam in each respective gantry angle. Results: It is observed that surface dose is energy dependent but more predominantly on the SOBP. It is found that as SSD increases, surface dose decreases. In general, SSD, and air gap has limited impact in clinical proton range. High energy has higher surface dose and so the beam angle. The OF rises with beam angle. Compared to OF of 1.0 at 0° beam angle, the value is 1.5, 1.6, 1,7 for small, medium and large range respectively for 60 degree angle. Conclusion: It is advised that just like range and SOBP, surface dose should be clearly understood and a method to reduce the surface dose should be employed. Obliquity factor is a critical parameter that should be accounted in proton beam therapy and a perpendicular beam should be used to reduce surface dose.« less

  6. Intensity-modulated radiotherapy for locally advanced non-small-cell lung cancer: a dose-escalation planning study.

    PubMed

    Lievens, Yolande; Nulens, An; Gaber, Mousa Amr; Defraene, Gilles; De Wever, Walter; Stroobants, Sigrid; Van den Heuvel, Frank

    2011-05-01

    To evaluate the potential for dose escalation with intensity-modulated radiotherapy (IMRT) in positron emission tomography-based radiotherapy planning for locally advanced non-small-cell lung cancer (LA-NSCLC). For 35 LA-NSCLC patients, three-dimensional conformal radiotherapy and IMRT plans were made to a prescription dose (PD) of 66 Gy in 2-Gy fractions. Dose escalation was performed toward the maximal PD using secondary endpoint constraints for the lung, spinal cord, and heart, with de-escalation according to defined esophageal tolerance. Dose calculation was performed using the Eclipse pencil beam algorithm, and all plans were recalculated using a collapsed cone algorithm. The normal tissue complication probabilities were calculated for the lung (Grade 2 pneumonitis) and esophagus (acute toxicity, grade 2 or greater, and late toxicity). IMRT resulted in statistically significant decreases in the mean lung (p <.0001) and maximal spinal cord (p = .002 and 0005) doses, allowing an average increase in the PD of 8.6-14.2 Gy (p ≤.0001). This advantage was lost after de-escalation within the defined esophageal dose limits. The lung normal tissue complication probabilities were significantly lower for IMRT (p <.0001), even after dose escalation. For esophageal toxicity, IMRT significantly decreased the acute NTCP values at the low dose levels (p = .0009 and p <.0001). After maximal dose escalation, late esophageal tolerance became critical (p <.0001), especially when using IMRT, owing to the parallel increases in the esophageal dose and PD. In LA-NSCLC, IMRT offers the potential to significantly escalate the PD, dependent on the lung and spinal cord tolerance. However, parallel increases in the esophageal dose abolished the advantage, even when using collapsed cone algorithms. This is important to consider in the context of concomitant chemoradiotherapy schedules using IMRT. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Clean to dirty limit and T c suppression in NdFeAsO0.7F0.3 studied by H c2 analysis

    NASA Astrophysics Data System (ADS)

    Pallecchi, I.; Tarantini, C.; Shen, Y.; Singh, R. K.; Newman, N.; Cheng, P.; Jia, Y.; Wen, H.-H.; Putti, M.

    2018-07-01

    In this work, we investigate the temperature dependence of the upper critical field, dH c2/dT, in an increasingly disordered NdFeAsO0.7F0.3 (NdFeAs(O,F)) single crystal that has been progressively irradiated up to a 5.25 × 1016 cm- 2 total α-particle dose. For the H∣∣ab-plane, dH c2/dT does not vary remarkably with irradiation, while for the H∣∣c-axis it increases sharply after the first irradiation of 3.60 × 1015 cm-2 and then more gradually with further irradiation doses. Focusing on the H∣∣c-axis, we develop a phenomenological analysis of the H c2 slope which allows us to inspect the crossover from the clean to the dirty regime. From the H c2 slope normalized to the critical temperature and to its clean limit value, we extract the ratio of the coherence length ξ BCS to the mean free path {\\ell } and we find that when T c is reduced by a factor of four from its pristine value, ξ BCS/{\\ell } becomes as large as ˜7 and {\\ell } reaches values of ˜1.8 nm, indicating that NdFeAs(O,F) is well into the dirty regime. Our analysis of the H c2 slope also allows us to compare the pair-breaking effectiveness of scattering in different superconductors, showing similarity between unconventional NdFeAs(O,F) and moderate-T c phonon-mediated devices, such as MgB2 and A15 compounds, but much a stronger difference with YBa2Cu3O7-δ . This work thus shows that dH c2/dT is a reliable parameter, providing an alternative to residual resistivity, for investigating the pair-breaking mechanism induced by impurity scattering in superconductors.

  8. Color-Coded Prefilled Medication Syringes Decrease Time to Delivery and Dosing Error in Simulated Emergency Department Pediatric Resuscitations.

    PubMed

    Moreira, Maria E; Hernandez, Caleb; Stevens, Allen D; Jones, Seth; Sande, Margaret; Blumen, Jason R; Hopkins, Emily; Bakes, Katherine; Haukoos, Jason S

    2015-08-01

    The Institute of Medicine has called on the US health care system to identify and reduce medical errors. Unfortunately, medication dosing errors remain commonplace and may result in potentially life-threatening outcomes, particularly for pediatric patients when dosing requires weight-based calculations. Novel medication delivery systems that may reduce dosing errors resonate with national health care priorities. Our goal was to evaluate novel, prefilled medication syringes labeled with color-coded volumes corresponding to the weight-based dosing of the Broselow Tape, compared with conventional medication administration, in simulated pediatric emergency department (ED) resuscitation scenarios. We performed a prospective, block-randomized, crossover study in which 10 emergency physician and nurse teams managed 2 simulated pediatric arrest scenarios in situ, using either prefilled, color-coded syringes (intervention) or conventional drug administration methods (control). The ED resuscitation room and the intravenous medication port were video recorded during the simulations. Data were extracted from video review by blinded, independent reviewers. Median time to delivery of all doses for the conventional and color-coded delivery groups was 47 seconds (95% confidence interval [CI] 40 to 53 seconds) and 19 seconds (95% CI 18 to 20 seconds), respectively (difference=27 seconds; 95% CI 21 to 33 seconds). With the conventional method, 118 doses were administered, with 20 critical dosing errors (17%); with the color-coded method, 123 doses were administered, with 0 critical dosing errors (difference=17%; 95% CI 4% to 30%). A novel color-coded, prefilled syringe decreased time to medication administration and significantly reduced critical dosing errors by emergency physician and nurse teams during simulated pediatric ED resuscitations. Copyright © 2015 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.

  9. Radiobiological modeling of two stereotactic body radiotherapy schedules in patients with stage I peripheral non-small cell lung cancer.

    PubMed

    Huang, Bao-Tian; Lin, Zhu; Lin, Pei-Xian; Lu, Jia-Yang; Chen, Chuang-Zhen

    2016-06-28

    This study aims to compare the radiobiological response of two stereotactic body radiotherapy (SBRT) schedules for patients with stage I peripheral non-small cell lung cancer (NSCLC) using radiobiological modeling methods. Volumetric modulated arc therapy (VMAT)-based SBRT plans were designed using two dose schedules of 1 × 34 Gy (34 Gy in 1 fraction) and 4 × 12 Gy (48 Gy in 4 fractions) for 19 patients diagnosed with primary stage I NSCLC. Dose to the gross target volume (GTV), planning target volume (PTV), lung and chest wall (CW) were converted to biologically equivalent dose in 2 Gy fraction (EQD2) for comparison. Five different radiobiological models were employed to predict the tumor control probability (TCP) value. Three additional models were utilized to estimate the normal tissue complication probability (NTCP) value for the lung and the modified equivalent uniform dose (mEUD) value to the CW. Our result indicates that the 1 × 34 Gy dose schedule provided a higher EQD2 dose to the tumor, lung and CW. Radiobiological modeling revealed that the TCP value for the tumor, NTCP value for the lung and mEUD value for the CW were 7.4% (in absolute value), 7.2% (in absolute value) and 71.8% (in relative value) higher on average, respectively, using the 1 × 34 Gy dose schedule.

  10. Individual dose reconstruction among residents living in the vicinity of the Semipalatinsk nuclear test site using EPR spectroscopy of tooth enamel.

    PubMed

    Ivannikov, A I; Zhumadilov, Zh; Gusev, B I; Miyazawa, Ch; Jiao, L; Skvortsov, V G; Stepanenko, V F; Takada, J; Hoshi, M

    2002-08-01

    Individual accumulated doses were determined by EPR spectroscopy of tooth enamel for 26 adult persons residing in territories adjacent to the Semipalatinsk Nuclear Test Site (SNTS). The absorbed dose values due to radiation from nuclear tests were obtained after subtracting the contribution of natural background radiation from the total accumulated dose. The determined dose values ranged up to 250 mGy, except for one person from Semipalatinsk city with a measured dose of 2.8 +/- 0.4 Gy. Increased dose values were determined for the individuals whose teeth were formed before 1962, the end of the atmospheric nuclear tests. These values were found to be significantly larger than those obtained for a group of younger residents of heavily exposed territories and the residents of territories not exposed to radioactive fallout. These increased dose values are consistent with those based on officially registered data for the Northeastern part of Kazakstan adjacent to SNTS, which was exposed to high levels of radioactive fallout from nuclear tests in period 1949-1962.

  11. Total dose bias dependency and ELDRS effects in bipolar linear devices

    NASA Technical Reports Server (NTRS)

    Yui, C. C.; McClure, S. S.; Rex, B. G.; Lehman, J. M.; Minto, T. D.; Wiedeman, M.

    2002-01-01

    Total dose tests of several bipolar linear devices show sensitivity to both dose rate and bias during exposure. All devices exhibited Enhanced Low Dose Rate Sensitivity (ELDRS). An accelerated ELDRS test method for three different devices demonstrate results similar to tests at low dose rate. Behavior and critical parameters from these tests are compared and discussed.

  12. Dose dependence of true stress parameters in irradiated bcc, fcc, and hcp metals

    NASA Astrophysics Data System (ADS)

    Byun, T. S.

    2007-04-01

    The dose dependence of true stress parameters has been investigated for nuclear structural materials: A533B pressure vessel steels, modified 9Cr-1Mo and 9Cr-2WVTa ferritic martensitic steels, 316 and 316LN stainless steels, and Zircaloy-4. After irradiation to significant doses, these alloys show radiation-induced strengthening and often experience prompt necking at yield followed by large necking deformation. In the present work, the critical true stresses for deformation and fracture events, such as yield stress (YS), plastic instability stress (PIS), and true fracture stress (FS), were obtained from uniaxial tensile tests or calculated using a linear strain-hardening model for necking deformation. At low dose levels where no significant embrittlement was detected, the true fracture stress was nearly independent of dose. The plastic instability stress was also independent of dose before the critical dose-to-prompt-necking at yield was reached. A few bcc alloys such as ferritic martensitic steels experienced significant embrittlement at doses above ∼1 dpa; and the true fracture stress decreased with dose. The materials fractured before yield at or above 10 dpa.

  13. OCCUPATIONAL DOSE DURING ADULT INTERVENTIONAL CARDIOLOGY: FIRST VALUES WITH PERSONAL ACTIVE DOSIMETERS IN CHILE.

    PubMed

    Ubeda, Carlos; Morales, Claudio; Gutiérrez, Diego; Oliveira, Marcus; Manterola, Carlos

    2018-05-11

    The objective of this article is to present initial occupational dose values using digital active personal dosimeters for medical staff during adult interventional cardiology procedures in a public hospital in Chile. Personal dose equivalent Hp(10) over the lead apron of physician, nurse and radiographer were measured during 59 procedures. Mean values of occupational dose Hp(10) per procedure were 47.6, 6.2 and 4.3 μSv for physician, nurse and radiographer, respectively. If no protective tools are used, physician dose can exceed the new eye lens dose limit.

  14. Pharmacokinetic profiles of repaglinide in elderly subjects with type 2 diabetes.

    PubMed

    Hatorp, V; Huang, W C; Strange, P

    1999-04-01

    Pharmacokinetic profiles of single- and multiple-dose regimens of repaglinide were evaluated in 12 elderly subjects with type 2 diabetes. On day 1, following a 10-hour fast, subjects received a single 2-mg dose of repaglinide. Starting on day 2 and continuing for 7 days, each subject received a 2-mg dose of repaglinide 15 minutes before each of the three main meals. On day 9, subjects received a single 2-mg dose of repaglinide. Pharmacokinetic profiles, including area under the curve (AUC), log(AUC), maximal concentration (Cmax), log(Cmax), time to maximal concentration (Tmax), and half-life (T(1/2)), were determined at completion of the single- and multiple-dose regimens (days 1 and 9, respectively). Trough repaglinide values were collected on days 2 through 7. The mean log(AUC) values after multiple dosing were significantly higher than the values obtained after a single dose. The mean values for log(Cmax), and Tmax were comparable after each dosing regimen. The T(1/2) of repaglinide after multiple dosing was 1.7 hours. The trough values for repaglinide were low. No hypoglycemic events were reported. The pharmacokinetic profiles of repaglinide after single- and multiple-dose regimens were similar, and repaglinide was well tolerated by elderly subjects with type 2 diabetes.

  15. Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit.

    PubMed

    Abdul-Aziz, Mohd H; Abd Rahman, Azrin N; Mat-Nor, Mohd-Basri; Sulaiman, Helmi; Wallis, Steven C; Lipman, Jeffrey; Roberts, Jason A; Staatz, Christine E

    2016-01-01

    Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL(CR)), such that a 30-ml/min increase in the estimated CL(CR) would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL(CR) of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL(CR) of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  16. Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit

    PubMed Central

    Abd Rahman, Azrin N.; Mat-Nor, Mohd-Basri; Sulaiman, Helmi; Wallis, Steven C.; Lipman, Jeffrey; Roberts, Jason A.; Staatz, Christine E.

    2015-01-01

    Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CLCR), such that a 30-ml/min increase in the estimated CLCR would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CLCR of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CLCR of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved. PMID:26482304

  17. Radiobiological impact of reduced margins and treatment technique for prostate cancer in terms of tumor control probability (TCP) and normal tissue complication probability (NTCP).

    PubMed

    Jensen, Ingelise; Carl, Jesper; Lund, Bente; Larsen, Erik H; Nielsen, Jane

    2011-01-01

    Dose escalation in prostate radiotherapy is limited by normal tissue toxicities. The aim of this study was to assess the impact of margin size on tumor control and side effects for intensity-modulated radiation therapy (IMRT) and 3D conformal radiotherapy (3DCRT) treatment plans with increased dose. Eighteen patients with localized prostate cancer were enrolled. 3DCRT and IMRT plans were compared for a variety of margin sizes. A marker detectable on daily portal images was presupposed for narrow margins. Prescribed dose was 82 Gy within 41 fractions to the prostate clinical target volume (CTV). Tumor control probability (TCP) calculations based on the Poisson model including the linear quadratic approach were performed. Normal tissue complication probability (NTCP) was calculated for bladder, rectum and femoral heads according to the Lyman-Kutcher-Burman method. All plan types presented essentially identical TCP values and very low NTCP for bladder and femoral heads. Mean doses for these critical structures reached a minimum for IMRT with reduced margins. Two endpoints for rectal complications were analyzed. A marked decrease in NTCP for IMRT plans with narrow margins was seen for mild RTOG grade 2/3 as well as for proctitis/necrosis/stenosis/fistula, for which NTCP <7% was obtained. For equivalent TCP values, sparing of normal tissue was demonstrated with the narrow margin approach. The effect was more pronounced for IMRT than 3DCRT, with respect to NTCP for mild, as well as severe, rectal complications. Copyright © 2011 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

  18. Obstructive urination problems after high-dose-rate brachytherapy boost treatment for prostate cancer are avoidable.

    PubMed

    Kragelj, Borut

    2016-03-01

    Aiming at improving treatment individualization in patients with prostate cancer treated with combination of external beam radiotherapy and high-dose-rate brachytherapy to boost the dose to prostate (HDRB-B), the objective was to evaluate factors that have potential impact on obstructive urination problems (OUP) after HDRB-B. In the follow-up study 88 patients consecutively treated with HDRB-B at the Institute of Oncology Ljubljana in the period 2006-2011 were included. The observed outcome was deterioration of OUP (DOUP) during the follow-up period longer than 1 year. Univariate and multivariate relationship analysis between DOUP and potential risk factors (treatment factors, patients' characteristics) was carried out by using binary logistic regression. ROC curve was constructed on predicted values and the area under the curve (AUC) calculated to assess the performance of the multivariate model. Analysis was carried out on 71 patients who completed 3 years of follow-up. DOUP was noted in 13/71 (18.3%) of them. The results of multivariate analysis showed statistically significant relationship between DOUP and anti-coagulation treatment (OR 4.86, 95% C.I. limits: 1.21-19.61, p = 0.026). Also minimal dose received by 90% of the urethra volume was close to statistical significance (OR = 1.23; 95% C.I. limits: 0.98-1.07, p = 0.099). The value of AUC was 0.755. The study emphasized the relationship between DOUP and anticoagulation treatment, and suggested the multivariate model with fair predictive performance. This model potentially enables a reduction of DOUP after HDRB-B. It supports the belief that further research should be focused on urethral sphincter as a critical structure for OUP.

  19. In vitro permeation and disposition of niacinamide in silicone and porcine skin of skin barrier-mimetic formulations.

    PubMed

    Haque, Tasnuva; Lane, Majella E; Sil, Bruno C; Crowther, Jonathan M; Moore, David J

    2017-03-30

    Niacinamide (NIA) is an amide form of vitamin B3 which is used in cosmetic formulations to improve various skin conditions and it has also been shown to increase stratum corneum thickness following repeated application. In this study, three doses (5, 20 and 50μL per cm 2 ) of two NIA containing oil-in-water skin barrier-mimetic formulations were evaluated in silicone membrane and porcine ear skin and compared with a commercial control formulation. Permeation studies were conducted over 24h in Franz cells and at the end of the experiment membranes were washed and niacinamide was extracted. For the three doses, retention or deposition of NIA was generally higher in porcine skin compared with silicone membrane, consistent with the hydrophilic nature of the active. Despite the control containing a higher amount of active, comparable amounts of NIA were deposited in skin for all formulations for all doses; total skin absorption values (permeation and retention) of NIA were also comparable across all formulations. For infinite (50μL) and finite (5μL) doses the absolute permeation of NIA from the control formulation was significantly higher in porcine skin compared with both test formulations. This likely reflects differences in formulation components and/or presence of skin penetration enhancers in the formulations. Higher permeation for the 50 and 20μL dose was also evident in porcine skin compared with silicone membrane but the opposite is the case for the finite dose. The findings point to the critical importance of dose and occlusion when evaluating topical formulations in vitro and also the likelihood of exaggerated effects of excipients on permeation at infinite and pseudo-finite dose applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. [SUBSTANTIATION OF DOSE LIMITS FOR A NEW NORMATIVE DOCUMENT ON RADIATION SAFETY OF LONG-DURATION SPACE MISSIONS AT ORBIT ALTITUDES OF UP TO 500 KM].

    PubMed

    Ushakov, I B; Grigoriev, Yu G; Shafirkin, A V; Shurshakov, V A

    2016-01-01

    Review of the data of experimental radiobiology and epidemiological follow-up of large groups of people subjected to radiation exposures on Earth has been undertaken to substantiate dose limits for critical organs of cosmonauts in order to ensure good performance and vitality while on long-duration orbital missions. The career dose limits for cosmonauts and astronauts established earlier in the USSR and USA amounted to nothing more but banning the risk of cancer death increase to 3%. To apply more rigorous criteria of delayed radiation risks, the Russian limits for cosmonauts were revised to substantiate a 4-fold reduction of the average tissue equivalent dose maximum to 1 Sv. The total of cancer and non-cancer radiation risks over lifetime and probable reduction of mean life expectancy (MLE) were calculated using the model of radiation-induced mortality for mammals and taken as the main damage to health. The established dose limit is equal to the career dose for nuclear industry personnel set forth by Russian standard document NRB 99/2009. For better agreement of admissible threshold doses to critical human organs (bone marrow, lens and skin) in the revised radiation limits for long-duration space missions and radiation safety limits on Earth, reduction of dose limits for the critical organs were substantiated additionally; these limits comply with those for planned over-exposure on Earth in document NRB 99/2009.

  1. Prophylactic ranitidine treatment in critically ill children – a population pharmacokinetic study

    PubMed Central

    Hawwa, Ahmed F; Westwood, Paul M; Collier, Paul S; Millership, Jeffrey S; Yakkundi, Shirish; Thurley, Gillian; Shields, Mike D; Nunn, Anthony J; Halliday, Henry L; McElnay, James C

    2013-01-01

    Aims To characterize the population pharmacokinetics of ranitidine in critically ill children and to determine the influence of various clinical and demographic factors on its disposition. Methods Data were collected prospectively from 78 paediatric patients (n = 248 plasma samples) who received oral or intravenous ranitidine for prophylaxis against stress ulcers, gastrointestinal bleeding or the treatment of gastro-oesophageal reflux. Plasma samples were analysed using high-performance liquid chromatography, and the data were subjected to population pharmacokinetic analysis using nonlinear mixed-effects modelling. Results A one-compartment model best described the plasma concentration profile, with an exponential structure for interindividual errors and a proportional structure for intra-individual error. After backward stepwise elimination, the final model showed a significant decrease in objective function value (−12.618; P < 0.001) compared with the weight-corrected base model. Final parameter estimates for the population were 32.1 l h−1 for total clearance and 285 l for volume of distribution, both allometrically modelled for a 70 kg adult. Final estimates for absorption rate constant and bioavailability were 1.31 h−1 and 27.5%, respectively. No significant relationship was found between age and weight-corrected ranitidine pharmacokinetic parameters in the final model, with the covariate for cardiac failure or surgery being shown to reduce clearance significantly by a factor of 0.46. Conclusions Currently, ranitidine dose recommendations are based on children's weights. However, our findings suggest that a dosing scheme that takes into consideration both weight and cardiac failure/surgery would be more appropriate in order to avoid administration of higher or more frequent doses than necessary. PMID:23016949

  2. Evaluation of [18F]Mefway biodistribution and dosimetry based on whole-body PET imaging of mice.

    PubMed

    Constantinescu, Cristian C; Sevrioukov, Evgueni; Garcia, Adriana; Pan, Min-Liang; Mukherjee, Jogeshwar

    2013-04-01

    [(18)F]Mefway is a novel radiotracer specific to the serotonin 5-HT1A receptor class. In preparation for using this tracer in humans, we have performed whole-body PET studies in mice to evaluate the biodistribution and dosimetry of [(18)F]Mefway. Six mice (three females and three males) received IV injections of [(18)F]Mefway and were scanned for 2 h in an Inveon-dedicated PET scanner. Each animal also received a high-resolution CT scan using an Inveon CT. The CT images were used to draw volume of interest on the following organs: the brain, large intestine, stomach, heart, kidneys, liver, lungs, pancreas, bone, spleen, testes, thymus, gallbladder, uterus, and urinary bladder. All organ time-activity curves without decay correction were normalized to the injected activity. The area under the normalized curves was then used to compute the residence times in each organ. Data were analyzed using PMOD and Matlab software. The absorbed doses in mouse organs were computed using the RAdiation Dose Assessment Resource animal models for dose assessment. The residence times in mouse organs were converted to human values using scale factors based on differences between organ and body weights. OLINDA/EXM 1.1 software was used to compute the absorbed human doses in multiple organs for both female and male phantoms. The highest mouse residence times were found in the liver, urinary bladder, and kidneys. The largest doses in mice were found in the urinary bladder (critical organ), kidney, and liver for both females and males, indicating primary elimination via urinary system. The projected human effective doses were 1.21E - 02 mSv/MBq for the adult female model and 1.13E - 02 mSv/MBq for the adult male model. The estimated human biodistribution of [(18)F]Mefway was similar to that of [(11)C]WAY 100,635, a 5-HT1A tracer for which dosimetry has been evaluated in humans. The elimination of radiotracer was primarily via the kidney and urinary bladder with the urinary bladder being the critical organ. Whole-body mouse imaging can be used as a preclinical tool to provide initial estimates of the absorbed doses of [(18)F]Mefway in humans.

  3. SU-F-T-50: Evaluation of Monte Carlo Simulations Performance for Pediatric Brachytherapy Dosimetry

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chatzipapas, C; Kagadis, G; Papadimitroulas, P

    Purpose: Pediatric tumors are generally treated with multi-modal procedures. Brachytherapy can be used with pediatric tumors, especially given that in this patient population low toxicity on normal tissues is critical as is the suppression of the probability for late malignancies. Our goal is to validate the GATE toolkit on realistic brachytherapy applications, and evaluate brachytherapy plans on pediatrics for accurate dosimetry on sensitive and critical organs of interest. Methods: The GATE Monte Carlo (MC) toolkit was used. Two High Dose Rate (HDR) 192Ir brachytherapy sources were simulated (Nucletron mHDR-v1 and Varian VS2000), and fully validated using the AAPM and ESTROmore » protocols. A realistic brachytherapy plan was also simulated using the XCAT anthropomorphic computational model .The simulated data were compared to the clinical dose points. Finally, a 14 years old girl with vaginal rhabdomyosarcoma was modelled based on clinical procedures for the calculation of the absorbed dose per organ. Results: The MC simulations resulted in accurate dosimetry in terms of dose rate constant (Λ), radial dose gL(r) and anisotropy function F(r,θ) for both sources.The simulations were executed using ∼1010 number of primaries resulting in statistical uncertainties lower than 2%.The differences between the theoretical values and the simulated ones ranged from 0.01% up to 3.3%, with the largest discrepancy (6%) being observed in the dose rate constant calculation.The simulated DVH using an adult female XCAT model was also compared to a clinical one resulting in differences smaller than 5%. Finally, a realistic pediatric brachytherapy simulation was performed to evaluate the absorbed dose per organ and to calculate DVH with respect to heterogeneities of the human anatomy. Conclusion: GATE is a reliable tool for brachytherapy simulations both for source modeling and for dosimetry in anthropomorphic voxelized models. Our project aims to evaluate a variety of pediatric brachytherapy schemes using a population of pediatric phantoms for several pathological cases. This study is part of a project that has received funding from the European Union Horizon2020 research and innovation programme under the MarieSklodowska-Curiegrantagreement.No691203.The results published in this study reflect only the authors view and the Research Executive Agency (REA) and the European Commission is not responsible for any use that may be madeof the information it contains.« less

  4. Is high–dose rate RapidArc-based radiosurgery dosimetrically advantageous for the treatment of intracranial tumors?

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhao, Bo; Yang, Yong, E-mail: yangy2@upmc.edu; Li, Xiang

    In linac-based stereotactic radiosurgery (SRS) and radiotherapy (SRT), circular cone(s) or conformal arc(s) are conventionally used to treat intracranial lesions. However, when the target is in close proximity to critical structures, it is frequently quite challenging to generate a quality plan using these techniques. In this study, we investigated the dosimetric characteristics of using high–dose rate RapidArc (RA) technique for radiosurgical treatment of intracranial lesions. A total of 10 intracranial SRS/SRT cases previously planned using dynamic conformal arc (DCA) or cone-based techniques have been included in this study. For each case, 3 treatment plans were generated: (1) a DCA planmore » with multiple noncoplanar arcs, (2) a high–dose rate RA plan with arcs oriented the same as DCA (multiple-arc RA), and 3) a high–dose rate RA plan with a single coplanar arc (single-arc RA). All treatment plans were generated under the same prescription and similar critical structure dose limits. Plan quality for different plans was evaluated by comparing various dosimetric parameters such as target coverage, conformity index (CI), homogeneity index (HI), critical structures, and normal brain tissue doses as well as beam delivery time. With similar critical structure sparing, high–dose rate RA plans can achieve much better target coverage, dose conformity, and dose homogeneity than the DCA plans can. Plan quality indices CI and HI, for the DCA, multiple-arc RA, and single-arc RA techniques, were measured as 1.67 ± 0.39, 1.32 ± 0.28, and 1.38 ± 0.30 and 1.24 ± 0.11, 1.10 ± 0.04, and 1.12 ± 0.07, respectively. Normal brain tissue dose (V{sub 12} {sub Gy}) was found to be similar for DCA and multiple-arc RA plans but much larger for the single-arc RA plans. Beam delivery was similar for DCA and multiple-arc RA plans but shorter with single-arc RA plans. Multiple-arc RA SRS/SRT can provide better treatment plans than conventional DCA plans, especially for complex cases.« less

  5. SU-C-207-02: A Method to Estimate the Average Planar Dose From a C-Arm CBCT Acquisition

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Supanich, MP

    2015-06-15

    Purpose: The planar average dose in a C-arm Cone Beam CT (CBCT) acquisition had been estimated in the past by averaging the four peripheral dose measurements in a CTDI phantom and then using the standard 2/3rds peripheral and 1/3 central CTDIw method (hereafter referred to as Dw). The accuracy of this assumption has not been investigated and the purpose of this work is to test the presumed relationship. Methods: Dose measurements were made in the central plane of two consecutively placed 16cm CTDI phantoms using a 0.6cc ionization chamber at each of the 4 peripheral dose bores and in themore » central dose bore for a C-arm CBCT protocol. The same setup was scanned with a circular cut-out of radiosensitive gafchromic film positioned between the two phantoms to capture the planar dose distribution. Calibration curves for color pixel value after scanning were generated from film strips irradiated at different known dose levels. The planar average dose for red and green pixel values was calculated by summing the dose values in the irradiated circular film cut out. Dw was calculated using the ionization chamber measurements and film dose values at the location of each of the dose bores. Results: The planar average dose using both the red and green pixel color calibration curves were within 10% agreement of the planar average dose estimated using the Dw method of film dose values at the bore locations. Additionally, an average of the planar average doses calculated using the red and green calibration curves differed from the ionization chamber Dw estimate by only 5%. Conclusion: The method of calculating the planar average dose at the central plane of a C-arm CBCT non-360 rotation by calculating Dw from peripheral and central dose bore measurements is a reasonable approach to estimating the planar average dose. Research Grant, Siemens AG.« less

  6. Higher criticism approach to detect rare variants using whole genome sequencing data

    PubMed Central

    2014-01-01

    Because of low statistical power of single-variant tests for whole genome sequencing (WGS) data, the association test for variant groups is a key approach for genetic mapping. To address the features of sparse and weak genetic effects to be detected, the higher criticism (HC) approach has been proposed and theoretically has proven optimal for detecting sparse and weak genetic effects. Here we develop a strategy to apply the HC approach to WGS data that contains rare variants as the majority. By using Genetic Analysis Workshop 18 "dose" genetic data with simulated phenotypes, we assess the performance of HC under a variety of strategies for grouping variants and collapsing rare variants. The HC approach is compared with the minimal p-value method and the sequence kernel association test. The results show that the HC approach is preferred for detecting weak genetic effects. PMID:25519367

  7. Flucytosine Pharmacokinetics in a Critically Ill Patient Receiving Continuous Renal Replacement Therapy.

    PubMed

    Kunka, Megan E; Cady, Elizabeth A; Woo, Heejung C; Thompson Bastin, Melissa L

    2015-01-01

    Purpose. A case report evaluating flucytosine dosing in a critically ill patient receiving continuous renal replacement therapy. Summary. This case report outlines an 81-year-old male who was receiving continuous venovenous hemofiltration (CVVH) for acute renal failure and was being treated with flucytosine for the treatment of disseminated Cryptococcus neoformans infection. Due to patient specific factors, flucytosine was empirically dose adjusted approximately 50% lower than intermittent hemodialysis (iHD) recommendations and approximately 33% lower than CRRT recommendations. Peak and trough levels were obtained, which were supratherapeutic, and pharmacokinetic parameters were calculated. The patient experienced thrombocytopenia, likely due to elevated flucytosine levels, and flucytosine was ultimately discontinued. Conclusion. Despite conservative flucytosine dosing for a patient receiving CVVH, peak and trough serum flucytosine levels were supratherapeutic (120 μg/mL at 2 hours and 81 μg/mL at 11.5 hours), which increased drug-related adverse effects. The results indicate that this conservative dosing regimen utilizing the patient's actual body weight was too aggressive. This case report provides insight into flucytosine dosing in CVVH, a topic that has not been investigated previously. Further pharmacokinetic studies of flucytosine dosing in critically ill patients receiving CVVH are needed in order to optimize pharmacokinetic and pharmacodynamic parameters while avoiding toxic flucytosine exposure.

  8. Challenging the One-Dose-Fits-All Model for Insulin in the Acute Treatment of Pediatric Diabetic Ketoacidosis. A Critical Appraisal of "Low-Dose Versus Standard-Dose Insulin in Pediatric Diabetic Ketoacidosis: A Randomized Clinical Trial" by Nallasamy et al (JAMA Pediatrics 2014; 168:999-1005).

    PubMed

    Orwoll, Benjamin Edward

    2016-10-01

    To review the findings and discuss the implications of the use of low-dose insulin infusions in pediatric diabetic ketoacidosis compared with standard-dose insulin. A search of the electronic PubMed database was used to perform the clinical query as well as to search for additional relevant literature. The article by Nallasamy K et al "Low-Dose vs Standard-Dose Insulin in Pediatric Diabetic Ketoacidosis: A Randomized Clinical Trial. JAMA Pediatrics 2014; 17:e477-e480" was selected for critical appraisal and literature review. The authors performed a randomized controlled trial among 50 consecutive patients of 0-12 years old presenting to the emergency department in diabetic ketoacidosis. They found that low-dose (0.05 U/kg/hr) insulin infusion was noninferior to standard-dose (0.1 U/kg/hr) insulin in terms of resolution of hyperglycemia and acidosis with a trend toward lower rates of therapy-related complications in the low-dose group. Low-dose insulin infusion is noninferior to standard-dose insulin in the treatment of younger pediatric patients with diabetic ketoacidosis and may lead to fewer therapy-related complications.

  9. Derivation of a no-significant-risk-level for tetrabromobisphenol A based on a threshold non-mutagenic cancer mode of action.

    PubMed

    Pecquet, Alison M; Martinez, Jeanelle M; Vincent, Melissa; Erraguntla, Neeraja; Dourson, Michael

    2018-06-01

    A no-significant-risk-level of 20 mg day -1 was derived for tetrabromobisphenol A (TBBPA). Uterine tumors (adenomas, adenocarcinomas, and malignant mixed Müllerian) observed in female Wistar Han rats from a National Toxicology Program 2-year cancer bioassay were identified as the critical effect. Studies suggest that TBBPA is acting through a non-mutagenic mode of action. Thus, the most appropriate approach to derivation of a cancer risk value based on US Environmental Protection Agency guidelines is a threshold approach, akin to a cancer safe dose (RfD cancer ). Using the National Toxicology Program data, we utilized Benchmark dose software to derive a benchmark dose lower limit (BMDL 10 ) as the point of departure (POD) of 103 mg kg -1  day -1 . The POD was adjusted to a human equivalent dose of 25.6 mg kg -1  day -1 using allometric scaling. We applied a composite adjustment factor of 100 to the POD to derive an RfD cancer of 0.26 mg kg -1  day -1 . Based on a human body weight of 70 kg, the RfD cancer was adjusted to a no-significant-risk-level of 20 mg day -1 . This was compared to other available non-cancer and cancer risk values, and aligns well with our understanding of the underlying biology based on the toxicology data. Overall, the weight of evidence from animal studies indicates that TBBPA has low toxicity and suggests that high doses over long exposure durations are needed to induce uterine tumor formation. Future research needs include a thorough and detailed vetting of the proposed adverse outcome pathway, including further support for key events leading to uterine tumor formation and a quantitative weight of evidence analysis. Copyright © 2018 John Wiley & Sons, Ltd.

  10. Effect of mixed pinning landscapes produced by 6 MeV oxygen irradiation on the resulting critical current densities Jc in 1.3 μm thick GdBa2Cu3O7-d coated conductors grown by co-evaporation

    NASA Astrophysics Data System (ADS)

    Haberkorn, N.; Suárez, S.; Pérez, P. D.; Troiani, H.; Granell, P.; Golmar, F.; Lee, Jae-Hun; Moon, S. H.

    2017-11-01

    We report the influence of crystalline defects introduced by 6 MeV 16O3+ irradiation on the critical current densities Jc and flux creep rates in 1.3 μm thick GdBa2Cu3O7-δ coated conductor produced by co-evaporation. Pristine films with pinning produced mainly by random nanoparticles with diameter close to 50 nm were irradiated with doses between 2 × 1013 cm-2 and 4 × 1014 cm-2. The irradiations were performed with the ion beam perpendicular to the surface of the samples. The Jc and the flux creep rates were analyzed for two magnetic field configurations: magnetic field applied parallel (H║c) and at 45° (H║45°) to the c-axis. The results show that at temperatures below 40 K the in-field Jc dependences can be significantly improved by irradiation. For doses of 1 × 1014 cm-2 the Jc values at μ0H = 5 T are doubled without affecting significantly the Jc at small fields. Analyzing the flux creep rates as function of the temperature in both magnetic field configurations, it can be observed that the irradiation suppresses the peak associated with double-kink relaxation and increases the flux creep rates at intermediate and high temperatures. Under 0.5 T, the flux relaxation for H‖c and H||45° in pristine films presents characteristic glassy exponents μ = 1.63 and μ = 1.45, respectively. For samples irradiated with 1 × 1014 cm-2, these values drop to μ = 1.45 and μ = 1.24, respectively

  11. Entrance radiation doses during paediatric cardiac catheterisations performed for diagnosis or the treatment of congenital heart disease.

    PubMed

    Papadopoulou, D; Yakoumakis, Em; Sandilos, P; Thanopoulos, V; Makri, Tr; Gialousis, G; Houndas, D; Yakoumakis, N; Georgiou, Ev

    2005-01-01

    The purpose of this study was to estimate the radiation exposure of children, during cardiac catheterisations for the diagnosis or treatment of congenital heart disease. Radiation doses were estimated for 45 children aged from 1 d to 13 y old. Thermoluminescent dosemeters (TLDs) were used to estimate the posterior entrance dose (DP), the lateral entrance dose (DLAT), the thyroid dose and the gonads dose. A dose-area product (DAP) meter was also attached externally to the tube of the angiographic system and gave a direct value in mGy cm2 for each procedure. Posterior and lateral entrance dose values during cardiac catheterisations ranged from 1 to 197 mGy and from 1.1 to 250.3 mGy, respectively. Radiation exposure to the thyroid and the gonads ranged from 0.3 to 8.4 mGy to 0.1 and 0.7 mGy, respectively. Finally, the DAP meter values ranged between 360 and 33,200 mGy cm2. Radiation doses measured in this study are comparable with those reported to previous studies. Moreover, strong correlation was found between the DAP values and the entrance radiation dose measured with TLDs.

  12. Analysis of the characteristics and management of critical values in a newborn tertiary center in China.

    PubMed

    Wang, Zheng-Li; Du, Li-Zhong; Chen, Yi-Yu; Li, Lu-Quan; Lu, Qi; Liu, Ying; Cao, Lu-Ying; He, Yu; Yu, Jia-Lin

    2017-02-01

    Critical value reporting has been widely adopted by hospitals throughout the world, but there were few reports about neonatal critical values. This study aimed to analyze characteristics of the neonatal critical values considered at our center and to provide information on improving neonatal intensive care. A retrospective study of critical values at a newborn tertiary center in China was conducted to assess neonatal critical values according to test, distribution, reporting time, patient outcome and the impact to the therapy. In total, 926 critical values were recorded. Overall, 66.52% (616/926) of the items were reported within 24 hours of admission, 50.28% (465/926) during duty times and 54.75% (507/926) in the neonatal intensive care unit (NICU). The routine coagulation test was the most frequent source of critical values. Electrocardiography, blood gas analysis and therapeutic drug monitoring of drug levels were associated with the highest rates of treatment intervention (100%); routine coagulation tests were the lowest (23.14%). Sample quality was the main cause of false-positive critical values. The incidence of neonatal critical values peaked during the first 24 hours post-admission and during duty periods. Each newborn center needs to enact rapid treatment guidelines to address common critical values in order to facilitate clinical interventions. Periodically reviewing critical values could help to optimize clinical practices.

  13. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Demirag, N

    Purpose: To verify the benefits of the biological cost functions. Methods: TG166 patients were used for the test case scenarios. Patients were planned using Monaco V5.0 (CMS/Elekta, St.Louis, MO) Monaco has 3 biological and 8 physical CFs. In this study the plans were optimized using 3 different scenarios. 1- Biological CFs only 2-Physical CFs only 3- Combination of Physical and Biological CFsMonaco has 3 biological CFs. Target EUD used for the targets, derived from the poisson cell kill model, has an α value that controls the cold spots inside the target. α values used in the optimization were 0.5 andmore » 0.8. if cold spots needs to be penalized α value increased. Serial CF: it's called serial to mimic the behaviour of the serial organs, if a high k value like 12 or 14 is used it controls the maximum dose. Serial CF has a k parameter that is used to shape the whole dvh curve. K value ranges between 1–20. k:1 is used to control the mean dose, lower k value controls the mean dose, higher k value controls the higher dose, using 2 serial CFs with different k values controls the whole DVH. Paralel CF controls the percentage of the volume that tolerates higher doses than the reference dose to mimic the behaviour of the paralel organs. Results: It was possible to achive clinically accepted plans in all 3 scenarios. The benefit of the biological cost functions were to control the mean dose for target and OAR, to shape the DVH curve using one EUD value and one k value simplifies the optimization process. Using the biological CFs alone, it was hard to control the dose at a point. Conclusion: Biological CFs in Monaco doesn't require the ntcp/tcp values from the labs and useful to shape the whole dvh curve. I work as an applications support specialist for Elekta and I am a Ph.D. Student in Istanbul University for radiation therapy physics.« less

  14. Do Intermediate Radiation Doses Contribute to Late Rectal Toxicity? An Analysis of Data From Radiation Therapy Oncology Group Protocol 94-06

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tucker, Susan L., E-mail: sltucker@mdanderson.org; Dong, Lei; Michalski, Jeff M.

    2012-10-01

    Purpose: To investigate whether the volumes of rectum exposed to intermediate doses, from 30 to 50 Gy, contribute to the risk of Grade {>=}2 late rectal toxicity among patients with prostate cancer receiving radiotherapy. Methods and Materials: Data from 1009 patients treated on Radiation Therapy Oncology Group protocol 94-06 were analyzed using three approaches. First, the contribution of intermediate doses to a previously published fit of the Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) model was determined. Next, the extent to which intermediate doses provide additional risk information, after taking the LKB model into account, was investigated. Third, the proportionmore » of rectum receiving doses higher than a threshold, VDose, was computed for doses ranging from 5 to 85 Gy, and a multivariate Cox proportional hazards model was used to determine which of these parameters were significantly associated with time to Grade {>=}2 late rectal toxicity. Results: Doses <60 Gy had no detectable impact on the fit of the LKB model, as expected on the basis of the small estimate of the volume parameter (n = 0.077). Furthermore, there was no detectable difference in late rectal toxicity among cohorts with similar risk estimates from the LKB model but with different volumes of rectum exposed to intermediate doses. The multivariate Cox proportional hazards model selected V75 as the only value of VDose significantly associated with late rectal toxicity. Conclusions: There is no evidence from these data that intermediate doses influence the risk of Grade {>=}2 late rectal toxicity. Instead, the critical doses for this endpoint seem to be {>=}75 Gy. It is hypothesized that cases of Grade {>=}2 late rectal toxicity occurring among patients with V75 less than approximately 12% may be due to a 'background' level of risk, likely due mainly to biological factors.« less

  15. Transfer of environmental plutonium and americium across the human gut.

    PubMed

    Hunt, G J; Leonard, D R; Lovett, M B

    1986-08-01

    Data on gut transfer factors for environmental forms of radionuclides are essential for estimates of public radiation exposures following ingestion, and thus in decisions on controlling waste discharges. Dose estimates for transuranic nuclides are particularly sensitive to uncertainties stemming from gut transfer data being related to non-environmental forms and/or derived from animal experiments. We have measured human gut transfer factors for plutonium and americium in two experiments using marine foods obtained near Sellafield, Cumbria. Firstly, the urine of volunteer members of the critical group of shellfish consumers was analysed for transuranics and the results related to their consumption rates. Secondly, remotely-based volunteers ate single quantities of shellfish obtained near Sellafield, and their urine was analysed. An overall result for the gut transfer factor for environmental plutonium of 0.8 X 10(-4) indicates no need to increase the value of 1 X 10(-4), currently used by the International Commission on Radiological Protection (ICRP) for soluble forms. Results for americium show that the ICRP value of 5 X 10(-4) is maximising, and that a value of 1 X 10(-4) would be supportable. The results from the study of critical group members provide confidence in our habits survey techniques and reassurance that there are no significant pathways for intake of transuranics by these people that have not been recognised.

  16. Reduced lung dose during radiotherapy for thoracic esophageal carcinoma: VMAT combined with active breathing control for moderate DIBH.

    PubMed

    Gong, Guanzhong; Wang, Ruozheng; Guo, Yujie; Zhai, Deyin; Liu, Tonghai; Lu, Jie; Chen, Jinhu; Liu, Chengxin; Yin, Yong

    2013-12-20

    Lung radiation injury is a critical complication of radiotherapy (RT) for thoracic esophageal carcinoma (EC). Therefore, the goal of this study was to investigate the feasibility and dosimetric effects of reducing the lung tissue irradiation dose during RT for thoracic EC by applying volumetric modulated arc radiotherapy (VMAT) combined with active breathing control (ABC) for moderate deep inspiration breath-hold (mDIBH). Fifteen patients with thoracic EC were randomly selected to undergo two series of computed tomography (CT) simulation scans with ABC used to achieve mDIBH (representing 80% of peak DIBH value) versus free breathing (FB). Gross tumor volumes were contoured on different CT images, and planning target volumes (PTVs) were obtained using different margins. For PTV-FB, intensity-modulated radiotherapy (IMRT) was designed with seven fields, and VMAT included two whole arcs. For PTV-DIBH, VMAT with three 135° arcs was applied, and the corresponding plans were named: IMRT-FB, VMAT-FB, and VMAT-DIBH, respectively. Dosimetric differences between the different plans were compared. The heart volumes decreased by 19.85%, while total lung volume increased by 52.54% in mDIBH, compared to FB (p < 0.05). The mean conformality index values and homogeneity index values for VMAT-DIBH (0.86, 1.07) were slightly worse than those for IMRT-FB (0.90, 1.05) and VMAT-FB (0.90, 1.06) (p > 0.05). Furthermore, compared to IMRT-FB and VMAT-FB, VMAT-DIBH reduced the mean total lung dose by 18.64% and 17.84%, respectively (p < 0.05); moreover, the V5, V10, V20, and V30 values for IMRT-FB and VMAT-FB were reduced by 10.84% and 10.65% (p > 0.05), 12.5% and 20% (p < 0.05), 30.77% and 33.33% (p < 0.05), and 50.33% and 49.15% (p < 0.05), respectively. However, the heart dose-volume indices were similar between VMAT-DIBH and VMAT-FB which were lower than IMRT-FB without being statistically significant (p > 0.05). The monitor units and treatment time of VMAT-DIBH were also the lowest (p < 0.05). VMAT combined with ABC to achieve mDIBH is a feasible approach for RT of thoracic EC. Furthermore, this method has the potential to effectively reduce lung dose in a shorter treatment time and with better targeting accuracy.

  17. Gamma irradiator dose mapping simulation using the MCNP code and benchmarking with dosimetry.

    PubMed

    Sohrabpour, M; Hassanzadeh, M; Shahriari, M; Sharifzadeh, M

    2002-10-01

    The Monte Carlo transport code, MCNP, has been applied in simulating dose rate distribution in the IR-136 gamma irradiator system. Isodose curves, cumulative dose values, and system design data such as throughputs, over-dose-ratios, and efficiencies have been simulated as functions of product density. Simulated isodose curves, and cumulative dose values were compared with dosimetry values obtained using polymethyle-methacrylate, Fricke, ethanol-chlorobenzene, and potassium dichromate dosimeters. The produced system design data were also found to agree quite favorably with those of the system manufacturer's data. MCNP has thus been found to be an effective transport code for handling of various dose mapping excercises for gamma irradiators.

  18. SU-E-J-85: Leave-One-Out Perturbation (LOOP) Fitting Algorithm for Absolute Dose Film Calibration

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chu, A; Ahmad, M; Chen, Z

    2014-06-01

    Purpose: To introduce an outliers-recognition fitting routine for film dosimetry. It cannot only be flexible with any linear and non-linear regression but also can provide information for the minimal number of sampling points, critical sampling distributions and evaluating analytical functions for absolute film-dose calibration. Methods: The technique, leave-one-out (LOO) cross validation, is often used for statistical analyses on model performance. We used LOO analyses with perturbed bootstrap fitting called leave-one-out perturbation (LOOP) for film-dose calibration . Given a threshold, the LOO process detects unfit points (“outliers”) compared to other cohorts, and a bootstrap fitting process follows to seek any possibilitiesmore » of using perturbations for further improvement. After that outliers were reconfirmed by a traditional t-test statistics and eliminated, then another LOOP feedback resulted in the final. An over-sampled film-dose- calibration dataset was collected as a reference (dose range: 0-800cGy), and various simulated conditions for outliers and sampling distributions were derived from the reference. Comparisons over the various conditions were made, and the performance of fitting functions, polynomial and rational functions, were evaluated. Results: (1) LOOP can prove its sensitive outlier-recognition by its statistical correlation to an exceptional better goodness-of-fit as outliers being left-out. (2) With sufficient statistical information, the LOOP can correct outliers under some low-sampling conditions that other “robust fits”, e.g. Least Absolute Residuals, cannot. (3) Complete cross-validated analyses of LOOP indicate that the function of rational type demonstrates a much superior performance compared to the polynomial. Even with 5 data points including one outlier, using LOOP with rational function can restore more than a 95% value back to its reference values, while the polynomial fitting completely failed under the same conditions. Conclusion: LOOP can cooperate with any fitting routine functioning as a “robust fit”. In addition, it can be set as a benchmark for film-dose calibration fitting performance.« less

  19. Controlled Administration of Penicillamine Reduces Radiation Exposure in Critical Organs during 64Cu-ATSM Internal Radiotherapy: A Novel Strategy for Liver Protection

    PubMed Central

    Yoshii, Yukie; Matsumoto, Hiroki; Yoshimoto, Mitsuyoshi; Furukawa, Takako; Morokoshi, Yukie; Sogawa, Chizuru; Zhang, Ming-Rong; Wakizaka, Hidekatsu; Yoshii, Hiroshi; Fujibayashi, Yasuhisa; Saga, Tsuneo

    2014-01-01

    Purpose 64Cu-diacetyl-bis (N 4-methylthiosemicarbazone) (64Cu-ATSM) is a promising theranostic agent that targets hypoxic regions in tumors related to malignant characteristics. Its diagnostic usefulness has been recognized in clinical studies. Internal radiotherapy (IRT) with 64Cu-ATSM is reportedly effective in preclinical studies; however, for clinical applications, improvements to reduce radiation exposure in non-target organs, particularly the liver, are required. We developed a strategy to reduce radiation doses to critical organs while preserving tumor radiation doses by controlled administration of copper chelator penicillamine during 64Cu-ATSM IRT. Methods Biodistribution was evaluated in HT-29 tumor-bearing mice injected with 64Cu-ATSM (185 kBq) with or without oral penicillamine administration. The appropriate injection interval between 64Cu-ATSM and penicillamine was determined. Then, the optimal penicillamine administration schedule was selected from single (100, 300, and 500 mg/kg) and fractionated doses (100 mg/kg×3 at 1- or 2-h intervals from 1 h after 64Cu-ATSM injection). PET imaging was performed to confirm the effect of penicillamine with a therapeutic 64Cu-ATSM dose (37 MBq). Dosimetry analysis was performed to estimate human absorbed doses. Results Penicillamine reduced 64Cu accumulation in the liver and small intestine. Tumor uptake was not affected by penicillamine administration at 1 h after 64Cu-ATSM injection, when radioactivity was almost cleared from the blood and tumor uptake had plateaued. Of the single doses, 300 mg/kg was most effective. Fractionated administration at 2-h intervals further decreased liver accumulation at later time points. PET indicated that penicillamine acts similarly with the therapeutic 64Cu-ATSM dose. Dosimetry demonstrated that appropriately scheduled penicillamine administration reduced radiation doses to critical organs (liver, ovaries, and red marrow) below tolerance levels. Laxatives reduced radiation doses to the large intestine. Conclusions We developed a novel strategy to reduce radiation exposure in critical organs during 64Cu-ATSM IRT, thus promoting its clinical applications. This method could be beneficial for other 64Cu-labeled compounds. PMID:24466309

  20. Declines in Outpatient Antimicrobial Use in Canada (1995–2010)

    PubMed Central

    Finley, Rita; Glass-Kaastra, Shiona K.; Hutchinson, Jim; Patrick, David M.; Weiss, Karl; Conly, John

    2013-01-01

    Background With rising reports of antimicrobial resistance in outpatient communities, surveillance of antimicrobial use is imperative for supporting stewardship programs. The primary objective of this article is to assess the levels of antimicrobial use in Canada over time. Methods Canadian antimicrobial use data from 1995 to 2010 were acquired and assessed by four metrics: population-adjusted prescriptions, Defined Daily Doses, spending on antimicrobials (inflation-adjusted), and average Defined Daily Doses per prescription. Linear mixed models were built to assess significant differences among years and antimicrobial groups, and to account for repeated measurements over time. Measures were also compared to published reports from European countries. Results Temporal trends in antimicrobial use in Canada vary by metric and antimicrobial grouping. Overall reductions were seen for inflation-adjusted spending, population-adjusted prescription rates and Defined Daily Doses, and increases were observed for the average number of Defined Daily Doses per prescription. The population-adjusted prescription and Defined Daily Doses values for 2009 were comparable to those reported by many European countries, while the average Defined Daily Dose per prescription for Canada ranked high. A significant reduction in the use of broad spectrum penicillins occurred between 1995 and 2004, coupled with increases in macrolide and quinolone use, suggesting that replacement of antimicrobial drugs may occur as new products arrive on the market. Conclusions There have been modest decreases of antimicrobial use in Canada over the past 15 years. However, continued surveillance of antimicrobial use coupled with data detailing antimicrobial resistance within bacterial pathogens affecting human populations is critical for targeting interventions and maintaining the effectiveness of these products for future generations. PMID:24146863

  1. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hobbs, R; Le, Y; Armour, E

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

  2. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tobler, Matt; Watson, Gordon; Leavitt, Dennis

    Radiotherapy plays a key role in the definitive or adjuvant management of patients with mesothelioma of the pleural surface. Many patients are referred for radiation with intact lung following biopsy or subtotal pleurectomy. Delivery of efficacious doses of radiation to the pleural lining while avoiding lung parenchyma toxicity has been a difficult technical challenge. Using opposed photon fields produce doses in lung that result in moderate-to-severe pulmonary toxicity in 100% of patients treated. Combined photon-electron beam treatment, at total doses of 4250 cGy to the pleural surface, results in two-thirds of the lung volume receiving over 2100 cGy. We havemore » developed a technique using intensity-modulated photon arc therapy (IMRT) that significantly improves the dose distribution to the pleural surface with concomitant decrease in dose to lung parenchyma compared to traditional techniques. IMRT treatment of the pleural lining consists of segments of photon arcs that can be intensity modulated with varying beam weights and multileaf positions to produce a more uniform distribution to the pleural surface, while at the same time reducing the overall dose to the lung itself. Computed tomography (CT) simulation is critical for precise identification of target volumes as well as critical normal structures (lung and heart). Rotational arc trajectories and individual leaf positions and weightings are then defined for each CT plane within the patient. This paper will describe the proposed rotational IMRT technique and, using simulated isodose distributions, show the improved potential for sparing of dose to the critical structures of the lung, heart, and spinal cord.« less

  3. Role of particle radiotherapy in the management of head and neck cancer.

    PubMed

    Laramore, George E

    2009-05-01

    Modern imaging techniques and powerful computers allow a radiation oncologist to design treatments delivering higher doses of radiation than previously possible. Dose distributions imposed by the physics of 'standard' photon and electron beams limit further dose escalation. Hadron radiotherapy offers advantages in either dose distribution and/or improved radiobiology that may significantly improve the treatment of certain head and neck malignancies. Clinical studies support the effectiveness of fast-neutron radiotherapy in the treatment of major and minor salivary gland tumors. Data show highly favorable outcomes with proton radiotherapy for skull-base malignancies and tumors near highly critical normal tissues compared with that expected with standard radiotherapy. Heavy-ion radiotherapy clinical studies are mainly being conducted with fully stripped carbon ions, and limited data seem to indicate a possible improvement over proton radiotherapy for the same subset of radioresistant tumors where neutrons show a benefit over photons. Fast-neutron radiotherapy has different radiobiological properties compared with standard radiotherapy but similar depth dose distributions. Its role in the treatment of head and neck cancer is currently limited to salivary gland malignancies and certain radioresistant tumors such as sarcomas. Protons have the same radiobiological properties as standard radiotherapy beams but more optimal depth dose distributions, making it particularly advantageous when treating tumors adjacent to highly critical structures. Heavy ions combine the radiobiological properties of fast neutrons with the physical dose distributions of protons, and preliminary data indicate their utility for radioresistant tumors adjacent to highly critical structures.

  4. Gamma-ray spectra and doses from the Little Boy replica

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moss, C.E.; Lucas, M.C.; Tisinger, E.W.

    1984-01-01

    Most radiation safety guidelines in the nuclear industry are based on the data concerning the survivors of the nuclear explosions at Hiroshima and Nagasaki. Crucial to determining these guidelines is the radiation from the explosions. We have measured gamma-ray pulse-height distributions from an accurate replica of the Little Boy device used at Hiroshima, operated at low power levels near critical. The device was placed outdoors on a stand 4 m from the ground to minimize environmental effects. The power levels were based on a monitor detector calibrated very carefully in independent experiments. High-resolution pulse-height distributions were acquired with a germaniummore » detector to identify the lines and to obtain line intensities. The 7631 to 7645 keV doublet from neutron capture in the heavy steel case was dominant. Low-resolution pulse-height distributions were acquired with bismuth-germanate detectors. We calculated flux spectra from these distributions using accurately measured detector response functions and efficiency curves. We then calculated dose-rate spectra from the flux spectra using a flux-to-dose-rate conversion procedure. The integral of each dose-rate spectrum gave an integral dose rate. The integral doses at 2 m ranged from 0.46 to 1.03 mrem per 10/sup 13/ fissions. The output of the Little Boy replica can be calculated with Monte Carlo codes. Comparison of our experimental spectra, line intensities, and integral doses can be used to verify these calculations at low power levels and give increased confidence to the calculated values from the explosion at Hiroshima. These calculations then can be used to establish better radiation safety guidelines. 7 references, 7 figures, 2 tables.« less

  5. Dosimetric comparison of IMRT rectal and anal canal plans generated using an anterior dose avoidance structure

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Leicher, Brian, E-mail: bleicher@wpahs.org; Day, Ellen; Colonias, Athanasios

    2014-10-01

    To describe a dosimetric method using an anterior dose avoidance structure (ADAS) during the treatment planning process for intensity-modulated radiation therapy (IMRT) for patients with anal canal and rectal carcinomas. A total of 20 patients were planned on the Elekta/CMS XiO treatment planning system, version 4.5.1 (Maryland Heights MO) with a superposition algorithm. For each patient, 2 plans were created: one employing an ADAS (ADAS plan) and the other replanned without an ADAS (non-ADAS plan). The ADAS was defined to occupy the volume between the inguinal nodes and primary target providing a single organ at risk that is completely outsidemore » of the target volume. Each plan used the same beam parameters and was analyzed by comparing target coverage, overall plan dose conformity using a conformity number (CN) equation, bowel dose-volume histograms, and the number of segments, daily treatment duration, and global maximum dose. The ADAS and non-ADAS plans were equivalent in target coverage, mean global maximum dose, and sparing of small bowel in low-dose regions (5, 10, 15, and 20 Gy). The mean difference between the CN value for the non-ADAS plans and ADAS plans was 0.04 ± 0.03 (p < 0.001). The mean difference in the number of segments was 15.7 ± 12.7 (p < 0.001) in favor of ADAS plans. The ADAS plan delivery time was shorter by 2.0 ± 1.5 minutes (p < 0.001) than the non-ADAS one. The ADAS has proven to be a powerful tool when planning rectal and anal canal IMRT cases with critical structures partially contained inside the target volume.« less

  6. A revised probabilistic estimate of the maternal methyl mercury intake dose corresponding to a measured cord blood mercury concentration.

    PubMed

    Stern, Alan H

    2005-02-01

    In 2001, the U.S. Environmental Protection Agency (EPA) adopted a revised reference dose (RfD) for methyl mercury (MeHg) of 0.1 microg/kg/day. The RfD is based on neurologic developmental effects measured in children associated with exposure in utero to MeHg from the maternal diet. The RfD derivation proceeded from a point of departure based on measured concentration of mercury in fetal cord blood (micrograms per liter). The RfD, however, is a maternal dose (micrograms per kilogram per day). Reconstruction of the maternal dose corresponding to this cord blood concentration, including the variability around this estimate, is a critical step in the RfD derivation. The dose reconstruction employed by the U.S. EPA using the one-compartment pharmacokinetic model contains two areas of significant uncertainty: It does not directly account for the influence of the ratio of cord blood: maternal blood Hg concentration, and it does not resolve uncertainty regarding the most appropriate central tendency estimates for pregnancy and third-trimester-specific model parameters. A probabilistic reassessment of this dose reconstruction was undertaken to address these areas of uncertainty and generally to reconsider the specification of model input parameters. On the basis of a thorough review of the literature and recalculation of the one-compartment model including sensitivity analyses, I estimated that the 95th and 99th percentiles (i.e., the lower 5th and 1st percentiles) of the maternal intake dose corresponding to a fetal cord blood Hg concentration of 58 microg/L are 0.3 and 0.2 microg/kg/day, respectively. For the 99th percentile, this is half the value previously estimated by the U.S. EPA.

  7. Minimizing human error in radiopharmaceutical preparation and administration via a bar code-enhanced nuclear pharmacy management system.

    PubMed

    Hakala, John L; Hung, Joseph C; Mosman, Elton A

    2012-09-01

    The objective of this project was to ensure correct radiopharmaceutical administration through the use of a bar code system that links patient and drug profiles with on-site information management systems. This new combined system would minimize the amount of manual human manipulation, which has proven to be a primary source of error. The most common reason for dosing errors is improper patient identification when a dose is obtained from the nuclear pharmacy or when a dose is administered. A standardized electronic transfer of information from radiopharmaceutical preparation to injection will further reduce the risk of misadministration. Value stream maps showing the flow of the patient dose information, as well as potential points of human error, were developed. Next, a future-state map was created that included proposed corrections for the most common critical sites of error. Transitioning the current process to the future state will require solutions that address these sites. To optimize the future-state process, a bar code system that links the on-site radiology management system with the nuclear pharmacy management system was proposed. A bar-coded wristband connects the patient directly to the electronic information systems. The bar code-enhanced process linking the patient dose with the electronic information reduces the number of crucial points for human error and provides a framework to ensure that the prepared dose reaches the correct patient. Although the proposed flowchart is designed for a site with an in-house central nuclear pharmacy, much of the framework could be applied by nuclear medicine facilities using unit doses. An electronic connection between information management systems to allow the tracking of a radiopharmaceutical from preparation to administration can be a useful tool in preventing the mistakes that are an unfortunate reality for any facility.

  8. Biokinetics and dosimetric studies about 99mTc(V)-DMSA distribution.

    PubMed

    Correia, M B L; Magnata, S S L P; Silva, I M S; Catanho, M T J A; Lima, F F

    2010-05-10

    Research for radiodiagnostic agents should considerate biological critical parameters which will give own contribution on the absorbed dose. The dimercaptosuccinic acid (DMSA) labeled with (99m)Tc(V) is a radiopharmaceutical which has well established role in medullar thyroid carcinoma and has been proposed in evaluation of bone metastasis. This work studied the biokinetics and dosimetry of (99m)Tc(V)-DMSA by animal model. The (99m)Tc(V)-DMSA was prepared from a (III)DMSA kit alkalized. Mice (n=5) received (99m)Tc(V)DMSA i.v., they were sacrificed (30 min, 1h, 5h and 12h), the organs excised and the activities measured by a gamma counter. The results were evaluated based on %activity/g and the absorbed dose was estimated (MIRDOSE 3.0 program) by extrapolation of data from animal to human scale. The results showed the majority of organs reached the top uptake at 30 min, the greatest kidney uptake was (4.81 +/- 1.38)% activity/g, while the bone presented its highest uptake at 1h (5.49+/- 0.47)% activity/g, after 1h all the organs had activity exponential decrease. The biokinetic profile of (99m)Tc(V)-DMSA was well established, allowing quantifying of residence time, and the radiation dose estimates were made for this agent. About the absorbed dose, the preliminary results showed higher value to bone, being the soft tissue dose relatively low.

  9. DOSE-DEPENDENT TRANSITIONS IN MECHANISMS OF TOXICITY: CASE STUDIES

    EPA Science Inventory

    Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed ...

  10. In vivo dosimetry using a linear Mosfet-array dosimeter to determine the urethra dose in 125I permanent prostate implants.

    PubMed

    Bloemen-van Gurp, Esther J; Murrer, Lars H P; Haanstra, Björk K C; van Gils, Francis C J M; Dekker, Andre L A J; Mijnheer, Ben J; Lambin, Philippe

    2009-01-01

    In vivo dosimetry during brachytherapy of the prostate with (125)I seeds is challenging because of the high dose gradients and low photon energies involved. We present the results of a study using metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to evaluate the dose in the urethra after a permanent prostate implantation procedure. Phantom measurements were made to validate the measurement technique, determine the measurement accuracy, and define action levels for clinical measurements. Patient measurements were performed with a MOSFET array in the urinary catheter immediately after the implantation procedure. A CT scan was performed, and dose values, calculated by the treatment planning system, were compared to in vivo dose values measured with MOSFET dosimeters. Corrections for temperature dependence of the MOSFET array response and photon attenuation in the catheter on the in vivo dose values are necessary. The overall uncertainty in the measurement procedure, determined in a simulation experiment, is 8.0% (1 SD). In vivo dose values were obtained for 17 patients. In the high-dose region (> 100 Gy), calculated and measured dose values agreed within 1.7% +/- 10.7% (1 SD). In the low-dose region outside the prostate (< 100 Gy), larger deviations occurred. MOSFET detectors are suitable for in vivo dosimetry during (125)I brachytherapy of prostate cancer. An action level of +/- 16% (2 SD) for detection of errors in the implantation procedure is achievable after validation of the detector system and measurement conditions.

  11. IMRT vs. 3D Noncoplanar Treatment Plans for Maxillary Sinus Tumors: A New Tool for Quantitative Evaluation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Levin, Daphne; Menhel, Janna; Alezra, Dror

    2008-01-01

    We compared 9-field, equispaced intensity modulated radiation therapy (IMRT), 4- to 5-field, directionally optimized IMRT, and 3-dimensional (3D) noncoplanar planning approaches for tumors of the maxillary sinus. Ten patients were planned retrospectively to compare the different treatment techniques. Prescription doses were 60 to 70 Gy. Critical structures contoured included optic nerves and chiasm, lacrimal glands, lenses, and retinas. As an aid for plan assessment, we introduced a new tool: Critical Organ Scoring Index (COSI), which allows quantitative evaluation of the tradeoffs between target coverage and critical organ sparing. This index was compared with other, commonly used conformity indices. For amore » reliable assessment of both tumor coverage and dose to critical organs in the different planning techniques, we introduced a 2D, graphical representation of COSI vs. conformity index (CI). Dose-volume histograms and mean, maximum, and minimum organ doses were also compared. IMRT plans delivered lower doses to ipsilateral structures, but were unable to spare them. 3D plans delivered less dose to contralateral structures, and were more homogeneous, as well. Both IMRT approaches gave similar results. In cases where choice of optimal plan was difficult, the novel 2D COSI-CI representation gave an accurate picture of the tradeoffs between target coverage and organ sparing, even in cases where other conformity indices failed. Due to their unique anatomy, maxillary sinus tumors may benefit more from a noncoplanar approach than from IMRT. The new graphical representation proposed is a quick, visual, reliable tool, which may facilitate the physician's choice of best treatment plan for a given patient.« less

  12. PNNL Measurement Results for the 2016 Criticality Accident Dosimetry Exercise at the Nevada National Security Stite (IER-148)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rathbone, Bruce A.; Morley, Shannon M.; Stephens, John A.

    The Pacific Northwest National Laboratory (PNNL) participated in a criticality accident dosimetry intercomparison exercise held at the Nevada National Security Site (NNSS) May 24-27, 2016. The exercise was administered by Lawrence Livermore National Laboratory (LLNL) and consisted of three exposures performed using the Godiva-IV critical assembly housed in the Device Assembly Facility (DAF) located on the NNSS site. The exercise allowed participants to test the ability of their nuclear accident dosimeters to meet the performance criteria in ANSI/HPS N13.3-2013, Dosimetry for Criticality Accidents and to obtain new measurement data for use in revising dose calculation methods and quick sort screeningmore » methods where appropriate. PNNL participated with new prototype Personal Nuclear Accident Dosimeter (PNAD) and Fixed Nuclear Accident Dosimeter (FNAD) designs as well as the existing historical PNAD design. The new prototype designs incorporate optically stimulated luminescence (OSL) dosimeters in place of thermoluminescence dosimeters (TLDs), among other design changes, while retaining the same set of activation foils historically used. The default dose calculation methodology established decades ago for use with activation foils in PNNL PNADs and FNADs was used to calculate neutron dose results for both the existing and prototype dosimeters tested in the exercise. The results indicate that the effective cross sections and/or dose conversion factors used historically need to be updated to accurately measure the operational quantities recommended for nuclear accident dosimetry in ANSI/HPS N13.3-2013 and to ensure PNAD and FNAD performance meets the ANSI/HPS N13.3-2013 performance criteria. The operational quantities recommended for nuclear accident dosimetry are personal absorbed dose, Dp(10), and ambient absorbed dose, D*(10).« less

  13. Radiation doses to critical groups since the early 1950s due to discharges of liquid radioactive waste from Sellafield.

    PubMed

    Hunt, G J

    1997-04-01

    First, some of the early work is reviewed on exposure pathways in connection with proposed and early liquid radioactive waste discharges from Sellafield. The main historical features of these discharges, affected by relevant plant operations, are then briefly described. The important radiological exposure pathways resulting from the discharges and people's consumption and occupancy habits are considered. To place the changing scenario onto a consistent basis using present-day methodology, a reconstruction of exposures has been carried out using environmental monitoring data and models. The three major pathways are examined of Porphyra/laverbread consumption in South Wales, fish and shellfish consumption near Sellafield, and external exposure over local and more distant sediments. The results show that over the period 1952 to about 1970 the laverbread pathway was probably critical, taking a cautious approach. Effective dose rates fluctuated at around 1 mSv y(-1) from about 1956 to 1971. From about 1970 to 1985, the fish and shellfish pathway was likely to have been critical, with effective dose rates peaking at about 2 mSv y(-1) in 1975-1976. External exposure was likely to have been of lesser importance than the other two pathways until about 1985, when with the retention of previously-released radiocesium on sediments it has become dominant. This phenomenon applies particularly further afield where radiocesium concentrations have been slower to decline; in the Ribble estuary, houseboat dwellers have been the critical group from about 1985. Effective doses have been at about 0.3 mSv y(-1) and declining; they are due to the effects of radiocesium discharges in earlier years. Dose rates have remained within contemporary ICRP dose limits.

  14. INTERNAL RADIATION DOSE MEASUREMENTS IN LIVE EXPERIMENTAL ANIMALS. PART II

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nold, M.M.; Hayes, R.L.; Comar, C.L.

    1960-12-01

    Silver phosphate glass dosimeter rods were implanted in various portions of the digestive tract and the radiation dose was measured after ingestion of a known amount of Y/sup 90/. It was found that a state of diarrhea reduced the average radiation dose by a factor of from 2 to 4. In the constipated animal the dose was increased by a factor of from 3 to 7. Investigation was made to determine the role of various processes governing the radiation dose delivered to gastrointestinal mucosa. The total dose to a particular site along the intestinal tract was obtained by determination ofmore » the time integral of the radioactive concentration. Serial sacrifices were made at specific times after administration of the radioactivity. Calculations in this manner agreed exceptionally well with the doses that were measured by the glass dosimeter method. It is estimated that 4 and 17 - c of Y/sup 90/ for the dog and goat, respectively, will deliver a 300mrad dose to the critical organ, the lower large intestine. The twelve-fold average difference in dose between the diarrhea and constipation groups of dogs emphasizes the importance of the physical state of bowel passages upon the dose delivered to the critical organ. (auth)« less

  15. Studies on the physicochemical characteristics of oil extracted from gamma irradiated pistachio (Pistacia vera L.).

    PubMed

    Al-Bachir, Mahfouz

    2015-01-15

    The present study evaluated the quality of pistachio oil, as a function of irradiation, to determine the dose level causing undesirable changes to pistachio oil. Physicochemical fatty acid composition, acidity value, peroxide value, iodine value specification number, thiobarbituric acid (TBA) value and colour of pistachio oil extracted from samples treated with 0, 1, 2 and 3 kGy doses of gamma irradiation were determined. Gamma irradiation caused the alteration of fatty acids of pistachio oil which showed a decrease in oleic acid (C18:1) and an increase in linoleic acid (C18:2). All other fatty acids remained unaffected after irradiation. The higher used doses (2 and 3 kGy) decreased acidity value, peroxide value and iodine value, and increased specification number, with no effect on TBA value. Irradiation had a significant effect on colour values of pistachio oil. Parameters L, a and b increased at doses of 1 and 2 kGy. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Value of public health and safety actions and radiation dose avoided

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Baum, J.W.

    1994-05-01

    The values judged best to reflect the willingness of society to pay for the avoidance or reduction of risk were deduced from studies of costs of health care, transportation safety, consumer product safety, government agency actions, wage-risk compensation, consumer behavior (market) studies, and willingness-to-pay surveys. The results ranged from $1,400,000 to $2,700,000 per life saved. Applying the mean of these values ($2,100,000) and the latest risk per unit dose coefficients used by the ICRP (1991), which take into account risks to the general public, including genetic effects and nonfatal cancers, yields a value of dose avoided of $750 to $1,500more » per person-cSv for public exposures. The lower value applies if adjustments are made for years of life lost per fatality. A nominal value of $1,000 per person-cSv seems appropriate in light of the many uncertainties involved in deducing these values. These values are consistent with values recommended by several European countries for individual doses in the region of 1 mSv/y (100 mrem/y). Below this dose rate, most countries have values a factor of 7 to 10 lower, based on the assumption that society is less concerned with fatality risks below about 10{sup {minus}4}/y.« less

  17. Dosimetry for nonuniform activity distributions: a method for the calculation of 3D absorbed-dose distribution without the use of voxel S-values, point kernels, or Monte Carlo simulations.

    PubMed

    Traino, A C; Marcatili, S; Avigo, C; Sollini, M; Erba, P A; Mariani, G

    2013-04-01

    Nonuniform activity within the target lesions and the critical organs constitutes an important limitation for dosimetric estimates in patients treated with tumor-seeking radiopharmaceuticals. The tumor control probability and the normal tissue complication probability are affected by the distribution of the radionuclide in the treated organ/tissue. In this paper, a straightforward method for calculating the absorbed dose at the voxel level is described. This new method takes into account a nonuniform activity distribution in the target/organ. The new method is based on the macroscopic S-values (i.e., the S-values calculated for the various organs, as defined in the MIRD approach), on the definition of the number of voxels, and on the raw-count 3D array, corrected for attenuation, scatter, and collimator resolution, in the lesion/organ considered. Starting from these parameters, the only mathematical operation required is to multiply the 3D array by a scalar value, thus avoiding all the complex operations involving the 3D arrays. A comparison with the MIRD approach, fully described in the MIRD Pamphlet No. 17, using S-values at the voxel level, showed a good agreement between the two methods for (131)I and for (90)Y. Voxel dosimetry is becoming more and more important when performing therapy with tumor-seeking radiopharmaceuticals. The method presented here does not require calculating the S-values at the voxel level, and thus bypasses the mathematical problems linked to the convolution of 3D arrays and to the voxel size. In the paper, the results obtained with this new simplified method as well as the possibility of using it for other radionuclides commonly employed in therapy are discussed. The possibility of using the correct density value of the tissue/organs involved is also discussed.

  18. Designing drug regimens for special intensive care unit populations

    PubMed Central

    Erstad, Brian L

    2015-01-01

    This review is intended to help clinicians design drug regimens for special populations of critically ill patients with extremes of body size, habitus and composition that make drug choice or dosing particularly challenging due to the lack of high-level evidence on which to make well-informed clinical decisions. The data sources included a literature search of MEDLINE and EMBASE with reviews of reference lists of retrieved articles. Abstracts of original research investigations and review papers were reviewed for their relevance to drug choice or dosing in the following special critically ill populations: patients with more severe forms of bodyweight or height, patients with amputations or missing limbs, pregnant patients, and patients undergoing extracorporeal membrane oxygenation or plasma exchange. Relevant papers were retrieved and evaluated, and their associated reference lists were reviewed for citations that may have been missed through the electronic search strategy. Relevant original research investigations and review papers that could be used to formulate general principles for drug choice or dosing in special populations of critically ill patients were extracted. Randomized studies with clinically relevant endpoints were not available for performing quantitative analyses. Critically ill patients with changes in body size, habitus and composition require special consideration when designing medication regimens, but there is a paucity of literature on which to make drug-specific, high-level evidence-based recommendations. Based on the evidence that is available, general recommendations are provided for drug choice or dosing in special critically ill populations. PMID:25938029

  19. TH-CD-202-08: Feasibility Study of Planning Phase Optimization Using Patient Geometry-Driven Information for Better Dose Sparing of Organ at Risks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kang, S; Kim, D; Kim, T

    2016-06-15

    Purpose: To propose a simple and effective cost value function to search optimal planning phase (gating window) and demonstrated its feasibility for respiratory correlated radiation therapy. Methods: We acquired 4DCT of 10 phases for 10 lung patients who have tumor located near OARs such as esophagus, heart, and spinal cord (i.e., central lung cancer patients). A simplified mathematical optimization function was established by using overlap volume histogram (OVH) between the target and organ at risk (OAR) at each phase and the tolerance dose of selected OARs to achieve surrounding OARs dose-sparing. For all patients and all phases, delineation of themore » target volume and selected OARs (esophagus, heart, and spinal cord) was performed (by one observer to avoid inter-observer variation), then cost values were calculated for all phases. After the breathing phases were ranked according to cost value function, the relationship between score and dose distribution at highest and lowest cost value phases were evaluated by comparing the mean/max dose. Results: A simplified mathematical cost value function showed noticeable difference from phase to phase, implying it is possible to find optimal phases for gating window. The lowest cost value which may result in lower mean/max dose to OARs was distributed at various phases for all patients. The mean doses of the OARs significantly decreased about 10% with statistical significance for all 3 OARs at the phase with the lowest cost value. Also, the max doses of the OARs were decreased about 2∼5% at the phase with the lowest cost value compared to the phase with the highest cost value. Conclusion: It is demonstrated that optimal phases (in dose distribution perspective) for gating window could exist differently through each patient and the proposed cost value function can be a useful tool for determining such phases without performing dose optimization calculations. This research was supported by the Mid-career Researcher Program through NRF funded by the Ministry of Science, ICT & Future Planning of Korea (NRF-2014R1A2A1A10050270) and by the Radiation Technology R&D program through the National Research Foundation of Korea funded by the Ministry of Science, ICT & Future Planning (No. 2013M2A2A7038291)« less

  20. In-situ intestinal rat perfusions for human Fabs prediction and BCS permeability class determination: Investigation of the single-pass vs. the Doluisio experimental approaches.

    PubMed

    Lozoya-Agullo, Isabel; Zur, Moran; Wolk, Omri; Beig, Avital; González-Álvarez, Isabel; González-Álvarez, Marta; Merino-Sanjuán, Matilde; Bermejo, Marival; Dahan, Arik

    2015-03-01

    Intestinal drug permeability has been recognized as a critical determinant of the fraction dose absorbed, with direct influence on bioavailability, bioequivalence and biowaiver. The purpose of this research was to compare intestinal permeability values obtained by two different intestinal rat perfusion methods: the single-pass intestinal perfusion (SPIP) model and the Doluisio (closed-loop) rat perfusion method. A list of 15 model drugs with different permeability characteristics (low, moderate, and high, as well as passively and actively absorbed) was constructed. We assessed the rat intestinal permeability of these 15 model drugs in both SPIP and the Doluisio methods, and evaluated the correlation between them. We then evaluated the ability of each of these methods to predict the fraction dose absorbed (Fabs) in humans, and to assign the correct BCS permeability class membership. Excellent correlation was obtained between the two experimental methods (r(2)=0.93). An excellent correlation was also shown between literature Fabs values and the predictions made by both rat perfusion techniques. Similar BCS permeability class membership was designated by literature data and by both SPIP and Doluisio methods for all compounds. In conclusion, the SPIP model and the Doluisio (closed-loop) rat perfusion method are both equally useful for obtaining intestinal permeability values that can be used for Fabs prediction and BCS classification. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Effect of Patient Set-up and Respiration motion on Defining Biological Targets for Image-Guided Targeted Radiotherapy

    NASA Astrophysics Data System (ADS)

    McCall, Keisha C.

    Identification and monitoring of sub-tumor targets will be a critical step for optimal design and evaluation of cancer therapies in general and biologically targeted radiotherapy (dose-painting) in particular. Quantitative PET imaging may be an important tool for these applications. Currently radiotherapy planning accounts for tumor motion by applying geometric margins. These margins create a motion envelope to encompass the most probable positions of the tumor, while also maintaining the appropriate tumor control and normal tissue complication probabilities. This motion envelope is effective for uniform dose prescriptions where the therapeutic dose is conformed to the external margins of the tumor. However, much research is needed to establish the equivalent margins for non-uniform fields, where multiple biological targets are present and each target is prescribed its own dose level. Additionally, the size of the biological targets and close proximity make it impractical to apply planning margins on the sub-tumor level. Also, the extent of high dose regions must be limited to avoid excessive dose to the surrounding tissue. As such, this research project is an investigation of the uncertainty within quantitative PET images of moving and displaced dose-painting targets, and an investigation of the residual errors that remain after motion management. This included characterization of the changes in PET voxel-values as objects are moved relative to the discrete sampling interval of PET imaging systems (SPECIFIC AIM 1). Additionally, the repeatability of PET distributions and the delineating dose-painting targets were measured (SPECIFIC AIM 2). The effect of imaging uncertainty on the dose distributions designed using these images (SPECIFIC AIM 3) has also been investigated. This project also included analysis of methods to minimize motion during PET imaging and reduce the dosimetric impact of motion/position-induced imaging uncertainty (SPECIFIC AIM 4).

  2. Experimental design and statistical analysis for three-drug combination studies.

    PubMed

    Fang, Hong-Bin; Chen, Xuerong; Pei, Xin-Yan; Grant, Steven; Tan, Ming

    2017-06-01

    Drug combination is a critically important therapeutic approach for complex diseases such as cancer and HIV due to its potential for efficacy at lower, less toxic doses and the need to move new therapies rapidly into clinical trials. One of the key issues is to identify which combinations are additive, synergistic, or antagonistic. While the value of multidrug combinations has been well recognized in the cancer research community, to our best knowledge, all existing experimental studies rely on fixing the dose of one drug to reduce the dimensionality, e.g. looking at pairwise two-drug combinations, a suboptimal design. Hence, there is an urgent need to develop experimental design and analysis methods for studying multidrug combinations directly. Because the complexity of the problem increases exponentially with the number of constituent drugs, there has been little progress in the development of methods for the design and analysis of high-dimensional drug combinations. In fact, contrary to common mathematical reasoning, the case of three-drug combinations is fundamentally more difficult than two-drug combinations. Apparently, finding doses of the combination, number of combinations, and replicates needed to detect departures from additivity depends on dose-response shapes of individual constituent drugs. Thus, different classes of drugs of different dose-response shapes need to be treated as a separate case. Our application and case studies develop dose finding and sample size method for detecting departures from additivity with several common (linear and log-linear) classes of single dose-response curves. Furthermore, utilizing the geometric features of the interaction index, we propose a nonparametric model to estimate the interaction index surface by B-spine approximation and derive its asymptotic properties. Utilizing the method, we designed and analyzed a combination study of three anticancer drugs, PD184, HA14-1, and CEP3891 inhibiting myeloma H929 cell line. To our best knowledge, this is the first ever three drug combinations study performed based on the original 4D dose-response surface formed by dose ranges of three drugs.

  3. Development of a vancomycin dosing approach for critically ill patients receiving hybrid hemodialysis using Monte Carlo simulation.

    PubMed

    Lewis, Susan J; Mueller, Bruce A

    2018-01-01

    Prolonged intermittent renal replacement therapy is an increasingly popular treatment for acute kidney injury in critically ill patients that runs at different flow rates and durations than conventional hemodialysis or continuous renal replacement therapies. Pharmacokinetic studies conducted in patients receiving prolonged intermittent renal replacement therapy are scarce; consequently, clinicians are challenged to dose antibiotics effectively. The purpose of this study was to develop vancomycin dosing recommendations for patients receiving prolonged intermittent renal replacement therapy. Monte Carlo simulations were performed in thousands of virtual patients derived from previously published demographic, pharmacokinetic, and dialytic information derived from critically ill patients receiving vancomycin and other forms of renal replacement therapy. We conducted "in silico" vancomycin pharmacokinetic/pharmacodynamics analyses in these patients receiving prolonged intermittent renal replacement therapy to determine what vancomycin dose would achieve vancomycin 24-h area under the curve (AUC 24h ) of 400-700 mg·h/L, a target associated with positive clinical outcomes. Nine different vancomycin dosing regimens were tested using four different, commonly used prolonged intermittent renal replacement therapy modalities. A dosing nomogram based on serum concentration data achieved after the third dose was developed to individualize vancomycin therapy. An initial vancomycin dose of 15 or 20 mg/kg immediately followed by 15 mg/kg after subsequent prolonged intermittent renal replacement therapy treatments achieved AUC 24h of ≥400 mg·h/L for ≥90% of patients regardless of prolonged intermittent renal replacement therapy duration, modality, or time of vancomycin dose relative to prolonged intermittent renal replacement therapy. Many patients experienced AUC 24h of ≥700 mg·h/L, but once the dosing nomogram was applied to serum concentrations obtained after the third vancomycin dose, 67%-88% of patients achieved AUC 24h of 400-700 mg·h/L. An initial loading dose of 15-20 mg/kg followed by a maintenance regimen of 15 mg/kg after every prolonged intermittent renal replacement therapy session coupled with serum concentration monitoring should be used to individualize vancomycin dosing. These predictions need clinical verification.

  4. Total body irradiation, toward optimal individual delivery: dose evaluation with metal oxide field effect transistors, thermoluminescence detectors, and a treatment planning system.

    PubMed

    Bloemen-van Gurp, Esther J; Mijnheer, Ben J; Verschueren, Tom A M; Lambin, Philippe

    2007-11-15

    To predict the three-dimensional dose distribution of our total body irradiation technique, using a commercial treatment planning system (TPS). In vivo dosimetry, using metal oxide field effect transistors (MOSFETs) and thermoluminescence detectors (TLDs), was used to verify the calculated dose distributions. A total body computed tomography scan was performed and loaded into our TPS, and a three-dimensional-dose distribution was generated. In vivo dosimetry was performed at five locations on the patient. Entrance and exit dose values were converted to midline doses using conversion factors, previously determined with phantom measurements. The TPS-predicted dose values were compared with the MOSFET and TLD in vivo dose values. The MOSFET and TLD dose values agreed within 3.0% and the MOSFET and TPS data within 0.5%. The convolution algorithm of the TPS, which is routinely applied in the clinic, overestimated the dose in the lung region. Using a superposition algorithm reduced the calculated lung dose by approximately 3%. The dose inhomogeneity, as predicted by the TPS, can be reduced using a simple intensity-modulated radiotherapy technique. The use of a TPS to calculate the dose distributions in individual patients during total body irradiation is strongly recommended. Using a TPS gives good insight of the over- and underdosage in a patient and the influence of patient positioning on dose homogeneity. MOSFETs are suitable for in vivo dosimetry purposes during total body irradiation, when using appropriate conversion factors. The MOSFET, TLD, and TPS results agreed within acceptable margins.

  5. Detailed characterisation of focused ion beam induced lateral damage on silicon carbide samples by electrical scanning probe microscopy and transmission electron microscopy

    NASA Astrophysics Data System (ADS)

    Stumpf, F.; Abu Quba, A. A.; Singer, P.; Rumler, M.; Cherkashin, N.; Schamm-Chardon, S.; Cours, R.; Rommel, M.

    2018-03-01

    The lateral damage induced by focused ion beam on silicon carbide was characterized using electrical scanning probe microscopy (SPM), namely, scanning spreading resistance microscopy and conductive atomic force microscopy (c-AFM). It is shown that the damage exceeds the purposely irradiated circles with a radius of 0.5 μm by several micrometres, up to 8 μm for the maximum applied ion dose of 1018 cm-2. Obtained SPM results are critically compared with earlier findings on silicon. For doses above the amorphization threshold, in both cases, three different areas can be distinguished. The purposely irradiated area exhibits resistances smaller than the non-affected substrate. A second region with strongly increasing resistance and a maximum saturation value surrounds it. The third region shows the transition from maximum resistance to the base resistance of the unaffected substrate. It correlates to the transition from amorphized to defect-rich to pristine crystalline substrate. Additionally, conventional transmission electron microscopy (TEM) and annular dark-field STEM were used to complement and explain the SPM results and get a further understanding of the defect spreading underneath the surface. Those measurements also show three different regions that correlate well with the regions observed from electrical SPM. TEM results further allow to explain observed differences in the electrical results for silicon and silicon carbide which are most prominent for ion doses above 3 × 1016 cm-2. Furthermore, the conventional approach to perform current-voltage measurements by c-AFM was critically reviewed and several improvements for measurement and analysis process were suggested that result in more reliable and impactful c-AFM data.

  6. Prophylactic ranitidine treatment in critically ill children--a population pharmacokinetic study.

    PubMed

    Hawwa, Ahmed F; Westwood, Paul M; Collier, Paul S; Millership, Jeffrey S; Yakkundi, Shirish; Thurley, Gillian; Shields, Mike D; Nunn, Anthony J; Halliday, Henry L; McElnay, James C

    2013-05-01

    To characterize the population pharmacokinetics of ranitidine in critically ill children and to determine the influence of various clinical and demographic factors on its disposition. Data were collected prospectively from 78 paediatric patients (n = 248 plasma samples) who received oral or intravenous ranitidine for prophylaxis against stress ulcers, gastrointestinal bleeding or the treatment of gastro-oesophageal reflux. Plasma samples were analysed using high-performance liquid chromatography, and the data were subjected to population pharmacokinetic analysis using nonlinear mixed-effects modelling. A one-compartment model best described the plasma concentration profile, with an exponential structure for interindividual errors and a proportional structure for intra-individual error. After backward stepwise elimination, the final model showed a significant decrease in objective function value (-12.618; P < 0.001) compared with the weight-corrected base model. Final parameter estimates for the population were 32.1 l h(-1) for total clearance and 285 l for volume of distribution, both allometrically modelled for a 70 kg adult. Final estimates for absorption rate constant and bioavailability were 1.31 h(-1) and 27.5%, respectively. No significant relationship was found between age and weight-corrected ranitidine pharmacokinetic parameters in the final model, with the covariate for cardiac failure or surgery being shown to reduce clearance significantly by a factor of 0.46. Currently, ranitidine dose recommendations are based on children's weights. However, our findings suggest that a dosing scheme that takes into consideration both weight and cardiac failure/surgery would be more appropriate in order to avoid administration of higher or more frequent doses than necessary. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.

  7. Criticality accident dosimetry with ESR spectroscopy.

    PubMed

    d'Errico, F; Fattibene, P; Onori, S; Pantaloni, M

    1996-01-01

    The suitability of the ESR alanine and sugar detectors for criticality accident dosimetry was experimentally investigated during an intercomparison of dosimetry techniques. Tests were performed irradiating detectors both free-in-air and on-phantom during controlled critcality excursions at the SILENE reactor in Valduc, France. Several grays of absorbed dose were imparted in neutron gamma-ray fields of various relative intensities and spectral distributions. Analysed results confirmed the potential of these systems which can immediately provide an acute dose assessment with an average underestimate of 30%in the various fields. This performance allows for the screening of severely exposed individuals and meets the IAEA recommendations on the early estimate of accident absorbed doses.

  8. Issues raised by the reference doses for perfluorooctane sulfonate and perfluorooctanoic acid.

    PubMed

    Dong, Zhaomin; Bahar, Md Mezbaul; Jit, Joytishna; Kennedy, Bruce; Priestly, Brian; Ng, Jack; Lamb, Dane; Liu, Yanju; Duan, Luchun; Naidu, Ravi

    2017-08-01

    On 25th May 2016, the U.S. EPA released reference doses (RfDs) for Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoic Acid (PFOA) of 20ng/kg/day, which were much more conservative than previous values. These RfDs rely on the choices of animal point of departure (PoD) and the toxicokinetics (TK) model. At this stage, considering that the human evidence is not strong enough for RfD determination, using animal data may be appropriate but with more uncertainties. In this article, the uncertainties concerning RfDs from the choices of PoD and TK models are addressed. Firstly, the candidate PoDs should include more critical endpoints (such as immunotoxicity), which may lead to lower RfDs. Secondly, the reliability of the adopted three-compartment TK model is compromised: the parameters are not non-biologically plausible; and this TK model was applied to simulate gestation and lactation exposures, while the two exposure scenarios were not actually included in the model structure. Copyright © 2017. Published by Elsevier Ltd.

  9. Synchronous γ (Co60) photons and thermal processing induced insulator metal transition in amorphous chalcogenide As4Se3Te3 composition

    NASA Astrophysics Data System (ADS)

    El-Sayed, S. A.; Morsy, M. A.

    2018-05-01

    Amorphous chalcogenide composition AS4Se3Te3 is prepared by conventional quenching technique. The separate annealing or γ quanta irradiation not effect on the dc conductivity properties of the prepared composition. When the prepared samples are subjected to simultaneous annealing at temperature 413 K and γ quanta irradiation the dc conductivity increases. The dark dc conductivity increases by increasing the time of exposure to γ irradiation. At irradiation dose 1.47 × 104 Gy the dc conductivity starts to have metallic like conductivity character. These samples could be used as high temperature γ quanta dosimeter. By applying scaling theory on the samples irradiated with different dose of γ irradiation the critical exponents are determined and found to be < 2. The dark dc conductivity continuously decreases to 0 as temperature tends to zero. The steric value is low in the insulator side of conductivity, but high and almost saturated in the metallic side of conductivity.

  10. The value of online learning and MRI: finding a niche for expensive technologies.

    PubMed

    Cook, David A

    2014-11-01

    The benefits of online learning come at a price. How can we optimize the overall value? Critically appraise the value of online learning. Narrative review. Several prevalent myths overinflate the value of online learning. These include that online learning is cheap and easy (it is usually more expensive), that it is more efficient (efficiency depends on the instructional design, not the modality), that it will transform education (fundamental learning principles have not changed), and that the Net Generation expects it (there is no evidence of pent-up demand). However, online learning does add real value by enhancing flexibility, control and analytics. Costs may also go down if disruptive innovations (e.g. low-cost, low-tech, but instructionally sound "good enough" online learning) supplant technically superior but more expensive online learning products. Cost-lowering strategies include focusing on core principles of learning rather than technologies, using easy-to-learn authoring tools, repurposing content (organizing and sequencing existing resources rather than creating new content) and using course templates. Online learning represents just one tool in an educator's toolbox, as does the MRI for clinicians. We need to use the right tool(s) for the right learner at the right dose, time and route.

  11. Additional value of computer assisted semen analysis (CASA) compared to conventional motility assessments in pig artificial insemination.

    PubMed

    Broekhuijse, M L W J; Soštarić, E; Feitsma, H; Gadella, B M

    2011-11-01

    In order to obtain a more standardised semen motility evaluation, Varkens KI Nederland has introduced a computer assisted semen analysis (CASA) system in all their pig AI laboratories. The repeatability of CASA was enhanced by standardising for: 1) an optimal sample temperature (39 °C); 2) an optimal dilution factor; 3) optimal mixing of semen and dilution buffer by using mechanical mixing; 4) the slide chamber depth, and together with the previous points; 5) the optimal training of technicians working with the CASA system; and 6) the use of a standard operating procedure (SOP). Once laboratory technicians were trained in using this SOP, they achieved a coefficient of variation of < 5% which was superior to the variation found when the SOP was not strictly used. Microscopic semen motility assessments by eye were subjective and not comparable to the data obtained by standardised CASA. CASA results are preferable as accurate continuous motility dates are generated rather than discrimination motility percentage increments of 10% motility as with motility estimation by laboratory technicians. The higher variability of sperm motility found with CASA and the continuous motility values allow better analysis of the relationship between semen motility characteristics and fertilising capacity. The benefits of standardised CASA for AI is discussed both with respect to estimate the correct dilution factor of the ejaculate for the production of artificial insemination (AI) doses (critical for reducing the number of sperm per AI doses) and thus to get more reliable fertility data from these AI doses in return. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Overcoming the Practical Barriers to Spinal Cord Cell Transplantation for ALS

    DTIC Science & Technology

    2012-10-01

    ABSTRACT: This grant will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Rigorous...Surgical Technique) will provide critical data on tolerance and toxicity of cell dosing and numbers of permissible spinal cord injections. Aim 2 (Graft...connected to a rigid needle of the same gauge as the floating cannula one – Figure 7) using the maximum volume/number of injections could result in

  13. Investigation of the environmental impacts of naturally occurring radionuclides in the processing of sulfide ores for gold using gamma spectrometry.

    PubMed

    Gbadago, J K; Faanhof, A; Darko, E O; Schandorf, C

    2011-09-01

    The possible environmental impacts of naturally occurring radionuclides on workers and a critical community, as a result of milling and processing sulfide ores for gold by a mining company at Bogoso in the western region of Ghana, have been investigated using gamma spectroscopy. Indicative doses for the workers during sulfide ore processing were calculated from the activity concentrations measured at both physical and chemical processing stages. The dose rate, annual effective dose equivalent, radium equivalent activity, external and internal hazard indices, and radioactivity level index for tailings, for the de-silted sediments of run-off from the vicinity of the tailings dam through the critical community, and for the soils of the critical community's basic schools were calculated and found to be lower than their respective permissible limits. The environmental impact of the radionuclides is therefore expected to be low in this mining environment.

  14. The clinical pharmacology of alkylating agents in high-dose chemotherapy.

    PubMed

    Huitema, A D; Smits, K D; Mathôt, R A; Schellens, J H; Rodenhuis, S; Beijnen, J H

    2000-08-01

    Alkylating agents are widely used in high-dose chemotherapy regimens in combination with hematological support. Knowledge about the pharmacokinetics and pharmacodynamics of these agents administered in high doses is critical for the safe and efficient use of these regimens. The aim of this review is to summarize the clinical pharmacology of the alkylating agents (including the platinum compounds) in high-dose chemotherapy. Differences between conventional and high doses will be discussed.

  15. Feasibility of tomotherapy to reduce normal lung and cardiac toxicity for distal esophageal cancer compared to three-dimensional radiotherapy.

    PubMed

    Nguyen, Nam P; Krafft, Shane P; Vinh-Hung, Vincent; Vos, Paul; Almeida, Fabio; Jang, Siyoung; Ceizyk, Misty; Desai, Anand; Davis, Rick; Hamilton, Russ; Modarresifar, Homayoun; Abraham, Dave; Smith-Raymond, Lexie

    2011-12-01

    To compare the effectiveness of tomotherapy and three-dimensional (3D) conformal radiotherapy to spare normal critical structures (spinal cord, lungs, and ventricles) from excessive radiation in patients with distal esophageal cancers. A retrospective dosimetric study of nine patients who had advanced gastro-esophageal (GE) junction cancer (7) or thoracic esophageal cancer (2) extending into the distal esophagus. Two plans were created for each of the patients. A three-dimensional plan was constructed with either three (anteroposterior, right posterior oblique, and left posterior oblique) or four (right anterior oblique, left anterior oblique, right posterior oblique, and left posterior oblique) fields. The second plan was for tomotherapy. Doses were 45 Gy to the PTV with an integrated boost of 5 Gy for tomotherapy. Mean lung dose was respectively 7.4 and 11.8 Gy (p=0.004) for tomotherapy and 3D plans. Corresponding values were 12.4 and 18.3 Gy (p=0.006) for cardiac ventricles. Maximum spinal cord dose was respectively 31.3 and 37.4 Gy (p < 0.007) for tomotherapy and 3D plans. Homogeneity index was two for both groups. Compared to 3D conformal radiotherapy, tomotherapy decreased significantly the amount of normal tissue irradiated and may reduce treatment toxicity for possible dose escalation in future prospective studies. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Four-dimensional dose evaluation using deformable image registration in radiotherapy for liver cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hoon Jung, Sang; Min Yoon, Sang; Ho Park, Sung

    2013-01-15

    Purpose: In order to evaluate the dosimetric impact of respiratory motion on the dose delivered to the target volume and critical organs during free-breathing radiotherapy, a four-dimensional dose was evaluated using deformable image registration (DIR). Methods: Four-dimensional computed tomography (4DCT) images were acquired for 11 patients who were treated for liver cancer. Internal target volume-based treatment planning and dose calculation (3D dose) were performed using the end-exhalation phase images. The four-dimensional dose (4D dose) was calculated based on DIR of all phase images from 4DCT to the planned image. Dosimetric parameters from the 4D dose, were calculated and compared withmore » those from the 3D dose. Results: There was no significant change of the dosimetric parameters for gross tumor volume (p > 0.05). The increase D{sub mean} and generalized equivalent uniform dose (gEUD) for liver were by 3.1%{+-} 3.3% (p= 0.003) and 2.8%{+-} 3.3% (p= 0.008), respectively, and for duodenum, they were decreased by 15.7%{+-} 11.2% (p= 0.003) and 15.1%{+-} 11.0% (p= 0.003), respectively. The D{sub max} and gEUD for stomach was decreased by 5.3%{+-} 5.8% (p= 0.003) and 9.7%{+-} 8.7% (p= 0.003), respectively. The D{sub max} and gEUD for right kidney was decreased by 11.2%{+-} 16.2% (p= 0.003) and 14.9%{+-} 16.8% (p= 0.005), respectively. For left kidney, D{sub max} and gEUD were decreased by 11.4%{+-} 11.0% (p= 0.003) and 12.8%{+-} 12.1% (p= 0.005), respectively. The NTCP values for duodenum and stomach were decreased by 8.4%{+-} 5.8% (p= 0.003) and 17.2%{+-} 13.7% (p= 0.003), respectively. Conclusions: The four-dimensional dose with a more realistic dose calculation accounting for respiratory motion revealed no significant difference in target coverage and potentially significant change in the physical and biological dosimetric parameters in normal organs during free-breathing treatment.« less

  17. NEUROTOXIC EFFECTS OF ENVIRONMENTAL AGENTS: DATA GAPS THAT CHALLENGE DOSE-RESPONSE ESTIMATION

    EPA Science Inventory

    Neurotoxic effects of environmental agents: Data gaps that challenge dose-response estimation
    S Gutter*, P Mendola+, SG Selevan**, D Rice** (*UNC Chapel Hill; +US EPA, NHEERL; **US EPA, NCEA)

    Dose-response estimation is a critical feature of risk assessment. It can be...

  18. Application of a loading dose of colistin methanesulfonate in critically ill patients: population pharmacokinetics, protein binding, and prediction of bacterial kill.

    PubMed

    Mohamed, Ami F; Karaiskos, Ilias; Plachouras, Diamantis; Karvanen, Matti; Pontikis, Konstantinos; Jansson, Britt; Papadomichelakis, Evangelos; Antoniadou, Anastasia; Giamarellou, Helen; Armaganidis, Apostolos; Cars, Otto; Friberg, Lena E

    2012-08-01

    A previous pharmacokinetic study on dosing of colistin methanesulfonate (CMS) at 240 mg (3 million units [MU]) every 8 h indicated that colistin has a long half-life, resulting in insufficient concentrations for the first 12 to 48 h after initiation of treatment. A loading dose would therefore be beneficial. The aim of this study was to evaluate CMS and colistin pharmacokinetics following a 480-mg (6-MU) loading dose in critically ill patients and to explore the bacterial kill following the use of different dosing regimens obtained by predictions from a pharmacokinetic-pharmacodynamic model developed from an in vitro study on Pseudomonas aeruginosa. The unbound fractions of colistin A and colistin B were determined using equilibrium dialysis and considered in the predictions. Ten critically ill patients (6 males; mean age, 54 years; mean creatinine clearance, 82 ml/min) with infections caused by multidrug-resistant Gram-negative bacteria were enrolled in the study. The pharmacokinetic data collected after the first and eighth doses were analyzed simultaneously with the data from the previous study (total, 28 patients) in the NONMEM program. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.026 and 2.2 h, respectively. For colistin, a one-compartment model was sufficient and the estimated half-life was 18.5 h. The unbound fractions of colistin in the patients were 26 to 41% at clinical concentrations. Colistin A, but not colistin B, had a concentration-dependent binding. The predictions suggested that the time to 3-log-unit bacterial kill for a 480-mg loading dose was reduced to half of that for the dose of 240 mg.

  19. Application of a Loading Dose of Colistin Methanesulfonate in Critically Ill Patients: Population Pharmacokinetics, Protein Binding, and Prediction of Bacterial Kill

    PubMed Central

    Karaiskos, Ilias; Plachouras, Diamantis; Karvanen, Matti; Pontikis, Konstantinos; Jansson, Britt; Papadomichelakis, Evangelos; Antoniadou, Anastasia; Giamarellou, Helen; Armaganidis, Apostolos; Cars, Otto; Friberg, Lena E.

    2012-01-01

    A previous pharmacokinetic study on dosing of colistin methanesulfonate (CMS) at 240 mg (3 million units [MU]) every 8 h indicated that colistin has a long half-life, resulting in insufficient concentrations for the first 12 to 48 h after initiation of treatment. A loading dose would therefore be beneficial. The aim of this study was to evaluate CMS and colistin pharmacokinetics following a 480-mg (6-MU) loading dose in critically ill patients and to explore the bacterial kill following the use of different dosing regimens obtained by predictions from a pharmacokinetic-pharmacodynamic model developed from an in vitro study on Pseudomonas aeruginosa. The unbound fractions of colistin A and colistin B were determined using equilibrium dialysis and considered in the predictions. Ten critically ill patients (6 males; mean age, 54 years; mean creatinine clearance, 82 ml/min) with infections caused by multidrug-resistant Gram-negative bacteria were enrolled in the study. The pharmacokinetic data collected after the first and eighth doses were analyzed simultaneously with the data from the previous study (total, 28 patients) in the NONMEM program. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.026 and 2.2 h, respectively. For colistin, a one-compartment model was sufficient and the estimated half-life was 18.5 h. The unbound fractions of colistin in the patients were 26 to 41% at clinical concentrations. Colistin A, but not colistin B, had a concentration-dependent binding. The predictions suggested that the time to 3-log-unit bacterial kill for a 480-mg loading dose was reduced to half of that for the dose of 240 mg. PMID:22615285

  20. How to optimise antimicrobial prescriptions in the Intensive Care Unit: principles of individualised dosing using pharmacokinetics and pharmacodynamics.

    PubMed

    Roberts, Jason A; Joynt, Gavin M; Choi, Gordon Y S; Gomersall, Charles D; Lipman, Jeffrey

    2012-03-01

    Optimising antimicrobial dosing for critically ill patients is highly challenging and when it is not achieved can lead to worse patient outcomes. To this end, use of dosing regimens recommended in package inserts from drug manufacturers is frequently insufficient to guide dosing in these patients appropriately. Whilst the effect of critical illness pathophysiology on the pharmacokinetic (PK) behaviour of antimicrobials can be profound, the variability of these changes between patients is still being quantified. The PK effects of hypoproteinaemia, organ dysfunction and the presence of augmented renal clearance may lead to plasma antimicrobial concentrations that are difficult to predict at the bedside, which may result in excess toxicity or suboptimal bacterial killing. This paper outlines the factors that affect pharmacokinetics in critically ill patients and how knowledge of these factors can increase the likelihood of achieving optimal antimicrobial plasma concentrations. In selected settings, we advocate individualised dosing of renally cleared antimicrobials using physiological data such as measured creatinine clearance and published non-renal clearance data. Where such data do not exist, therapeutic drug monitoring may be a useful alternative and has been associated with significant clinical benefits, although it is not currently widely available. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  1. Comparison of different approaches of estimating effective dose from reported exposure data in 3D imaging with interventional fluoroscopy systems

    NASA Astrophysics Data System (ADS)

    Svalkvist, Angelica; Hansson, Jonny; Bâth, Magnus

    2014-03-01

    Three-dimensional (3D) imaging with interventional fluoroscopy systems is today a common examination. The examination includes acquisition of two-dimensional projection images, used to reconstruct section images of the patient. The aim of the present study was to investigate the difference in resulting effective dose obtained using different levels of complexity in calculations of effective doses from these examinations. In the study the Siemens Artis Zeego interventional fluoroscopy system (Siemens Medical Solutions, Erlangen, Germany) was used. Images of anthropomorphic chest and pelvis phantoms were acquired. The exposure values obtained were used to calculate the resulting effective doses from the examinations, using the computer software PCXMC (STUK, Helsinki, Finland). The dose calculations were performed using three different methods: 1. using individual exposure values for each projection image, 2. using the mean tube voltage and the total DAP value, evenly distributed over the projection images, and 3. using the mean kV and the total DAP value, evenly distributed over smaller selection of projection images. The results revealed that the difference in resulting effective dose between the first two methods was smaller than 5%. When only a selection of projection images were used in the dose calculations the difference increased to over 10%. Given the uncertainties associated with the effective dose concept, the results indicate that dose calculations based on average exposure values distributed over a smaller selection of projection angles can provide reasonably accurate estimations of the radiation doses from 3D imaging using interventional fluoroscopy systems.

  2. Evaluation of an artificial intelligence guided inverse planning system: clinical case study.

    PubMed

    Yan, Hui; Yin, Fang-Fang; Willett, Christopher

    2007-04-01

    An artificial intelligence (AI) guided method for parameter adjustment of inverse planning was implemented on a commercial inverse treatment planning system. For evaluation purpose, four typical clinical cases were tested and the results from both plans achieved by automated and manual methods were compared. The procedure of parameter adjustment mainly consists of three major loops. Each loop is in charge of modifying parameters of one category, which is carried out by a specially customized fuzzy inference system. A physician prescribed multiple constraints for a selected volume were adopted to account for the tradeoff between prescription dose to the PTV and dose-volume constraints for critical organs. The searching process for an optimal parameter combination began with the first constraint, and proceeds to the next until a plan with acceptable dose was achieved. The initial setup of the plan parameters was the same for each case and was adjusted independently by both manual and automated methods. After the parameters of one category were updated, the intensity maps of all fields were re-optimized and the plan dose was subsequently re-calculated. When final plan arrived, the dose statistics were calculated from both plans and compared. For planned target volume (PTV), the dose for 95% volume is up to 10% higher in plans using the automated method than those using the manual method. For critical organs, an average decrease of the plan dose was achieved. However, the automated method cannot improve the plan dose for some critical organs due to limitations of the inference rules currently employed. For normal tissue, there was no significant difference between plan doses achieved by either automated or manual method. With the application of AI-guided method, the basic parameter adjustment task can be accomplished automatically and a comparable plan dose was achieved in comparison with that achieved by the manual method. Future improvements to incorporate case-specific inference rules are essential to fully automate the inverse planning process.

  3. Effects of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects

    NASA Technical Reports Server (NTRS)

    Ahmed, S.; Sileno, A. P.; deMeireles, J. C.; Dua, R.; Pimplaskar, H. K.; Xia, W. J.; Marinaro, J.; Langenback, E.; Matos, F. J.; Putcha, L.; hide

    2000-01-01

    PURPOSE: The present study was conducted to evaluate the effects of formulation pH and dose on nasal absorption of scopolamine hydrobromide, the single most effective drug available for the prevention of nausea and vomiting induced by motion sickness. METHODS: Human subjects received scopolamine nasally at a dose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected at different time points, and plasma scopolamine concentrations were determined by LC-MS/MS. RESULTS: Following administration of a 0.2 mg dose, the average Cmax values were found to be 262+/-118, 419+/-161, and 488+/-331 pg/ mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At the 0.4 mg dose the average Cmax values were found to be 503+/-199, 933+/-449, and 1,308+/-473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a 0.2 mg dose, the AUC values were found to be 23,208+/-6,824, 29,145+/-9,225, and 25,721+/-5,294 pg x min/mL for formulation pH 4.0, 7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value was found to be high for pH 9.0 formulation (70,740+/-29,381 pg x min/mL) as compared to those of pH 4.0 (59,573+/-13,700 pg x min/mL) and pH 7.0 (55,298+/-17,305 pg x min/mL) formulations. Both the Cmax and AUC values were almost doubled with doubling the dose. On the other hand, the average Tmax, values decreased linearly with a decrease in formulation pH at both doses. For example, at a 0.4 mg dose, the average Tmax values were 26.7+/-5.8, 15.0+/-10.0, and 8.8+/-2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively. CONCLUSIONS: Nasal absorption of scopolamine hydrobromide in human subjects increased substantially with increases in formulation pH and dose.

  4. Effect of rhamnolipid biosurfactant on solubilization of polycyclic aromatic hydrocarbons.

    PubMed

    Li, Shudong; Pi, Yongrui; Bao, Mutai; Zhang, Cong; Zhao, Dongwei; Li, Yiming; Sun, Peiyan; Lu, Jinren

    2015-12-15

    Rhamnolipid biosurfactant-producing bacteria, Bacillus Lz-2, was isolated from oil polluted water collected from Dongying Shengli oilfield, China. The factors that influence PAH solubilization such as biosurfactant concentration, pH, ionic strength and temperature were discussed. The results showed that the solubilities of naphthalene, phenanthrene and pyrene increased linearly with the rise of rhamnolipid biosurfactant dose above the biosurfactant critical micelle concentration (CMC). Furthermore, the molar solubilization ratio (MSR) values decreased in the following order: naphthalene>phenanthrene>pyrene. However, the solubility percentage increased and followed the opposite order: pyrene>phenanthrene>naphthalene. The solubilities of PAHs in rhamnolipid biosurfactant solution increased with the rise of pH and ionic strength, and reached the maximum values under the conditions of pH11 and NaCl concentration 8 g · L(-1). The solubility of phenanthrene and pyrene increased with the rise of temperature. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. A Monte Carlo study of the impact of the choice of rectum volume definition on estimates of equivalent uniform doses and the volume parameter

    NASA Astrophysics Data System (ADS)

    Kvinnsland, Yngve; Muren, Ludvig Paul; Dahl, Olav

    2004-08-01

    Calculations of normal tissue complication probability (NTCP) values for the rectum are difficult because it is a hollow, non-rigid, organ. Finding the true cumulative dose distribution for a number of treatment fractions requires a CT scan before each treatment fraction. This is labour intensive, and several surrogate distributions have therefore been suggested, such as dose wall histograms, dose surface histograms and histograms for the solid rectum, with and without margins. In this study, a Monte Carlo method is used to investigate the relationships between the cumulative dose distributions based on all treatment fractions and the above-mentioned histograms that are based on one CT scan only, in terms of equivalent uniform dose. Furthermore, the effect of a specific choice of histogram on estimates of the volume parameter of the probit NTCP model was investigated. It was found that the solid rectum and the rectum wall histograms (without margins) gave equivalent uniform doses with an expected value close to the values calculated from the cumulative dose distributions in the rectum wall. With the number of patients available in this study the standard deviations of the estimates of the volume parameter were large, and it was not possible to decide which volume gave the best estimates of the volume parameter, but there were distinct differences in the mean values of the values obtained.

  6. Intensity-modulated radiotherapy improves lymph node coverage and dose to critical structures compared with three-dimensional conformal radiation therapy in clinically localized prostate cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang-Chesebro, Alice; Xia Ping; Coleman, Joy

    2006-11-01

    Purpose: The aim of this study was to quantify gains in lymph node coverage and critical structure dose reduction for whole-pelvis (WP) and extended-field (EF) radiotherapy in prostate cancer using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3DCRT) for the first treatment phase of 45 Gy in the concurrent treatment of lymph nodes and prostate. Methods and Materials: From January to August 2005, 35 patients with localized prostate cancer were treated with pelvic IMRT; 7 had nodes defined up to L5-S1 (Group 1), and 28 had nodes defined above L5-S1 (Group 2). Each patient had 2 plans retrospectively generated:more » 1 WP 3DCRT plan using bony landmarks, and 1 EF 3DCRT plan to cover the vascular defined volumes. Dose-volume histograms for the lymph nodes, rectum, bladder, small bowel, and penile bulb were compared by group. Results: For Group 1, WP 3DCRT missed 25% of pelvic nodes with the prescribed dose 45 Gy and missed 18% with the 95% prescribed dose 42.75 Gy, whereas WP IMRT achieved V{sub 45Gy} = 98% and V{sub 42.75Gy} = 100%. Compared with WP 3DCRT, IMRT reduced bladder V{sub 45Gy} by 78%, rectum V{sub 45Gy} by 48%, and small bowel V{sub 45Gy} by 232 cm{sup 3}. EF 3DCRT achieved 95% coverage of nodes for all patients at high cost to critical structures. For Group 2, IMRT decreased bladder V{sub 45Gy} by 90%, rectum V{sub 45Gy} by 54% and small bowel V{sub 45Gy} by 455 cm{sup 3} compared with EF 3DCRT. Conclusion: In this study WP 3DCRT missed a significant percentage of pelvic nodes. Although EF 3DCRT achieved 95% pelvic nodal coverage, it increased critical structure doses. IMRT improved pelvic nodal coverage while decreasing dose to bladder, rectum, small bowel, and penile bulb. For patients with extended node involvement, IMRT especially decreases small bowel dose.« less

  7. Organ dose assessment in pediatric fluoroscopy and CT via a tomographic computational phantom of the newborn patient

    NASA Astrophysics Data System (ADS)

    Staton, Robert J.

    Of the various types of imaging modalities used in pediatric radiology, fluoroscopy and computed tomography (CT) have the highest associated radiation dose. While these examinations are commonly used for pediatric patients, little data exists on the magnitude of the organ and effective dose values for these procedures. Calculation of these dose values is necessary because of children's increased sensitivity to radiation and their long life expectancy for which to express radiation's latent effects. In this study, a newborn tomographic phantom has been implemented in a radiation transport code to evaluate organ and effective doses for newborn patients in commonly performed fluoroscopy and CT examinations. Organ doses were evaluated for voiding cystourethrogram (VCUG) fluoroscopy studies of infant patients. Time-sequence analysis was performed for videotaped VCUG studies of five different patients. Organ dose values were then estimated for each patient through Monte Carlo (MC) simulations. The effective dose values of the VCUG examination for five patients ranged from 0.6 mSv to 3.2 mSv, with a mean of 1.8 +/- 0.9 mSv. Organ doses were also assessed for infant upper gastrointestinal (UGI) fluoroscopy exams. The effective dose values of the UGI examinations for five patients ranged from 1.05 mSv to 5.92 mSv, with a mean of 2.90 +/- 1.97 mSv. MC simulations of helical multislice CT (MSCT) exams were also completed using, the newborn tomographic phantom and a stylized newborn phantom. The helical path of the source, beam shaping filter, beam profile, patient table, were all included in the MC simulations of the helical MSCT scanner. Organ doses and effective doses and their dependence on scan parameters were evaluated for newborn patients. For all CT scans, the effective dose was found to range approximately 1-13 mSv, with the largest values occurring for CAP scans. Tube current modulation strategies to reduce patient dose were also evaluated for newborn patients. Overall, utilization of the newborn tomographic phantom in MC simulations has shown the need for and usefulness of pediatric tomographic phantoms. The newborn tomographic model has shown more versatility and realistic anatomical modeling when compared to the existing stylized newborn phantom. This work has provided important organ dose data for infant patients in common examinations in pediatric radiology.

  8. Changes in mammary histology and transcriptome profiles by low-dose exposure to environmental phenols at critical windows of development.

    PubMed

    Gopalakrishnan, Kalpana; Teitelbaum, Susan L; Lambertini, Luca; Wetmur, James; Manservisi, Fabiana; Falcioni, Laura; Panzacchi, Simona; Belpoggi, Fiorella; Chen, Jia

    2017-01-01

    Exposure to environmental chemicals has been linked to altered mammary development and cancer risk at high doses using animal models. Effects at low doses comparable to human exposure remain poorly understood, especially during critical developmental windows. We investigated the effects of two environmental phenols commonly used in personal care products - methyl paraben (MPB) and triclosan (TCS) - on the histology and transcriptome of normal mammary glands at low doses mimicking human exposure during critical windows of development. Sprague-Dawley rats were exposed during perinatal, prepubertal and pubertal windows, as well as from birth to lactation. Low-dose exposure to MPB and TCS induced measurable changes in both mammary histology (by Masson's Trichrome Stain) and transcriptome (by microarrays) in a window-specific fashion. Puberty represented a window of heightened sensitivity to MPB, with increased glandular tissue and changes of expression in 295 genes with significant enrichment in functions such as DNA replication and cell cycle regulation. Long-term exposure to TCS from birth to lactation was associated with increased adipose and reduced glandular and secretory tissue, with expression alterations in 993 genes enriched in pathways such as cholesterol synthesis and adipogenesis. Finally, enrichment analyses revealed that genes modified by MPB and TCS were over-represented in human breast cancer gene signatures, suggesting possible links with breast carcinogenesis. These findings highlight the issues of critical windows of susceptibility that may confer heightened sensitivity to environmental insults and implicate the potential health effects of these ubiquitous environmental chemicals in breast cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Changes in Mammary Histology and Transcriptome Profiles by Low-Dose Exposure to Environmental Phenols at Critical Windows of Development1

    PubMed Central

    Gopalakrishnan, Kalpana; Teitelbaum, Susan L.; Lambertini, Luca; Wetmur, James; Manservisi, Fabiana; Falcioni, Laura; Panzacchi, Simona; Belpoggi, Fiorella; Chen, Jia

    2016-01-01

    Exposure to environmental chemicals has been linked to altered mammary development and cancer risk at high doses using animal models. Effects at low doses comparable to human exposure remain poorly understood, especially during critical developmental windows. We investigated the effects of two environmental phenols commonly used in personal care products – methyl paraben (MPB) and triclosan (TCS) – on the histology and transcriptome of normal mammary glands at low doses mimicking human exposure during critical windows of development. Sprague-Dawley rats were exposed during perinatal, prepubertal and pubertal windows, as well as from birth to lactation. Low-dose exposure to MPB and TCS induced measurable changes in both mammary histology (by Masson’s Trichrome Stain) and transcriptome (by microarrays) in a window-specific fashion. Puberty represented a window of heightened sensitivity to MPB, with increased glandular tissue and changes of expression in 295 genes with significant enrichment in functions such as DNA replication and cell cycle regulation. Long-term exposure to TCS from birth to lactation was associated with increased adipose and reduced glandular and secretory tissue, with expression alterations in 993 genes enriched in pathways such as cholesterol synthesis and adipogenesis. Finally, enrichment analyses revealed that genes modified by MPB and TCS were over-represented in human breast cancer gene signatures, suggesting possible links with breast carcinogenesis. These findings highlight the issues of critical windows of susceptibility that may confer heightened sensitivity to environmental insults and implicate the potential health effects of these ubiquitous environmental chemicals in breast cancer. PMID:27810681

  10. Pharmacokinetics, pharmacodynamics, and dose-response relationship of repaglinide in type 2 diabetes.

    PubMed

    Strange, P; Schwartz, S L; Graf, R J; Polvino, W; Weston, I; Marbury, T C; Huang, W C; Goldberg, R B

    1999-01-01

    The pharmacodynamics and dose-response relationship of repaglinide, a novel oral hypoglycemic agent, were evaluated in steady-state treatment of patients with type 2 diabetes. Efficacy of repaglinide (0.25 mg, 0.5 mg, 1 mg, 2 mg, and 4 mg) was compared to that of placebo in a double-blind, randomized, parallel-group, 4-week dose-response clinical trial in 143 patients. Repaglinide was administered 15 minutes before meals (breakfast, lunch, and dinner). Efficacy of repaglinide therapy was assessed by measuring changes from baseline in mean levels of blood glucose (BGmean), fasting serum glucose (FSG), and mean levels of serum insulin (INSmean). Blood concentrations of repaglinide were proportional to the dose administered. INSmean values increased in all repaglinide treatment groups (by 6.7 to 12.9 microU/mL). All doses of repaglinide significantly decreased values of BGmean and FSG as compared with the placebo group. BGmean values stabilized between the second and third week of repaglinide treatment. A well-defined dose-response relationship was observed for BGmean and FSG values. All doses of repaglinide were well tolerated, and there were no serious adverse events. These findings show that the therapeutic reduction of serum glucose levels produced by repaglinide is dose-dependent for the 0.25- to 4-mg dose range. All doses of repaglinide tested were effective and well tolerated in patients with type 2 diabetes.

  11. A single institution study of radiation dose received from CT imaging: A comparison to Malaysian NDRL

    NASA Astrophysics Data System (ADS)

    Osman, N. D.; Shamsuri, S. B. M.; Tan, Y. W.; Razali, M. A. S. M.; Isa, S. M.

    2017-05-01

    Advancement of CT technology has led to an increase in CT scanning as it improves the diagnosis. However, it is important to assess health risk of patients associated with ionising radiation received from CT. This study evaluated current dose distributions at Advanced Medical and Dental Institute (AMDI), Malaysia and was used to establish Local Diagnostic Reference Level (LDRL). Dose indicators such as CT Dose Index (CTDIvol and CTDIw) and Dose-Length Product (DLP) were gathered for all routine CT examinations performed at the Imaging Unit, AMDI from January 2015 to June 2016. The first and third quartile values for each dose indicator were determined. A total of 364 CT studies were performed during that period with the highest number of cases being Thorax-Abdomen-Pelvis (TAP) study (57% of total study). The CTDIw ranged between 2.0 mGy to 23.4 mGy per procedure. DLP values were ranged between 94 mGy.cm to 1687 mGy.cm. The local dose data was compared with the national DRL to monitor the current CT practice at AMDI and LDRL will be established from the calculated third quartile values of dose distribution. From the results, some of the local dose values exceeded the Malaysian and further evaluation is important to ensure the dose optimisation for patients.

  12. Use of computer code for dose distribution studies in A 60CO industrial irradiator

    NASA Astrophysics Data System (ADS)

    Piña-Villalpando, G.; Sloan, D. P.

    1995-09-01

    This paper presents a benchmark comparison between calculated and experimental absorbed dose values tor a typical product, in a 60Co industrial irradiator, located at ININ, México. The irradiator is a two levels, two layers system with overlapping product configuration with activity around 300kCi. Experimental values were obtanied from routine dosimetry, using red acrylic pellets. Typical product was Petri dishes packages, apparent density 0.13 g/cm3; that product was chosen because uniform size, large quantity and low density. Minimum dose was fixed in 15 kGy. Calculated values were obtained from QAD-CGGP code. This code uses a point kernel technique, build-up factors fitting was done by geometrical progression and combinatorial geometry is used for system description. Main modifications for the code were related with source sumilation, using punctual sources instead of pencils and an energy and anisotropic emission spectrums were included. Results were, for maximum dose, calculated value (18.2 kGy) was 8% higher than experimental average value (16.8 kGy); for minimum dose, calculated value (13.8 kGy) was 3% higher than experimental average value (14.3 kGy).

  13. [The determination of the discrepancy between the mathematically ascertained and experimentally provable efficiency of UV facilities for water disinfection].

    PubMed

    Leuker, G; Hingst, V

    1992-10-01

    Using three UV-plants of different technical designs for water disinfection, we studied the conformity between experimental germ reduction using standard test organisms and calculated UV-doses under various water flow conditions. Taking into consideration the style of construction of the UV-plants, the irradiation area and the layer thickness were used as constant parameters for dose calculations. This was also employed for the irradiation intensity, since the experiments were performed for a relatively short period compared of the life span of the UV-irradiators. Both exposure time and water transmission were employed as variable parameters in the dose calculations and experimental procedures respectively. The calculated UV-dose and experimentally obtained germ reduction values were comparatively the same for two of the three UV-plants studied. However, no correlation was observed between the reduction of E. coli and the corresponding calculated UV-dose values. Therefore, the calculated UV-dose values for any given UV-plant should be considered to be relative and by no means absolute values. We are of the opinion that within a certain range of water flow rate and transmission, antimicrobial effectiveness of different UV-plants should be demonstrated independent of dose values, technical and other construction characteristics. The applicability of the UV-plants studied is discussed.

  14. Effect of proton pump inhibitors on gastric juice volume, gastric pH and gastric intramucosal pH in critically ill patients : a randomized, double-blind, placebo-controlled study.

    PubMed

    Gursoy, Olcay; Memiş, Dilek; Sut, Necdet

    2008-01-01

    This study aimed to determine the effect of administration of a single-dose proton pump inhibitor (PPI) on gastric intramucosal pH (pHi), gastric juice volume and gastric pH in critically ill patients. This prospective, randomized, double-blind, placebo-controlled study included 75 patients who were divided into five groups that received the following treatment: group C (n = 15), saline 100 mL; group O (n = 15), omeprazole 20 mg; group P (n = 15), pantoprazole 40 mg; group E (n = 15), esomeprazole 20 mg; and group R (n = 15), rabeprazole 20 mg. All treatments were administered nasogastrically in 100 mL of physiological saline. Measurements of gastric pHi, gastric juice volume and gastric pH were obtained immediately before and 2, 4 and 6 hours after administration of treatments. In addition, gastric content was aspirated and its volume was recorded. Initial gastric pHi, gastric juice volume and gastric pH values were not statistically significantly different among the groups (p > 0.05). No statistically significant difference in gastric pHi was seen among the groups before or 2, 4 or 6 hours after saline or PPI administration. At hours 2, 4 and 6, gastric pH in the pantoprazole, esomeprazole and rabeprazole groups increased significantly, whereas gastric juice volume decreased significantly, compared with the omeprazole and placebo groups (p < 0.001). No statistically significant differences were seen between the pantoprazole, esomeprazole and rabeprazole groups. This is the first study to show that single-dose pantoprazole, esomeprazole and rabeprazole are associated with greater gastric pH increase and greater gastric juice volume decrease than omeprazole in critically ill patients. Our study also suggests that PPIs do not affect gastric pHi measurements in critically ill patients and can be administered during pH monitoring.

  15. Double-blind evaluation of the safety and pharmacokinetics of multiple oral once-daily 750-milligram and 1-gram doses of levofloxacin in healthy volunteers.

    PubMed

    Chien, S C; Wong, F A; Fowler, C L; Callery-D'Amico, S V; Williams, R R; Nayak, R; Chow, A T

    1998-04-01

    The safety and pharmacokinetics of once-daily oral levofloxacin in 16 healthy male volunteers were investigated in a randomized, double-blind, placebo-controlled study. Subjects were randomly assigned to the treatment (n = 10) or placebo group (n = 6). In study period 1, 750 mg of levofloxacin or a placebo was administered orally as a single dose on day 1, followed by a washout period on days 2 and 3; dosing resumed for days 4 to 10. Following a 3-day washout period, 1 g of levofloxacin or a placebo was administered in a similar fashion in period 2. Plasma and urine levofloxacin concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by model-independent methods. Levofloxacin was rapidly absorbed after single and multiple once-daily 750-mg and 1-g doses with an apparently large volume of distribution. Peak plasma levofloxacin concentration (Cmax) values were generally attained within 2 h postdose. The mean values of Cmax and area under the concentration-time curve from 0 to 24 h (AUC0-24) following a single 750-mg dose were 7.1 microg/ml and 71.3 microg x h/ml, respectively, compared to 8.6 microg/ml and 90.7 microg x h/ml, respectively, at steady state. Following the single 1-g dose, mean Cmax and AUC0-24 values were 8.9 microg/ml and 95.4 microg x h/ml, respectively; corresponding values at steady state were 11.8 microg/ml and 118 microg x h/ml. These Cmax and AUC0-24 values indicate modest and similar degrees of accumulation upon multiple dosing at the two dose levels. Values of apparent total body clearance (CL/F), apparent volume of distribution (Vss/F), half-life (t1/2), and renal clearance (CL[R]) were similar for the two dose levels and did not vary from single to multiple dosing. Mean steady-state values for CL/F, Vss/F, t1/2, and CL(R) following 750 mg of levofloxacin were 143 ml/min, 100 liters, 8.8 h, and 116 ml/min, respectively; corresponding values for the 1-g dose were 146 ml/min, 105 liters, 8.9 h, and 105 ml/min. In general, the pharmacokinetics of levofloxacin in healthy subjects following 750-mg and 1-g single and multiple once-daily oral doses appear to be consistent with those found in previous studies of healthy volunteers given 500-mg doses. Levofloxacin was well tolerated at either high dose level. The most frequently reported drug-related adverse events were nausea and headache.

  16. Double-Blind Evaluation of the Safety and Pharmacokinetics of Multiple Oral Once-Daily 750-Milligram and 1-Gram Doses of Levofloxacin in Healthy Volunteers

    PubMed Central

    Chien, Shu-Chean; Wong, Frank A.; Fowler, Cynthia L.; Callery-D’Amico, Susan V.; Williams, R. Rex; Nayak, Ramchandra; Chow, Andrew T.

    1998-01-01

    The safety and pharmacokinetics of once-daily oral levofloxacin in 16 healthy male volunteers were investigated in a randomized, double-blind, placebo-controlled study. Subjects were randomly assigned to the treatment (n = 10) or placebo group (n = 6). In study period 1, 750 mg of levofloxacin or a placebo was administered orally as a single dose on day 1, followed by a washout period on days 2 and 3; dosing resumed for days 4 to 10. Following a 3-day washout period, 1 g of levofloxacin or a placebo was administered in a similar fashion in period 2. Plasma and urine levofloxacin concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by model-independent methods. Levofloxacin was rapidly absorbed after single and multiple once-daily 750-mg and 1-g doses with an apparently large volume of distribution. Peak plasma levofloxacin concentration (Cmax) values were generally attained within 2 h postdose. The mean values of Cmax and area under the concentration-time curve from 0 to 24 h (AUC0–24) following a single 750-mg dose were 7.1 μg/ml and 71.3 μg · h/ml, respectively, compared to 8.6 μg/ml and 90.7 μg · h/ml, respectively, at steady state. Following the single 1-g dose, mean Cmax and AUC0–24 values were 8.9 μg/ml and 95.4 μg · h/ml, respectively; corresponding values at steady state were 11.8 μg/ml and 118 μg · h/ml. These Cmax and AUC0–24 values indicate modest and similar degrees of accumulation upon multiple dosing at the two dose levels. Values of apparent total body clearance (CL/F), apparent volume of distribution (Vss/F), half-life (t1/2), and renal clearance (CLR) were similar for the two dose levels and did not vary from single to multiple dosing. Mean steady-state values for CL/F, Vss/F, t1/2, and CLR following 750 mg of levofloxacin were 143 ml/min, 100 liters, 8.8 h, and 116 ml/min, respectively; corresponding values for the 1-g dose were 146 ml/min, 105 liters, 8.9 h, and 105 ml/min. In general, the pharmacokinetics of levofloxacin in healthy subjects following 750-mg and 1-g single and multiple once-daily oral doses appear to be consistent with those found in previous studies of healthy volunteers given 500-mg doses. Levofloxacin was well tolerated at either high dose level. The most frequently reported drug-related adverse events were nausea and headache. PMID:9559801

  17. Levosimendan in Critical Illness: A Literature Review

    PubMed Central

    Pierrakos, Charalampos; Velissaris, Dimitrios; Franchi, Federico; Muzzi, Luigi; Karanikolas, Menelaos; Scolletta, Sabino

    2014-01-01

    Levosimendan, the active enantiomer of simendan, is a calcium sensitizer developed for treatment of decompensated heart failure, exerts its effects independently of the beta adrenergic receptor and seems beneficial in cases of severe, intractable heart failure. Levosimendan is usually administered as 24-h infusion, with or without a loading dose, but dosing needs adjustment in patients with severe liver or renal dysfunction. Despite several promising reports, the role of levosimendan in critical illness has not been thoroughly evaluated. Available evidence suggests that levosimendan is a safe treatment option in critically ill patients and may reduce mortality from cardiac failure. However, data from well-designed randomized controlled trials in critically ill patients are needed to validate or refute these preliminary conclusions. This literature review is an attempt to synthesize available evidence on the role and possible benefits of levosimendan in critically ill patients with severe heart failure. PMID:24578748

  18. Dependence of normal brain integral dose and normal tissue complication probability on the prescription isodose values for γ-knife radiosurgery

    NASA Astrophysics Data System (ADS)

    Ma, Lijun

    2001-11-01

    A recent multi-institutional clinical study suggested possible benefits of lowering the prescription isodose lines for stereotactic radiosurgery procedures. In this study, we investigate the dependence of the normal brain integral dose and the normal tissue complication probability (NTCP) on the prescription isodose values for γ-knife radiosurgery. An analytical dose model was developed for γ-knife treatment planning. The dose model was commissioned by fitting the measured dose profiles for each helmet size. The dose model was validated by comparing its results with the Leksell gamma plan (LGP, version 5.30) calculations. The normal brain integral dose and the NTCP were computed and analysed for an ensemble of treatment cases. The functional dependence of the normal brain integral dose and the NCTP versus the prescribing isodose values was studied for these cases. We found that the normal brain integral dose and the NTCP increase significantly when lowering the prescription isodose lines from 50% to 35% of the maximum tumour dose. Alternatively, the normal brain integral dose and the NTCP decrease significantly when raising the prescribing isodose lines from 50% to 65% of the maximum tumour dose. The results may be used as a guideline for designing future dose escalation studies for γ-knife applications.

  19. MO-D-BRC-01: Memorial Lecture

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fraass, B.

    Treatment planning is a central part of radiation therapy, including delineation in tumor volumes and critical organs, setting treatment goals of prescription doses to the tumor targets and tolerance doses to the critical organs, and finally generation of treatment plans to meet the treatment goals. National groups like RTOG have led the effort to standardize treatment goals of the prescription doses to the tumor targets and tolerance doses to the critical organs based on accumulated knowledge from decades of abundant clinical trial experience. The challenge for each clinical department is how to achieve or surpass these set goals within themore » time constraints of clinical practice. Using fifteen testing cases from different treatment sites such as head and neck, prostate with and without pelvic lymph nodes, SBRT spine, we will present clinically utility of advanced planning tools, including knowledge based, automatic based, and multiple criteria based tools that are clinically implemented. The objectives of this session are: Understand differences among these three advanced planning tools Provide clinical assessments on the utility of the advanced planning tools Discuss clinical challenges of treatment planning with large variations in tumor volumes and their relationships with adjacent critical organs. Ping Xia received research grant from Philips. Jackie Wu received research grant from Varian; P. Xia, Research support by Philips and Varian; Q. Wu, NIH, Varian Medical.« less

  20. MO-D-BRC-03: Knowledge-Based Planning

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, Q.

    Treatment planning is a central part of radiation therapy, including delineation in tumor volumes and critical organs, setting treatment goals of prescription doses to the tumor targets and tolerance doses to the critical organs, and finally generation of treatment plans to meet the treatment goals. National groups like RTOG have led the effort to standardize treatment goals of the prescription doses to the tumor targets and tolerance doses to the critical organs based on accumulated knowledge from decades of abundant clinical trial experience. The challenge for each clinical department is how to achieve or surpass these set goals within themore » time constraints of clinical practice. Using fifteen testing cases from different treatment sites such as head and neck, prostate with and without pelvic lymph nodes, SBRT spine, we will present clinically utility of advanced planning tools, including knowledge based, automatic based, and multiple criteria based tools that are clinically implemented. The objectives of this session are: Understand differences among these three advanced planning tools Provide clinical assessments on the utility of the advanced planning tools Discuss clinical challenges of treatment planning with large variations in tumor volumes and their relationships with adjacent critical organs. Ping Xia received research grant from Philips. Jackie Wu received research grant from Varian; P. Xia, Research support by Philips and Varian; Q. Wu, NIH, Varian Medical.« less

  1. MO-D-BRC-04: Multiple-Criteria Optimization Planning

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Donaghue, J.

    Treatment planning is a central part of radiation therapy, including delineation in tumor volumes and critical organs, setting treatment goals of prescription doses to the tumor targets and tolerance doses to the critical organs, and finally generation of treatment plans to meet the treatment goals. National groups like RTOG have led the effort to standardize treatment goals of the prescription doses to the tumor targets and tolerance doses to the critical organs based on accumulated knowledge from decades of abundant clinical trial experience. The challenge for each clinical department is how to achieve or surpass these set goals within themore » time constraints of clinical practice. Using fifteen testing cases from different treatment sites such as head and neck, prostate with and without pelvic lymph nodes, SBRT spine, we will present clinically utility of advanced planning tools, including knowledge based, automatic based, and multiple criteria based tools that are clinically implemented. The objectives of this session are: Understand differences among these three advanced planning tools Provide clinical assessments on the utility of the advanced planning tools Discuss clinical challenges of treatment planning with large variations in tumor volumes and their relationships with adjacent critical organs. Ping Xia received research grant from Philips. Jackie Wu received research grant from Varian; P. Xia, Research support by Philips and Varian; Q. Wu, NIH, Varian Medical.« less

  2. MO-D-BRC-00: In Memoriam of Jan Van De Geijn: Knowledge-Based Planning

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    Treatment planning is a central part of radiation therapy, including delineation in tumor volumes and critical organs, setting treatment goals of prescription doses to the tumor targets and tolerance doses to the critical organs, and finally generation of treatment plans to meet the treatment goals. National groups like RTOG have led the effort to standardize treatment goals of the prescription doses to the tumor targets and tolerance doses to the critical organs based on accumulated knowledge from decades of abundant clinical trial experience. The challenge for each clinical department is how to achieve or surpass these set goals within themore » time constraints of clinical practice. Using fifteen testing cases from different treatment sites such as head and neck, prostate with and without pelvic lymph nodes, SBRT spine, we will present clinically utility of advanced planning tools, including knowledge based, automatic based, and multiple criteria based tools that are clinically implemented. The objectives of this session are: Understand differences among these three advanced planning tools Provide clinical assessments on the utility of the advanced planning tools Discuss clinical challenges of treatment planning with large variations in tumor volumes and their relationships with adjacent critical organs. Ping Xia received research grant from Philips. Jackie Wu received research grant from Varian; P. Xia, Research support by Philips and Varian; Q. Wu, NIH, Varian Medical.« less

  3. MO-D-BRC-02: Auto-Planning

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Xia, P.

    Treatment planning is a central part of radiation therapy, including delineation in tumor volumes and critical organs, setting treatment goals of prescription doses to the tumor targets and tolerance doses to the critical organs, and finally generation of treatment plans to meet the treatment goals. National groups like RTOG have led the effort to standardize treatment goals of the prescription doses to the tumor targets and tolerance doses to the critical organs based on accumulated knowledge from decades of abundant clinical trial experience. The challenge for each clinical department is how to achieve or surpass these set goals within themore » time constraints of clinical practice. Using fifteen testing cases from different treatment sites such as head and neck, prostate with and without pelvic lymph nodes, SBRT spine, we will present clinically utility of advanced planning tools, including knowledge based, automatic based, and multiple criteria based tools that are clinically implemented. The objectives of this session are: Understand differences among these three advanced planning tools Provide clinical assessments on the utility of the advanced planning tools Discuss clinical challenges of treatment planning with large variations in tumor volumes and their relationships with adjacent critical organs. Ping Xia received research grant from Philips. Jackie Wu received research grant from Varian; P. Xia, Research support by Philips and Varian; Q. Wu, NIH, Varian Medical.« less

  4. TH-CD-201-03: A Real-Time Method to Simultaneously Measure Linear Energy Transfer and Dose for Proton Therapy Using Organic Scintillators

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Alsanea, F; Therriault-Proulx, F; Sawakuchi, G

    Purpose: The light generated in organic scintillators depends on both the radiation dose and the linear energy transfer (LET). The LET dependence leads to an under-response of the detector in the Bragg peak of proton beams. This phenomenon, called ionization quenching, must be corrected to obtain accurate dose measurements of proton beams. This work exploits the ionization quenching phenomenon to provide a method of measuring LET and auto correcting quenching. Methods: We exposed simultaneously four different organic scintillators (BCF-12, PMMA, PVT, and LSD; 1mm in diameter) and a plane parallel ionization chamber in passively scattered proton beams to doses betweenmore » 32 and 43 cGy and fluence averaged LET values from 0.47 to 1.26 keV/µm. The LET values for each irradiation condition were determined using a validated Monte Carlo model of the beam line. We determined the quenching parameter in the Birk’s equation for scintillation in BCF-12 for dose measurements. One set of irradiation conditions was used to correlate the scintillation response ratio to the LET values and plot a scintillation response ratio versus LET calibration curve. Irradiation conditions independent from the calibration ones were used to validate this method. Comparisons to the expected values were made on both the basis of dose and LET. Results: Among all the scintillators investigated, the ratio of PMMA to BCF-12 provided the best correlation to LET values and was used as the LET calibration curve. The expected LET values in the validation set were within 2%±6%, which resulted in dose accuracy of 1.5%±5.8% for the range of LET values investigated in this work. Conclusion: We have demonstrated the feasibility of using the ratio between the light output of two organic scintillators to simultaneously measure LET and dose of therapeutic proton beams. Further studies are needed to verify the response in higher LET values.« less

  5. Radiation Dose-Volume Effects and the Penile Bulb

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Roach, Mack, E-mail: mroach@radonc.ucsf.ed; Nam, Jiho; Gagliardi, Giovanna

    2010-03-01

    The dose, volume, and clinical outcome data for penile bulb are reviewed for patients treated with external-beam radiotherapy. Most, but not all, studies find an association between impotence and dosimetric parameters (e.g., threshold doses) and clinical factors (e.g., age, comorbid diseases). According to the data available, it is prudent to keep the mean dose to 95% of the penile bulb volume to <50 Gy. It may also be prudent to limit the D70 and D90 to 70 Gy and 50 Gy, respectively, but coverage of the planning target volume should not be compromised. It is acknowledged that the penile bulbmore » may not be the critical component of the erectile apparatus, but it seems to be a surrogate for yet to be determined structure(s) critical for erectile function for at least some techniques.« less

  6. Comparison of doses to the rectum derived from treatment planning system with in-vivo dose values in vaginal vault brachytherapy using cylinder applicators

    PubMed Central

    Obed, Rachel Ibhade; Akinlade, Bidemi Idayat; Ntekim, Atara

    2015-01-01

    Purpose In-vivo measurements to determine doses to organs-at-risk can be an essential part of brachytherapy quality assurance (QA). This study compares calculated doses to the rectum with measured dose values as a means of QA in vaginal vault brachytherapy using cylinder applicators. Material and methods At the Department of Radiotherapy, University College Hospital (UCH), Ibadan, Nigeria, intracavitary brachytherapy (ICBT) was delivered by a GyneSource high-dose-rate (HDR) unit with 60Co. Standard 2D treatment plans were created with HDR basic 2.6 software for prescription doses 5-7 Gy at points 5 mm away from the posterior surface of vaginal cylinder applicators (20, 25, and 30 mm diameters). The LiF:Mg, Ti thermoluminescent dosimeter rods (1 x 6 mm) were irradiated to a dose of 7 Gy on Theratron 60Co machine for calibration purpose prior to clinical use. Measurements in each of 34 insertions involving fourteen patients were performed with 5 TLD-100 rods placed along a re-usable rectal marker positioned in the rectum. The dosimeters were read in Harshaw 3500 TLD reader and compared with doses derived from the treatment planning system (TPS) at 1 cm away from the dose prescription points. Results The mean calculated and measured doses ranged from 2.1-3.8 Gy and 1.2-5.6 Gy with averages of 3.0 ± 0.5 Gy and 3.1 ± 1.1 Gy, respectively, for treatment lengths 2-8 cm along the cylinder-applicators. The mean values correspond to 48.9% and 50.8% of the prescribed doses, respectively. The deviations of the mean in-vivo doses from the TPS values ranged from –1.9 to 2.1 Gy with a p-value of 0.427. Conclusions This study was part of efforts to verify rectal dose obtained from the TPS during vaginal vault brachytherapy. There was no significant difference in the dose to the rectum from the two methods of measurements. PMID:26816506

  7. SU-F-J-109: Generate Synthetic CT From Cone Beam CT for CBCT-Based Dose Calculation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, H; Barbee, D; Wang, W

    Purpose: The use of CBCT for dose calculation is limited by its HU inaccuracy from increased scatter. This study presents a method to generate synthetic CT images from CBCT data by a probabilistic classification that may be robust to CBCT noise. The feasibility of using the synthetic CT for dose calculation is evaluated in IMRT for unilateral H&N cancer. Methods: In the training phase, a fuzzy c-means classification was performed on HU vectors (CBCT, CT) of planning CT and registered day-1 CBCT image pair. Using the resulting centroid CBCT and CT values for five classified “tissue” types, a synthetic CTmore » for a daily CBCT was created by classifying each CBCT voxel to obtain its probability belonging to each tissue class, then assigning a CT HU with a probability-weighted summation of the classes’ CT centroids. Two synthetic CTs from a CBCT were generated: s-CT using the centroids from classification of individual patient CBCT/CT data; s2-CT using the same centroids for all patients to investigate the applicability of group-based centroids. IMRT dose calculations for five patients were performed on the synthetic CTs and compared with CT-planning doses by dose-volume statistics. Results: DVH curves of PTVs and critical organs calculated on s-CT and s2-CT agree with those from planning-CT within 3%, while doses calculated with heterogeneity off or on raw CBCT show DVH differences up to 15%. The differences in PTV D95% and spinal cord max are 0.6±0.6% and 0.6±0.3% for s-CT, and 1.6±1.7% and 1.9±1.7% for s2-CT. Gamma analysis (2%/2mm) shows 97.5±1.6% and 97.6±1.6% pass rates for using s-CTs and s2-CTs compared with CT-based doses, respectively. Conclusion: CBCT-synthesized CTs using individual or group-based centroids resulted in dose calculations that are comparable to CT-planning dose for unilateral H&N cancer. The method may provide a tool for accurate dose calculation based on daily CBCT.« less

  8. Treatment plan comparison of linac step and shoot, tomotherapy, rapidarc, and proton therapy for prostate cancer by using the dosimetrical and the biological indices

    NASA Astrophysics Data System (ADS)

    Lee, Suk; Cao, Yuan Jie; Chang, Kyung Hwan; Shim, Jang Bo; Kim, Kwang Hyeon; Lee, Nam Kwon; Park, Young Je; Kim, Chul Yong; Cho, Sam Ju; Lee, Sang Hoon; Min, Chul Kee; Kim, Woo Chul; Cho, Kwang Hwan; Huh, Hyun Do; Lim, Sangwook; Shin, Dongho

    2015-07-01

    The purpose of this study was to use various dosimetrical indices to determine the best intensitymodulated radiation therapy (IMRT) modality - for treating patients with prostate cancer. Ten patients with prostate cancer were included in this study. IMRT plans were designed to include different modalities, including the linac step and shoot, tomotherapy, RapidArc, and proton systems. Various dosimetrical indices, like the prescription isodose to target volume (PITV) ratio, conformity index (CI), homogeneity index (HI), target coverage index (TCI), modified dose homogeneity index (MHI), conformation number (CN), critical organ scoring index (COSI), and quality factor (QF), were determined to compare the different treatment plans. Biological indices, such as the generalized equivalent uniform dose (gEUD) based the tumor control probability (TCP), and the normal tissue complication probability (NTCP), were also calculated and used to compare the treatment plans. The RapidArc plan attained better PTV coverage, as evidenced by its superior PITV, CI, TCI, MHI, and CN values. Regarding organ at risks (OARs), proton therapy exhibited superior dose sparing for the rectum and the bowel in low dose volumes, whereas the tomotherapy and RapidArc plans achieved better dose sparing in high dose volumes. The QF scores showed no significant difference among these plans (p = 0.701). The average TCPs for prostate tumors in the RapidArc, linac and proton plans were higher than the average TCP for Tomotherapy (98.79%, 98.76%, and 98.75% vs. 98.70%, respectively). Regarding the rectum NTCP, RapidArc showed the most favorable result (0.09%) whereas linac resulted in the best bladder NTCP (0.08%).

  9. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Menegotti, L.; Delana, A.; Martignano, A.

    Film dosimetry is an attractive tool for dose distribution verification in intensity modulated radiotherapy (IMRT). A critical aspect of radiochromic film dosimetry is the scanner used for the readout of the film: the output needs to be calibrated in dose response and corrected for pixel value and spatial dependent nonuniformity caused by light scattering; these procedures can take a long time. A method for a fast and accurate calibration and uniformity correction for radiochromic film dosimetry is presented: a single film exposure is used to do both calibration and correction. Gafchromic EBT films were read with two flatbed charge coupledmore » device scanners (Epson V750 and 1680Pro). The accuracy of the method is investigated with specific dose patterns and an IMRT beam. The comparisons with a two-dimensional array of ionization chambers using a 18x18 cm{sup 2} open field and an inverse pyramid dose pattern show an increment in the percentage of points which pass the gamma analysis (tolerance parameters of 3% and 3 mm), passing from 55% and 64% for the 1680Pro and V750 scanners, respectively, to 94% for both scanners for the 18x18 open field, and from 76% and 75% to 91% for the inverse pyramid pattern. Application to an IMRT beam also shows better gamma index results, passing from 88% and 86% for the two scanners, respectively, to 94% for both. The number of points and dose range considered for correction and calibration appears to be appropriate for use in IMRT verification. The method showed to be fast and to correct properly the nonuniformity and has been adopted for routine clinical IMRT dose verification.« less

  10. Sensitivity of NTCP parameter values against a change of dose calculation algorithm.

    PubMed

    Brink, Carsten; Berg, Martin; Nielsen, Morten

    2007-09-01

    Optimization of radiation treatment planning requires estimations of the normal tissue complication probability (NTCP). A number of models exist that estimate NTCP from a calculated dose distribution. Since different dose calculation algorithms use different approximations the dose distributions predicted for a given treatment will in general depend on the algorithm. The purpose of this work is to test whether the optimal NTCP parameter values change significantly when the dose calculation algorithm is changed. The treatment plans for 17 breast cancer patients have retrospectively been recalculated with a collapsed cone algorithm (CC) to compare the NTCP estimates for radiation pneumonitis with those obtained from the clinically used pencil beam algorithm (PB). For the PB calculations the NTCP parameters were taken from previously published values for three different models. For the CC calculations the parameters were fitted to give the same NTCP as for the PB calculations. This paper demonstrates that significant shifts of the NTCP parameter values are observed for three models, comparable in magnitude to the uncertainties of the published parameter values. Thus, it is important to quote the applied dose calculation algorithm when reporting estimates of NTCP parameters in order to ensure correct use of the models.

  11. Sensitivity of NTCP parameter values against a change of dose calculation algorithm

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brink, Carsten; Berg, Martin; Nielsen, Morten

    2007-09-15

    Optimization of radiation treatment planning requires estimations of the normal tissue complication probability (NTCP). A number of models exist that estimate NTCP from a calculated dose distribution. Since different dose calculation algorithms use different approximations the dose distributions predicted for a given treatment will in general depend on the algorithm. The purpose of this work is to test whether the optimal NTCP parameter values change significantly when the dose calculation algorithm is changed. The treatment plans for 17 breast cancer patients have retrospectively been recalculated with a collapsed cone algorithm (CC) to compare the NTCP estimates for radiation pneumonitis withmore » those obtained from the clinically used pencil beam algorithm (PB). For the PB calculations the NTCP parameters were taken from previously published values for three different models. For the CC calculations the parameters were fitted to give the same NTCP as for the PB calculations. This paper demonstrates that significant shifts of the NTCP parameter values are observed for three models, comparable in magnitude to the uncertainties of the published parameter values. Thus, it is important to quote the applied dose calculation algorithm when reporting estimates of NTCP parameters in order to ensure correct use of the models.« less

  12. A procedure to determine the planar integral spot dose values of proton pencil beam spots

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Anand, Aman; Sahoo, Narayan; Zhu, X. Ronald

    2012-02-15

    Purpose: Planar integral spot dose (PISD) of proton pencil beam spots (PPBSs) is a required input parameter for beam modeling in some treatment planning systems used in proton therapy clinics. The measurement of PISD by using commercially available large area ionization chambers, like the PTW Bragg peak chamber (BPC), can have large uncertainties due to the size limitation of these chambers. This paper reports the results of our study of a novel method to determine PISD values from the measured lateral dose profiles and peak dose of the PPBS. Methods: The PISDs of 72.5, 89.6, 146.9, 181.1, and 221.8 MeVmore » energy PPBSs were determined by area integration of their planar dose distributions at different depths in water. The lateral relative dose profiles of the PPBSs at selected depths were measured by using small volume ion chambers and were investigated for their angular anisotropies using Kodak XV films. The peak spot dose along the beam's central axis (D{sub 0}) was determined by placing a small volume ion chamber at the center of a broad field created by the superposition of spots at different locations. This method allows eliminating positioning uncertainties and the detector size effect that could occur when measuring it in single PPBS. The PISD was then calculated by integrating the measured lateral relative dose profiles for two different upper limits of integration and then multiplying it with corresponding D{sub 0}. The first limit of integration was set to radius of the BPC, namely 4.08 cm, giving PISD{sub RBPC}. The second limit was set to a value of the radial distance where the profile dose falls below 0.1% of the peak giving the PISD{sub full}. The calculated values of PISD{sub RBPC} obtained from area integration method were compared with the BPC measured values. Long tail dose correction factors (LTDCFs) were determined from the ratio of PISD{sub full}/PISD{sub RBPC} at different depths for PPBSs of different energies. Results: The spot profiles were found to have angular anisotropy. This anisotropy in PPBS dose distribution could be accounted in a reasonable approximate manner by taking the average of PISD values obtained using the in-line and cross-line profiles. The PISD{sub RBPC} values fall within 3.5% of those measured by BPC. Due to inherent dosimetry challenges associated with PPBS dosimetry, which can lead to large experimental uncertainties, such an agreement is considered to be satisfactory for validation purposes. The PISD{sub full} values show differences ranging from 1 to 11% from BPC measured values, which are mainly due to the size limitation of the BPC to account for the dose in the long tail regions of the spots extending beyond its 4.08 cm radius. The dose in long tail regions occur both for high energy beams such as 221.8 MeV PPBS due to the contributions of nuclear interactions products in the medium, and for low energy PPBS because of their larger spot sizes. The calculated LTDCF values agree within 1% with those determined by the Monte Carlo (MC) simulations. Conclusions: The area integration method to compute the PISD from PPBS lateral dose profiles is found to be useful both to determine the correction factors for the values measured by the BPC and to validate the results from MC simulations.« less

  13. Georgia fishery study: implications for dose calculations. Revision 1

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Turcotte, M.D.S.

    Fish consumption will contribute a major portion of the estimated individual and population doses from L-Reactor liquid releases and Cs-137 remobilization in Steel Creek. It is therefore important that the values for fish consumption used in dose calculations be as realistic as possible. Since publication of the L-Reactor Environmental Information Document (EID), data have become available on sport fishing in the Savannah River. These data provide SRP with a site-specific sport fish harvest and consumption values for use in dose calculations. The Georgia fishery data support the total population fish consumption and calculated dose reported in the EID. The datamore » indicate, however, that both the EID average and maximum individual fish consumption have been underestimated, although each to a different degree. The average fish consumption value used in the EID is approximately 3% below the lower limit of the fish consumption range calculated using the Georgia data. Maximum fish consumption in the EID has been underestimated by approximately 60%, and doses to the maximum individual should also be recalculated. Future dose calculations should utilize an average adult fish consumption value of 11.3 kg/yr, and a maximum adult fish consumption value of 34 kg/yr. Consumption values for the teen and child age groups should be increased proportionally: (1) teen average = 8.5; maximum = 25.9 kg/yr; and (2) child average = 3.6; maximum = 11.2 kg/yr. 8 refs.« less

  14. Quantifying the Reduction in Potential Health Risks by Determining the Sensitivity of Poliovirus Type 1 Chat Strain and Rotavirus SA-11 to Electron Beam Irradiation of Iceberg Lettuce and Spinach

    PubMed Central

    Espinosa, Ana Cecilia; Jesudhasan, Palmy; Arredondo, René; Cepeda, Martha; Mazari-Hiriart, Marisa; Mena, Kristi D.

    2012-01-01

    Fresh produce, such as lettuce and spinach, serves as a route of food-borne illnesses. The U.S. FDA has approved the use of ionizing irradiation up to 4 kGy as a pathogen kill step for fresh-cut lettuce and spinach. The focus of this study was to determine the inactivation of poliovirus and rotavirus on lettuce and spinach when exposed to various doses of high-energy electron beam (E-beam) irradiation and to calculate the theoretical reduction in infection risks that can be achieved under different contamination scenarios and E-beam dose applications. The D10 value (dose required to reduce virus titers by 90%) (standard error) of rotavirus on spinach and lettuce was 1.29 (± 0.64) kGy and 1.03 (± 0.05) kGy, respectively. The D10 value (standard error) of poliovirus on spinach and lettuce was 2.35 (± 0.20) kGy and 2.32 (± 0.08) kGy, respectively. Risk assessment of data showed that if a serving (∼14 g) of lettuce was contaminated with 10 PFU/g of poliovirus, E-beam irradiation at 3 kGy will reduce the risk of infection from >2 in 10 persons to approximately 6 in 100 persons. Similarly, if a serving size (∼0.8 g) of spinach is contaminated with 10 PFU/g of rotavirus, E-beam irradiation at 3 kGy will reduce infection risks from >3 in 10 persons to approximately 5 in 100 persons. The results highlight the value of employing E-beam irradiation to reduce public health risks but also the critical importance of adhering to good agricultural practices that limit enteric virus contamination at the farm and in packing houses. PMID:22179244

  15. Improved predictive model for n-decane kinetics across species, as a component of hydrocarbon mixtures.

    PubMed

    Merrill, E A; Gearhart, J M; Sterner, T R; Robinson, P J

    2008-07-01

    n-Decane is considered a major component of various fuels and industrial solvents. These hydrocarbon products are complex mixtures of hundreds of components, including straight-chain alkanes, branched chain alkanes, cycloalkanes, diaromatics, and naphthalenes. Human exposures to the jet fuel, JP-8, or to industrial solvents in vapor, aerosol, and liquid forms all have the potential to produce health effects, including immune suppression and/or neurological deficits. A physiologically based pharmacokinetic (PBPK) model has previously been developed for n-decane, in which partition coefficients (PC), fitted to 4-h exposure kinetic data, were used in preference to measured values. The greatest discrepancy between fitted and measured values was for fat, where PC values were changed from 250-328 (measured) to 25 (fitted). Such a large change in a critical parameter, without any physiological basis, greatly impedes the model's extrapolative abilities, as well as its applicability for assessing the interactions of n-decane or similar alkanes with other compounds in a mixture model. Due to these limitations, the model was revised. Our approach emphasized the use of experimentally determined PCs because many tissues had not approached steady-state concentrations by the end of the 4-h exposures. Diffusion limitation was used to describe n-decane kinetics for the brain, perirenal fat, skin, and liver. Flow limitation was used to describe the remaining rapidly and slowly perfused tissues. As expected from the high lipophilicity of this semivolatile compound (log K(ow) = 5.25), sensitivity analyses showed that parameters describing fat uptake were next to blood:air partitioning and pulmonary ventilation as critical in determining overall systemic circulation and uptake in other tissues. In our revised model, partitioning into fat took multiple days to reach steady state, which differed considerably from the previous model that assumed steady-state conditions in fat at 4 h post dosing with 1200 ppm. Due to these improvements, and particularly the reconciliation between measured and fitted partition coefficients, especially fat, we have greater confidence in using the proposed model for dose, species, and route of exposure extrapolations and as a harmonized model approach for other hydrocarbon components of mixtures.

  16. SU-F-J-59: Assessment of Dose Response Distribution in Individual Human Tumor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yan, D; Chen, S; Krauss, D

    Purpose: To fulfill precision radiotherapy via adaptive dose painting by number, voxel-by-voxel dose response or radio-sensitivity in individual human tumor needs to be determined in early treatment to guide treatment adaptation. In this study, multiple FDG PET images obtained pre- and weekly during the treatment course were utilized to determine the distribution/spectrum of dose response parameters in individual human tumors. Methods: FDG PET/CT images of 18 HN cancer patients were used in the study. Spatial parametric image of tumor metabolic ratio (dSUV) was created following voxel by voxel deformable image registration. Each voxel value in dSUV was a function ofmore » pre-treatment baseline SUV and treatment delivered dose, and used as a surrogate of tumor survival fraction (SF). Regression fitting with break points was performed using the LQ-model with tumor proliferation for the control and failure group of tumors separately. The distribution and spectrum of radiation sensitivity and growth in individual tumors were determined and evaluated. Results: Spectrum of tumor dose-sensitivity and proliferation in the controlled group was broad with α in tumor survival LQ-model from 0.17 to 0.8. It was proportional to the baseline SUV. Tlag was about 21∼25 days, and Tpot about 0.56∼1.67 days respectively. Commonly tumor voxels with high radio-sensitivity or larger α had small Tlag and Tpot. For the failure group, the radio-sensitivity α was low within 0.05 to 0.3, but did not show clear Tlag. In addition, tumor voxel radio-sensitivity could be estimated during the early treatment weeks. Conclusion: Dose response distribution with respect to radio-sensitivity and growth in individual human tumor can be determined using FDG PET imaging based tumor metabolic ratio measured in early treatment course. The discover is critical and provides a potential quantitative objective to implement tumor specific precision radiotherapy via adaptive dose painting by number.« less

  17. Medical and occupational dose reduction in pediatric barium meal procedures

    NASA Astrophysics Data System (ADS)

    Filipov, D.; Schelin, H. R.; Denyak, V.; Paschuk, S. A.; Ledesma, J. A.; Legnani, A.; Bunick, A. P.; Sauzen, J.; Yagui, A.; Vosiak, P.

    2017-11-01

    Doses received in pediatric Barium Meal procedure can be rather high. It is possible to reduce dose values following the recommendations of the European Communities (EC) and the International Commission on Radiological Protection (ICRP). In the present work, the modifications of radiographic techniques made in a Brazilian hospital according to the EC and the ICRP recommendations and their influence on medical and occupational exposure are reported. The procedures of 49 patients before and 44 after the optimization were studied and air kerma-area product (PK,A) values and the effective doses were evaluated. The occupational equivalent doses were measured next to the eyes, under the thyroid shield and on each hand of both professionals who remained inside the examination room. The implemented modifications reduced by 70% and 60% the PK,A and the patient effective dose, respectively. The obtained dose values are lower than approximately 75% of the results from similar studies. The occupational annual equivalent doses for all studied organs became lower than the limits set by the ICRP. The equivalent doses in one examination were on average below than 75% of similar studies.

  18. Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

    PubMed Central

    2013-01-01

    Background Vaccine protection investigation includes three processes: vaccination, pathogen challenge, and vaccine protection efficacy assessment. Many variables can affect the results of vaccine protection. Brucella, a genus of facultative intracellular bacteria, is the etiologic agent of brucellosis in humans and multiple animal species. Extensive research has been conducted in developing effective live attenuated Brucella vaccines. We hypothesized that some variables play a more important role than others in determining vaccine protective efficacy. Using Brucella vaccines and vaccine candidates as study models, this hypothesis was tested by meta-analysis of Brucella vaccine studies reported in the literature. Results Nineteen variables related to vaccine-induced protection of mice against infection with virulent brucellae were selected based on modeling investigation of the vaccine protection processes. The variable "vaccine protection efficacy" was set as a dependent variable while the other eighteen were set as independent variables. Discrete or continuous values were collected from papers for each variable of each data set. In total, 401 experimental groups were manually annotated from 74 peer-reviewed publications containing mouse protection data for live attenuated Brucella vaccines or vaccine candidates. Our ANOVA analysis indicated that nine variables contributed significantly (P-value < 0.05) to Brucella vaccine protection efficacy: vaccine strain, vaccination host (mouse) strain, vaccination dose, vaccination route, challenge pathogen strain, challenge route, challenge-killing interval, colony forming units (CFUs) in mouse spleen, and CFU reduction compared to control group. The other 10 variables (e.g., mouse age, vaccination-challenge interval, and challenge dose) were not found to be statistically significant (P-value > 0.05). The protection level of RB51 was sacrificed when the values of several variables (e.g., vaccination route, vaccine viability, and challenge pathogen strain) change. It is suggestive that it is difficult to protect against aerosol challenge. Somewhat counter-intuitively, our results indicate that intraperitoneal and subcutaneous vaccinations are much more effective to protect against aerosol Brucella challenge than intranasal vaccination. Conclusions Literature meta-analysis identified variables that significantly contribute to Brucella vaccine protection efficacy. The results obtained provide critical information for rational vaccine study design. Literature meta-analysis is generic and can be applied to analyze variables critical for vaccine protection against other infectious diseases. PMID:23735014

  19. Evaluation of the effect of prostate volume change on tumor control probability in LDR brachytherapy.

    PubMed

    Knaup, Courtney; Mavroidis, Panayiotis; Stathakis, Sotirios; Smith, Mark; Swanson, Gregory; Papanikolaou, Niko

    2011-09-01

    This study evaluates low dose-rate brachytherapy (LDR) prostate plans to determine the biological effect of dose degradation due to prostate volume changes. In this study, 39 patients were evaluated. Pre-implant prostate volume was determined using ultrasound. These images were used with the treatment planning system (Nucletron Spot Pro 3.1(®)) to create treatment plans using (103)Pd seeds. Following the implant, patients were imaged using CT for post-implant dosimetry. From the pre and post-implant DVHs, the biologically equivalent dose and the tumor control probability (TCP) were determined using the biologically effective uniform dose. The model used RBE = 1.75 and α/β = 2 Gy. The prostate volume changed between pre and post implant image sets ranged from -8% to 110%. TCP and the mean dose were reduced up to 21% and 56%, respectively. TCP is observed to decrease as the mean dose decreases to the prostate. The post-implant tumor dose was generally observed to decrease, compared to the planned dose. A critical uniform dose of 130 Gy was established. Below this dose, TCP begins to fall-off. It was also determined that patients with a small prostates were more likely to suffer TCP decrease. The biological effect of post operative prostate growth due to operative trauma in LDR was evaluated using the concept. The post-implant dose was lower than the planned dose due to an increase of prostate volume post-implant. A critical uniform dose of 130 Gy was determined, below which TCP begun to decline.

  20. Evaluation of the UF/NCI hybrid computational phantoms for use in organ dosimetry of pediatric patients undergoing fluoroscopically guided cardiac procedures

    NASA Astrophysics Data System (ADS)

    Marshall, Emily L.; Borrego, David; Tran, Trung; Fudge, James C.; Bolch, Wesley E.

    2018-03-01

    Epidemiologic data demonstrate that pediatric patients face a higher relative risk of radiation induced cancers than their adult counterparts at equivalent exposures. Infants and children with congenital heart defects are a critical patient population exposed to ionizing radiation during life-saving procedures. These patients will likely incur numerous procedures throughout their lifespan, each time increasing their cumulative radiation absorbed dose. As continued improvements in long-term prognosis of congenital heart defect patients is achieved, a better understanding of organ radiation dose following treatment becomes increasingly vital. Dosimetry of these patients can be accomplished using Monte Carlo radiation transport simulations, coupled with modern anatomical patient models. The aim of this study was to evaluate the performance of the University of Florida/National Cancer Institute (UF/NCI) pediatric hybrid computational phantom library for organ dose assessment of patients that have undergone fluoroscopically guided cardiac catheterizations. In this study, two types of simulations were modeled. A dose assessment was performed on 29 patient-specific voxel phantoms (taken as representing the patient’s true anatomy), height/weight-matched hybrid library phantoms, and age-matched reference phantoms. Two exposure studies were conducted for each phantom type. First, a parametric study was constructed by the attending pediatric interventional cardiologist at the University of Florida to model the range of parameters seen clinically. Second, four clinical cardiac procedures were simulated based upon internal logfiles captured by a Toshiba Infinix-i Cardiac Bi-Plane fluoroscopic unit. Performance of the phantom library was quantified by computing both the percent difference in individual organ doses, as well as the organ dose root mean square values for overall phantom assessment between the matched phantoms (UF/NCI library or reference) and the patient-specific phantoms. The UF/NCI hybrid phantoms performed at percent differences of between 15% and 30% for the parametric set of irradiation events. Among internal logfile reconstructed procedures, the UF/NCI hybrid phantoms performed with RMS organ dose values between 7% and 29%. Percent improvement in organ dosimetry via the use of hybrid library phantoms over the reference phantoms ranged from 6.6% to 93%. The use of a hybrid phantom library, Monte Carlo radiation transport methods, and clinical information on irradiation events provide a means for tracking organ dose in these radiosensitive patients undergoing fluoroscopically guided cardiac procedures. This work was supported by Advanced Laboratory for Radiation Dosimetry Studies, University of Florida, American Association of University Women, National Cancer Institute Grant 1F31 CA159464.

  1. Dosimetry and image quality assessment in a direct radiography system

    PubMed Central

    Oliveira, Bruno Beraldo; de Oliveira, Marcio Alves; Paixão, Lucas; Teixeira, Maria Helena Araújo; Nogueira, Maria do Socorro

    2014-01-01

    Objective To evaluate the mean glandular dose with a solid state detector and the image quality in a direct radiography system, utilizing phantoms. Materials and Methods Irradiations were performed with automatic exposure control and polymethyl methacrylate slabs with different thicknesses to calculate glandular dose values. The image quality was evaluated by means of the structures visualized on the images of the phantoms. Results Considering the uncertainty of the measurements, the mean glandular dose results are in agreement with the values provided by the equipment and with internationally adopted reference levels. Results obtained from images of the phantoms were in agreement with the reference values. Conclusion The present study contributes to verify the equipment conformity as regards dose values and image quality. PMID:25741119

  2. Towards quantitative imaging: stability of fully automated nodule segmentation across varied dose levels and reconstruction parameters in a low-dose CT screening patient cohort

    NASA Astrophysics Data System (ADS)

    Wahi-Anwar, M. Wasil; Emaminejad, Nastaran; Hoffman, John; Kim, Grace H.; Brown, Matthew S.; McNitt-Gray, Michael F.

    2018-02-01

    Quantitative imaging in lung cancer CT seeks to characterize nodules through quantitative features, usually from a region of interest delineating the nodule. The segmentation, however, can vary depending on segmentation approach and image quality, which can affect the extracted feature values. In this study, we utilize a fully-automated nodule segmentation method - to avoid reader-influenced inconsistencies - to explore the effects of varied dose levels and reconstruction parameters on segmentation. Raw projection CT images from a low-dose screening patient cohort (N=59) were reconstructed at multiple dose levels (100%, 50%, 25%, 10%), two slice thicknesses (1.0mm, 0.6mm), and a medium kernel. Fully-automated nodule detection and segmentation was then applied, from which 12 nodules were selected. Dice similarity coefficient (DSC) was used to assess the similarity of the segmentation ROIs of the same nodule across different reconstruction and dose conditions. Nodules at 1.0mm slice thickness and dose levels of 25% and 50% resulted in DSC values greater than 0.85 when compared to 100% dose, with lower dose leading to a lower average and wider spread of DSC values. At 0.6mm, the increased bias and wider spread of DSC values from lowering dose were more pronounced. The effects of dose reduction on DSC for CAD-segmented nodules were similar in magnitude to reducing the slice thickness from 1.0mm to 0.6mm. In conclusion, variation of dose and slice thickness can result in very different segmentations because of noise and image quality. However, there exists some stability in segmentation overlap, as even at 1mm, an image with 25% of the lowdose scan still results in segmentations similar to that seen in a full-dose scan.

  3. Solar particle event organ doses and dose equivalents for interplanetary crews: variations due to body size

    NASA Technical Reports Server (NTRS)

    Zapp, E. N.; Townsend, L. W.; Cucinotta, F. A.

    2002-01-01

    Proper assessments of spacecraft shielding requirements and concomitant estimates of risk to critical body organs of spacecraft crews from energetic space radiation require accurate, quantitative methods of characterizing the compositional changes in these radiation fields as they pass through the spacecraft and overlying tissue. When estimating astronaut radiation organ doses and dose equivalents it is customary to use the Computerized Anatomical Man (CAM) model of human geometry to account for body self-shielding. Usually, the distribution for the 50th percentile man (175 cm height; 70 kg mass) is used. Most male members of the U.S. astronaut corps are taller and nearly all have heights that deviate from the 175 cm mean. In this work, estimates of critical organ doses and dose equivalents for interplanetary crews exposed to an event similar to the October 1989 solar particle event are presented for male body sizes that vary from the 5th to the 95th percentiles. Overall the results suggest that calculations of organ dose and dose equivalent may vary by as much as approximately 15% as body size is varied from the 5th to the 95th percentile in the population used to derive the CAM model data. c2002 Published by Elsevier Science Ltd on behalf of COSPAR.

  4. [Carboxyhemoglobin concentration in carbon monoxide poisoning. Critical appraisal of the predictive value].

    PubMed

    Köthe, L; Radke, J

    2010-06-01

    In cases of unclear depression of conciousness, arrhythmia and symptoms of cardiac insufficiency inadvertent carbon monoxide intoxication should always be taken into consideration. Rapid diagnosis of acute carbon monoxide intoxication with mostly unspecific symptoms requires an immediate supply of high dose oxygen which enables a distinct reduction of mortality and long-term morbidity. Levels of carboxyhemoglobin, however, should not be used as a parameter to decide whether to supply normobaric or the more efficient hyperbaric oxygen. There is no sufficient coherence between carboxyhemoglobin blood levels and clinical symptoms. Increased carboxyhemoglobin concentrations help to diagnose acute carbon monoxide intoxication but do not allow conclusions to be drawn about possible long-term neuropsychiatric or cardiac consequences.

  5. SU-F-BRD-05: Dosimetric Comparison of Protocol-Based SBRT Lung Treatment Modalities: Statistically Significant VMAT Advantages Over Fixed- Beam IMRT

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Best, R; Harrell, A; Geesey, C

    2014-06-15

    Purpose: The purpose of this study is to inter-compare and find statistically significant differences between flattened field fixed-beam (FB) IMRT with flattening-filter free (FFF) volumetric modulated arc therapy (VMAT) for stereotactic body radiation therapy SBRT. Methods: SBRT plans using FB IMRT and FFF VMAT were generated for fifteen SBRT lung patients using 6 MV beams. For each patient, both IMRT and VMAT plans were created for comparison. Plans were generated utilizing RTOG 0915 (peripheral, 10 patients) and RTOG 0813 (medial, 5 patients) lung protocols. Target dose, critical structure dose, and treatment time were compared and tested for statistical significance. Parametersmore » of interest included prescription isodose surface coverage, target dose heterogeneity, high dose spillage (location and volume), low dose spillage (location and volume), lung dose spillage, and critical structure maximum- and volumetric-dose limits. Results: For all criteria, we found equivalent or higher conformality with VMAT plans as well as reduced critical structure doses. Several differences passed a Student's t-test of significance: VMAT reduced the high dose spillage, evaluated with conformality index (CI), by an average of 9.4%±15.1% (p=0.030) compared to IMRT. VMAT plans reduced the lung volume receiving 20 Gy by 16.2%±15.0% (p=0.016) compared with IMRT. For the RTOG 0915 peripheral lesions, the volumes of lung receiving 12.4 Gy and 11.6 Gy were reduced by 27.0%±13.8% and 27.5%±12.6% (for both, p<0.001) in VMAT plans. Of the 26 protocol pass/fail criteria, VMAT plans were able to achieve an average of 0.2±0.7 (p=0.026) more constraints than the IMRT plans. Conclusions: FFF VMAT has dosimetric advantages over fixed beam IMRT for lung SBRT. Significant advantages included increased dose conformity, and reduced organs-at-risk doses. The overall improvements in terms of protocol pass/fail criteria were more modest and will require more patient data to establish difference trends of more statistical significance.« less

  6. SU-F-19A-03: Dosimetric Advantages in Critical Structure Dose Sparing by Using a Multichannel Cylinder in High Dose Rate Brachytherapy to Treat Vaginal Cuff Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Syh, J; Syh, J; Patel, B

    2014-06-15

    Purpose: The multichannel cylindrical vaginal applicator is a variation of traditional single channel cylindrical vaginal applicator. The multichannel applicator has additional peripheral channels that provide more flexibility in the planning process. The dosimetric advantage is to reduce dose to adjacent organ at risk (OAR) such as bladder and rectum while maintaining target coverage with the dose optimization from additional channels. Methods: Vaginal HDR brachytherapy plans are all CT based. CT images were acquired in 2 mm thickness to keep integrity of cylinder contouring. The CTV of 5mm Rind with prescribed treatment length was reconstructed from 5mm expansion of inserted cylinder.more » The goal was 95% of CTV covered by 95% of prescribed dose in both single channel planning (SCP)and multichannel planning (MCP) before proceeding any further optimization for dose reduction to critical structures with emphasis on D2cc and V2Gy . Results: This study demonstrated noticeable dose reduction to OAR was apparent in multichannel plans. The D2cc of the rectum and bladder were showing the reduced dose for multichannel versus single channel. The V2Gy of the rectum was 93.72% and 83.79% (p=0.007) for single channel and multichannel respectively (Figure 1 and Table 1). To assure adequate coverage to target while reducing the dose to the OAR without any compromise is the main goal in using multichannel vaginal applicator in HDR brachytherapy. Conclusion: Multichannel plans were optimized using anatomical based inverse optimization algorithm of inverse planning simulation annealing. The optimization solution of the algorithm was to improve the clinical target volume dose coverage while reducing the dose to critical organs such as bladder, rectum and bowels. The comparison between SCP and MCP demonstrated MCP is superior to SCP where the dwell positions were based on geometric array only. It concluded that MCP is preferable and is able to provide certain features superior to SCP.« less

  7. Cell engineering: nanometric grafting of poly-N-isopropylacrylamide onto polystyrene film by different doses of gamma radiation

    PubMed Central

    Biazar, Esmaeil; Zeinali, Reza; Montazeri, Naser; Pourshamsian, Khalil; Behrouz, Mahmoud Jabarvand; Asefnejad, Azadeh; Khoshzaban, Ahad; Shahhosseini, Gholamreza; Najafabadi, Mostafa Soleimannejad; Abyani, Reza; Jamalzadeh, Hamidreza; Fouladi, Mahdi; Hagh, Sasan Rahbar F; Khamaneh, Aylar Shams; Kabiri, Soudabeh; Keshel, Saeed Heidari; Mansourkiaei, Ana

    2010-01-01

    Poly-N-isopropylacrylamide was successfully grafted onto a polystyrene cell culture dish and γ-preirradiated in air. In this study, the effect of a γ-pre-irradiation dose of radiation (radiation absorbed dosages of 10, 20, 30, 40 KGy) under appropriate temperature and grafting conditions was investigated. The Fourier transform infrared spectroscopy analysis showed the existence of the graft poly-N-isopropylacrylamide (PNIPAAm) on the substrate. The optimal value of the dose for grafting was 40 KGy at 50°C. The scanning electron microscopy and atomic force microscopy (AFM) images clearly showed that increasing the absorbed dose of radiation would increase the amount of grafting. Surface topography and graft thickness in AFM images of the radiated samples showed that the PNIPAAm at the absorbed dose of radiation was properly grafted. The thickness of these grafts was about 50–100 nm. The drop water contact angles of the best grafted sample at 37°C and 10°C were 55.3 ± 1.2° and 61.2 ± 0.9° respectively, which showed the hydrophilicity and hydrophobicity of the grafted surfaces. Differential scanning calorimetry analysis also revealed the low critical solution temperature of the grafted sample to be 32°C. Thermoresponsive polymers were grafted to dishes covalently which allowed fibroblast cells to attach and proliferate at 37°C; the cells also detached spontaneously without using enzymes when the temperature dropped below 32°C. This characteristic proves that this type of grafted material has potential as a biomaterial for cell sheet engineering. PMID:20957116

  8. Diagnostic performance and radiation dose of lower extremity CT angiography using a 128-slice dual source CT at 80 kVp and high pitch.

    PubMed

    Kim, Jin Woo; Choo, Ki Seok; Jeon, Ung Bae; Kim, Tae Un; Hwang, Jae Yeon; Yeom, Jeong A; Jeong, Hee Seok; Choi, Yoon Young; Nam, Kyung Jin; Kim, Chang Won; Jeong, Dong Wook; Lim, Soo Jin

    2016-07-01

    Multi-detector computed tomography (MDCT) angiography is now used for the diagnosing patients with peripheral arterial disease. The dose of radiation is related to variable factors, such as tube current, tube voltage, and helical pitch. To assess the diagnostic performance and radiation dose of lower extremity CT angiography (CTA) using a 128-slice dual source CT at 80 kVp and high pitch in patients with critical limb ischemia (CLI). Twenty-eight patients (mean, 64.1 years; range, 39-80 years) with CLI were enrolled in this retrospective study and underwent CTA using a 128-slice dual source CT at 80 kVp and high pitch and subsequent intra-arterial digital subtraction angiography (DSA), which was used as a reference standard for assessing diagnostic performance. For arterial segments with significant disease (>50% stenosis), overall sensitivity, specificity, and accuracy of lower extremity CTA were 94.8% (95% CI, 91.7-98.0%), 91.5% (95% CI, 87.7-95.2%), and 93.1% (95% CI, 90.6-95.6%), respectively, and its positive and negative predictive values were 91.0% (95% CI, 87.1-95.0%), and 95.1% (95% CI, 92.1-98.1%), respectively. Mean radiation dose delivered to lower extremities was 266.6 mGy.cm. Lower extremity CTA using a 128-slice dual source CT at 80 kVp and high pitch was found to have good diagnostic performance for the assessment of patients with CLI using an extremely low radiation dose. © The Foundation Acta Radiologica 2015.

  9. NOTE: Dose area product evaluations with Gafchromic® XR-R films and a flat-bed scanner

    NASA Astrophysics Data System (ADS)

    Rampado, O.; Garelli, E.; Deagostini, S.; Ropolo, R.

    2006-12-01

    Gafchromic® XR-R films are a useful tool to evaluate entrance skin dose in interventional radiology. Another dosimetric quantity of interest in diagnostic and interventional radiology is the dose area product (DAP). In this study, a method to evaluate DAP using Gafchromic® XR-R films and a flat-bed scanner was developed and tested. Film samples were exposed to an x-ray beam of 80 kVp over a dose range of 0 10 Gy. DAP measurements with films were obtained from the digitalization of a film sample positioned over the x-ray beam window during the exposure. DAP values obtained with this method were compared for 23 cardiological interventional procedures with DAP values displayed by the equipment. The overall one-sigma dose measurement uncertainty depended on the absorbed dose, with values below 6% for doses above 1 Gy. A maximum discrepancy of 16% was found, which is of the order of the differences in the DAP measurements that may occur with different calibration procedures. Based on the results presented, after an accurate calibration procedure and a thorough inspection of the relationship between the actual dose and the direct measured quantity (net optical density or net pixel value variation), Gafchromic® XR-R films can be used to assess the DAP.

  10. Estimating systemic exposure to ethinyl estradiol from an oral contraceptive.

    PubMed

    Westhoff, Carolyn L; Pike, Malcolm C; Tang, Rosalind; DiNapoli, Marianne N; Sull, Monica; Cremers, Serge

    2015-05-01

    This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive with steady-state values and to assess whether any simpler measures could provide an adequate proxy of the "gold standard" 24-hour steady-state area under the curve (AUC) value. Identification of a simple, less expensive measure of systemic ethinyl estradiol exposure would be useful for larger studies that are designed to assess the relationship between an individual's ethinyl estradiol exposure and side-effects. We collected 13 samples over 24 hours for pharmacokinetic analysis on days 1 and 21 of the first cycle of a monophasic oral contraceptive that contained 30 μg ethinyl estradiol and 150 μg levonorgestrel in 17 nonobese healthy white women. We also conducted an abbreviated single-dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of a full 13-sample steady-state pharmacokinetic analysis with results that had been calculated with the use of fewer samples (9 or 5) and after the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. The AUC, maximum, and 24-hour values were similar after the 2 single oral contraceptive doses (AUC; r=0.92). The steady-state 13-sample 24-hour AUC value was correlated highly with the average 9-sample AUC value after the 2 single doses (r=0.81; P=.0002). This correlation remained the same if the number of single-dose samples was reduced to 4, taken at time 1, 2.5, 4, and 24 hours. The 24-hour value at steady-state was correlated highly with the 24-hour steady-state AUC value (r=0.92; P<.0001). The average of the 24-hour values after the 2 single doses was also correlated quite highly with the steady-state AUC value (r=0.72; P=.0026). Limited blood sampling, including results from 2 single doses, gave highly correlated estimates of an oral contraceptive user's steady-state ethinyl estradiol exposure. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Sizes of particles formed during municipal wastewater treatment.

    PubMed

    Lech, Smoczynski; Marta, Kosobucka; Michal, Smoczynski; Harsha, Ratnaweera; Krystyna, Pieczulis-Smoczynska

    2017-02-01

    Volumetric diameters Dv and specific surface area SpS of sludge particles formed during chemical coagulation and electrocoagulation of sewage were determined. The obtained aggregate-flocs differed substantially in both Dv and SpS values. The differences in Dv and SpS values of the analyzed particles were interpreted based on theoretical models for expanding aggregates. The most uniform particles were formed under exposure to: (a) optimal and maximal doses of PIX, (b) optimal doses of PAX, (c) maximal doses of the Al electro-coagulant. The lowest PIX dose produced the least uniform particles. Sludge aggregates-particles produced under exposure to minimal doses of PIX and the Al electro-coagulant were characterized by the lowest SpS values. Sludge particles coagulated by PAX and the particles formed at higher doses of PIX and the Al electro-coagulant had higher SpS values. The particles formed at all doses of the applied coagulants and electro-coagulants were generally classified into two size ranges: the main range and the secondary range. Most particles belonged to the main size range. An increase in the percentage of colloidal hydroxide particles in sewage sludge increased SpS.

  12. Using physiologically based pharmacokinetic modeling and benchmark dose methods to derive an occupational exposure limit for N-methylpyrrolidone.

    PubMed

    Poet, T S; Schlosser, P M; Rodriguez, C E; Parod, R J; Rodwell, D E; Kirman, C R

    2016-04-01

    The developmental effects of NMP are well studied in Sprague-Dawley rats following oral, inhalation, and dermal routes of exposure. Short-term and chronic occupational exposure limit (OEL) values were derived using an updated physiologically based pharmacokinetic (PBPK) model for NMP, along with benchmark dose modeling. Two suitable developmental endpoints were evaluated for human health risk assessment: (1) for acute exposures, the increased incidence of skeletal malformations, an effect noted only at oral doses that were toxic to the dam and fetus; and (2) for repeated exposures to NMP, changes in fetal/pup body weight. Where possible, data from multiple studies were pooled to increase the predictive power of the dose-response data sets. For the purposes of internal dose estimation, the window of susceptibility was estimated for each endpoint, and was used in the dose-response modeling. A point of departure value of 390 mg/L (in terms of peak NMP in blood) was calculated for skeletal malformations based on pooled data from oral and inhalation studies. Acceptable dose-response model fits were not obtained using the pooled data for fetal/pup body weight changes. These data sets were also assessed individually, from which the geometric mean value obtained from the inhalation studies (470 mg*hr/L), was used to derive the chronic OEL. A PBPK model for NMP in humans was used to calculate human equivalent concentrations corresponding to the internal dose point of departure values. Application of a net uncertainty factor of 20-21, which incorporates data-derived extrapolation factors, to the point of departure values yields short-term and chronic occupational exposure limit values of 86 and 24 ppm, respectively. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  13. A Measurement and Analysis of Buildup Region Dose for Open Field Photon Beams (Cobalt-60 through 24 MV)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McCullough, Edwin C.

    2015-01-15

    The central axis depth dose in the build-up region (surface to d{sub max}) of single open field photon beams (cobalt-60 through 24 MV) has been measured utilizing parallel plate and extrapolation chamber methodology. These data were used to derive, for a prescription dose of 100 cGy, values of surface dose, the maximum value of dose along the central axis (D{sub max}) and the depth (nearest the surface) at which 90% of the prescription dose occurs (d{sub 90}). For both single and parallel opposed pair (POP) open field configurations, data are presented at field sizes of 5 × 5, 15 ×more » 15 and 25 × 25 cm{sup 2} for prescription depths of 10, 15 and 20 cm (midplane for POP). For the treatment machines, field sizes, and prescription depths studied, it is possible to conclude that: for single open field irradiation, surface dose values (as a percentage of the prescription dose) can be either low (<10%) or comparable to the prescription dose itself; for POP open fields, surface dose values are relatively independent of photon energy and midplane depth, and range between 30% and 70% of prescription dose, being principally dependent on field size; the depth of the initial 90 cGy point for a prescription dose of 100 cGy, d{sub 90}, was larger for POP fields. For either single or POP open field treatments, d{sub 90} was always less than 22 mm, while for 6 MV or less, values of d{sub 90} were less than 4 mm; D{sub max} values can be very large (e.g., above 300 cGy) for certain treatment situations and are reduced significantly for POP treatments; for open field POP treatments, the percent reduction in D{sub max} with each increment in beam energy above 10 MV is reduced over that seen at 10 MV or less and, possibly, this further reduction may be clinically insignificant; for open field POP treatments, changes in surface dose, d{sub 90} and D{sub max} with beam energy above 10 MV do not suggest, with regard to these specific build-up curve parameters, any obvious advantage for treatment with beam energies greater than 10 MV for the specific machines and situations studied.« less

  14. Measurements of SNAC2 area dosimeters placed in different configurations around the PROSPERO reactor and comparison with TRIPOLI-4 calculations

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rousseau, G.; Chambru, L.; Authier, N.

    2015-07-01

    In the context of criticality accident alarm system tests, several experiments were carried out in 2013 on the PROSPERO reactor to study the response to neutron and gamma of different devices and dosimeters, particularly on the SNAC2 dosimeter. This article presents the results of this criticality dosimeter in different configurations, and compares the experimental measurements with the results of calculation performed with the TRIPOLI-4 Monte-Carlo Neutral Particles transport code. PROSPERO is a metallic critical assembly managed by the Criticality, Neutron Science and Measurement Department located at the French CEA Research Center of Valduc. The core, surrounded by a reflector ofmore » depleted uranium, is composed of 2 horizontal cylindrical blocks made of a highly enriched uranium alloy which can be placed in contact, and of 4 depleted uranium control rods which allow the reactor to be driven. This reactor, placed in a cell 10 m x 8 m x 6 m high, with 1.4-meter-thick concrete walls, is used as a fast neutron spectrum source and is operated at stable power level in delayed critical state, which can vary from 3 mW to 3 kW. PROSPERO is extensively used for electronic hardening or to study the effect of the neutrons on various materials. The SNAC2 criticality dosimeter is a zone dosimeter allowing the off line measurement of criticality accident neutron doses. This dosimeter consists of the pile up of seven activation foils embedded into a 23 mm diameter x 21 mm height cadmium container. The activation measurement of each foil, using a gamma spectroscopy technique, gives information about the neutron reaction rates. The SNAC2 software allows the spectrum unfolding from these values, taking into account the hypothesis of a particular spectrum shape, in three components: a Maxwell spectrum component for the thermal range, a 1/E component for the epithermal range, and a Watt spectrum component for the high energy range. Moreover, from the neutron spectrum, the SNAC software can calculate the neutron fluence integrated by the dosimeter and the neutron dose. During the 3 weeks measurement campaign many radioprotection devices were used. To modify the spectrum seen by these devices, several shields of various thicknesses made of concrete or polyethylene, with or without cadmium covers, were placed in the PROSPERO cell. These devices allow the study of criticality accident spectra in several environments: from metal to pseudo liquid. The fluxes measured by the SNAC2 devices were compared with TRIPOLI-4 calculations. (authors)« less

  15. SU-E-T-20: A Correlation Study of 2D and 3D Gamma Passing Rates for Prostate IMRT Plans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, D; Sun Yat-sen University Cancer Center, Guangzhou, Guangdong; Wang, B

    2015-06-15

    Purpose: To investigate the correlation between the two-dimensional gamma passing rate (2D %GP) and three-dimensional gamma passing rate (3D %GP) in prostate IMRT quality assurance. Methods: Eleven prostate IMRT plans were randomly selected from the clinical database and were used to obtain dose distributions in the phantom and patient. Three types of delivery errors (MLC bank sag errors, central MLC errors and monitor unit errors) were intentionally introduced to modify the clinical plans through an in-house Matlab program. This resulted in 187 modified plans. The 2D %GP and 3D %GP were analyzed using different dose-difference and distance-toagreement (1%-1mm, 2%-2mm andmore » 3%-3mm) and 20% dose threshold. The 2D %GP and 3D %GP were then compared not only for the whole region, but also for the PTVs and critical structures using the statistical Pearson’s correlation coefficient (γ). Results: For different delivery errors, the average comparison of 2D %GP and 3D %GP showed different conclusions. The statistical correlation coefficients between 2D %GP and 3D %GP for the whole dose distribution showed that except for 3%/3mm criterion, 2D %GP and 3D %GP of 1%/1mm criterion and 2%/2mm criterion had strong correlations (Pearson’s γ value >0.8). Compared with the whole region, the correlations of 2D %GP and 3D %GP for PTV were better (the γ value for 1%/1mm, 2%/2mm and 3%/3mm criterion was 0.959, 0.931 and 0.855, respectively). However for the rectum, there was no correlation between 2D %GP and 3D %GP. Conclusion: For prostate IMRT, the correlation between 2D %GP and 3D %GP for the PTV is better than that for normal structures. The lower dose-difference and DTA criterion shows less difference between 2D %GP and 3D %GP. Other factors such as the dosimeter characteristics and TPS algorithm bias may also influence the correlation between 2D %GP and 3D %GP.« less

  16. SU-G-TeP3-01: A New Approach for Calculating Variable Relative Biological Effectiveness in IMPT Optimization

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cao, W; Randeniya, K; Grosshans, D

    2016-06-15

    Purpose: To investigate the impact of a new approach for calculating relative biological effectiveness (RBE) in intensity-modulated proton therapy (IMPT) optimization on RBE-weighted dose distributions. This approach includes the nonlinear RBE for the high linear energy transfer (LET) region, which was revealed by recent experiments at our institution. In addition, this approach utilizes RBE data as a function of LET without using dose-averaged LET in calculating RBE values. Methods: We used a two-piece function for calculating RBE from LET. Within the Bragg peak, RBE is linearly correlated to LET. Beyond the Bragg peak, we use a nonlinear (quadratic) RBE functionmore » of LET based on our experimental. The IMPT optimization was devised to incorporate variable RBE by maximizing biological effect (based on the Linear Quadratic model) in tumor and minimizing biological effect in normal tissues. Three glioblastoma patients were retrospectively selected from our institution in this study. For each patient, three optimized IMPT plans were created based on three RBE resolutions, i.e., fixed RBE of 1.1 (RBE-1.1), variable RBE based on linear RBE and LET relationship (RBE-L), and variable RBE based on linear and quadratic relationship (RBE-LQ). The RBE weighted dose distributions of each optimized plan were evaluated in terms of different RBE values, i.e., RBE-1.1, RBE-L and RBE-LQ. Results: The RBE weighted doses recalculated from RBE-1.1 based optimized plans demonstrated an increasing pattern from using RBE-1.1, RBE-L to RBE-LQ consistently for all three patients. The variable RBE (RBE-L and RBE-LQ) weighted dose distributions recalculated from RBE-L and RBE-LQ based optimization were more homogenous within the targets and better spared in the critical structures than the ones recalculated from RBE-1.1 based optimization. Conclusion: We implemented a new approach for RBE calculation and optimization and demonstrated potential benefits of improving tumor coverage and normal sparing in IMPT planning.« less

  17. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chang Jenghwa; Kowalski, Alex; Hou, Bob

    The purpose of this work was to study the feasibility of incorporating functional magnetic resonance imaging (fMRI) information for intensity modulated radiotherapy (IMRT) treatment planning of brain tumors. Three glioma patients were retrospectively replanned for radiotherapy (RT) with additional fMRI information. The fMRI of each patient was acquired using a bilateral finger-tapping paradigm with a gradient echo EPI (Echo Planer Imaging) sequence. The fMRI data were processed using the Analysis of Functional Neuroimaging (AFNI) software package for determining activation volumes, and the volumes were fused with the simulation computed tomography (CT) scan. The actived pixels in left and right primarymore » motor cortexes (PMCs) were contoured as critical structures for IMRT planning. The goal of replanning was to minimize the RT dose to the activation volumes in the PMC regions, while maintaining a similar coverage to the planning target volume (PTV) and keeping critical structures within accepted dose tolerance. Dose-volume histograms of the treatment plans with and without considering the fMRI information were compared. Beam angles adjustment or additional beams were needed for 2 cases to meet the planning criteria. Mean dose to the contralateral and ipsilateral PMC was significantly reduced by 66% and 55%, respectively, for 1 patient. For the other 2 patients, mean dose to contralateral PMC region was lowered by 73% and 69%. In general, IMRT optimization can reduce the RT dose to the PMC regions without compromising the PTV coverage or sparing of other critical organs. In conclusion, it is feasible to incorporate the fMRI information into the RT treatment planning. IMRT planning allows a significant reduction in RT dose to the PMC regions, especially if the region does not lie within the PTV.« less

  18. Estimating patient dose from CT exams that use automatic exposure control: Development and validation of methods to accurately estimate tube current values.

    PubMed

    McMillan, Kyle; Bostani, Maryam; Cagnon, Christopher H; Yu, Lifeng; Leng, Shuai; McCollough, Cynthia H; McNitt-Gray, Michael F

    2017-08-01

    The vast majority of body CT exams are performed with automatic exposure control (AEC), which adapts the mean tube current to the patient size and modulates the tube current either angularly, longitudinally or both. However, most radiation dose estimation tools are based on fixed tube current scans. Accurate estimates of patient dose from AEC scans require knowledge of the tube current values, which is usually unavailable. The purpose of this work was to develop and validate methods to accurately estimate the tube current values prescribed by one manufacturer's AEC system to enable accurate estimates of patient dose. Methods were developed that took into account available patient attenuation information, user selected image quality reference parameters and x-ray system limits to estimate tube current values for patient scans. Methods consistent with AAPM Report 220 were developed that used patient attenuation data that were: (a) supplied by the manufacturer in the CT localizer radiograph and (b) based on a simulated CT localizer radiograph derived from image data. For comparison, actual tube current values were extracted from the projection data of each patient. Validation of each approach was based on data collected from 40 pediatric and adult patients who received clinically indicated chest (n = 20) and abdomen/pelvis (n = 20) scans on a 64 slice multidetector row CT (Sensation 64, Siemens Healthcare, Forchheim, Germany). For each patient dataset, the following were collected with Institutional Review Board (IRB) approval: (a) projection data containing actual tube current values at each projection view, (b) CT localizer radiograph (topogram) and (c) reconstructed image data. Tube current values were estimated based on the actual topogram (actual-topo) as well as the simulated topogram based on image data (sim-topo). Each of these was compared to the actual tube current values from the patient scan. In addition, to assess the accuracy of each method in estimating patient organ doses, Monte Carlo simulations were performed by creating voxelized models of each patient, identifying key organs and incorporating tube current values into the simulations to estimate dose to the lungs and breasts (females only) for chest scans and the liver, kidney, and spleen for abdomen/pelvis scans. Organ doses from simulations using the actual tube current values were compared to those using each of the estimated tube current values (actual-topo and sim-topo). When compared to the actual tube current values, the average error for tube current values estimated from the actual topogram (actual-topo) and simulated topogram (sim-topo) was 3.9% and 5.8% respectively. For Monte Carlo simulations of chest CT exams using the actual tube current values and estimated tube current values (based on the actual-topo and sim-topo methods), the average differences for lung and breast doses ranged from 3.4% to 6.6%. For abdomen/pelvis exams, the average differences for liver, kidney, and spleen doses ranged from 4.2% to 5.3%. Strong agreement between organ doses estimated using actual and estimated tube current values provides validation of both methods for estimating tube current values based on data provided in the topogram or simulated from image data. © 2017 American Association of Physicists in Medicine.

  19. DALI: defining antibiotic levels in intensive care unit patients: are current β-lactam antibiotic doses sufficient for critically ill patients?

    PubMed

    Roberts, Jason A; Paul, Sanjoy K; Akova, Murat; Bassetti, Matteo; De Waele, Jan J; Dimopoulos, George; Kaukonen, Kirsi-Maija; Koulenti, Despoina; Martin, Claude; Montravers, Philippe; Rello, Jordi; Rhodes, Andrew; Starr, Therese; Wallis, Steven C; Lipman, Jeffrey

    2014-04-01

    Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations associated with maximal activity and whether antibiotic concentrations affect patient outcome. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (MIC) of the pathogen at both 50% (50% f T>MIC) and 100% (100% f T>MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (interquartile range [IQR], 48-73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14-24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f T>MIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P = .009). Positive clinical outcome was associated with increasing 50% f T>MIC and 100% f T>MIC ratios (OR, 1.02 and 1.56, respectively; P < .03), with significant interaction with sickness severity status. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.

  20. The role of dose rate in radiation cancer risk: evaluating the effect of dose rate at the molecular, cellular and tissue levels using key events in critical pathways following exposure to low LET radiation

    PubMed Central

    Brooks, Antone L.; Hoel, David G.; Preston, R. Julian

    2016-01-01

    Abstract Purpose: This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). Conclusions: Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2–30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP (2007) and BEIR VII (NRC/NAS 2006). PMID:27266588

  1. Dose in x-ray computed tomography

    NASA Astrophysics Data System (ADS)

    Kalender, Willi A.

    2014-02-01

    Radiation dose in x-ray computed tomography (CT) has become a topic of high interest due to the increasing numbers of CT examinations performed worldwide. This review aims to present an overview of current concepts for both scanner output metrics and for patient dosimetry and will comment on their strengths and weaknesses. Controversial issues such as the appropriateness of the CT dose index (CTDI) are discussed in detail. A review of approaches to patient dose assessment presently in practice, of the dose levels encountered and options for further dose optimization are also given and discussed. Patient dose assessment remains a topic for further improvement and for international consensus. All approaches presently in use are based on Monte Carlo (MC) simulations. Estimates for effective dose are established, but they are crude and not patient-specific; organ dose estimates are rarely available. Patient- and organ-specific dose estimates can be provided with adequate accuracy and independent of CTDI phantom measurements by fast MC simulations. Such information, in particular on 3D dose distributions, is important and helpful in optimization efforts. Dose optimization has been performed very successfully in recent years and even resulted in applications with effective dose values of below 1 mSv. In general, a trend towards lower dose values based on technical innovations has to be acknowledged. Effective dose values are down to clearly below 10 mSv on average, and there are a number of applications such as cardiac and pediatric CT which are performed routinely below 1 mSv on modern equipment.

  2. The feasibility of a scanner-independent technique to estimate organ dose from MDCT scans: Using CTDI{sub vol} to account for differences between scanners

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Turner, Adam C.; Zankl, Maria; DeMarco, John J.

    2010-04-15

    Purpose: Monte Carlo radiation transport techniques have made it possible to accurately estimate the radiation dose to radiosensitive organs in patient models from scans performed with modern multidetector row computed tomography (MDCT) scanners. However, there is considerable variation in organ doses across scanners, even when similar acquisition conditions are used. The purpose of this study was to investigate the feasibility of a technique to estimate organ doses that would be scanner independent. This was accomplished by assessing the ability of CTDI{sub vol} measurements to account for differences in MDCT scanners that lead to organ dose differences. Methods: Monte Carlo simulationsmore » of 64-slice MDCT scanners from each of the four major manufacturers were performed. An adult female patient model from the GSF family of voxelized phantoms was used in which all ICRP Publication 103 radiosensitive organs were identified. A 120 kVp, full-body helical scan with a pitch of 1 was simulated for each scanner using similar scan protocols across scanners. From each simulated scan, the radiation dose to each organ was obtained on a per mA s basis (mGy/mA s). In addition, CTDI{sub vol} values were obtained from each scanner for the selected scan parameters. Then, to demonstrate the feasibility of generating organ dose estimates from scanner-independent coefficients, the simulated organ dose values resulting from each scanner were normalized by the CTDI{sub vol} value for those acquisition conditions. Results: CTDI{sub vol} values across scanners showed considerable variation as the coefficient of variation (CoV) across scanners was 34.1%. The simulated patient scans also demonstrated considerable differences in organ dose values, which varied by up to a factor of approximately 2 between some of the scanners. The CoV across scanners for the simulated organ doses ranged from 26.7% (for the adrenals) to 37.7% (for the thyroid), with a mean CoV of 31.5% across all organs. However, when organ doses are normalized by CTDI{sub vol} values, the differences across scanners become very small. For the CTDI{sub vol}, normalized dose values the CoVs across scanners for different organs ranged from a minimum of 2.4% (for skin tissue) to a maximum of 8.5% (for the adrenals) with a mean of 5.2%. Conclusions: This work has revealed that there is considerable variation among modern MDCT scanners in both CTDI{sub vol} and organ dose values. Because these variations are similar, CTDI{sub vol} can be used as a normalization factor with excellent results. This demonstrates the feasibility of establishing scanner-independent organ dose estimates by using CTDI{sub vol} to account for the differences between scanners.« less

  3. Occupational dose reduction in cardiac catheterisation laboratory: a randomised trial using a shield drape placed on the patient.

    PubMed

    Ordiales, J M; Nogales, J M; Vano, E; López-Mínguez, J R; Alvarez, F J; Ramos, J; Martínez, G; Sánchez, R M

    2017-04-25

    The aim of this study was to evaluate the occupational radiation dose in interventional cardiology by using a shielding drape on the patient. A random study with and without the protective material was conducted. The following control parameters were registered: demographic data, number of stents, contrast media volume, fluoroscopy time, number of cine images, kerma-area product and cumulative air kerma. Occupational dose data were obtained by electronic active dosemeters. No statistically significant differences in the analysed control parameters were registered. The median dose value received by the interventional cardiologist was 50% lower in the group with a shielding drape with a statistically significant p-value <0.001. In addition, the median value of the maximum scatter radiation dose was 31% lower in this group with a statistically significant p-value <0.001. This study showed that a shielding drape is a useful tool for reducing the occupational radiation dose in a cardiac catheterisation laboratory. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Improving Outcomes for Esophageal Cancer using Proton Beam Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chuong, Michael D.; Hallemeier, Christopher L.; Jabbour, Salma K.

    Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with protonmore » beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT.« less

  5. Improving Outcomes for Esophageal Cancer using Proton Beam Therapy.

    PubMed

    Chuong, Michael D; Hallemeier, Christopher L; Jabbour, Salma K; Yu, Jen; Badiyan, Shahed; Merrell, Kenneth W; Mishra, Mark V; Li, Heng; Verma, Vivek; Lin, Steven H

    2016-05-01

    Radiation therapy (RT) plays an essential role in the management of esophageal cancer. Because the esophagus is a centrally located thoracic structure there is a need to balance the delivery of appropriately high dose to the target while minimizing dose to nearby critical structures. Radiation dose received by these critical structures, especially the heart and lungs, may lead to clinically significant toxicities, including pneumonitis, pericarditis, and myocardial infarction. Although technological advancements in photon RT delivery like intensity modulated RT have decreased the risk of such toxicities, a growing body of evidence indicates that further risk reductions are achieved with proton beam therapy (PBT). Herein we review the published dosimetric and clinical PBT literature for esophageal cancer, including motion management considerations, the potential for reirradiation, radiation dose escalation, and ongoing esophageal PBT clinical trials. We also consider the potential cost-effectiveness of PBT relative to photon RT. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. A Novel Simple Phantom for Verifying the Dose of Radiation Therapy

    PubMed Central

    Lee, J. H.; Chang, L. T.; Shiau, A. C.; Chen, C. W.; Liao, Y. J.; Li, W. J.; Lee, M. S.; Hsu, S. M.

    2015-01-01

    A standard protocol of dosimetric measurements is used by the organizations responsible for verifying that the doses delivered in radiation-therapy institutions are within authorized limits. This study evaluated a self-designed simple auditing phantom for use in verifying the dose of radiation therapy; the phantom design, dose audit system, and clinical tests are described. Thermoluminescent dosimeters (TLDs) were used as postal dosimeters, and mailable phantoms were produced for use in postal audits. Correction factors are important for converting TLD readout values from phantoms into the absorbed dose in water. The phantom scatter correction factor was used to quantify the difference in the scattered dose between a solid water phantom and homemade phantoms; its value ranged from 1.084 to 1.031. The energy-dependence correction factor was used to compare the TLD readout of the unit dose irradiated by audit beam energies with 60Co in the solid water phantom; its value was 0.99 to 1.01. The setup-condition factor was used to correct for differences in dose-output calibration conditions. Clinical tests of the device calibrating the dose output revealed that the dose deviation was within 3%. Therefore, our homemade phantoms and dosimetric system can be applied for accurately verifying the doses applied in radiation-therapy institutions. PMID:25883980

  7. Sensitivity and specificity of dosing alerts for dosing errors among hospitalized pediatric patients

    PubMed Central

    Stultz, Jeremy S; Porter, Kyle; Nahata, Milap C

    2014-01-01

    Objectives To determine the sensitivity and specificity of a dosing alert system for dosing errors and to compare the sensitivity of a proprietary system with and without institutional customization at a pediatric hospital. Methods A retrospective analysis of medication orders, orders causing dosing alerts, reported adverse drug events, and dosing errors during July, 2011 was conducted. Dosing errors with and without alerts were identified and the sensitivity of the system with and without customization was compared. Results There were 47 181 inpatient pediatric orders during the studied period; 257 dosing errors were identified (0.54%). The sensitivity of the system for identifying dosing errors was 54.1% (95% CI 47.8% to 60.3%) if customization had not occurred and increased to 60.3% (CI 54.0% to 66.3%) with customization (p=0.02). The sensitivity of the system for underdoses was 49.6% without customization and 60.3% with customization (p=0.01). Specificity of the customized system for dosing errors was 96.2% (CI 96.0% to 96.3%) with a positive predictive value of 8.0% (CI 6.8% to 9.3). All dosing errors had an alert over-ridden by the prescriber and 40.6% of dosing errors with alerts were administered to the patient. The lack of indication-specific dose ranges was the most common reason why an alert did not occur for a dosing error. Discussion Advances in dosing alert systems should aim to improve the sensitivity and positive predictive value of the system for dosing errors. Conclusions The dosing alert system had a low sensitivity and positive predictive value for dosing errors, but might have prevented dosing errors from reaching patients. Customization increased the sensitivity of the system for dosing errors. PMID:24496386

  8. Quantitative evaluation of 3D dosimetry for stereotactic volumetric‐modulated arc delivery using COMPASS

    PubMed Central

    Manigandan, Durai; Karrthick, Karukkupalayam Palaniappan; Sambasivaselli, Raju; Senniandavar, Vellaingiri; Ramu, Mahendran; Rajesh, Thiyagarajan; Lutz, Muller; Muthukumaran, Manavalan; Karthikeyan, Nithyanantham; Tejinder, Kataria

    2014-01-01

    The purpose of this study was to evaluate quantitatively the patient‐specific 3D dosimetry tool COMPASS with 2D array MatriXX detector for stereotactic volumetric‐modulated arc delivery. Twenty‐five patients CT images and RT structures from different sites (brain, head & neck, thorax, abdomen, and spine) were taken from CyberKnife Multiplan planning system for this study. All these patients underwent radical stereotactic treatment in CyberKnife. For each patient, linac based volumetric‐modulated arc therapy (VMAT) stereotactic plans were generated in Monaco TPS v3.1 using Elekta Beam Modulator MLC. Dose prescription was in the range of 5–20 Gy per fraction. Target prescription and critical organ constraints were tried to match the delivered treatment plans. Each plan quality was analyzed using conformity index (CI), conformity number (CN), gradient Index (GI), target coverage (TC), and dose to 95% of volume (D95). Monaco Monte Carlo (MC)‐calculated treatment plan delivery accuracy was quantitatively evaluated with COMPASS‐calculated (CCA) dose and COMPASS indirectly measured (CME) dose based on dose‐volume histogram metrics. In order to ascertain the potential of COMPASS 3D dosimetry for stereotactic plan delivery, 2D fluence verification was performed with MatriXX using MultiCube phantom. Routine quality assurance of absolute point dose verification was performed to check the overall delivery accuracy. Quantitative analyses of dose delivery verification were compared with pass and fail criteria of 3 mm and 3% distance to agreement and dose differences. Gamma passing rate was compared with 2D fluence verification from MatriXX with MultiCube. Comparison of COMPASS reconstructed dose from measured fluence and COMPASS computed dose has shown a very good agreement with TPS calculated dose. Each plan was evaluated based on dose volume parameters for target volumes such as dose at 95% of volume (D95) and average dose. For critical organs dose at 20% of volume (D20), dose at 50% of volume (D50), and maximum point doses were evaluated. Comparison was carried out using gamma analysis with passing criteria of 3 mm and 3%. Mean deviation of 1.9%±1% was observed for dose at 95% of volume (D95) of target volumes, whereas much less difference was noticed for critical organs. However, significant dose difference was noticed in two cases due to the smaller tumor size. Evaluation of this study revealed that the COMPASS 3D dosimetry is efficient and easy to use for patient‐specific QA of VMAT stereotactic delivery. 3D dosimetric QA with COMPASS provides additional degrees of freedom to check the high‐dose modulated stereotactic delivery with very high precision on patient CT images. PACS numbers: 87.55.Qr, 87.56.Fc PMID:25679152

  9. Approaches to the risk assessment of genotoxic carcinogens in food: a critical appraisal.

    PubMed

    O'Brien, J; Renwick, A G; Constable, A; Dybing, E; Müller, D J G; Schlatter, J; Slob, W; Tueting, W; van Benthem, J; Williams, G M; Wolfreys, A

    2006-10-01

    The present paper examines the particular difficulties presented by low levels of food-borne DNA-reactive genotoxic carcinogens, some of which may be difficult to eliminate completely from the diet, and proposes a structured approach for the evaluation of such compounds. While the ALARA approach is widely applicable to all substances in food that are both carcinogenic and genotoxic, it does not take carcinogenic potency into account and, therefore, does not permit prioritisation based on potential risk or concern. In the absence of carcinogenicity dose-response data, an assessment based on comparison with an appropriate threshold of toxicological concern may be possible. When carcinogenicity data from animal bioassays are available, a useful analysis is achieved by the calculation of margins of exposure (MOEs), which can be used to compare animal potency data with human exposure scenarios. Two reference points on the dose-response relationship that can be used for MOE calculation were examined; the T25 value, which is derived from linear extrapolation, and the BMDL10, which is derived from mathematical modelling of the dose-response data. The above approaches were applied to selected food-borne genotoxic carcinogens. The proposed approach is applicable to all substances in food that are DNA-reactive genotoxic carcinogens and enables the formulation of appropriate semi-quantitative advice to risk managers.

  10. Kidney Function in Obesity-Challenges in Indexing and Estimation.

    PubMed

    Chang, Alex R; Zafar, Waleed; Grams, Morgan E

    2018-01-01

    As the prevalence of obesity continues to increase worldwide, an increasing number of people are at risk for kidney disease. Thus, there is a critical need to understand how best to assess kidney function in this population, and several challenges exist. The convention of indexing glomerular filtration rate (GFR) to body surface area (BSA) attempts to normalize exposure to metabolic wastes across populations of differing body size. In obese individuals, this convention results in a significantly lower indexed GFR than unindexed GFR, which has practical implications for drug dosing. Recent data suggest that "unindexing" estimated GFR (multiplying by BSA/1.73 m 2 ) for drug dosing may be acceptable, but pharmocokinetic data to support this practice are lacking. Beyond indexing, biomarkers commonly used for estimating GFR may induce bias. Creatinine is influenced by muscle mass, whereas cystatin C correlates with fat mass, both independent of kidney function. Further research is needed to evaluate the performance of estimating equations and other filtration markers in obesity, and determine whether unindexed GFR might better predict optimal drug dosing and clinical outcomes in patients whose BSA is very different than the conventional normalized value of 1.73 m 2 . Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  11. Critical Value Reporting at Egyptian Laboratories.

    PubMed

    Mosallam, Rasha; Ibrahim, Samaa Zenhom

    2015-06-12

    To examine critical value reporting policies and practices and to identify critical value ranges for selected common laboratory assays at inpatient division of laboratories of Alexandria hospitals. A cross-sectional descriptive study design was used. Subjects were from inpatient division of all laboratories of Alexandria hospitals (40 laboratories). Data were collected using a questionnaire composed of 4 sections. The first section explored hospital and laboratory characteristics. The second section assessed policies and procedures of critical value reporting. The third section explored the reporting process. The fourth section explored critical value ranges for selected common laboratory assays. Written procedure for reporting of critical values was present in 77.5% of laboratories and a comprehensive list of critical values in 72.55%. For laboratories having a critical value list, the number of tests in the list ranged from 7 to 40. Three-fifths of laboratories had a policy for assessing the timeliness of reporting and 3 quarters stated that the laboratory policy requires feedback (60.0% and 75.0%, respectively). The hospital laboratory physician was responsible for critical value reporting followed by the laboratory technician (75.0% and 50.0%, respectively). The call is received mainly by nurses and physicians ordering the test (67.5% and 55.0%, respectively) and the channel of reporting is mainly the telephone or through sending test report to the ward (67.5% and 50.0%, respectively). Wireless technologies are used in reporting in only 10.0% of hospitals. The cutoff limits for reporting different assays showed considerable interlaboratory variation. Critical value policies and practices showed interinstitutional variation with deficiencies in some reporting practices. Selection of critical assays for notification and setting the limits of notification exhibited wide variation as well.

  12. Study of variables affecting critical value notification in a laboratory catering to tertiary care hospital.

    PubMed

    Agarwal, Rachna; Chhillar, Neelam; Tripathi, Chandra B

    2015-01-01

    During post-analytical phase, critical value notification to responsible caregiver in a timely manner has potential to improve patient safety which requires cooperative efforts between laboratory personnel and caregivers. It is widely accepted by hospital accreditors that ineffective notification can lead to diagnostic errors that potentially harm patients and are preventable. The objective of the study was to assess the variables affecting critical value notification, their role in affecting it's quality and approaches to improve it. In the present study 1,187 critical values were analysed in the Clinical Chemistry Laboratory catering to tertiary care hospital for neuropsychiatric diseases. During 25 months of study period, we evaluated critical value notification with respect to clinical care area, caregiver to whom it was notified and timeliness of notification. During the study period (25 months), the laboratory obtained 1,279 critical values in clinical chemistry. The analytes most commonly notified were sodium and potassium (20.97 & 20.8 % of total critical results). Analysis of critical value notification versus area of care showed that critical value notification was high in ICU and emergency area followed by inpatients and 64.61 % critical values were notified between 30 and 120 min after receiving the samples. It was found that failure to notify the responsible caregiver in timely manner represent an important patient safety issue and may lead to diagnostic errors. The major area of concern are notification of critical value for outpatient samples, incompleteness of test requisition forms regarding illegible writing, lack of information of treating physician and location of test ordering and difficulty in contacting the responsible caregiver.

  13. Red marrow and blood dosimetry in 131I treatment of metastatic thyroid carcinoma: pre-treatment versus in-therapy results

    NASA Astrophysics Data System (ADS)

    Giostra, A.; Richetta, E.; Pasquino, M.; Miranti, A.; Cutaia, C.; Brusasco, G.; Pellerito, R. E.; Stasi, M.

    2016-06-01

    Treatment with radioiodine is a standard procedure for patients with well-differentiated thyroid cancer, but the main approach to the therapy is still empiric, consisting of the administration of fixed activities. A predictive individualized dosimetric study may represent an important tool for physicians to determine the best activity to prescribe. The aim of this work is to compare red marrow and blood absorbed dose values obtained in the pre-treatment (PT) dosimetry phase with those obtained in the in-treatment (IT) dosimetry phase in order to estimate the predictive power of PT trial doses and to determine if they can be used as a decision-making tool to safely administer higher 131I activity to potentially increase the efficacy of treatment. The PT and IT dosimetry for 50 patients has been evaluated using three different dosimetric approaches. In all three approaches blood and red marrow doses, are calculated as the sum of two components, the dose from 131I activity in the blood and the dose from 131I activity located in the remainder of the body (i.e. the blood and whole-body contributions to the total dose). PT and IT dose values to blood and red marrow appear to be well correlated irrespective of the dosimetric approach used. Linear regression analyses of PT and IT total doses, for blood and red marrow, and the whole-body contribution to these doses, showed consistent best fit slope and correlation coefficient values of approximately 0.9 and 0.6, respectively: analyses of the blood dose contribution to the total doses also yielded similar values for the best fit slope but with correlation coefficient values of approximately 0.4 reflecting the greater variance in these dose estimates. These findings suggest that pre-treatment red marrow dose assessments may represent an important tool to personalize metastatic thyroid cancer treatment, removing the constraints of a fixed activity approach and permitting potentially more effective higher 131I activities to be safely used in-treatment.

  14. Differences in pharmacokinetics and pharmacodynamics of colistimethate sodium (CMS) and colistin between three different CMS dosage regimens in a critically ill patient infected by a multidrug-resistant Acinetobacter baumannii.

    PubMed

    Luque, Sònia; Grau, Santiago; Valle, Marta; Sorlí, Luisa; Horcajada, Juan Pablo; Segura, Concha; Alvarez-Lerma, Francisco

    2013-08-01

    Use of colistin has re-emerged for the treatment of infections caused by multidrug-resistant (MDR) Gram-negative bacteria, but information on its pharmacokinetics and pharmacodynamics is limited, especially in critically ill patients. Recent data from pharmacokinetic/pharmacodynamic (PK/PD) population studies have suggested that this population could benefit from administration of higher than standard doses of colistimethate sodium (CMS), but the relationship between administration of incremental doses of CMS and corresponding PK/PD parameters as well as its efficacy and toxicity have not yet been investigated in a clinical setting. The objective was to study the PK/PD differences of CMS and colistin between three different CMS dosage regimens in the same critically ill patient. A critically ill patient with nosocomial pneumonia caused by a MDR Acinetobacter baumannii received incremental doses of CMS. During administration of the different CMS dosage regimens, CMS and colistin plasma concentrations were determined and PK/PD indexes were calculated. With administration of the highest CMS dose once daily (720 mg every 24h), the peak plasma concentration of CMS and colistin increased to 40.51 mg/L and 1.81 mg/L, respectively, and the AUC0-24/MIC of colistin was 184.41. This dosage regimen was efficacious, and no nephrotoxicity or neurotoxicity was observed. In conclusion, a higher and extended-interval CMS dosage made it possible to increase the exposure of CMS and colistin in a critically ill patient infected by a MDR A. baumannii and allowed a clinical and microbiological optimal response to be achieved without evidence of toxicity. Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  15. Problems in evaluating radiation dose via terrestrial and aquatic pathways.

    PubMed Central

    Vaughan, B E; Soldat, J K; Schreckhise, R G; Watson, E C; McKenzie, D H

    1981-01-01

    This review is concerned with exposure risk and the environmental pathways models used for predictive assessment of radiation dose. Exposure factors, the adequacy of available data, and the model subcomponents are critically reviewed from the standpoint of absolute error propagation. Although the models are inherently capable of better absolute accuracy, a calculated dose is usually overestimated by from two to six orders of magnitude, in practice. The principal reason for so large an error lies in using "generic" concentration ratios in situations where site specific data are needed. Major opinion of the model makers suggests a number midway between these extremes, with only a small likelihood of ever underestimating the radiation dose. Detailed evaluations are made of source considerations influencing dose (i.e., physical and chemical status of released material); dispersal mechanisms (atmospheric, hydrologic and biotic vector transport); mobilization and uptake mechanisms (i.e., chemical and other factors affecting the biological availability of radioelements); and critical pathways. Examples are shown of confounding in food-chain pathways, due to uncritical application of concentration ratios. Current thoughts of replacing the critical pathways approach to calculating dose with comprehensive model calculations are also shown to be ill-advised, given present limitations in the comprehensive data base. The pathways models may also require improved parametrization, as they are not at present structured adequately to lend themselves to validation. The extremely wide errors associated with predicting exposure stand in striking contrast to the error range associated with the extrapolation of animal effects data to the human being. PMID:7037381

  16. SU-E-T-72: A Retrospective Correlation Analysis On Dose-Volume Control Points and Treatment Outcomes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Roy, A; Nohadani, O; Refaat, T

    2015-06-15

    Purpose: To quantify correlation between dose-volume control points and treatment outcomes. Specifically, two outcomes are analyzed: occurrence of radiation induced dysphagia and target complications. The results inform the treatment planning process when competing dose-volume criteria requires relaxations. Methods: 32 patients, treated with whole-field sequential intensity modulated radiation therapy during 2009–2010 period, are considered for this study. Acute dysphagia that is categorized into 3 grades is observed on all patients. 3 patients are observed in grade 1, 17 patients in grade 2, and 12 patients in grade 3. Ordinal logistic regression is employed to establish correlations between grades of dysphagia andmore » dose to cervico-thoracic esophagus. Particularly, minimum (Dmin), mean (Dmean), and maximum (Dmax) dose control points are analyzed. Additionally, target complication, which includes local-regional recurrence and/or distant metastasis, is observed on 4 patients. Binary logistic regression is used to quantify correlation between target complication and four dose control points. Namely, ICRU recommended dose control points, D2, D50, D95, and D98 are analyzed. Results: For correlation with dysphagia, Dmin on cervico-thoracic esophagus is statistically significant (p-value = 0.005). Additionally, Dmean on cervico-thoracic esophagus is also significant in association with dysphagia (p-value = 0.012). However, no correlation was observed between Dmax and dysphagia (p-value = 0.263). For target complications, D50 on the target is a statistically significant dose control point (p-value = 0.032). No correlations were observed between treatment complications and D2 (p-value = 0.866), D95 (p-value = 0.750), and D98 (p-value = 0.710) on the target. Conclusion: Significant correlations are observed between radiation induced dysphagia and Dmean (and Dmin) to cervico-thoracic esophagus. Additionally, correlation between target complications and median dose to target (D50) is observed. Quantification of these correlations can inform treatment planners when any competing objectives requires relaxation of target D50 or Dmean (or Dmin) to cervico-thoracic esophagus.« less

  17. SU-F-J-13: Choosing An IMRT Technique in the Treatment of Head and Neck Cancer with Daily Localization Uncertainties

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lin, T; Wang, L; Galloway, T

    Purpose: Head and Neck cancer treatment with IMRT/VMAT has two choices: split-filed IMRT(SFI), in which the LAN is treated with a separate anterior field and the extended whole-field IMRT(WFI) in which LAN is included with the IMRT/VMAT field. This study shows that under the same dose limit criteria, choosing the technique becomes a critical issue if daily localization and immobilization altered the dose distribution. Methods: Nine common head-and-neck cancer cases were chosen to illustrate how the daily localization and immobilization uncertainties affect to choose between SFI and WFI. Both SFI and WFI at upper target coverage were generated with VMAT.more » For each case, the same planning criteria were applied to the target and critical structures; therefore, similar target coverage and dose falloff can be observed in both techniques. Thirty days of kV cone beam CT(CBCT) images on each case were also delineated with contralateral and ipsilateral target as well as larynx as critical structure. About 300 CBCT images with daily delivered doses were analyzed and compared in a form of dose-volume histograms. Results: While both plans for SFI and WFI with VMAT planning utilized and meet the criteria of D95>prescription dose and for not-involved larynx with mean dose <35Gy and V55<10%, the daily localization and immobilization has a great contribution to the resulted dose delivery. With WFI, the better daily contralateral and ipsilateral neck target coverage can reflect a simpler or shorter localization; however, a much superior avoidance (WFI: mean dose a 42.5Gy; SFI: mean dose a 18.9Gy) of the non-involved larynx from the SFI is preferred. Conclusion: Dosimetrically, SFI and WFI are equally well for head and Neck cancer treatment with VMAT technique; however, if considering the contribution of daily localization(CBCT) method uncertainties, SFI is better with sparing non-involved larynx and WFI has better target coverage.« less

  18. Study protocol for a phase II dose evaluation randomized controlled trial of cholecalciferol in critically ill children with vitamin D deficiency (VITdAL-PICU study).

    PubMed

    McNally, Dayre; Amrein, Karin; O'Hearn, Katharine; Fergusson, Dean; Geier, Pavel; Henderson, Matt; Khamessan, Ali; Lawson, Margaret L; McIntyre, Lauralyn; Redpath, Stephanie; Weiler, Hope A; Menon, Kusum

    2017-01-01

    Clinical research has recently demonstrated that vitamin D deficiency (VDD) is highly prevalent in the pediatric intensive care unit (PICU) and associated with worse clinical course. Multiple adult ICU trials have suggested that optimization of vitamin D status through high-dose supplementation may reduce mortality and improve other clinically relevant outcomes; however, there have been no trials of rapid normalization in the PICU setting. The objective of this study is to evaluate the safety and efficacy of an enteral weight-based cholecalciferol loading dose regimen in critically ill children with VDD. The VITdAL-PICU pilot study is designed as a multicenter placebo-controlled phase II dose evaluation pilot randomized controlled trial. We aim to randomize 67 VDD critically ill children using a 2:1 randomization schema to receive loading dose enteral cholecalciferol (10,000 IU/kg, maximum of 400,000 IU) or a placebo solution. Participants, caregivers and outcome assessors will be blinded to allocation. Eligibility criteria include ICU patient, aged 37 weeks to 18 years, expected ICU length of stay more than 48 h, anticipated access to bloodwork at 7 days, and VDD (blood total 25 hydroxyvitamin D < 50 nmol/L). The primary objective is to determine whether the dosing protocol normalizes vitamin D status, defined as a blood total 25(OH)D concentration above 75 nmol/L. Secondary objectives include an examination of the safety of the dosing regimen (e.g. hypercalcemia, hypercalciuria, nephrocalcinosis), measures of vitamin D axis function (e.g. calcitriol levels, immune function), and protocol feasibility (eligibility criteria, protocol deviations, blinding). Despite significant observational literature suggesting VDD to be a modifiable risk factor in the PICU setting, there is no robust clinical trial evidence evaluating the benefits of rapid normalization. This phase II clinical trial will evaluate an innovative weight-based dosing regimen intended to rapidly and safely normalize vitamin D levels in critically ill children. Study findings will be used to inform the design of a multicenter phase III trial evaluating the clinical and economic benefits to rapid normalization. Recruitment for this trial was initiated in January 2016 and is expected to continue until November 30, 2017. Clinicaltrials.gov NCT02452762.

  19. Copper and cobalt accumulation in plants: a critical assessment of the current state of knowledge.

    PubMed

    Lange, Bastien; van der Ent, Antony; Baker, Alan John Martin; Echevarria, Guillaume; Mahy, Grégory; Malaisse, François; Meerts, Pierre; Pourret, Olivier; Verbruggen, Nathalie; Faucon, Michel-Pierre

    2017-01-01

    This review synthesizes contemporary understanding of copper-cobalt (Cu-Co) tolerance and accumulation in plants. Accumulation of foliar Cu and Co to > 300 μg g -1 is exceptionally rare globally, and known principally from the Copperbelt of Central Africa. Cobalt accumulation is also observed in a limited number of nickel (Ni) hyperaccumulator plants occurring on ultramafic soils around the world. None of the putative Cu or Co hyperaccumulator plants appears to comply with the fundamental principle of hyperaccumulation, as foliar Cu-Co accumulation is strongly dose-dependent. Abnormally high plant tissue Cu concentrations occur only when plants are exposed to high soil Cu with a low root to shoot translocation factor. Most Cu-tolerant plants are Excluders sensu Baker and therefore setting nominal threshold values for Cu hyperaccumulation is not informative. Abnormal accumulation of Co occurs under similar circumstances in the Copperbelt of Central Africa as well as sporadically in Ni hyperaccumulator plants on ultramafic soils; however, Co-tolerant plants behave physiologically as Indicators sensu Baker. Practical application of Cu-Co accumulator plants in phytomining is limited due to their dose-dependent accumulation characteristics, although for Co field trials may be warranted on highly Co-contaminated mineral wastes because of its relatively high metal value. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  20. Validation of a low dose simulation technique for computed tomography images.

    PubMed

    Muenzel, Daniela; Koehler, Thomas; Brown, Kevin; Zabić, Stanislav; Fingerle, Alexander A; Waldt, Simone; Bendik, Edgar; Zahel, Tina; Schneider, Armin; Dobritz, Martin; Rummeny, Ernst J; Noël, Peter B

    2014-01-01

    Evaluation of a new software tool for generation of simulated low-dose computed tomography (CT) images from an original higher dose scan. Original CT scan data (100 mAs, 80 mAs, 60 mAs, 40 mAs, 20 mAs, 10 mAs; 100 kV) of a swine were acquired (approved by the regional governmental commission for animal protection). Simulations of CT acquisition with a lower dose (simulated 10-80 mAs) were calculated using a low-dose simulation algorithm. The simulations were compared to the originals of the same dose level with regard to density values and image noise. Four radiologists assessed the realistic visual appearance of the simulated images. Image characteristics of simulated low dose scans were similar to the originals. Mean overall discrepancy of image noise and CT values was -1.2% (range -9% to 3.2%) and -0.2% (range -8.2% to 3.2%), respectively, p>0.05. Confidence intervals of discrepancies ranged between 0.9-10.2 HU (noise) and 1.9-13.4 HU (CT values), without significant differences (p>0.05). Subjective observer evaluation of image appearance showed no visually detectable difference. Simulated low dose images showed excellent agreement with the originals concerning image noise, CT density values, and subjective assessment of the visual appearance of the simulated images. An authentic low-dose simulation opens up opportunity with regard to staff education, protocol optimization and introduction of new techniques.

  1. Dexmedetomidine reduces pain associated with rocuronium injection without causing a decrease in BIS values: a dose-response study.

    PubMed

    Joo, Jin; Baek, Jungwon; Lee, Jaemin

    2014-09-01

    To examine whether dexmedetomidine reduces the injection pain of propofol and rocuronium and to investigate whether the decrease in injection pain is associated with the known sedative action of dexmedetomidine. Randomized, double-blind, placebo-controlled clinical comparison study. Patients undergoing general anesthesia with intubation received 40 mg of 1% lidocaine (lidocaine group; n = 28), 0.25 μg/kg of dexmedetomidine (low-dose group; n = 27), 0.5 μg/kg of dexmedetomidine (subclinical dose group; n = 28), 1.0 μg/kg of dexmedetomidine (clinical dose group, n = 27), or normal saline (saline group; n = 28) before anesthetic induction. Pain associated with propofol and rocuronium injection was assessed using a 10-point verbal analog scale (VAS) and a 4-point withdrawal movement scale, respectively. The BIS value was measured 60 seconds after administration of the study drug, and at the time of rocuronium injection and intubation. The overall incidence of withdrawal movements due to rocuronium decreased significantly as the dose of dexmedetomidine increased (92.8%, 85.2%, 78.6%, and 51.9% in the saline, low-dose, subclinical dose, and clinical dose groups, respectively; P = 0.001). There was no significant difference in BIS values among the groups 60 seconds after study drug administration or at the time of rocuronium injection. Dexmedetomidine reduced pain associated with rocuronium injection in a dose-dependent manner. This effect was not associated with the decrease in BIS value. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography.

    PubMed

    Gerritsen, M G; Willemink, M J; Pompe, E; van der Bruggen, T; van Rhenen, A; Lammers, J W J; Wessels, F; Sprengers, R W; de Jong, P A; Minnema, M C

    2017-01-01

    We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose.

  3. Improving early diagnosis of pulmonary infections in patients with febrile neutropenia using low-dose chest computed tomography

    PubMed Central

    Pompe, E.; van der Bruggen, T.; van Rhenen, A.; Lammers, J. W. J.; Wessels, F.; Sprengers, R. W.; de Jong, P. A.; Minnema, M. C.

    2017-01-01

    We performed a prospective study in patients with chemotherapy induced febrile neutropenia to investigate the diagnostic value of low-dose computed tomography compared to standard chest radiography. The aim was to compare both modalities for detection of pulmonary infections and to explore performance of low-dose computed tomography for early detection of invasive fungal disease. The low-dose computed tomography remained blinded during the study. A consensus diagnosis of the fever episode made by an expert panel was used as reference standard. We included 67 consecutive patients on the first day of febrile neutropenia. According to the consensus diagnosis 11 patients (16.4%) had pulmonary infections. Sensitivity, specificity, positive predictive value and negative predictive value were 36%, 93%, 50% and 88% for radiography, and 73%, 91%, 62% and 94% for low-dose computed tomography, respectively. An uncorrected McNemar showed no statistical difference (p = 0.197). Mean radiation dose for low-dose computed tomography was 0.24 mSv. Four out of 5 included patients diagnosed with invasive fungal disease had radiographic abnormalities suspect for invasive fungal disease on the low-dose computed tomography scan made on day 1 of fever, compared to none of the chest radiographs. We conclude that chest radiography has little value in the initial assessment of febrile neutropenia on day 1 for detection of pulmonary abnormalities. Low-dose computed tomography improves detection of pulmonary infiltrates and seems capable of detecting invasive fungal disease at a very early stage with a low radiation dose. PMID:28235014

  4. Determination of dosimetric quantities in pediatric abdominal computed tomography scans*

    PubMed Central

    Jornada, Tiago da Silva; da Silva, Teógenes Augusto

    2014-01-01

    Objective Aiming at contributing to the knowledge on doses in computed tomography (CT), this study has the objective of determining dosimetric quantities associated with pediatric abdominal CT scans, comparing the data with diagnostic reference levels (DRL). Materials and methods The study was developed with a Toshiba Asteion single-slice CT scanner and a GE BrightSpeed multi-slice CT unit in two hospitals. Measurements were performed with a pencil-type ionization chamber and a 16 cm-diameter polymethylmethacrylate trunk phantom. Results No significant difference was observed in the values for weighted air kerma index (CW), but the differences were relevant in values for volumetric air kerma index (CVOL), air kerma-length product (PKL,CT) and effective dose. Conclusion Only the CW values were lower than the DRL, suggesting that dose optimization might not be necessary. However, PKL,CT and effective dose values stressed that there still is room for reducing pediatric radiation doses. The present study emphasizes the importance of determining all dosimetric quantities associated with CT scans. PMID:25741103

  5. SU-E-T-657: Quantitative Assessment of Plan Robustness for Helical Tomotherapy for Head and Neck Cancer Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Matney, J; Lian, J; Chera, B

    2015-06-15

    Introduction: Geometric uncertainties in daily patient setup can lead to variations in the planned dose, especially when using highly conformal techniques such as helical Tomotherapy. To account for the potential effect of geometric uncertainty, our clinical practice is to expand critical structures by 3mm expansion into planning risk volumes (PRV). The PRV concept assumes the spatial dose cloud is insensitive to patient positioning. However, no tools currently exist to determine if a Tomotherapy plan is robust to the effects of daily setup variation. We objectively quantified the impact of geometric uncertainties on the 3D doses to critical normal tissues duringmore » helical Tomotherapy. Methods: Using a Matlab-based program created and validated by Accuray (Madison, WI), the planned Tomotherapy delivery sinogram recalculated dose on shifted CT datasets. Ten head and neck patients were selected for analysis. To simulate setup uncertainty, the patient anatomy was shifted ±3mm in the longitudinal, lateral and vertical axes. For each potential shift, the recalculated doses to various critical normal tissues were compared to the doses delivered to the PRV in the original plan Results: 18 shifted scenarios created from Tomotherapy plans for three patients with head and neck cancers were analyzed. For all simulated setup errors, the maximum doses to the brainstem, spinal cord, parotids and cochlea were no greater than 0.6Gy of the respective original PRV maximum. Despite 3mm setup shifts, the minimum dose delivered to 95% of the CTVs and PTVs were always within 0.4Gy of the original plan. Conclusions: For head and neck sites treated with Tomotherapy, the use of a 3mm PRV expansion provide a reasonable estimate of the dosimetric effects of 3mm setup uncertainties. Similarly, target coverage appears minimally effected by a 3mm setup uncertainty. Data from a larger number of patients will be presented. Future work will include other anatomical sites.« less

  6. SU-F-T-537: Prone Breast Accelerated Partial Breast Irradiation Using Non-Coplanar Volumetric Arc Therapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Beninati, G; Barbiere, J; Godfrey, L

    2016-06-15

    Purpose: To demonstrate that Volumetric Modulated Arc Therapy (VMAT) can be an alternative technique to Brachytherapy Accelerated Partial Breast Irradiation (APBI) for treating large breasted women. The non-coplanar VMAT technique uses a commercially available couch and a small number of angles. This technique with the patient in the prone position can reduce high skin and critical structure doses in large breasted women, which are usually associated with Brachytherapy APBI. Methods: Philips Pinnacle treatment planning system with Smart Arc was used to plan a left sided laterally located excision cavity on a standard prone breast patient setup. Three thirty-degree arcs enteredmore » from the lateral side at respective couch angles of 345, 0, and 15 degrees. A fourth thirty degree arc beam entered from the medial side at a couch angle of 0 degrees. The arcs were selected to avoid critical structures as much as possible. A test run was then performed to verify that the beams did not collide with the patient nor support structures. NSABP B-39/RTOG 0413 protocol guidelines were used for dose prescription, normal tissue, and target definition. Results: Dose Volume Histogram analysis indicated that all parameters were equal or better than RTOG recommendations. Of particular note regarding the plan quality:1.(a) For a prescribed dose of 3850cGy the PTV-EVAL target volume receiving 100 percent of the dose(V100) was 93; protocol recommendation is V90 > 90 percent. (b) Maximum dose was 110 percent versus the allowed 120 percent .2. Uninvolved percentage of normal breast V100 and V50 were 17 and 47 versus allowed 35 and 60 percent respectively.3. For the skin, V100 was 5.7cc and the max dose to 0.1 cc was 4190cGy. Conclusion: Prone Breast non-coplanar VMAT APBI can achieve better skin cosmesis and lower critical structure doses than Brachytherapy APBI.« less

  7. Quantitative Analysis of Electron Beam Damage in Organic Thin Films

    PubMed Central

    2017-01-01

    In transmission electron microscopy (TEM) the interaction of an electron beam with polymers such as P3HT:PCBM photovoltaic nanocomposites results in electron beam damage, which is the most important factor limiting acquisition of structural or chemical data at high spatial resolution. Beam effects can vary depending on parameters such as electron dose rate, temperature during imaging, and the presence of water and oxygen in the sample. Furthermore, beam damage will occur at different length scales. To assess beam damage at the angstrom scale, we followed the intensity of P3HT and PCBM diffraction rings as a function of accumulated electron dose by acquiring dose series and varying the electron dose rate, sample preparation, and the temperature during acquisition. From this, we calculated a critical dose for diffraction experiments. In imaging mode, thin film deformation was assessed using the normalized cross-correlation coefficient, while mass loss was determined via changes in average intensity and standard deviation, also varying electron dose rate, sample preparation, and temperature during acquisition. The understanding of beam damage and the determination of critical electron doses provides a framework for future experiments to maximize the information content during the acquisition of images and diffraction patterns with (cryogenic) transmission electron microscopy. PMID:28553431

  8. The influence of crystal structure on ion-irradiation tolerance in the Sm(x)Yb(2-x)TiO5 series

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Aughterson, R. D.; Lumpkin, G. R.; de los Reyes, M.

    2016-04-01

    his ion-irradiation study covers the four major crystal structure types in the Ln(2)TiO(5) series (Ln = lanthanide), namely orthorhombic Pnma, hexagonal P63/mmc, cubic (pyrochlore-like) Fd-3m and cubic (fluorite-like) Fm-3m. This is the first systematic examination of the complete Ln(2)TiO(5) crystal system and the first reported examination of the hexagonal structure. A series of samples, based on the stoichiometry Sm(x)Yb(2-x)TiO5 (where x = 2, 1.4, 1, 0.6, and 0) have been irradiated using 1 MeV Kr2+ ions and characterised in-situ using a transmission electron microscope. Two quantities are used to define ion-irradiation tolerance: critical dose of amorphisation (D-c), which is themore » irradiating ion dose required for a crystalline to amorphous transition, and the critical temperature (T-c), above which the sample cannot be rendered amorphous by ion irradiation. The structure type plus elements of bonding are correlated to ion-irradiation tolerance. The cubic phases, Yb2TiO5 and Sm0.6Yb1.4TiO5, were found to be the most radiation tolerant, with Tc values of 479 and 697 K respectively. The improved radiation tolerance with a change in symmetry to cubic is consistent with previous studies of similar compounds.« less

  9. Pediatric patient and staff dose measurements in barium meal fluoroscopic procedures

    NASA Astrophysics Data System (ADS)

    Filipov, D.; Schelin, H. R.; Denyak, V.; Paschuk, S. A.; Porto, L. E.; Ledesma, J. A.; Nascimento, E. X.; Legnani, A.; Andrade, M. E. A.; Khoury, H. J.

    2015-11-01

    This study investigates patient and staff dose measurements in pediatric barium meal series fluoroscopic procedures. It aims to analyze radiographic techniques, measure the air kerma-area product (PKA), and estimate the staff's eye lens, thyroid and hands equivalent doses. The procedures of 41 patients were studied, and PKA values were calculated using LiF:Mg,Ti thermoluminescent dosimeters (TLDs) positioned at the center of the patient's upper chest. Furthermore, LiF:Mg,Cu,P TLDs were used to estimate the equivalent doses. The results showed a discrepancy in the radiographic techniques when compared to the European Commission recommendations. Half of the results of the analyzed literature presented lower PKA and dose reference level values than the present study. The staff's equivalent doses strongly depends on the distance from the beam. A 55-cm distance can be considered satisfactory. However, a distance decrease of ~20% leads to, at least, two times higher equivalent doses. For eye lenses this dose is significantly greater than the annual limit set by the International Commission on Radiological Protection. In addition, the occupational doses were found to be much higher than in the literature. Changing the used radiographic techniques to the ones recommended by the European Communities, it is expected to achieve lower PKA values ​​and occupational doses.

  10. FIIDOS--A Computer Code for the Computation of Fallout Inhalation and Ingestion Dose to Organs Computer User’s Guide (Revision 4)

    DTIC Science & Technology

    2007-05-01

    35 5 Actinide product radionuclides... actinides , and fission products in fallout. Doses from low-linear energy transfer (LET) radiation (beta particles and gamma rays) are reported separately...assumptions about the critical parameters used in calculating internal doses – resuspension factor, breathing rate, fractionation, and scenario elements – to

  11. Dose-rate-dependent damage of cerium dioxide in the scanning transmission electron microscope.

    PubMed

    Johnston-Peck, Aaron C; DuChene, Joseph S; Roberts, Alan D; Wei, Wei David; Herzing, Andrew A

    2016-11-01

    Beam damage caused by energetic electrons in the transmission electron microscope is a fundamental constraint limiting the collection of artifact-free information. Through understanding the influence of the electron beam, experimental routines may be adjusted to improve the data collection process. Investigations of CeO 2 indicate that there is not a critical dose required for the accumulation of electron beam damage. Instead, measurements using annular dark field scanning transmission electron microscopy and electron energy loss spectroscopy demonstrate that the onset of measurable damage occurs when a critical dose rate is exceeded. The mechanism behind this phenomenon is that oxygen vacancies created by exposure to a 300keV electron beam are actively annihilated as the sample re-oxidizes in the microscope environment. As a result, only when the rate of vacancy creation exceeds the recovery rate will beam damage begin to accumulate. This observation suggests that dose-intensive experiments can be accomplished without disrupting the native structure of the sample when executed using dose rates below the appropriate threshold. Furthermore, the presence of an encapsulating carbonaceous layer inhibits processes that cause beam damage, markedly increasing the dose rate threshold for the accumulation of damage. Published by Elsevier B.V.

  12. Dose-rate-dependent damage of cerium dioxide in the scanning transmission electron microscope

    PubMed Central

    Johnston-Peck, Aaron C.; DuChene, Joseph S.; Roberts, Alan D.; Wei, Wei David; Herzing, Andrew A.

    2016-01-01

    Beam damage caused by energetic electrons in the transmission electron microscope is a fundamental constraint limiting the collection of artifact-free information. Through understanding the influence of the electron beam, experimental routines may be adjusted to improve the data collection process. Investigations of CeO2 indicate that there is not a critical dose required for the accumulation of electron beam damage. Instead, measurements using annular dark field scanning transmission electron microscopy and electron energy loss spectroscopy demonstrate that the onset of measurable damage occurs when a critical dose rate is exceeded. The mechanism behind this phenomenon is that oxygen vacancies created by exposure to a 300 keV electron beam are actively annihilated as the sample re-oxidizes in the microscope environment. As a result, only when the rate of vacancy creation exceeds the recovery rate will beam damage begin to accumulate. This observation suggests that dose-intensive experiments can be accomplished without disrupting the native structure of the sample when executed using dose rates below the appropriate threshold. Furthermore, the presence of an encapsulating carbonaceous layer inhibits processes that cause beam damage, markedly increasing the dose rate threshold for the accumulation of damage. PMID:27469265

  13. Variability of surface and center position radiation dose in MDCT: Monte Carlo simulations using CTDI and anthropomorphic phantoms

    PubMed Central

    Zhang, Di; Savandi, Ali S.; Demarco, John J.; Cagnon, Chris H.; Angel, Erin; Turner, Adam C.; Cody, Dianna D.; Stevens, Donna M.; Primak, Andrew N.; McCollough, Cynthia H.; McNitt-Gray, Michael F.

    2009-01-01

    The larger coverage afforded by wider z-axis beams in multidetector CT (MDCT) creates larger cone angles and greater beam divergence, which results in substantial surface dose variation for helical and contiguous axial scans. This study evaluates the variation of absorbed radiation dose in both cylindrical and anthropomorphic phantoms when performing helical or contiguous axial scans. The approach used here was to perform Monte Carlo simulations of a 64 slice MDCT. Simulations were performed with different radiation profiles (simulated beam widths) for a given collimation setting (nominal beam width) and for different pitch values and tube start angles. The magnitude of variation at the surface was evaluated under four different conditions: (a) a homogeneous CTDI phantom with different combinations of pitch and simulated beam widths, (b) a heterogeneous anthropomorphic phantom with one measured beam collimation and various pitch values, (c) a homogeneous CTDI phantom with fixed beam collimation and pitch, but with different tube start angles, and (d) pitch values that should minimize variations of surface dose—evaluated for both homogeneous and heterogeneous phantoms. For the CTDI phantom simulations, peripheral dose patterns showed variation with percent ripple as high as 65% when pitch is 1.5 and simulated beam width is equal to the nominal collimation. For the anterior surface dose on an anthropomorphic phantom, the percent ripple was as high as 40% when the pitch is 1.5 and simulated beam width is equal to the measured beam width. Low pitch values were shown to cause beam overlaps which created new peaks. Different x-ray tube start angles create shifts of the peripheral dose profiles. The start angle simulations showed that for a given table position, the surface dose could vary dramatically with minimum values that were 40% of the peak when all conditions are held constant except for the start angle. The last group of simulations showed that an “ideal” pitch value can be determined which reduces surface dose variations, but this pitch value must take into account the measured beam width. These results reveal the complexity of estimating surface dose and demonstrate a range of dose variability at surface positions for both homogeneous cylindrical and heterogeneous anthropomorphic phantoms. These findings have potential implications for small-sized dosimeter measurements in phantoms, such as with TLDs or small Farmer chambers. PMID:19378763

  14. Sex differences in nicotine self-administration in rats during progressive unit dose reduction: implications for nicotine regulation policy.

    PubMed

    Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G

    2013-12-01

    Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06mg/kg) under an FR 3 schedule during daily 23h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose-response relationships were very well described by the exponential demand function (r(2) values>0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from males. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Dosimetric verification of small fields in the lung using lung-equivalent polymer gel and Monte Carlo simulation.

    PubMed

    Gharehaghaji, Nahideh; Dadgar, Habib Alah

    2018-01-01

    The main purpose of this study was evaluate a polymer-gel-dosimeter (PGD) for three-dimensional verification of dose distributions in the lung that is called lung-equivalent gel (LEG) and then to compare its result with Monte Carlo (MC) method. In the present study, to achieve a lung density for PGD, gel is beaten until foam is obtained, and then sodium dodecyl sulfate is added as a surfactant to increase the surface tension of the gel. The foam gel was irradiated with 1 cm × 1 cm field size in the 6 MV photon beams of ONCOR SIEMENS LINAC, along the central axis of the gel. The LEG was then scanned on a 1.5 Tesla magnetic resonance imaging scanner after irradiation using a multiple-spin echo sequence. Least-square fitting the pixel values from 32 consecutive images using a single exponential decay function derived the R2 relaxation rates. Moreover, 6 and 18 MV photon beams of ONCOR SIEMENS LINAC are simulated using MCNPX MC Code. The MC model is used to calculate the depth dose water and low-density water resembling the soft tissue and lung, respectively. Percentages of dose reduction in the lung region relative to homogeneous phantom for 6 MV photon beam were 44.6%, 39%, 13%, and 7% for 0.5 cm × 0.5 cm, 1 cm × 1 cm, 2 cm × 2 cm, and 3 cm × 3 cm fields, respectively. For 18 MV photon beam, the results were found to be 82%, 69%, 46%, and 25.8% for the same field sizes, respectively. Preliminary results show good agreement between depth dose measured with the LEG and the depth dose calculated using MCNP code. Our study showed that the dose reduction with small fields in the lung was very high. Thus, inaccurate prediction of absorbed dose inside the lung and also lung/soft-tissue interfaces with small photon beams may lead to critical consequences for treatment outcome.

  16. Evaluation of dosimetry and image of very low-dose computed tomography attenuation correction for pediatric positron emission tomography/computed tomography: phantom study

    NASA Astrophysics Data System (ADS)

    Bahn, Y. K.; Park, H. H.; Lee, C. H.; Kim, H. S.; Lyu, K. Y.; Dong, K. R.; Chung, W. K.; Cho, J. H.

    2014-04-01

    In this study, phantom was used to evaluate attenuation correction computed tomography (CT) dose and image in case of pediatric positron emission tomography (PET)/CT scan. Three PET/CT scanners were used along with acryl phantom in the size for infant and ion-chamber dosimeter. The CT image acquisition conditions were changed from 10 to 20, 40, 80, 100 and 160 mA and from 80 to 100, 120 and 140 kVp, which aimed at evaluating penetrate dose and computed tomography dose indexvolume (CTDIvol) value. And NEMA PET Phantom™ was used to obtain PET image under the same CT conditions in order to evaluate each attenuation-corrected PET image based on standard uptake value (SUV) value and signal-to-noise ratio (SNR). In general, the penetrate dose was reduced by around 92% under the minimum CT conditions (80 kVp and 10 mA) with the decrease in CTDIvol value by around 88%, compared with the pediatric abdomen CT conditions (100 kVp and 100 mA). The PET image with its attenuation corrected according to each CT condition showed no change in SUV value and no influence on the SNR. In conclusion, if the minimum dose CT that is properly applied to body of pediatric patient is corrected for attenuation to ensure that the effective dose is reduced by around 90% or more compared with that for adult patient, this will be useful to reduce radiation exposure level.

  17. Dose reduction and cost-benefit analysis at Japan`s Tokai No. 2 Plant

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Humamoto, Hisao; Suzuki, Seishiro; Taniguchi, Kazufumi

    1995-03-01

    In the Tokai No. 2 power plant of the Japan Atomic Power Company, about 80% of the annual dose equivalent is received during periodic maintenance outages. A project group for dose reduction was organized at the company`s headquarters in 1986; in 1988, they proposed a five-year program to reduce by half the collective dose of 4 person-Sv per normal outage work. To achieve the target dose value, some dose-reduction measures were undertaken, namely, permanent radiation shielding, decontamination, automatic, operating machines, and ALARA organization. As the result, the collective dose from normal outage work was 1.6 person-Sv in 1992, which wasmore » less than the initial target value.« less

  18. Risk analysis of hematopoietic stem cell transplant process: failure mode, effect, and criticality analysis and hazard analysis critical control point methods integration based on guidelines to good manufacturing practice for medicinal product ANNEX 20 (February 2008).

    PubMed

    Gianassi, S; Bisin, S; Bindi, B; Spitaleri, I; Bambi, F

    2010-01-01

    The collection and handling of hematopoietic stem cells (HSCs) must meet high quality requirements. An integrated Quality Risk Management can help to identify and contain potential risks related to HSC production. Risk analysis techniques allow one to "weigh" identified hazards, considering the seriousness of their effects, frequency, and detectability, seeking to prevent the most harmful hazards. The Hazard Analysis Critical Point, recognized as the most appropriate technique to identify risks associated with physical, chemical, and biological hazards for cellular products, consists of classifying finished product specifications and limits of acceptability, identifying all off-specifications, defining activities that can cause them, and finally establishing both a monitoring system for each Critical Control Point and corrective actions for deviations. The severity of possible effects on patients, as well as the occurrence and detectability of critical parameters, are measured on quantitative scales (Risk Priority Number [RPN]). Risk analysis was performed with this technique on manipulation process of HPC performed at our blood center. The data analysis showed that hazards with higher values of RPN with greater impact on the process are loss of dose and tracking; technical skills of operators and manual transcription of data were the most critical parameters. Problems related to operator skills are handled by defining targeted training programs, while other critical parameters can be mitigated with the use of continuous control systems. The blood center management software was completed by a labeling system with forms designed to be in compliance with standards in force and by starting implementation of a cryopreservation management module. Copyright 2010 Elsevier Inc. All rights reserved.

  19. Vitamin A status of Filipino preschool children given a massive oral dose.

    PubMed

    Perlas, L A; Florentino, R F; Fuertes, R T; Madriaga, J R; Cheong, R L; Desnacido, J A; Marcos, J M; Cabrera, M I

    1996-12-01

    The protection period of a 200,000 IU of vitamin A on Filipino children was determined. Subjects were 105 children aged 1-5 years given a single massive dose during the "Araw ng Sangkap Pinoy" (ASAP) in March 1995. Serum retinol was measured by HPLC at baseline, one, two, four and six months after the administration of the dose. Results showed that baseline serum retinol levels were significantly lower than all follow-up values. Serum retinol values were maintained at levels higher than pre-supplementation values although the values decreased on the second month after supplementation. The proportions of deficient and low (< 20 microg/dl) levels were significantly lower one and six months after supplementation. All follow-up serum retinol levels of children with deficient and low values at baseline were significantly lower (p < 0.001) than those with normal values. The WHO recommendation of 200,000 IU was effective in increasing serum retinol concentrations and maintaining it above pre-supplementation levels up to 6 months after administration of the dose. It also replenished organic vitamin A reserves as shown by the dose response (S30DR) approach. Incidence of infection also decreased among the children. Supplementation with vitamin A has likewise resulted in an increase in hemoglobin values and a decrease in the proportion of anemics (Hb < 11.0 g/dl) among the children.

  20. Internal photon and electron dosimetry of the newborn patient—a hybrid computational phantom study

    NASA Astrophysics Data System (ADS)

    Wayson, Michael; Lee, Choonsik; Sgouros, George; Treves, S. Ted; Frey, Eric; Bolch, Wesley E.

    2012-03-01

    Estimates of radiation absorbed dose to organs of the nuclear medicine patient are a requirement for administered activity optimization and for stochastic risk assessment. Pediatric patients, and in particular the newborn child, represent that portion of the patient population where such optimization studies are most crucial owing to the enhanced tissue radiosensitivities and longer life expectancies of this patient subpopulation. In cases where whole-body CT imaging is not available, phantom-based calculations of radionuclide S values—absorbed dose to a target tissue per nuclear transformation in a source tissue—are required for dose and risk evaluation. In this study, a comprehensive model of electron and photon dosimetry of the reference newborn child is presented based on a high-resolution hybrid-voxel phantom from the University of Florida (UF) patient model series. Values of photon specific absorbed fraction (SAF) were assembled for both the reference male and female newborn using the radiation transport code MCNPX v2.6. Values of electron SAF were assembled in a unique and time-efficient manner whereby the collisional and radiative components of organ dose--for both self- and cross-dose terms—were computed separately. Dose to the newborn skeletal tissues were assessed via fluence-to-dose response functions reported for the first time in this study. Values of photon and electron SAFs were used to assemble a complete set of S values for some 16 radionuclides commonly associated with molecular imaging of the newborn. These values were then compared to those available in the OLINDA/EXM software. S value ratios for organ self-dose ranged from 0.46 to 1.42, while similar ratios for organ cross-dose varied from a low of 0.04 to a high of 3.49. These large discrepancies are due in large part to the simplistic organ modeling in the stylized newborn model used in the OLINDA/EXM software. A comprehensive model of internal dosimetry is presented in this study for the newborn nuclear medicine patient based upon the UF hybrid computational phantom. Photon dose response functions, photon and electron SAFs, and tables of radionuclide S values for the newborn child--both male and female--are given in a series of four electronic annexes available at stacks.iop.org/pmb/57/1433/mmedia. These values can be applied to optimization studies of image quality and stochastic risk for this most vulnerable class of pediatric patients.

  1. Considerations for theoretical modeling of thermal ablation with catheter-based ultrasonic sources: implications for treatment planning, monitoring and control

    PubMed Central

    Prakash, Punit; Diederich, Chris J.

    2012-01-01

    Purpose To determine the impact of including dynamic changes in tissue physical properties during heating on feedback controlled thermal ablation with catheter-based ultrasound. Additionally, we compared impact several indicators of thermal damage on predicted extents of ablation zones for planning and monitoring ablations with this modality. Methods A 3D model of ultrasound ablation with interstitial and transurethral applicators incorporating temperature based feedback control was used to simulate thermal ablations in prostate and liver tissue. We investigated five coupled models of heat dependent changes in tissue acoustic attenuation/absorption and blood perfusion of varying degrees of complexity.. Dimensions of the ablation zone were computed using temperature, thermal dose, and Arrhenius thermal damage indicators of coagulative necrosis. A comparison of the predictions by each of these models was illustrated on a patient-specific anatomy in the treatment planning setting. Results Models including dynamic changes in blood perfusion and acoustic attenuation as a function of thermal dose/damage predicted near-identical ablation zone volumes (maximum variation < 2.5%). Accounting for dynamic acoustic attenuation appeared to play a critical role in estimating ablation zone size, as models using constant values for acoustic attenuation predicted ablation zone volumes up to 50% larger or 47% smaller in liver and prostate tissue, respectively. Thermal dose (t43 ≥ 240min) and thermal damage (Ω ≥ 4.6) thresholds for coagulative necrosis are in good agreement for all heating durations, temperature thresholds in the range of 54 °C for short (< 5 min) duration ablations and 50 °C for long (15 min) ablations may serve as surrogates for determination of the outer treatment boundary. Conclusions Accounting for dynamic changes in acoustic attenuation/absorption appeared to play a critical role in predicted extents of ablation zones. For typical 5—15 min ablations with this modality, thermal dose and Arrhenius damage measures of ablation zone dimensions are in good agreement, while appropriately selected temperature thresholds provide a computationally cheaper surrogate. PMID:22235787

  2. Dose equivalent rate constants and barrier transmission data for nuclear medicine facility dose calculations and shielding design.

    PubMed

    Kusano, Maggie; Caldwell, Curtis B

    2014-07-01

    A primary goal of nuclear medicine facility design is to keep public and worker radiation doses As Low As Reasonably Achievable (ALARA). To estimate dose and shielding requirements, one needs to know both the dose equivalent rate constants for soft tissue and barrier transmission factors (TFs) for all radionuclides of interest. Dose equivalent rate constants are most commonly calculated using published air kerma or exposure rate constants, while transmission factors are most commonly calculated using published tenth-value layers (TVLs). Values can be calculated more accurately using the radionuclide's photon emission spectrum and the physical properties of lead, concrete, and/or tissue at these energies. These calculations may be non-trivial due to the polyenergetic nature of the radionuclides used in nuclear medicine. In this paper, the effects of dose equivalent rate constant and transmission factor on nuclear medicine dose and shielding calculations are investigated, and new values based on up-to-date nuclear data and thresholds specific to nuclear medicine are proposed. To facilitate practical use, transmission curves were fitted to the three-parameter Archer equation. Finally, the results of this work were applied to the design of a sample nuclear medicine facility and compared to doses calculated using common methods to investigate the effects of these values on dose estimates and shielding decisions. Dose equivalent rate constants generally agreed well with those derived from the literature with the exception of those from NCRP 124. Depending on the situation, Archer fit TFs could be significantly more accurate than TVL-based TFs. These results were reflected in the sample shielding problem, with unshielded dose estimates agreeing well, with the exception of those based on NCRP 124, and Archer fit TFs providing a more accurate alternative to TVL TFs and a simpler alternative to full spectral-based calculations. The data provided by this paper should assist in improving the accuracy and tractability of dose and shielding calculations for nuclear medicine facility design.

  3. An environmental dose experiment

    NASA Astrophysics Data System (ADS)

    Peralta, Luis

    2017-11-01

    Several radiation sources worldwide contribute to the delivered dose to the human population. This radiation also acts as a natural background when detecting radiation, for instance from radioactive sources. In this work a medium-sized plastic scintillation detector is used to evaluate the dose delivered by natural radiation sources. Calibration of the detector involved the use of radioactive sources and Monte Carlo simulation of the energy deposition per disintegration. A measurement of the annual dose due to background radiation to the body was then estimated. A dose value compatible with the value reported by the United Nations Scientific Committee on the Effects of Atomic Radiation was obtained.

  4. Effect of oral dosing vehicles on the developmental toxicity of flubendazole in rats.

    PubMed

    Yoshimura, Haruo

    2003-01-01

    Flubendazole was suspended in deionized water or olive oil and administered by gavage once daily to pregnant rats on Days 8-15 of pregnancy to examine if the embryolethal and teratogenic doses were affected by the vehicles used. Flubendazole in olive oil caused a statistically significant increase in embryolethality at doses of 7.83 mg/kg per day and higher, with complete resorption in all dams at 31.33 mg/kg per day. When flubendazole was suspended in deionized water, a significant increase in embryolethality occurred only at a maternal dose of 125.32 mg/kg per day. The proportion of litters with anomalous fetuses was significantly increased at doses of 31.33 mg/kg per day and above when flubendazole was administered in deionized water, but increased at doses at four times lower when flubendazole was administered as in olive oil. Administered as a single dose in olive oil on any one of Days 6-12 of pregnancy, a flubendazole dose of 31.33 mg/kg caused significant increases in embryolethality and decreased fetal body weights on Days 7-9, with an 82.7% incidence of embryolethality on Day 8, with complete resorption in 5 of the 8 dams. The critical periods for teratogenic effects were between Days 8 and 11 of pregnancy, with Day 9 being the most critical. Fetuses with gross, skeletal, or internal anomalies were seen in dams given a single dose of as low as 7.83 mg/kg.

  5. SU-E-T-91: Accuracy of Dose Calculation Algorithms for Patients Undergoing Stereotactic Ablative Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tajaldeen, A; Ramachandran, P; Geso, M

    2015-06-15

    Purpose: The purpose of this study was to investigate and quantify the variation in dose distributions in small field lung cancer radiotherapy using seven different dose calculation algorithms. Methods: The study was performed in 21 lung cancer patients who underwent Stereotactic Ablative Body Radiotherapy (SABR). Two different methods (i) Same dose coverage to the target volume (named as same dose method) (ii) Same monitor units in all algorithms (named as same monitor units) were used for studying the performance of seven different dose calculation algorithms in XiO and Eclipse treatment planning systems. The seven dose calculation algorithms include Superposition, Fastmore » superposition, Fast Fourier Transform ( FFT) Convolution, Clarkson, Anisotropic Analytic Algorithm (AAA), Acurous XB and pencil beam (PB) algorithms. Prior to this, a phantom study was performed to assess the accuracy of these algorithms. Superposition algorithm was used as a reference algorithm in this study. The treatment plans were compared using different dosimetric parameters including conformity, heterogeneity and dose fall off index. In addition to this, the dose to critical structures like lungs, heart, oesophagus and spinal cord were also studied. Statistical analysis was performed using Prism software. Results: The mean±stdev with conformity index for Superposition, Fast superposition, Clarkson and FFT convolution algorithms were 1.29±0.13, 1.31±0.16, 2.2±0.7 and 2.17±0.59 respectively whereas for AAA, pencil beam and Acurous XB were 1.4±0.27, 1.66±0.27 and 1.35±0.24 respectively. Conclusion: Our study showed significant variations among the seven different algorithms. Superposition and AcurosXB algorithms showed similar values for most of the dosimetric parameters. Clarkson, FFT convolution and pencil beam algorithms showed large differences as compared to superposition algorithms. Based on our study, we recommend Superposition and AcurosXB algorithms as the first choice of algorithms in lung cancer radiotherapy involving small fields. However, further investigation by Monte Carlo simulation is required to confirm our results.« less

  6. Relationship of glucose values to sliding scale insulin (correctional insulin) dose delivery and meal time in acute care patients with diabetes mellitus.

    PubMed

    Trotter, Barbara; Conaway, Mark R; Burns, Suzanne M

    2013-01-01

    Findings of this study suggest the traditional sliding scale insulin (SSI) method does not improve target glucose values among adult medical inpatients. Timing of blood glucose (BC) measurement does affect the required SSI dose. BC measurement and insulin dose administration should be accomplished immediately prior to mealtime.

  7. Retrieving atmospheric transmissivity for biologically active daily dose, in various european sites

    NASA Astrophysics Data System (ADS)

    de La Casinière, A.; Touré, M. L.; Lenoble, J.; Cabot, T.

    2003-04-01

    In the frame of the European Project EDUCE, global UV irradiance spectra recorded all along the year in several European sites are stored in a common database located in Finland. From the spectra set of some of these stations, are calculated atmospheric transmissivities for daily doses of four biologically active UV radiation, namely: UV-B, erythema, DNA damage, and plant damage. A transmissivity is defined as the ratio of the ground level value of the daily dose of interest to its corresponding extra-atmospheric value. Multiple linear correlation of the various transmissivities with three predictors (daily sunshine fraction, cosine of the daily minimum SZA, and daily total ozone column) assumed to be independent variables, are done for year 2000. The coefficients obtained from year 2000 correlation in a given site are expected to retrieve, from the local predictors, the daily dose for year 2001 in the same site, the average error being lesser than 10% for monthly mean values, and lesser than 5% for three-monthly mean values, depending on the daily dose type. Comparison of yearly mean daily doses retrieved in a given site from coefficients obtained in other sites is also presented.

  8. Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery.

    PubMed

    Ma, Lijun; Lee, Letitia; Barani, Igor; Hwang, Andrew; Fogh, Shannon; Nakamura, Jean; McDermott, Michael; Sneed, Penny; Larson, David A; Sahgal, Arjun

    2011-11-21

    Rapid delivery of multiple shots or isocenters is one of the hallmarks of Gamma Knife radiosurgery. In this study, we investigated whether the temporal order of shots delivered with Gamma Knife Perfexion would significantly influence the biological equivalent dose for complex multi-isocenter treatments. Twenty single-target cases were selected for analysis. For each case, 3D dose matrices of individual shots were extracted and single-fraction equivalent uniform dose (sEUD) values were determined for all possible shot delivery sequences, corresponding to different patterns of temporal dose delivery within the target. We found significant variations in the sEUD values among these sequences exceeding 15% for certain cases. However, the sequences for the actual treatment delivery were found to agree (<3%) and to correlate (R² = 0.98) excellently with the sequences yielding the maximum sEUD values for all studied cases. This result is applicable for both fast and slow growing tumors with α/β values of 2 to 20 according to the linear-quadratic model. In conclusion, despite large potential variations in different shot sequences for multi-isocenter Gamma Knife treatments, current clinical delivery sequences exhibited consistent biological target dosing that approached that maximally achievable for all studied cases.

  9. Improving plan quality for prostate volumetric-modulated arc therapy.

    PubMed

    Wright, Katrina; Ferrari-Anderson, Janet; Barry, Tamara; Bernard, Anne; Brown, Elizabeth; Lehman, Margot; Pryor, David

    2017-01-01

    We critically evaluated the quality and consistency of volumetric-modulated arc therapy (VMAT) prostate planning at a single institution to quantify objective measures for plan quality and establish clear guidelines for plan evaluation and quality assurance. A retrospective analysis was conducted on 34 plans generated on the Pinnacle 3 version 9.4 and 9.8 treatment planning system to deliver 78 Gy in 39 fractions to the prostate only using VMAT. Data were collected on contoured structure volumes, overlaps and expansions, planning target volume (PTV) and organs at risk volumes and relationship, dose volume histogram, plan conformity, plan homogeneity, low-dose wash, and beam parameters. Standard descriptive statistics were used to describe the data. Despite a standardized planning protocol, we found variability was present in all steps of the planning process. Deviations from protocol contours by radiation oncologists and radiation therapists occurred in 12% and 50% of cases, respectively, and the number of optimization parameters ranged from 12 to 27 (median 17). This contributed to conflicts within the optimization process reflected by the mean composite objective value of 0.07 (range 0.01 to 0.44). Methods used to control low-intermediate dose wash were inconsistent. At the PTV rectum interface, the dose-gradient distance from the 74.1 Gy to 40 Gy isodose ranged from 0.6 cm to 2.0 cm (median 1.0 cm). Increasing collimator angle was associated with a decrease in monitor units and a single full 6 MV arc was sufficient for the majority of plans. A significant relationship was found between clinical target volume-rectum distance and rectal tolerances achieved. A linear relationship was determined between the PTV volume and volume of 40 Gy isodose. Objective values and composite objective values were useful in determining plan quality. Anatomic geometry and overlap of structures has a measurable impact on the plan quality achieved for prostate patients being treated with VMAT. By evaluating multiple planning variables, we have been able to determine important factors influencing plan quality and develop predictive models for quality metrics that have been incorporated into our new protocol and will be tested and refined in future studies. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  10. Estimation of skin entrance doses (SEDs) for common medical X-ray diagnostic examinations in India and proposed diagnostic reference levels (DRLs).

    PubMed

    Sonawane, A U; Shirva, V K; Pradhan, A S

    2010-02-01

    Skin entrance doses (SEDs) were estimated by carrying out measurements of air kerma from 101 X-ray machines installed in 45 major and selected hospitals in the country by using a silicon detector-based dose Test-O-Meter. 1209 number of air kerma measurements of diagnostic projections for adults have been analysed for seven types of common diagnostic examinations, viz. chest (AP, PA, LAT), lumbar spine (AP, LAT), thoracic spine (AP, LAT), abdomen (AP), pelvis (AP), hip joints (AP) and skull (PA, LAT) for different film-screen combinations. The values of estimated diagnostic reference levels (DRLs) (third quartile values of SEDs) were compared with guidance levels/DRLs of doses published by the IAEA-BSS-Safety Series No. 115, 1996; HPA (NRPB) (2000 and 2005), UK; CRCPD/CDRH (USA), European Commission and other national values. The values of DRLs obtained in this study are comparable with the values published by the IAEA-BSS-115 (1996); HPA (NRPB) (2000 and 2005) UK; EC and CRCPD/CDRH, USA including values obtained in previous studies in India.

  11. Potential uncertainty reduction in model-averaged benchmark dose estimates informed by an additional dose study.

    PubMed

    Shao, Kan; Small, Mitchell J

    2011-10-01

    A methodology is presented for assessing the information value of an additional dosage experiment in existing bioassay studies. The analysis demonstrates the potential reduction in the uncertainty of toxicity metrics derived from expanded studies, providing insights for future studies. Bayesian methods are used to fit alternative dose-response models using Markov chain Monte Carlo (MCMC) simulation for parameter estimation and Bayesian model averaging (BMA) is used to compare and combine the alternative models. BMA predictions for benchmark dose (BMD) are developed, with uncertainty in these predictions used to derive the lower bound BMDL. The MCMC and BMA results provide a basis for a subsequent Monte Carlo analysis that backcasts the dosage where an additional test group would have been most beneficial in reducing the uncertainty in the BMD prediction, along with the magnitude of the expected uncertainty reduction. Uncertainty reductions are measured in terms of reduced interval widths of predicted BMD values and increases in BMDL values that occur as a result of this reduced uncertainty. The methodology is illustrated using two existing data sets for TCDD carcinogenicity, fitted with two alternative dose-response models (logistic and quantal-linear). The example shows that an additional dose at a relatively high value would have been most effective for reducing the uncertainty in BMA BMD estimates, with predicted reductions in the widths of uncertainty intervals of approximately 30%, and expected increases in BMDL values of 5-10%. The results demonstrate that dose selection for studies that subsequently inform dose-response models can benefit from consideration of how these models will be fit, combined, and interpreted. © 2011 Society for Risk Analysis.

  12. Influence of CT automatic tube current modulation on uncertainty in effective dose.

    PubMed

    Sookpeng, S; Martin, C J; Gentle, D J

    2016-01-01

    Computed tomography (CT) scanners are equipped with automatic tube current modulation (ATCM) systems that adjust the current to compensate for variations in patient attenuation. CT dosimetry variables are not defined for ATCM situations and, thus, only the averaged values are displayed and analysed. The patient effective dose (E), which is derived from a weighted sum of organ equivalent doses, will be modified by the ATCM. Values for E for chest-abdomen-pelvis CT scans have been calculated using the ImPACT spreadsheet for patients on five CT scanners. Values for E resulting from the z-axis modulation under ATCM have been compared with results assessed using the same effective mAs values with constant tube currents. Mean values for E under ATCM were within ±10 % of those for fixed tube currents for all scanners. Cumulative dose distributions under ATCM have been simulated for two patient scans using single-slice dose profiles measured in elliptical and cylindrical phantoms on one scanner. Contributions to the effective dose from organs in the upper thorax under ATCM are 30-35 % lower for superficial tissues (e.g. breast) and 15-20 % lower for deeper organs (e.g. lungs). The effect on doses to organs in the abdomen depends on body shape, and they can be 10-22 % higher for larger patients. Results indicate that scan dosimetry parameters, dose-length product and effective mAs averaged over the whole scan can provide an assessment in terms of E that is sufficiently accurate to quantify relative risk for routine patient exposures under ATCM. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  13. Correlation between Colon Transit Time Test Value and Initial Maintenance Dose of Laxative in Children with Chronic Functional Constipation.

    PubMed

    Kim, Mock Ryeon; Park, Hye Won; Son, Jae Sung; Lee, Ran; Bae, Sun Hwan

    2016-09-01

    To evaluate the correlation between colon transit time (CTT) test value and initial maintenance dose of polyethylene glycol (PEG) 4000 or lactulose. Of 415 children with chronic functional constipation, 190 were enrolled based on exclusion criteria using the CTT test, defecation diary, and clinical chart. The CTT test was performed with prior disimpaction. The laxative dose for maintenance was determined on the basis of the defecation diary and clinical chart. The Shapiro-Wilk test and Pearson's and Spearman's correlations were used for statistical analysis. The overall group median value and interquartile range of the CTT test was 43.8 (31.8) hours. The average PEG 4000 dose for maintenance in the overall group was 0.68±0.18 g/kg/d; according to age, the dose was 0.73±0.16 g/kg/d (<8 years), 0.53±0.12 g/kg/d (8 to <12 years), and 0.36±0.05 g/kg/d (12 to 15 years). The dose of lactulose was 1.99±0.43 mL/kg/d (<8 years) or 1.26±0.25 mL/kg/d (8 to <12 years). There was no significant correlation between CTT test value and initial dose of laxative, irrespective of the subgroup (encopresis, abnormal CTT test subtype) for either laxative. Even in the largest group (overall, n=109, younger than 8 years and on PEG 4000), the correlation was weak (Pearson's correlation coefficient [R]=0.268, p =0.005). Within the abnormal transit group, subgroup (n=73, younger than 8 years and on PEG 4000) correlation was weak (R=0.267, p =0.022). CTT test value cannot predict the initial maintenance dose of PEG 4000 or lactulose with linear correlation.

  14. Critical laboratory values in hemostasis: toward consensus.

    PubMed

    Lippi, Giuseppe; Adcock, Dorothy; Simundic, Ana-Maria; Tripodi, Armando; Favaloro, Emmanuel J

    2017-09-01

    The term "critical values" can be defined to entail laboratory test results that significantly lie outside the normal (reference) range and necessitate immediate reporting to safeguard patient health, as well as those displaying a highly and clinically significant variation compared to previous data. The identification and effective communication of "highly pathological" values has engaged the minds of many clinicians, health care and laboratory professionals for decades, since these activities are vital to good laboratory practice. This is especially true in hemostasis, where a timely and efficient communication of critical values strongly impacts patient management. Due to the heterogeneity of available data, this paper is hence aimed to analyze the state of the art and provide an expert opinion about the parameters, measurement units and alert limits pertaining to critical values in hemostasis, thus providing a basic document for future consultation that assists laboratory professionals and clinicians alike. KEY MESSAGES Critical values are laboratory test results significantly lying outside the normal (reference) range and necessitating immediate reporting to safeguard patient health. A broad heterogeneity exists about critical values in hemostasis worldwide. We provide here an expert opinion about the parameters, measurement units and alert limits pertaining to critical values in hemostasis.

  15. Effect of gamma-irradiation on the occurrence of pathogenic microorganisms and nutritive value of four principal cereal grains.

    PubMed

    Aziz, N H; Souzan, R M; Shahin Azza, A

    2006-12-01

    The effects of (60)Co gamma-photon-irradiation on the natural occurrence of pathogenic microorganisms in four principal cereal grains and on amino acids and vitamins in these cereals were investigated. The total numbers of aerobic bacteria were reduced by three logarithmic decades when grains were given a dose of 10kGy. Coliforms and "coagulase- positive" staphylococci were inhibited by a dose of 1kGy, whereas fungi were inhibited by a dose of 5kGy. The 15kGy dose eliminated viable microorganisms in cereal grains, and about 10-30 colony-forming units of Clostridium sp. per gram of grain survived after this dose. The dose of 10kGy did not cause any measurable destruction of total amino acids. Thiamin was reduced by 22-33% and riboflavin by 10-16% after a dose of 10kGy. Irradiation did not increase the acid values significantly, but did increase the peroxide values, which was not accompanied by the off-odors of cereals. We conclude that the overall dose of 10kGy is very effective for microbial decontamination of cereal grains, and does not adversely affect the nutritional quality of cereal grains.

  16. Radiochromic film calibration for the RQT9 quality beam

    NASA Astrophysics Data System (ADS)

    Costa, K. C.; Gomez, A. M. L.; Alonso, T. C.; Mourao, A. P.

    2017-11-01

    When ionizing radiation interacts with matter it generates energy deposition. Radiation dosimetry is important for medical applications of ionizing radiation due to the increasing demand for diagnostic radiology and radiotherapy. Different dosimetry methods are used and each one has its advantages and disadvantages. The film is a dose measurement method that records the energy deposition by the darkening of its emulsion. Radiochromic films have a little visible light sensitivity and respond better to ionizing radiation exposure. The aim of this study is to obtain the resulting calibration curve by the irradiation of radiochromic film strips, making it possible to relate the darkening of the film with the absorbed dose, in order to measure doses in experiments with X-ray beam of 120 kV, in computed tomography (CT). Film strips of GAFCHROMIC XR-QA2 were exposed according to RQT9 reference radiation, which defines an X-ray beam generated from a voltage of 120 kV. Strips were irradiated in "Laboratório de Calibração de Dosímetros do Centro de Desenvolvimento da Tecnologia Nuclear" (LCD / CDTN) at a dose range of 5-30 mGy, corresponding to the range values commonly used in CT scans. Digital images of the irradiated films were analyzed by using the ImageJ software. The darkening responses on film strips according to the doses were observed and they allowed obtaining the corresponding numeric values to the darkening for each specific dose value. From the numerical values of darkening, a calibration curve was obtained, which correlates the darkening of the film strip with dose values in mGy. The calibration curve equation is a simplified method for obtaining absorbed dose values using digital images of radiochromic films irradiated. With the calibration curve, radiochromic films may be applied on dosimetry in experiments on CT scans using X-ray beam of 120 kV, in order to improve CT acquisition image processes.

  17. DO3SE model applicability and O3 flux performance compared to AOT40 for an O3-sensitive tropical tree species (Psidium guajava L. 'Paluma').

    PubMed

    Assis, Pedro I L S; Alonso, Rocío; Meirelles, Sérgio T; Moraes, Regina M

    2015-07-01

    Phytotoxic ozone (O3) levels have been recorded in the Metropolitan Region of São Paulo (MRSP). Flux-based critical levels for O3 through stomata have been adopted for some northern hemisphere species, showing better accuracy than with accumulated ozone exposure above a threshold of 40 ppb (AOT40). In Brazil, critical levels for vegetation protection against O3 adverse effects do not exist. The study aimed to investigate the applicability of O3 deposition model (Deposition of Ozone for Stomatal Exchange (DO3SE)) to an O3-sensitive tropical tree species (Psidium guajava L. 'Paluma') under the MRSP environmental conditions, which are very unstable, and to assess the performance of O3 flux and AOT40 in relation to O3-induced leaf injuries. Stomatal conductance (g s) parameterization for 'Paluma' was carried out and used to calculate different rate thresholds (from 0 to 5 nmol O3 m(-2) projected leaf area (PLA) s(-1)) for the phytotoxic ozone dose (POD). The model performance was assessed through the relationship between the measured and modeled g sto. Leaf injuries were analyzed and associated with POD and AOT40. The model performance was satisfactory and significant (R (2) = 0.56; P < 0.0001; root-mean-square error (RMSE) = 116). As already expected, high AOT40 values did not result in high POD values. Although high POD values do not always account for more injuries, POD0 showed better performance than did AOT40 and other different rate thresholds for POD. Further investigation is necessary to improve our model and also to check if there is a critical level of ozone in which leaf injuries arise. The conclusion is that the DO3SE model for 'Paluma' is applicable in the MRSP as well as in temperate regions and may contribute to future directives.

  18. PAEDIATRIC CT EXPOSURE PRACTICE IN THE COUNTY OF RIO DE JANEIRO: THE NEED TO ESTABLISH DIAGNOSTIC REFERENCE LEVELS.

    PubMed

    de Jesus, Fillipe M; Magalhães, Luis A G; Kodlulovich, Simone

    2016-11-01

    A pilot study of dose indicators in paediatric computed tomography (CT) was conducted to prove the need to establish diagnostic reference levels (DRLs) for the county of Rio de Janeiro. The dose descriptors were estimated from the beam dosimetry by applying the protocols used in each examination. The total patient sample included 279 children. Regarding the comparison of the dose-length product values among the hospitals, the high-resolution chest CT scans were distinguished among the three types of examinations, due to the discrepancies of 1148 % (1-5 y age group) and 2248 % (5-10 y age group) presented in Hospital A's dose-length product values relative to Hospital D's dose-length product values. The results showed that without DRL, the dose variation can be significant between hospitals in the same county for the same age group in the same examination. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. SU-E-T-395: Evaluation of Multiple Brain Metastases Stereotactic Treatment Planning in Cyberknife Versus Linac

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vikraman, S; Rajesh, Thiyagarajan; Karrthick, Kp

    2015-06-15

    Purpose: The purpose of this study was to evaluate multiple brain metastases stereotactic treatment planning of Cyberknife versus linac using dose volume based indices. Methods: Fifteen multiple brain metastases patients were taken for this study from Cyberknife Multiplan TPSv4.6.0. All these patients underwent stereotactic treatment in Cyberknife. For each patient VMAT stereotactic treatment plan was generated in MONACO TPSv5.0 using Elekta beam modulator MLC and matched the delivered plan. A median dose of 8.5Gy(range 7–12Gy) per fraction was prescribed. Tumor volume was in the range of 0.06–4.33cc. Treatment plan quality was critically evaluated by comparing DVH indices such as D98,more » D95, CI, and HI for target volumes. Maximum point doses and volume doses were evaluated for critical organs. Results: For each case, target coverage of D98 was achieved with 100% prescription dose with SD of 0.29% and 0.41% in Linac and Cyberknife respectively. The average conformity index(CI) of 1.26±0.0796 SD for Cyberknife and 1.92±0.60SD for linac were observed. Better homogeneity Index (HI) of 1.17±0.09SD was observed in linac as compared to Cyberknife HI of 1.24±0.05SD.All the critical organ doses were well within tolerance limit in both linac and Cyberknife plans. There is no significant difference of maximum point doses for brainstem and optic chiasm. Treatment time and number of monitor units are more in Cyberknife compared to linac. The average volume receiving 12Gy in whole brain was 6% and 12% for Cyberknife and linac respectively. 1000cc of whole brain received 60% lesser dose in Linac compared to Cyberknife in all cases. Conclusion: The study shows that dosimetrically comparable plans are achievable Cyberknife and Linac. However, a better conformity, target coverage, lesser OAR dose is achieved with Cyberknife due to greater degrees of freedom with robotic gantry and smaller collimator for multiple targets.« less

  20. Validation of a Low Dose Simulation Technique for Computed Tomography Images

    PubMed Central

    Muenzel, Daniela; Koehler, Thomas; Brown, Kevin; Žabić, Stanislav; Fingerle, Alexander A.; Waldt, Simone; Bendik, Edgar; Zahel, Tina; Schneider, Armin; Dobritz, Martin; Rummeny, Ernst J.; Noël, Peter B.

    2014-01-01

    Purpose Evaluation of a new software tool for generation of simulated low-dose computed tomography (CT) images from an original higher dose scan. Materials and Methods Original CT scan data (100 mAs, 80 mAs, 60 mAs, 40 mAs, 20 mAs, 10 mAs; 100 kV) of a swine were acquired (approved by the regional governmental commission for animal protection). Simulations of CT acquisition with a lower dose (simulated 10–80 mAs) were calculated using a low-dose simulation algorithm. The simulations were compared to the originals of the same dose level with regard to density values and image noise. Four radiologists assessed the realistic visual appearance of the simulated images. Results Image characteristics of simulated low dose scans were similar to the originals. Mean overall discrepancy of image noise and CT values was −1.2% (range −9% to 3.2%) and −0.2% (range −8.2% to 3.2%), respectively, p>0.05. Confidence intervals of discrepancies ranged between 0.9–10.2 HU (noise) and 1.9–13.4 HU (CT values), without significant differences (p>0.05). Subjective observer evaluation of image appearance showed no visually detectable difference. Conclusion Simulated low dose images showed excellent agreement with the originals concerning image noise, CT density values, and subjective assessment of the visual appearance of the simulated images. An authentic low-dose simulation opens up opportunity with regard to staff education, protocol optimization and introduction of new techniques. PMID:25247422

  1. EVALUATION OF PROMPT DOSE ENVIRONMENT IN THE NATIONAL IGNITION FACILITY DURING D-D AND THD SHOTS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Khater, H; Dauffy, L; Sitaraman, S

    2009-04-28

    Evaluation of the prompt dose environment expected in the National Ignition Facility (NIF) during Deuterium-Deuterium (D-D) and Tritium-Hydrogen-Deuterium (THD) shots have been completed. D-D shots resulting in the production of an annual fusion yield of up to 2.4 kJ (200 shots with 10{sup 13} neutrons per shot) are considered. During the THD shot campaign, shots generating a total of 2 x 10{sup 14} neutrons per shot are also planned. Monte Carlo simulations have been performed to estimate prompt dose values inside the facility as well as at different locations outside the facility shield walls. The Target Chamber shielding, along withmore » Target Bay and Switchyard walls, roofs, and shield doors (when needed) will reduce dose levels in occupied areas to acceptable values during these shot campaigns. The calculated dose values inside occupied areas are small, estimated at 25 and 85 {micro}rem per shot during the D-D and THD shots, respectively. Dose values outside the facility are insignificant. The nearest building to the NIF facility where co-located workers may reside is at a distance of about 100 m from the Target Chamber Center (TCC). The dose in such a building is estimated at a fraction of a ?rem during a D-D or a THD shot. Dose at the nearest site boundary location (350 m from TCC), is caused by skyshine and to a lesser extent by direct radiation. The maximum off-site dose during any of the shots considered is less than 10 nano rem.« less

  2. Nanoparticle formulations of cisplatin for cancer therapy

    PubMed Central

    Duan, Xiaopin; He, Chunbai; Kron, Stephen J.; Lin, Wenbin

    2016-01-01

    The genotoxic agent cisplatin, used alone or in combination with radiation and/or other chemotherapeutic agents, is an important first-line chemotherapy for a broad range of cancers. The clinical utility of cisplatin is limited both by intrinsic and acquired resistance and dose-limiting normal tissue toxicity. That cisplatin shows little selectivity for tumor versus normal tissue may be a critical factor limiting its value. To overcome the low therapeutic ratio of the free drug, macromolecular, liposomal and nanoparticle drug delivery systems have been explored toward leveraging the enhanced permeability and retention (EPR) effect and promoting delivery of cisplatin to tumors. Here, we survey recent advances in nanoparticle formulations of cisplatin, focusing on agents that show promise in preclinical or clinical settings. PMID:26848041

  3. Permutational distribution of the log-rank statistic under random censorship with applications to carcinogenicity assays.

    PubMed

    Heimann, G; Neuhaus, G

    1998-03-01

    In the random censorship model, the log-rank test is often used for comparing a control group with different dose groups. If the number of tumors is small, so-called exact methods are often applied for computing critical values from a permutational distribution. Two of these exact methods are discussed and shown to be incorrect. The correct permutational distribution is derived and studied with respect to its behavior under unequal censoring in the light of recent results proving that the permutational version and the unconditional version of the log-rank test are asymptotically equivalent even under unequal censoring. The log-rank test is studied by simulations of a realistic scenario from a bioassay with small numbers of tumors.

  4. Methods of space radiation dose analysis with applications to manned space systems

    NASA Technical Reports Server (NTRS)

    Langley, R. W.; Billings, M. P.

    1972-01-01

    The full potential of state-of-the-art space radiation dose analysis for manned missions has not been exploited. Point doses have been overemphasized, and the critical dose to the bone marrow has been only crudely approximated, despite the existence of detailed man models and computer codes for dose integration in complex geometries. The method presented makes it practical to account for the geometrical detail of the astronaut as well as the vehicle. Discussed are the major assumptions involved and the concept of applying the results of detailed proton dose analysis to the real-time interpretation of on-board dosimetric measurements.

  5. Pharmacokinetics of Ampicillin/Sulbactam in Critically Ill Patients with Acute Kidney Injury undergoing Extended Dialysis

    PubMed Central

    Lorenzen, Johan M.; Broll, Michael; Kaever, Volkhard; Burhenne, Heike; Hafer, Carsten; Clajus, Christian; Knitsch, Wolfgang; Burkhardt, Olaf

    2012-01-01

    Summary Background and objectives The fixed antibacterial combination of ampicillin and sulbactam is frequently used for various infections. Intact kidneys eliminate approximately 71% of ampicillin and 78% of sulbactam. Patients on thrice-weekly low-flux hemodialysis exhibit an ampicillin t1/2 of 2.3 hours on and 17.4 hours off dialysis. Despite its frequent use in intensive care units, there are no available dosing recommendations for patients with AKI undergoing renal replacement therapy. The aims of this study were to evaluate the pharmacokinetics of ampicillin/sulbactam in critically ill patients with AKI undergoing extended dialysis (ED) and to establish a dosing recommendation for this treatment method. Design, setting, participants, & measurements Twelve critically ill patients with anuric AKI being treated with ED were enrolled in a prospective, open-label, observational pharmacokinetic study. Pharmacokinetics after a single dose of ampicillin/sulbactam (2 g/1 g) was obtained in 12 patients. Multiple-dose pharmacokinetics after 4 days of twice-daily ampicillin/sulbactam (2 g/1 g) was obtained in three patients. Results The mean dialyzer clearance for ampicillin/sulbactam was 80.1±7.7/83.3±12.1 ml/min. The t1/2 of ampicillin and sulbactam in patients with AKI undergoing ED were 2.8±0.8 hours and 3.5±1.5 hours, respectively. There was no significant accumulation using a twice-daily dosage of 2 g/1 g ampicillin/sulbactam. Conclusions Our data suggest that in patients treated with ED using a high-flux dialyzer (polysulphone, 1.3 m2; blood and dialysate flow, 160 ml/min; treatment time, 480 minutes), a twice-daily dosing schedule of at least 2 g/1 g ampicillin/sulbactam, with one dose given after ED, should be used to avoid underdosing. PMID:22223613

  6. Identification of Granulocyte Colony-Stimulating Factor and Interleukin-6 as Candidate Biomarkers of CBLB502 Efficacy as a Medical Radiation Countermeasure

    PubMed Central

    Krivokrysenko, Vadim I.; Shakhov, Alexander N.; Singh, Vijay K.; Bone, Frederick; Kononov, Yevgeniy; Shyshynova, Inna; Cheney, Alec; Maitra, Ratan K.; Purmal, Andrei; Whitnall, Mark H.; Feinstein, Elena

    2012-01-01

    Given an ever-increasing risk of nuclear and radiological emergencies, there is a critical need for development of medical radiation countermeasures (MRCs) that are safe, easily administered, and effective in preventing and/or mitigating the potentially lethal tissue damage caused by acute high-dose radiation exposure. Because the efficacy of MRCs for this indication cannot be ethically tested in humans, development of such drugs is guided by the Food and Drug Administration's Animal Efficacy Rule. According to this rule, human efficacious doses can be projected from experimentally established animal efficacious doses based on the equivalence of the drug's effects on efficacy biomarkers in the respective species. Therefore, identification of efficacy biomarkers is critically important for drug development under the Animal Efficacy Rule. CBLB502 is a truncated derivative of the Salmonella flagellin protein that acts by triggering Toll-like receptor 5 (TLR5) signaling and is currently under development as a MRC. Here, we report identification of two cytokines, granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), as candidate biomarkers of CBLB502's radioprotective/mitigative efficacy. Induction of both G-CSF and IL-6 by CBLB502 1) is strictly TLR5-dependent, 2) occurs in a CBLB502 dose-dependent manner within its efficacious dose range in both nonirradiated and irradiated mammals, including nonhuman primates, and 3) is critically important for the ability of CBLB502 to rescue irradiated animals from death. After evaluation of CBLB502 effects on G-CSF and IL-6 levels in humans, these biomarkers will be useful for accurate prediction of human efficacious CBLB502 doses, a key step in the development of this prospective radiation countermeasure. PMID:22837010

  7. Patient size and x-ray technique factors in head computed tomography examinations. I. Radiation doses.

    PubMed

    Huda, Walter; Lieberman, Kristin A; Chang, Jack; Roskopf, Marsha L

    2004-03-01

    We investigated how patient age, size and composition, together with the choice of x-ray technique factors, affect radiation doses in head computed tomography (CT) examinations. Head size dimensions, cross-sectional areas, and mean Hounsfield unit (HU) values were obtained from head CT images of 127 patients. For radiation dosimetry purposes patients were modeled as uniform cylinders of water. Dose computations were performed for 18 x 7 mm sections, scanned at a constant 340 mAs, for x-ray tube voltages ranging from 80 to 140 kV. Values of mean section dose, energy imparted, and effective dose were computed for patients ranging from the newborn to adults. There was a rapid growth of head size over the first two years, followed by a more modest increase of head size until the age of 18 or so. Newborns have a mean HU value of about 50 that monotonically increases with age over the first two decades of life. Average adult A-P and lateral dimensions were 186+/-8 mm and 147+/-8 mm, respectively, with an average HU value of 209+/-40. An infant head was found to be equivalent to a water cylinder with a radius of approximately 60 mm, whereas an adult head had an equivalent radius 50% greater. Adult males head dimensions are about 5% larger than for females, and their average x-ray attenuation is approximately 20 HU greater. For adult examinations performed at 120 kV, typical values were 32 mGy for the mean section dose, 105 mJ for the total energy imparted, and 0.64 mSv for the effective dose. Increasing the x-ray tube voltage from 80 to 140 kV increases patient doses by about a factor of 5. For the same technique factors, mean section doses in infants are 35% higher than in adults. Energy imparted for adults is 50% higher than for infants, but infant effective doses are four times higher than for adults. CT doses need to take into account patient age, head size, and composition as well as the selected x-ray technique factors.

  8. An influential factor for external radiation dose estimation for residents after the Fukushima Daiichi Nuclear Power Plant accident-time spent outdoors for residents in Iitate Village.

    PubMed

    Ishikawa, Tetsuo; Yasumura, Seiji; Ohtsuru, Akira; Sakai, Akira; Akahane, Keiichi; Yonai, Shunsuke; Sakata, Ritsu; Ozasa, Kotaro; Hayashi, Masayuki; Ohira, Tetsuya; Kamiya, Kenji; Abe, Masafumi

    2016-06-01

    Many studies have been conducted on radiation doses to residents after the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. Time spent outdoors is an influential factor for external dose estimation. Since little information was available on actual time spent outdoors for residents, different values of average time spent outdoors per day have been used in dose estimation studies on the FDNPP accident. The most conservative value of 24 h was sometimes used, while 2.4 h was adopted for indoor workers in the UNSCEAR 2013 report. Fukushima Medical University has been estimating individual external doses received by residents as a part of the Fukushima Health Management Survey by collecting information on the records of moves and activities (the Basic Survey) after the accident from each resident. In the present study, these records were analyzed to estimate an average time spent outdoors per day. As an example, in Iitate Village, its arithmetic mean was 2.08 h (95% CI: 1.64-2.51) for a total of 170 persons selected from respondents to the Basic Survey. This is a much smaller value than commonly assumed. When 2.08 h is used for the external dose estimation, the dose is about 25% (23-26% when using the above 95% CI) less compared with the dose estimated for the commonly used value of 8 h.

  9. The big bang of hemofiltration: the beginning of a new era in the third millennium for extra-corporeal blood purification!

    PubMed

    Honore', P M; Joannes-Boyau, O; Merson, L; Boer, W; Piette, V; Galloy, A-C; Janvier, G

    2006-07-01

    Since the last decade, hemofiltration and especially high volume hemofiltration has rapidly evolved from a somewhat experimental treatment towards a potentially effective 'adjunctive' therapy in severe septic shock and especially refractory or catecholamine resistant hypodynamic septic shock. Nevertheless, this approach lacks prospective randomized studies (PRT'S) evaluating the critical role of early hemofiltration in sepsis. An important step forward which could be called the 'big bang' in term of hemofiltration was the publication of a PRT in patients with acute renal failure (ARF) (1). Before this study (2), nobody believed that hemofiltration could change the survival rate in intensive care. Since that big bang, many physicians consider that hemofiltration at a certain dose can change the survival rate in intensive care. So the world of hemofiltration in ICU is not a definitive world, it is still in expansion. Indeed, we now have to try to define what will be the exact dose we need in septic acute renal failure. This dose might well be 'higher' than 35 ml/kg/hour in the septic acute renal failure 'group' as suggested by many studies (2-5). At present, it is the issue of continuous dose of high volume hemofiltration that has to be tested in future randomized studies. Since the Vicenza study (2) has shown that 35 ml/kg/h is the best dose in terms of survival, dealing with non septic acute renal failure in ICU, several studies from different groups have shown that, in septic acute renal failure, a higher dose might correlate with better survival. This has also been shown in some way by the study of the 'Vicenza group' but not with a statistically significant value (2). New PRT'S have just started in Europe like the IVOIRE study (hIgh VOlume in Intensive caRE) (6) and the RENAL study. Another large study is looking more basically at dose in non septic acute renal failure in Australasia and is led by the group of Rinaldo Bellomo in Melbourne (7) as well as the ATN study (8) led by Palevsky and colleagues in the USA, also testing the importance of dose in the treatment for ARF. Nevertheless, 'early goal-directed hemofiltration therapy' like early goal directed therapy (9) has to be studied in our critical ill patients. Regarding this issue, fewer studies, mainly retrospective exist, but again the IVOIRE study (6) will address this issue by studying septic patients with acute renal injury according to the Rifle classification (10). So, this review focuses on the early application and on the adequate dose of continuous high volume hemofiltration in septic shock in order to improve not only hemodynamics, but survival in this very severely ill cohort of patients. This could well be called the 'big bang of hemofiltration' as one could never have anticipated that an adequate dose of hemofiltration could markedly influence the survival rate of ICU-septic acute renal failure patients. On top of the use of early and adequate dose of hemofiltration in sepsis, a higher dose could also provide better renal recovery rate and reduce the risk of associate chronic dialysis in these patients. Furthermore, this paper also reviews 'brand' new theories regarding the rationale for hemofiltration in sepsis. Finally, this paper also addresses the so-called negative studies as well anticipated side effects.

  10. SU-E-T-184: Clinical VMAT QA Practice Using LINAC Delivery Log Files

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johnston, H; Jacobson, T; Gu, X

    2015-06-15

    Purpose: To evaluate the accuracy of volumetric modulated arc therapy (VMAT) treatment delivery dose clouds by comparing linac log data to doses measured using an ionization chamber and film. Methods: A commercial IMRT quality assurance (QA) process utilizing a DICOM-RT framework was tested for clinical practice using 30 prostate and 30 head and neck VMAT plans. Delivered 3D VMAT dose distributions were independently checked using a PinPoint ionization chamber and radiographic film in a solid water phantom. DICOM RT coordinates were used to extract the corresponding point and planar doses from 3D log file dose distributions. Point doses were evaluatedmore » by computing the percent error between log file and chamber measured values. A planar dose evaluation was performed for each plan using a 2D gamma analysis with 3% global dose difference and 3 mm isodose point distance criteria. The same analysis was performed to compare treatment planning system (TPS) doses to measured values to establish a baseline assessment of agreement. Results: The mean percent error between log file and ionization chamber dose was 1.0%±2.1% for prostate VMAT plans and −0.2%±1.4% for head and neck plans. The corresponding TPS calculated and measured ionization chamber values agree within 1.7%±1.6%. The average 2D gamma passing rates for the log file comparison to film are 98.8%±1.0% and 96.2%±4.2% for the prostate and head and neck plans, respectively. The corresponding passing rates for the TPS comparison to film are 99.4%±0.5% and 93.9%±5.1%. Overall, the point dose and film data indicate that log file determined doses are in excellent agreement with measured values. Conclusion: Clinical VMAT QA practice using LINAC treatment log files is a fast and reliable method for patient-specific plan evaluation.« less

  11. Dosimetric and delivery efficiency investigation for treating hepatic lesions with a MLC-equipped robotic radiosurgery-radiotherapy combined system.

    PubMed

    Jin, Lihui; Price, Robert A; Wang, Lu; Meyer, Joshua; Fan, James Jiajin; Ma, Chang Ming Charlie

    2016-02-01

    The CyberKnife M6 (CK-M6) Series introduced a multileaf collimator (MLC) for extending its capability from stereotactic radiosurgery/stereotactic radiotherapy (SBRT) to conventionally fractionated radiotherapy. This work is to investigate the dosimetric quality of plans that are generated using MLC-shaped beams on the CK-M6, as well as their delivery time, via comparisons with the intensity modulated radiotherapy plans that were clinically used on a Varian Linac for treating hepatic lesions. Nine patient cases were selected and divided into three groups with three patients in each group: (1) the group-one patients were treated conventionally (25 fractions); (2) the group-two patients were treated with SBRT-like hypofractionation (5 fractions); and (3) the group-three patients were treated similar to group-one patients, but with two planning target volumes (PTVs) and two different prescription dose levels correspondingly. The clinically used plans were generated on the eclipse treatment planning system (TPS) and delivered on a Varian Linac (E-V plans). The multiplan (MP) TPS was used to replan these clinical cases with the MLC as the beam device for the CK-M6 (C-M plans). After plans were normalized to the same PTV dose coverage, comparisons between the C-M and E-V plans were performed based on D(99%) (percentage of prescription dose received by 99% of the PTV), D(0.1cm(3)) (the percentage of prescription dose to 0.1 cm(3) of the PTV), and doses received by critical structures. Then, the delivery times for the C-M plans will be obtained, which are the MP TPS generated estimations assuming having an imaging interval of 60 s. The difference in D(99%) between C-M and E-V plans is +0.6% on average (+ or - indicating a higher or lower dose from C-M plans than from E-V plans) with a range from -4.1% to +3.8%, and the difference in D(0.1cm(3)) was -1.0% on average with a range from -5.1% to +2.9%. The PTV conformity index (CI) for the C-M plans ranges from 1.07 to 1.29 with a mean of 1.19, slightly inferior to the E-V plans, in which the CI ranges from 1.00 to 1.15 with a mean of 1.07. Accounting for all nine patients in three groups, 45% of the critical structures received a lower mean dose for the C-M plans as compared with the E-V plans, and similarly, 48% received a lower maximum dose. Furthermore, the average difference of the mean critical structure dose between the C-M and E-V plans over all critical structures for all patients showed only +2.10% relative to the prescription dose and the similar comparison finds the average difference of the maximum critical structure dose of only +1.24%. The estimated delivery times for the C-M plans on the CK-M6 range from 18 to 24 minutes while they are from 7 to 13.7 min for the E-V plans on the Varian Linac. For treating hepatic lesions, for the C-M plans that are comparable to E-V plans in quality, the times needed to deliver these C-M plans on the CK-M6 are longer than the delivery time for the E-V plans on the Varian Linac, but may be clinically acceptable.

  12. Fault handling schemes in electronic systems with specific application to radiation tolerance and VLSI design

    NASA Technical Reports Server (NTRS)

    Attia, John Okyere

    1993-01-01

    Naturally occurring space radiation particles can produce transient and permanent changes in the electrical properties of electronic devices and systems. In this work, the transient radiation effects on DRAM and CMOS SRAM were considered. In addition, the effect of total ionizing dose radiation of the switching times of CMOS logic gates were investigated. Effects of transient radiation on the column and cell of MOS dynamic memory cell was simulated using SPICE. It was found that the critical charge of the bitline was higher than that of the cell. In addition, the critical charge of the combined cell-bitline was found to be dependent on the gate voltage of the access transistor. In addition, the effect of total ionizing dose radiation on the switching times of CMOS logic gate was obtained. The results of this work indicate that, the rise time of CMOS logic gates increases, while the fall time decreases with an increase in total ionizing dose radiation. Also, by increasing the size of the P-channel transistor with respect to that of the N-channel transistor, the propagation delay of CMOS logic gate can be made to decrease with, or be independent of an increase in total ionizing dose radiation. Furthermore, a method was developed for replacing polysilicon feedback resistance of SRAMs with a switched capacitor network. A switched capacitor SRAM was implemented using MOS Technology. The critical change of the switched capacitor SRAM has a very large critical charge. The results of this work indicate that switched capacitor SRAM is a viable alternative to SRAM with polysilicon feedback resistance.

  13. Results on Dose Distributions in a Human Body from the Matroshka-R Experiment onboard the ISS Obtained with the Tissue-Equivalent Spherical Phantom

    NASA Astrophysics Data System (ADS)

    Shurshakov, Vyacheslav; Nikolaev, Igor; Kartsev, Ivan; Tolochek, Raisa; Lyagushin, Vladimir

    The tissue-equivalent spherical phantom (32 kg mass, 35 cm diameter and 10 cm central spherical cave) made in Russia has been used on board the ISS in Matroshka-R experiment for more than 10 years. Both passive and active space radiation detectors can be located inside the phantom and on its surface. Due to the specially chosen phantom shape and size, the chord length distributions of the detector locations are attributed to self-shielding properties of the critical organs in a human body. Originally the spherical phantom was installed in the star board crew cabin of the ISS Service Module, then in the Piers-1, MIM-2, and MIM-1 modules of the ISS Russian segment, and finally in JAXA Kibo module. Total duration of the detector exposure is more than 2000 days in 9 sessions of the space experiment. In the first phase of the experiment with the spherical phantom the dose measurements were realized with only passive detectors (thermoluminescent and solid state track detectors). The detectors are placed inside the phantom along the axes of 20 containers and on the phantom outer surface in 32 pockets of the phantom jacket. After each session the passive detectors are returned to the ground. The results obtained show the dose difference on the phantom surface as much as a factor of 2, the highest dose being usually observed close to the outer wall of the compartment, and the lowest dose being in the opposite location along the phantom diameter. However, because of the ISS module shielding properties an inverse dose distribution in a human body can be observed when the dose rate maximum is closer to the geometrical center of the module. Maximum dose rate measured in the phantom is obviously due to the action of two radiation sources, namely, galactic cosmic rays (GCR) and Earth’ radiation belts. Minimum dose rate is produced mainly by the strongly penetrating GCR particles and is mostly observed behind more than 5 g/cm2 tissue shielding. Critical organ doses, mean-tissue and effective doses of a crew member in the ISS compartments are also estimated with the spherical phantom data. The estimated effective dose rate is found to be from 10 % to 15 % lower than the averaged dose on the phantom surface as dependent on the attitude of the critical organs. If compared with the anthropomorphic phantom Rando used inside and outside the ISS earlier, the Matroshka-R space experiment spherical phantom has lower mass, smaller size, and requires less crew time for the detector installation/retrieval; its tissue-equivalent properties are closer to the standard human body tissue than the Rando-phantom material. New sessions with the two tissue-equivalent phantoms are of great interest. Development of modified passive and active detector sets is in progress for the future ISS expeditions. Both the spherical and Rando-type phantoms proved their effectiveness to measure the critical organ doses and effective doses in-flight and if supplied with modernized dosimeters can be recommended for future exploratory manned missions to monitor continuously the crew exposure to space radiation.

  14. Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Luo, Wei, E-mail: wei.luo@uky.edu; Molloy, Janelle; Aryal, Prakash

    2014-02-15

    Purpose: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. Methods: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescriptionmore » doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (F{sub r}: with resensitization, F{sub n}: without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, β, and relative biological effectiveness for different types of tumors were used for the calculation. Results: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (F{sub r}) and without (F{sub n}) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of F{sub r}/F{sub n} were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of F{sub r}/F{sub n} were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of F{sub r}/F{sub n} were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of F{sub r} was 1.07/1.11 (rounded to 1.1), and the averaged value of F{sub n} was 1.75/1.18. F{sub r} of 1.1 has been applied to gynecological cancer implants with expected acute reactions and outcomes as expected based on extensive experience with permanent implants. The calculation also gave the average Cs-131 dose of 126 Gy converted from the I-125 dose of 144 Gy for prostate implants. Conclusions: Inclusion of an allowance for resensitization led to significant dose corrections for Cs-131 permanent implants, and should be applied to prescription dose calculation. The adjustment of the Cs-131 prescription doses with resensitization correction for gynecological permanent implants was consistent with clinical experience and observations. However, the Cs-131 prescription doses converted from other implant doses can be further adjusted based on new experimental results, clinical observations, and clinical outcomes.« less

  15. Determination of prescription dose for Cs-131 permanent implants using the BED formalism including resensitization correction

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Luo, Wei, E-mail: wei.luo@uky.edu; Molloy, Janelle; Aryal, Prakash

    Purpose: The current widely used biological equivalent dose (BED) formalism for permanent implants is based on the linear-quadratic model that includes cell repair and repopulation but not resensitization (redistribution and reoxygenation). The authors propose a BED formalism that includes all the four biological effects (4Rs), and the authors propose how it can be used to calculate appropriate prescription doses for permanent implants with Cs-131. Methods: A resensitization correction was added to the BED calculation for permanent implants to account for 4Rs. Using the same BED, the prescription doses with Au-198, I-125, and Pd-103 were converted to the isoeffective Cs-131 prescriptionmore » doses. The conversion factor F, ratio of the Cs-131 dose to the equivalent dose with the other reference isotope (F{sub r}: with resensitization, F{sub n}: without resensitization), was thus derived and used for actual prescription. Different values of biological parameters such as α, β, and relative biological effectiveness for different types of tumors were used for the calculation. Results: Prescription doses with I-125, Pd-103, and Au-198 ranging from 10 to 160 Gy were converted into prescription doses with Cs-131. The difference in dose conversion factors with (F{sub r}) and without (F{sub n}) resensitization was significant but varied with different isotopes and different types of tumors. The conversion factors also varied with different doses. For I-125, the average values of F{sub r}/F{sub n} were 0.51/0.46, for fast growing tumors, and 0.88/0.77 for slow growing tumors. For Pd-103, the average values of F{sub r}/F{sub n} were 1.25/1.15 for fast growing tumors, and 1.28/1.22 for slow growing tumors. For Au-198, the average values of F{sub r}/F{sub n} were 1.08/1.25 for fast growing tumors, and 1.00/1.06 for slow growing tumors. Using the biological parameters for the HeLa/C4-I cells, the averaged value of F{sub r} was 1.07/1.11 (rounded to 1.1), and the averaged value of F{sub n} was 1.75/1.18. F{sub r} of 1.1 has been applied to gynecological cancer implants with expected acute reactions and outcomes as expected based on extensive experience with permanent implants. The calculation also gave the average Cs-131 dose of 126 Gy converted from the I-125 dose of 144 Gy for prostate implants. Conclusions: Inclusion of an allowance for resensitization led to significant dose corrections for Cs-131 permanent implants, and should be applied to prescription dose calculation. The adjustment of the Cs-131 prescription doses with resensitization correction for gynecological permanent implants was consistent with clinical experience and observations. However, the Cs-131 prescription doses converted from other implant doses can be further adjusted based on new experimental results, clinical observations, and clinical outcomes.« less

  16. Radiobiological and treatment planning study of a simultaneously integrated boost for canine nasal tumors using helical tomotherapy.

    PubMed

    Gutíerrez, Alonso N; Deveau, Michael; Forrest, Lisa J; Tomé, Wolfgang A; Mackie, Thomas R

    2007-01-01

    Feasibility of delivering a simultaneously integrated boost to canine nasal tumors using helical tomotherapy to improve tumor control probability (TCP) via an increase in total biological equivalent uniform dose (EUD) was evaluated. Eight dogs with varying size nasal tumors (5.8-110.9 cc) were replanned to 42 Gy to the nasal cavity and integrated dose boosts to gross disease of 45.2, 48.3, and 51.3 Gy in 10 fractions. EUD values were calculated for tumors and mean normalized total doses (NTD(mean)) for organs at risk (OAR). Normal Tissue Complication Probability (NTCP) values were obtained for OARs, and estimated TCP values were computed using a logistic dose-response model and based on deliverable EUD boost doses. Significant increases in estimated TCP to 54%, 74%, and 86% can be achieved with 10%, 23%, and 37% mean relative EUD boosts to the gross disease, respectively. NTCP values for blindness of either eye and for brain necrosis were < 0.01% for all boosts. Values for cataract development were 31%, 42%, and 46% for studied boost schemas, respectively. Average NTD(mean) to eyes and brain for mean EUD boosts were 10.2, 11.3, and 12.1 Gy3, and 7.5, 7.2, and 7.9 Gy2, respectively. Using helical tomotherapy, simultaneously integrated dose boosts can be delivered to increase the estimated TCP at 1-year without significantly increasing the NTD(mean) to eyes and brain. Delivery of these treatments in a prospective trial may allow quantification of a dose-response relationship in canine nasal tumors.

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

    PubMed

    Belley, Matthew D; Wang, Chu; Nguyen, Giao; Gunasingha, Rathnayaka; Chao, Nelson J; Chen, Benny J; Dewhirst, Mark W; Yoshizumi, Terry T

    2014-03-01

    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. 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. 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. 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.

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

    PubMed Central

    Belley, Matthew D.; Wang, Chu; Nguyen, Giao; Gunasingha, Rathnayaka; Chao, Nelson J.; Chen, Benny J.; Dewhirst, Mark W.; Yoshizumi, Terry T.

    2014-01-01

    Purpose: Accurate dosimetry is essential when irradiating mice to ensure that functional and molecular endpoints are well understood for the radiation dose delivered. Conventional methods of prescribing dose in mice involve the use of a single dose rate measurement and assume a uniform average dose throughout all organs of the entire mouse. Here, the authors report the individual average organ dose values for the irradiation of a 12, 23, and 33 g mouse on a 320 kVp x-ray irradiator and calculate the resulting error from using conventional dose prescription methods. Methods: Organ doses were simulated in the Geant4 application for tomographic emission toolkit using the MOBY mouse whole-body phantom. Dosimetry was performed for three beams utilizing filters A (1.65 mm Al), B (2.0 mm Al), and C (0.1 mm Cu + 2.5 mm Al), respectively. In addition, simulated x-ray spectra were validated with physical half-value layer measurements. Results: Average doses in soft-tissue organs were found to vary by as much as 23%–32% depending on the filter. Compared to filters A and B, filter C provided the hardest beam and had the lowest variation in soft-tissue average organ doses across all mouse sizes, with a difference of 23% for the median mouse size of 23 g. Conclusions: This work suggests a new dose prescription method in small animal dosimetry: it presents a departure from the conventional approach of assigning a 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. PMID:24593746

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Belley, Matthew D.; Wang, Chu; Nguyen, Giao

    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 formore » 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.« less

  20. Evaluation of external and internal irradiation on uranium mining enterprise staff by tooth enamel EPR spectroscopy

    NASA Astrophysics Data System (ADS)

    Zhumadilov, Kassym; Ivannikov, Alexander; Khailov, Artem; Orlenko, Sergei; Skvortsov, Valeriy; Stepanenko, Valeriy; Kuterbekov, Kairat; Toyoda, Shin; Kazymbet, Polat; Hoshi, Masaharu

    2017-11-01

    In order to estimate radiation effects on uranium enterprise staff and population teeth samples were collected for EPR tooth enamel dosimetry from population of Stepnogorsk city and staff of uranium mining enterprise in Shantobe settlment (Akmola region, North of Kazakhstan). By measurements of tooth enamel EPR spectra, the total absorbed dose in the enamel samples and added doses after subtraction of the contribution of natural background radiation are determined. For the population of Stepnogorsk city average added dose value of 4 +/- 11 mGy with variation of 51 mGy was obtained. For the staff of uranium mining enterprise in Shantobe settlment average value of added dose 95 +/- 20 mGy, with 85 mGy variation was obtained. Higher doses and the average value and a large variation for the staff, probably is due to the contribution of occupational exposure.

  1. Proton irradiation studies on Al and Al5083 alloy

    NASA Astrophysics Data System (ADS)

    Bhattacharyya, P.; Gayathri, N.; Bhattacharya, M.; Gupta, A. Dutta; Sarkar, Apu; Dhar, S.; Mitra, M. K.; Mukherjee, P.

    2017-10-01

    The change in the microstructural parameters and microhardness values in 6.5 MeV proton irradiated pure Al and Al5083 alloy samples have been evaluated using different model based techniques of X-ray diffraction Line Profile Analysis (XRD) and microindendation techniques. The detailed line profile analysis of the XRD data showed that the domain size increases and saturates with irradiation dose both in the case of Al and Al5083 alloy. The corresponding microstrain values did not show any change with irradiation dose in the case of the pure Al but showed an increase at higher irradiation doses in the case of Al5083 alloy. The microindendation results showed that unirradiated Al5083 alloy has higher hardness value compared to that of unirradiated pure Al. The hardness increased marginally with irradiation dose in the case of Al5083, whereas for pure Al, there was no significant change with dose.

  2. Derivation of the expressions for γ50 and D50 for different individual TCP and NTCP models

    NASA Astrophysics Data System (ADS)

    Stavreva, N.; Stavrev, P.; Warkentin, B.; Fallone, B. G.

    2002-10-01

    This paper presents a complete set of formulae for the position (D50) and the normalized slope (γ50) of the dose-response relationship based on the most commonly used radiobiological models for tumours as well as for normal tissues. The functional subunit response models (critical element and critical volume) are used in the derivation of the formulae for the normal tissue. Binomial statistics are used to describe the tumour control probability, the functional subunit response as well as the normal tissue complication probability. The formulae are derived for the single hit and linear quadratic models of cell kill in terms of the number of fractions and dose per fraction. It is shown that the functional subunit models predict very steep, almost step-like, normal tissue individual dose-response relationships. Furthermore, the formulae for the normalized gradient depend on the cellular parameters α and β when written in terms of number of fractions, but not when written in terms of dose per fraction.

  3. Antibiotic dosing in critically ill patients receiving CRRT: underdosing is overprevalent.

    PubMed

    Lewis, Susan J; Mueller, Bruce A

    2014-01-01

    Published CRRT drug dosing algorithms and other dosing guidelines appear to result in underdosed antibiotics, leading to failure to attain pharmacodynamic targets. High mortality rates persist with inadequate antibiotic therapy as the most important risk factor for death. Reasons for unintended antibiotic underdosing in patients receiving CRRT are many. Underdosing may result from lack of the recognition that better hepatic function in AKI patients yields higher nonrenal antibiotic clearance compared to ESRD patients. Other factors include the variability in body size and fluid composition of patients, the serious consequence of delayed achievement of antibiotic pharmacodynamic targets in septic patients, potential subtherapeutic antibiotic concentrations at the infection site, and the influence of RRT intensity on antibiotic concentrations. Too often, clinicians weigh the benefits of overcautious antibiotic dosing to avoid antibiotic toxicity too heavily against the benefits of rapid attainment of therapeutic antibiotic concentrations in critically ill patients receiving CRRT. We urge clinicians to prescribe antibiotics aggressively for these vulnerable patients. © 2014 Wiley Periodicals, Inc.

  4. Statistical analysis of radiation dose derived from ingestion of foods

    NASA Astrophysics Data System (ADS)

    Dougherty, Ward L.

    2001-09-01

    This analysis undertook the task of designing and implementing a methodology to determine an individual's probabilistic radiation dose from ingestion of foods utilizing Crystal Ball. A dietary intake model was determined by comparing previous existing models. Two principal radionuclides were considered-Lead210 (Pb-210) and Radium 226 (Ra-226). Samples from three different local grocery stores-Publix, Winn Dixie, and Albertsons-were counted on a gamma spectroscopy system with a GeLi detector. The same food samples were considered as those in the original FIPR database. A statistical analysis, utilizing the Crystal Ball program, was performed on the data to assess the most accurate distribution to use for these data. This allowed a determination of a radiation dose to an individual based on the above-information collected. Based on the analyses performed, radiation dose for grocery store samples was lower for Radium-226 than FIPR debris analyses, 2.7 vs. 5.91 mrem/yr. Lead-210 had a higher dose in the grocery store sample than the FIPR debris analyses, 21.4 vs. 518 mrem/yr. The output radiation dose was higher for all evaluations when an accurate estimation of distributions for each value was considered. Radium-226 radiation dose for FIPR and grocery rose to 9.56 and 4.38 mrem/yr. Radiation dose from ingestion of Pb-210 rose to 34.7 and 854 mrem/yr for FIPR and grocery data, respectively. Lead-210 was higher than initial doses for many reasons: Different peak examined, lower edge of detection limit, and minimum detectable concentration was considered. FIPR did not utilize grocery samples as a control because they calculated radiation dose that appeared unreasonably high. Consideration of distributions with the initial values allowed reevaluation of radiation does and showed a significant difference to original deterministic values. This work shows the value and importance of considering distributions to ensure that a person's radiation dose is accurately calculated. Probabilistic dose methodology was proved to be a more accurate and realistic method of radiation dose determination. This type of methodology provides a visual presentation of dose distribution that can be a vital aid in risk methodology.

  5. Estimation of staff lens doses during interventional procedures. Comparing cardiology, neuroradiology and interventional radiology.

    PubMed

    Vano, E; Sanchez, R M; Fernandez, J M

    2015-07-01

    The purpose of this article is to estimate lens doses using over apron active personal dosemeters in interventional catheterisation laboratories (cardiology IC, neuroradiology IN and radiology IR) and to investigate correlations between occupational lens doses and patient doses. Active electronic personal dosemeters placed over the lead apron were used on a sample of 204 IC procedures, 274 IN and 220 IR (all performed at the same university hospital). Patient dose values (kerma area product) were also recorded to evaluate correlations with occupational doses. Operators used the ceiling-suspended screen in most cases. The median and third quartile values of equivalent dose Hp(10) per procedure measured over the apron for IC, IN and IR resulted, respectively, in 21/67, 19/44 and 24/54 µSv. Patient dose values (median/third quartile) were 75/128, 83/176 and 61/159 Gy cm(2), respectively. The median ratios for dosemeters worn over the apron by operators (protected by the ceiling-suspended screen) and patient doses were 0.36; 0.21 and 0.46 µSv Gy(-1) cm(-2), respectively. With the conservative approach used (lens doses estimated from the over apron chest dosemeter) we came to the conclusion that more than 800 procedures y(-1) and per operator were necessary to reach the new lens dose limit for the three interventional specialties. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Temporary organ displacement coupled with image-guided, intensity-modulated radiotherapy for paraspinal tumors

    PubMed Central

    2013-01-01

    Background To investigate the feasibility and dosimetric improvements of a novel technique to temporarily displace critical structures in the pelvis and abdomen from tumor during high-dose radiotherapy. Methods Between 2010 and 2012, 11 patients received high-dose image-guided intensity-modulated radiotherapy with temporary organ displacement (TOD) at our institution. In all cases, imaging revealed tumor abutting critical structures. An all-purpose drainage catheter was introduced between the gross tumor volume (GTV) and critical organs at risk (OAR) and infused with normal saline (NS) containing 5-10% iohexol. Radiation planning was performed with the displaced OARs and positional reproducibility was confirmed with cone-beam CT (CBCT). Patients were treated within 36 hours of catheter placement. Radiation plans were re-optimized using pre-TOD OARs to the same prescription and dosimetrically compared with post-TOD plans. A two-tailed permutation test was performed on each dosimetric measure. Results The bowel/rectum was displaced in six patients and kidney in four patients. One patient was excluded due to poor visualization of the OAR; thus 10 patients were analyzed. A mean of 229 ml (range, 80–1000) of NS 5-10% iohexol infusion resulted in OAR mean displacement of 17.5 mm (range, 7–32). The median dose prescribed was 2400 cGy in one fraction (range, 2100–3000 in 3 fractions). The mean GTV Dmin and PTV Dmin pre- and post-bowel TOD IG-IMRT dosimetry significantly increased from 1473 cGy to 2086 cGy (p=0.015) and 714 cGy to 1214 cGy (p=0.021), respectively. TOD increased mean PTV D95 by 27.14% of prescription (p=0.014) while the PTV D05 decreased by 9.2% (p=0.011). TOD of the bowel resulted in a 39% decrease in mean bowel Dmax (p=0.008) confirmed by CBCT. TOD of the kidney significantly decreased mean kidney dose and Dmax by 25% (0.022). Conclusions TOD was well tolerated, reproducible, and facilitated dose escalation to previously radioresistant tumors abutting critical structures while minimizing dose to OARs. PMID:23800073

  7. Helical irradiation of the total skin with dose painting to replace total skin electron beam therapy for therapy-refractory cutaneous CD4+ T-cell lymphoma.

    PubMed

    Hsieh, Chen-Hsi; Shueng, Pei-Wei; Lin, Shih-Chiang; Tien, Hui-Ju; Shiau, An-Cheng; Chou, Yueh-Hung; Wu, Meng-Hao; Wang, Jen-Yu; Chen, Chi-Kuan; Chen, Yu-Jen

    2013-01-01

    A 36-year-old woman was diagnosed with a therapy-refractory cutaneous CD4+ T-cell lymphoma, T3N0M0B0, and stage IIB. Helical irradiation of the total skin (HITS) and dose painting techniques, with 30 Gy in 40 fractions interrupted at 20 fractions with one week resting, 4 times per week were prescribed. The diving suit was dressed whole body to increase the superficial dose and using central core complete block (CCCB) technique for reducing the internal organ dose. The mean doses of critical organs of head, chest, and abdomen were 2.1 to 29.9 Gy, 2.9 to 8.1 Gy, and 3.6 to 15.7 Gy, respectively. The mean dose of lesions was 84.0 cGy. The dosage of left side pretreated area was decreased 57%. The tumor regressed progressively without further noduloplaques. During the HITS procedure, most toxicity was grade I except leukocytopenia with grade 3. No epitheliolysis, phlyctenules, tumor lysis syndrome, fever, vomiting, dyspnea, edema of the extremities, or diarrhea occurred during the treatment. HITS with dose painting techniques provides precise dosage delivery with impressive results, sparing critical organs, and offering limited transient and chronic sequelae for previously locally irradiated, therapy-refractory cutaneous T-cell lymphoma.

  8. Dose-Response Modelling of Paralytic Shellfish Poisoning (PSP) in Humans

    PubMed Central

    Arnich, Nathalie; Thébault, Anne

    2018-01-01

    Paralytic shellfish poisoning (PSP) is caused by a group of marine toxins with saxitoxin (STX) as the reference compound. Symptoms in humans after consumption of contaminated shellfish vary from slight neurological and gastrointestinal effects to fatal respiratory paralysis. A systematic review was conducted to identify reported cases of human poisoning associated with the ingestion of shellfish contaminated with paralytic shellfish toxins (PSTs). Raw data were collected from 143 exposed individuals (113 with symptoms, 30 without symptoms) from 13 studies. Exposure estimates were based on mouse bioassays except in one study. A significant relationship between exposure to PSTs and severity of symptoms was established by ordinal modelling. The critical minimal dose with a probability higher than 10% of showing symptoms is 0.37 µg STX eq./kg b.w. This means that 10% of the individuals exposed to this dose would have symptoms (without considering the severity of the symptoms). This dose is four-fold lower than the lowest-observed-adverse-effect-level (LOAEL) established by the European Food Safety Authority (EFSA, 2009) in the region of 1.5 μg STX eq./kg b.w. This work provides critical doses that could be used as point of departure to update the acute reference dose for STX. This is the first time a dose-symptoms model could be built for marine toxins using epidemiological data. PMID:29597338

  9. Pharmacokinetics of sulfamethoxazole and trimethoprim in Pacific white shrimp, Litopenaeus vannamei, after oral administration of single-dose and multiple-dose.

    PubMed

    Ma, Rongrong; Wang, Yuan; Zou, Xiong; Hu, Kun; Sun, Beibei; Fang, Wenhong; Fu, Guihong; Yang, Xianle

    2017-06-01

    The tissue distribution and depletion of sulfamethoxazole (SMZ) and trimethoprim (TMP) were studied in Pacific white shrimp, Litopenaeus vannamei, after single-dose and multiple-dose oral administration of SMZ-TMP (5:1) via medicated feed. In single-dose oral administration, shrimps were fed once at a dose of 100 mg/kg (drug weight/body weight). In multiple-dose oral administration, shrimps were fed three times a day for three consecutive days at a dose of 100mg/kg. The results showed the kinetic characteristic of SMZ was different from TMP in Pacific white shrimp. In the single-dose administration, the SMZ was widely distributed in the tissues, while TMP was highly concentrated in the hepatopancreas. The t 1/2z values of SMZ were larger and persist longer than TMP in Pacific white shrimp. In the multiple-dose administration, SMZ accumulated well in the tissues, and reached steady state level after successive administrations, while TMP did not. TMP concentration even appeared the downward trend with the increase of drug times. Compared with the single dose, the t 1/2z values of SMZ in hepatopancreas (8.22-11.33h) and muscle (6.53-10.92h) of Pacific white shrimps rose, but the haemolymph dropped (13.76-11.03) in the multiple-dose oral administration. Meanwhile, the corresponding values of TMP also rose in hepatopancreas (4.53-9.65h) and muscle (2.12-2.71h), and declined in haemolymph (7.38-5.25h) following single-dose and multiple-dose oral administration in Pacific white shrimps. In addition, it is worth mentioning that the ratios of SMZ and TMP were unusually larger than the general aim ratio. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Development of posture-specific computational phantoms using motion capture technology and application to radiation dose-reconstruction for the 1999 Tokai-Mura nuclear criticality accident

    NASA Astrophysics Data System (ADS)

    Vazquez, Justin A.; Caracappa, Peter F.; Xu, X. George

    2014-09-01

    The majority of existing computational phantoms are designed to represent workers in typical standing anatomical postures with fixed arm and leg positions. However, workers found in accident-related scenarios often assume varied postures. This paper describes the development and application of two phantoms with adjusted postures specified by data acquired from a motion capture system to simulate unique human postures found in a 1999 criticality accident that took place at a JCO facility in Tokai-Mura, Japan. In the course of this accident, two workers were fatally exposed to extremely high levels of radiation. Implementation of the emergent techniques discussed produced more accurate and more detailed dose estimates for the two workers than were reported in previous studies. A total-body dose of 6.43 and 26.38 Gy was estimated for the two workers, who assumed a crouching and a standing posture, respectively. Additionally, organ-specific dose estimates were determined, including a 7.93 Gy dose to the thyroid and 6.11 Gy dose to the stomach for the crouching worker and a 41.71 Gy dose to the liver and a 37.26 Gy dose to the stomach for the standing worker. Implications for the medical prognosis of the workers are discussed, and the results of this study were found to correlate better with the patient outcome than previous estimates, suggesting potential future applications of such methods for improved epidemiological studies involving next-generation computational phantom tools.

  11. Development of posture-specific computational phantoms using motion capture technology and application to radiation dose-reconstruction for the 1999 Tokai-Mura nuclear criticality accident.

    PubMed

    Vazquez, Justin A; Caracappa, Peter F; Xu, X George

    2014-09-21

    The majority of existing computational phantoms are designed to represent workers in typical standing anatomical postures with fixed arm and leg positions. However, workers found in accident-related scenarios often assume varied postures. This paper describes the development and application of two phantoms with adjusted postures specified by data acquired from a motion capture system to simulate unique human postures found in a 1999 criticality accident that took place at a JCO facility in Tokai-Mura, Japan. In the course of this accident, two workers were fatally exposed to extremely high levels of radiation. Implementation of the emergent techniques discussed produced more accurate and more detailed dose estimates for the two workers than were reported in previous studies. A total-body dose of 6.43 and 26.38 Gy was estimated for the two workers, who assumed a crouching and a standing posture, respectively. Additionally, organ-specific dose estimates were determined, including a 7.93 Gy dose to the thyroid and 6.11 Gy dose to the stomach for the crouching worker and a 41.71 Gy dose to the liver and a 37.26 Gy dose to the stomach for the standing worker. Implications for the medical prognosis of the workers are discussed, and the results of this study were found to correlate better with the patient outcome than previous estimates, suggesting potential future applications of such methods for improved epidemiological studies involving next-generation computational phantom tools.

  12. Effect of heavy-ion and electron irradiation on properties of Fe-based superconductors

    NASA Astrophysics Data System (ADS)

    Konczykowski, Marcin

    2013-03-01

    The introduction of defects by particle irradiation is used to reveal the role of disorder in matter, which is unavoidable in all crystalline solids. In superconductors defects introduce flux pinning, controlling critical current, Jc; as well as pair-breaking scattering, limiting the critical temperature, Tc. To elucidate defect related properties of Fe-based superconductors (FBS) we precede in two types of irradiation: heavy ion (6GeV Pb) to create disorder in the form of amorphous tracks and low temperature electron irradiation (2.5MeV at 20K) to create point like defects. Substantial increase of irreversible magnetization and an upward shift of the irreversibility line are observed after heavy ion irradiation of all FBS investigated to date. In BaK 122 , signatures of a Bose-glass vortex state; angular dependence and variable-range hopping flux creep are revealed. Remarkably, heavy ion irradiation does not depress Tc, however, point-like disorder introduced by electron irradiation does substantially. In isovalently substituted Ba(FeAs1 - xPx) 2 and Ba(Fe1 - x Rux As) 2 crystals, Tc decreases linearly with dose. Suppression to 40 % of initial value of Tc was achieved in Ba(FeAs1 - xPx) 2 . An increase of normal state resistivity is observed and correlated to depression of Tc. Change of superconducting gap structure with disorder was determined from penetration depth measurements, λ (T) dependence, at various stages of irradiation. Linear in T variation of pristine samples, indicative of the presence of nodes in gap, turned at low irradiation dose to exponential T variation, indicative of a fully gaped state. T2 variation of λ is observed at higher doses. This behaviour is incompatible with symmetry-imposed nodes of d-wave pairing but consistent with S + / - , S + / + mechanisms. This is the first observation of the impurity-induced node lifting expected in anisotropic s-wave superconductors

  13. Monitoring Haloperidol Plasma Concentration and Associated Adverse Events in Critically Ill Children With Delirium: First Results of a Clinical Protocol Aimed to Monitor Efficacy and Safety.

    PubMed

    Slooff, Valerie D; van den Dungen, Desley K; van Beusekom, Babette S; Jessurun, Naomi; Ista, Erwin; Tibboel, Dick; de Wildt, Saskia N

    2018-02-01

    As delirium in critically ill children is increasingly recognized, more children are treated with the antipsychotic drug haloperidol, while current dosing guidelines are lacking solid evidence and appear to be associated with a high risk of adverse events. We aim to report on the safety and efficacy of a recently implemented clinical dose-titration protocol with active monitoring of adverse events. From July 2014 until June 2015, when a potential delirium was identified by regular delirium scores and confirmed by a child psychiatrist, haloperidol was prescribed according to the Dutch Pediatric Formulary. Daily, adverse events were systematically assessed, haloperidol plasma concentrations were measured, and delirium symptoms followed. Dependent on the clinical response, plasma concentration, and adverse event, the dose was adjusted. A 28-bed tertiary PICU in the Netherlands. All patients admitted to the PICU diagnosed with delirium. Treatment with haloperidol according to a dose-titration protocol MEASUREMENTS AND MAIN RESULTS:: Thirteen children (median age [range] 8.3 yr [0.4-13.8 yr]) received haloperidol, predominantly IV (median dose [range] 0.027 mg/kg/d [0.005-0.085 mg/kg/d]). In all patients, pediatric delirium resolved, but five of 13 patients developed possible adverse event. These were reversed after biperiden (n = 2), discontinuing (n = 3), and/or lowering the dose (n = 3). Plasma concentrations were all below the presumed therapeutic threshold of 3-12 µg/L. Prospective systematic monitoring of adverse event in critically ill children receiving haloperidol revealed a significant proportion of possible adverse events. Adverse event developed despite low plasma concentrations and recommended dose administration in the majority of the patients. Our data suggest that haloperidol can potentially improve pediatric delirium, but it might also put patients at risk for developing adverse events.

  14. SU-E-T-197: Helical Cranial-Spinal Treatments with a Linear Accelerator

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Anderson, J; Bernard, D; Liao, Y

    2014-06-01

    Purpose: Craniospinal irradiation (CSI) of systemic disease requires a high level of beam intensity modulation to reduce dose to bone marrow and other critical structures. Current helical delivery machines can take 30 minutes or more of beam-on time to complete these treatments. This pilot study aims to test the feasibility of performing helical treatments with a conventional linear accelerator using longitudinal couch travel during multiple gantry revolutions. Methods: The VMAT optimization package of the Eclipse 10.0 treatment planning system was used to optimize pseudo-helical CSI plans of 5 clinical patient scans. Each gantry revolution was divided into three 120° arcsmore » with each isocenter shifted longitudinally. Treatments requiring more than the maximum 10 arcs used multiple plans with each plan after the first being optimized including the dose of the others (Figure 1). The beam pitch was varied between 0.2 and 0.9 (couch speed 5- 20cm/revolution and field width of 22cm) and dose-volume histograms of critical organs were compared to tomotherapy plans. Results: Viable pseudo-helical plans were achieved using Eclipse. Decreasing the pitch from 0.9 to 0.2 lowered the maximum lens dose by 40%, the mean bone marrow dose by 2.1% and the maximum esophagus dose by 17.5%. (Figure 2). Linac-based helical plans showed dose results comparable to tomotherapy delivery for both target coverage and critical organ sparing, with the D50 of bone marrow and esophagus respectively 12% and 31% lower in the helical linear accelerator plan (Figure 3). Total mean beam-on time for the linear accelerator plan was 8.3 minutes, 54% faster than the tomotherapy average for the same plans. Conclusions: This pilot study has demonstrated the feasibility of planning pseudo-helical treatments for CSI targets using a conventional linac and dynamic couch movement, and supports the ongoing development of true helical optimization and delivery.« less

  15. Dosimetric equivalence of nonstandard HDR brachytherapy catheter patterns

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cunha, J. A. M.; Hsu, I-C.; Pouliot, J.

    2009-01-15

    Purpose: To determine whether alternative high dose rate prostate brachytherapy catheter patterns can result in similar or improved dose distributions while providing better access and reducing trauma. Materials and Methods: Standard prostate cancer high dose rate brachytherapy uses a regular grid of parallel needle positions to guide the catheter insertion. This geometry does not easily allow the physician to avoid piercing the critical structures near the penile bulb nor does it provide position flexibility in the case of pubic arch interference. This study used CT datasets with 3 mm slice spacing from ten previously treated patients and digitized new cathetersmore » following three hypothetical catheter patterns: conical, bi-conical, and fireworks. The conical patterns were used to accommodate a robotic delivery using a single entry point. The bi-conical and fireworks patterns were specifically designed to avoid the critical structures near the penile bulb. For each catheter distribution, a plan was optimized with the inverse planning algorithm, IPSA, and compared with the plan used for treatment. Irrelevant of catheter geometry, a plan must fulfill the RTOG-0321 dose criteria for target dose coverage (V{sub 100}{sup Prostate}>90%) and organ-at-risk dose sparing (V{sub 75}{sup Bladder}<1 cc, V{sub 75}{sup Rectum}<1 cc, V{sub 125}{sup Urethra}<<1 cc). Results: The three nonstandard catheter patterns used 16 nonparallel, straight divergent catheters, with entry points in the perineum. Thirty plans from ten patients with prostate sizes ranging from 26 to 89 cc were optimized. All nonstandard patterns fulfilled the RTOG criteria when the clinical plan did. In some cases, the dose distribution was improved by better sparing the organs-at-risk. Conclusion: Alternative catheter patterns can provide the physician with additional ways to treat patients previously considered unsuited for brachytherapy treatment (pubic arch interference) and facilitate robotic guidance of catheter insertion. In addition, alternative catheter patterns may decrease toxicity by avoidance of the critical structures near the penile bulb while still fulfilling the RTOG criteria.« less

  16. Dosimetric comparison of deep inspiration breath hold and free breathing technique in stereotactic body radiotherapy for localized lung tumor using Flattening Filter Free beam

    NASA Astrophysics Data System (ADS)

    Mani, Karthick Raj; Bhuiyan, Md. Anisuzzaman; Alam, Md. Mahbub; Ahmed, Sharif; Sumon, Mostafa Aziz; Sengupta, Ashim Kumar; Rahman, Md. Shakilur; Azharul Islam, Md. S. M.

    2018-03-01

    Aim: To compare the dosimetric advantage of stereotactic body radiotherapy (SBRT) for localized lung tumor between deep inspiration breath hold technique and free breathing technique. Materials and methods: We retrospectively included ten previously treated lung tumor patients in this dosimetric study. All the ten patients underwent CT simulation using 4D-CT free breathing (FB) and deep inspiration breath hold (DIBH) techniques. Plans were created using three coplanar full modulated arc using 6 MV flattening filter free (FFF) bream with a dose rate of 1400 MU/min. Same dose constraints for the target and the critical structures for a particular patient were used during the plan optimization process in DIBH and FB datasets. We intend to deliver 50 Gy in 5 fractions for all the patients. For standardization, all the plans were normalized at target mean of the planning target volume (PTV). Doses to the critical structures and targets were recorded from the dose volume histogram for evaluation. Results: The mean right and left lung volumes were inflated by 1.55 and 1.60 times in DIBH scans compared to the FB scans. The mean internal target volume (ITV) increased in the FB datasets by 1.45 times compared to the DIBH data sets. The mean dose followed by standard deviation (x¯ ± σx¯) of ipsilateral lung for DIBH-SBRT and FB-SBRT plans were 7.48 ± 3.57 (Gy) and 10.23 ± 4.58 (Gy) respectively, with a mean reduction of 36.84% in DIBH-SBRT plans. Ipsilateral lung were reduced to 36.84% in DIBH plans compared to FB plans. Conclusion: Significant dose reduction in ipsilateral lung due to the lung inflation and target motion restriction in DIBH-SBRT plans were observed compare to FB-SBRT. DIBH-SBRT plans demonstrate superior dose reduction to the normal tissues and other critical structures.

  17. Czech results at criticality dosimetry intercomparison 2002.

    PubMed

    Frantisek, Spurný; Jaroslav, Trousil

    2004-01-01

    Two criticality dosimetry systems were tested by Czech participants during the intercomparison held in Valduc, France, June 2002. The first consisted of the thermoluminescent detectors (TLDs) (Al-P glasses) and Si-diodes as passive neutron dosemeters. Second, it was studied to what extent the individual dosemeters used in the Czech routine personal dosimetry service can give a reliable estimation of criticality accident exposure. It was found that the first system furnishes quite reliable estimation of accidental doses. For routine individual dosimetry system, no important problems were encountered in the case of photon dosemeters (TLDs, film badge). For etched track detectors in contact with the 232Th or 235U-Al alloy, the track density saturation for the spark counting method limits the upper dose at approximately 1 Gy for neutrons with the energy >1 MeV.

  18. Critical Value Reporting in Transfusion Medicine

    PubMed Central

    Reese, Erika M.; Nelson, Randin C.; Flegel, Willy A.; Byrne, Karen M.; Booth, Garrett S.

    2017-01-01

    Abstract Objectives: While critical value procedures have been adopted in most areas of the clinical laboratory, their use in transfusion medicine has not been reviewed in detail. The results of this study present a comprehensive overview of critical value reporting and communication practices in transfusion medicine in the United States. Methods: A web-based survey was developed to collect data on the prevalence of critical value procedures and practices of communicating results. The survey was distributed via email to US hospital-based blood banks. Results: Of 123 facilities surveyed, 84 (68.3%) blood banks had a critical value procedure. From a panel of 23 common blood bank results, nine results were selected by more than 70% of facilities as either a critical value or requiring rapid communication as defined by an alternate procedure. Conclusions: There was overlap among results communicated by facilities with and without a critical value procedure. The most frequently communicated results, such as incompatible crossmatch for RBC units issued uncrossmatched, delay in finding compatible blood due to a clinically significant antibody, and transfusion reaction evaluation suggestive of a serious adverse event, addressed scenarios associated with the leading reported causes of transfusion-related fatalities. PMID:28371931

  19. Global trends in critical values practices and their harmonization.

    PubMed

    Kost, Gerald J; Hale, Kristin N

    2011-02-01

    The objectives of this article were 1) to identify current trends in critical values practices in North America, Europe, and other regions; 2) to describe progress toward harmonization of critical limits; and 3) to synthesize strategies that will encourage global consensus. Critical limits are described in national surveys. Critical value practices are guided by federal statutes, The Joint Commission regulations, and accreditation requirements in the US; by provincial healthcare agencies in Canada; by thought leaders and ISO EN 15189:2007 in Europe; and in SE Asia, mostly by ad hoc policies lacking statutory grip. Review of databases, literature, websites, federal statutes, litigation, official policies, current affairs, and accreditation agency requirements. Practical strategies will accelerate harmonization of critical values practices, as follows: a) continue national and international survey comparisons; b) clarify age, ethnic, and subject dependencies; c) standardize qualitative and quantitative decision levels for urgent clinician notification; d) monitor compliance and timeliness for safety; and e) alert high frequencies of critical values related to adverse events. New expectations and communication technologies present opportunities for enhanced performance using wireless closed-loop reporting with recipient acknowledgment to reduce phone calls and improve efficiency. Hospitals worldwide can benefit from developing consensus for critical values practices.

  20. Spatiotemporal radiotherapy planning using a global optimization approach

    NASA Astrophysics Data System (ADS)

    Adibi, Ali; Salari, Ehsan

    2018-02-01

    This paper aims at quantifying the extent of potential therapeutic gain, measured using biologically effective dose (BED), that can be achieved by altering the radiation dose distribution over treatment sessions in fractionated radiotherapy. To that end, a spatiotemporally integrated planning approach is developed, where the spatial and temporal dose modulations are optimized simultaneously. The concept of equivalent uniform BED (EUBED) is used to quantify and compare the clinical quality of spatiotemporally heterogeneous dose distributions in target and critical structures. This gives rise to a large-scale non-convex treatment-plan optimization problem, which is solved using global optimization techniques. The proposed spatiotemporal planning approach is tested on two stylized cancer cases resembling two different tumor sites and sensitivity analysis is performed for radio-biological and EUBED parameters. Numerical results validate that spatiotemporal plans are capable of delivering a larger BED to the target volume without increasing the BED in critical structures compared to conventional time-invariant plans. In particular, this additional gain is attributed to the irradiation of different regions of the target volume at different treatment sessions. Additionally, the trade-off between the potential therapeutic gain and the number of distinct dose distributions is quantified, which suggests a diminishing marginal gain as the number of dose distributions increases.

  1. Antibiotic Dosing in Continuous Renal Replacement Therapy.

    PubMed

    Shaw, Alexander R; Mueller, Bruce A

    2017-07-01

    Appropriate antibiotic dosing is critical to improve outcomes in critically ill patients with sepsis. The addition of continuous renal replacement therapy makes achieving appropriate antibiotic dosing more difficult. The lack of continuous renal replacement therapy standardization results in treatment variability between patients and may influence whether appropriate antibiotic exposure is achieved. The aim of this study was to determine if continuous renal replacement therapy effluent flow rate impacts attaining appropriate antibiotic concentrations when conventional continuous renal replacement therapy antibiotic doses were used. This study used Monte Carlo simulations to evaluate the effect of effluent flow rate variance on pharmacodynamic target attainment for cefepime, ceftazidime, levofloxacin, meropenem, piperacillin, and tazobactam. Published demographic and pharmacokinetic parameters for each antibiotic were used to develop a pharmacokinetic model. Monte Carlo simulations of 5000 patients were evaluated for each antibiotic dosing regimen at the extremes of Kidney Disease: Improving Global Outcomes guidelines recommended effluent flow rates (20 and 35 mL/kg/h). The probability of target attainment was calculated using antibiotic-specific pharmacodynamic targets assessed over the first 72 hours of therapy. Most conventional published antibiotic dosing recommendations, except for levofloxacin, reach acceptable probability of target attainment rates when effluent rates of 20 or 35 mL/kg/h are used. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  2. Cerebral Glucose Metabolism and Sedation in Brain-injured Patients: A Microdialysis Study.

    PubMed

    Hertle, Daniel N; Santos, Edgar; Hagenston, Anna M; Jungk, Christine; Haux, Daniel; Unterberg, Andreas W; Sakowitz, Oliver W

    2015-07-01

    Disturbed brain metabolism is a signature of primary damage and/or precipitates secondary injury processes after severe brain injury. Sedatives and analgesics target electrophysiological functioning and are as such well-known modulators of brain energy metabolism. Still unclear, however, is how sedatives impact glucose metabolism and whether they differentially influence brain metabolism in normally active, healthy brain and critically impaired, injured brain. We therefore examined and compared the effects of anesthetic drugs under both critical (<1 mmol/L) and noncritical (>1 mmol/L) extracellular brain glucose levels. We performed an explorative, retrospective analysis of anesthetic drug administration and brain glucose concentrations, obtained by bedside microdialysis, in 19 brain-injured patients. Our investigations revealed an inverse linear correlation between brain glucose and both the concentration of extracellular glutamate (Pearson r=-0.58, P=0.01) and the lactate/glucose ratio (Pearson r=-0.55, P=0.01). For noncritical brain glucose levels, we observed a positive linear correlation between midazolam dose and brain glucose (P<0.05). For critical brain glucose levels, extracellular brain glucose was unaffected by any type of sedative. These findings suggest that the use of anesthetic drugs may be of limited value in attempts to influence brain glucose metabolism in injured brain tissue.

  3. Evaluation of material heterogeneity dosimetric effects using radiochromic film for COMS eye plaques loaded with {sup 125}I seeds (model I25.S16)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Acar, Hilal; Chiu-Tsao, Sou-Tung; Oezbay, Ismail

    Purpose: (1) To measure absolute dose distributions in eye phantom for COMS eye plaques with {sup 125}I seeds (model I25.S16) using radiochromic EBT film dosimetry. (2) To determine the dose correction function for calculations involving the TG-43 formalism to account for the presence of the COMS eye plaque using Monte Carlo (MC) method specific to this seed model. (3) To test the heterogeneous dose calculation accuracy of the new version of Plaque Simulator (v5.3.9) against the EBT film data for this seed model. Methods: Using EBT film, absolute doses were measured for {sup 125}I seeds (model I25.S16) in COMS eyemore » plaques (1) along the plaque's central axis for (a) uniformly loaded plaques (14-20 mm in diameter) and (b) a 20 mm plaque with single seed, and (2) in off-axis direction at depths of 5 and 12 mm for all four plaque sizes. The EBT film calibration was performed at {sup 125}I photon energy. MC calculations using MCNP5 code for a single seed at the center of a 20 mm plaque in homogeneous water and polystyrene medium were performed. The heterogeneity dose correction function was determined from the MC calculations. These function values at various depths were entered into PS software (v5.3.9) to calculate the heterogeneous dose distributions for the uniformly loaded plaques (of all four sizes). The dose distributions with homogeneous water assumptions were also calculated using PS for comparison. The EBT film measured absolute dose rate values (film) were compared with those calculated using PS with homogeneous assumption (PS Homo) and heterogeneity correction (PS Hetero). The values of dose ratio (film/PS Homo) and (film/PS Hetero) were obtained. Results: The central axis depth dose rate values for a single seed in 20 mm plaque measured using EBT film and calculated with MCNP5 code (both in ploystyrene phantom) were compared, and agreement within 9% was found. The dose ratio (film/PS Homo) values were substantially lower than unity (mostly between 0.8 and 0.9) for all four plaque sizes, indicating dose reduction by COMS plaque compared with homogeneous assumption. The dose ratio (film/PS Hetero) values were close to unity, indicating the PS Hetero calculations agree with those from the film study. Conclusions: Substantial heterogeneity effect on the {sup 125}I dose distributions in an eye phantom for COMS plaques was verified using radiochromic EBT film dosimetry. The calculated doses for uniformly loaded plaques using PS with heterogeneity correction option enabled were corroborated by the EBT film measurement data. Radiochromic EBT film dosimetry is feasible in measuring absolute dose distributions in eye phantom for COMS eye plaques loaded with single or multiple {sup 125}I seeds. Plaque Simulator is a viable tool for the calculation of dose distributions if one understands its limitations and uses the proper heterogeneity correction feature.« less

  4. Volumetric Modulated Arc Radiotherapy for Vestibular Schwannomas

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lagerwaard, Frank J.; Meijer, Otto W.M.; Hoorn, Elles A.P. van der

    2009-06-01

    Purpose: To evaluate volumetric modulated arc radiotherapy (RapidArc [RA]), a novel approach allowing for rapid treatment delivery, for the treatment of vestibular schwannoma (VS). Methods and Materials: The RA plans were generated for a small (0.5 cm{sup 3}), intermediate (2.8 cm{sup 3}), and large (14.8 cm{sup 3}) VS. The prescription dose was 12.5 Gy to the encompassing 80% isodose. The RA plans were compared with conventional radiosurgery plans using both a single dynamic conformal arc (1DCA) and five noncoplanar dynamic conformal arcs (5DCA). Conformity indices (CI) and dose-volume histograms of critical organs were compared. The RA plan for the medium-sizedmore » VS was measured in a phantom using Gafchromic EBT films and compared with calculated dose distributions. Results: The RA planning was completed within 30 min in all cases, and calculated treatment delivery time (after patient setup) was 5 min vs. 20 min for 5DCA. A superior CI was achieved with RA, with a substantial decrease in low-dose irradiation of the normal brain achieved relative to 5DCA plans. Maximum doses to critical organs were similar for RA and 5DCA but were higher for 1DCA. Film measurements showed the differences between calculated and measured doses to be smaller than 1.5% in the high-dose area and smaller than 3% in the low-dose area. Conclusion: The RA plans consistently achieved a higher CI and decrease in areas of low-dose irradiation. This, together with shorter treatment delivery times, has led to RA replacing our conventional five-arc radiosurgery technique for VS.« less

  5. Dose-Response Calculator for ArcGIS

    USGS Publications Warehouse

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

    2011-01-01

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

  6. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Seco, J; Giantsoudi, D; Eaton, BR

    Purpose: To investigate the trade-off between vertebral column sparing and thecal-sac target coverage in craniospinal irradiation (CSI) of pediatric patients treated with passive-scattering (PS) and intensity modulated (IMPT) proton therapy. Methods: We selected 2 pediatric patients treated with PS CSI for medulloblastoma. Spinal irradiation was re-planned with IMPT. For all cases, we assumed prescription dose of 23.4 Gy(RBE), with the spinal canal receiving at least 95% of 23.4 Gy(RBE). PS planning was performed using the commercial system XiO. IMPT planning was done using the Astroid planning system. Beam arrangements consisted of (a) PS posterior-anterior (PA) field, PS-PA, (b) IMPT PAmore » field, IMPT-PA, and (c) two posterior oblique IMPT fields, IMPT2 (-35°, 35°). Dose distributions were re-calculated using TOPAS Monte Carlo, along with LET distributions, to investigate LET variations within the target and vertebra anatomy. Variable RBE-weighed dose distributions were also calculated based on a dose and LET-dependent biophysical model. Dosimetric data were compared among the plans for the target volume, spinal cord and adjacent critical organs (thecal-sac and cauda equina). Results: IMPT2 resulted in better sparing of the posterior vertebral column (entrance region posterior to thecal-sac), where planned dose was approximately 6–8Gy(RBE). For IMPT-PA and PS-PA the MC-calculated dose to the posterior vertebral column was, on average, 20Gy and 18Gy respectively. For IMPT2 higher mean-LET (5keV/µm/(g/cm3)) values were observed in anterior vertebral column (beyond the thecal-sac) relative to IMPT-PA and PS-PA, where mean-LET was 3.5keV/µm/(g/cm3) and 2.5keV/µm/(g/cm3) respectively. The higher LET region observed for both IMPT plans was in the distal end of treatment fields, where dose delivered was less 5Gy(RBE). Conclusion: The two-oblique proton beams IMPT2 best spared the spinal column, while reducing the dose to the posterior spinal column from 18–20 to 6–8 Gy(RBE). The best LET distribution was obtained with the PS-PA fields.« less

  7. Shot sequencing based on biological equivalent dose considerations for multiple isocenter Gamma Knife radiosurgery

    NASA Astrophysics Data System (ADS)

    Ma, Lijun; Lee, Letitia; Barani, Igor; Hwang, Andrew; Fogh, Shannon; Nakamura, Jean; McDermott, Michael; Sneed, Penny; Larson, David A.; Sahgal, Arjun

    2011-11-01

    Rapid delivery of multiple shots or isocenters is one of the hallmarks of Gamma Knife radiosurgery. In this study, we investigated whether the temporal order of shots delivered with Gamma Knife Perfexion would significantly influence the biological equivalent dose for complex multi-isocenter treatments. Twenty single-target cases were selected for analysis. For each case, 3D dose matrices of individual shots were extracted and single-fraction equivalent uniform dose (sEUD) values were determined for all possible shot delivery sequences, corresponding to different patterns of temporal dose delivery within the target. We found significant variations in the sEUD values among these sequences exceeding 15% for certain cases. However, the sequences for the actual treatment delivery were found to agree (<3%) and to correlate (R2 = 0.98) excellently with the sequences yielding the maximum sEUD values for all studied cases. This result is applicable for both fast and slow growing tumors with α/β values of 2 to 20 according to the linear-quadratic model. In conclusion, despite large potential variations in different shot sequences for multi-isocenter Gamma Knife treatments, current clinical delivery sequences exhibited consistent biological target dosing that approached that maximally achievable for all studied cases.

  8. Radionuclide administration to nursing mothers: mathematically derived guidelines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Romney, B.M.; Nickoloff, E.L.; Esser, P.D.

    We determined a formula to establish objective guidelines for the administration of radionuclides to nursing mothers. The formula is based on the maximum permissible dose to the infant's critical organ, serial measurements of breast milk activity, milk volume, and dose to the critical organ per microcurie in milk. Using worst-case assumptions, we believe that cessation of nursing for 24 hours after administration of technetium labeled radiopharmaceuticals is sufficient for safety. Longer-lived agents require greater delays. Iodine-123 radiopharmaceuticals are preferable to iodine-131 agents and should always be used when studying the unblocked thyroid.

  9. A pragmatic approach to determine the optimal kVp in cone beam CT: balancing contrast-to-noise ratio and radiation dose

    PubMed Central

    Silkosessak, O; Jacobs, R; Bogaerts, R; Bosmans, H; Panmekiate, S

    2014-01-01

    Objectives: To determine the optimal kVp setting for a particular cone beam CT (CBCT) device by maximizing technical image quality at a fixed radiation dose. Methods: The 3D Accuitomo 170 (J. Morita Mfg. Corp., Kyoto, Japan) CBCT was used. The radiation dose as a function of kVp was measured in a cylindrical polymethyl methacrylate (PMMA) phantom using a small-volume ion chamber. Contrast-to-noise ratio (CNR) was measured using a PMMA phantom containing four materials (air, aluminium, polytetrafluoroethylene and low-density polyethylene), which was scanned using 180 combinations of kVp/mA, ranging from 60/1 to 90/8. The CNR was measured for each material using PMMA as background material. The pure effect of kVp and mAs on the CNR values was analysed. Using a polynomial fit for CNR as a function of mA for each kVp value, the optimal kVp was determined at five dose levels. Results: Absorbed doses ranged between 0.034 mGy mAs−1 (14 × 10 cm, 60 kVp) and 0.108 mGy mAs−1 (14 × 10 cm, 90 kVp). The relation between kVp and dose was quasilinear (R2 > 0.99). The effect of mA and kVp on CNR could be modelled using a second-degree polynomial. At a fixed dose, there was a tendency for higher CNR values at increasing kVp values, especially at low dose levels. A dose reduction through mA was more efficient than an equivalent reduction through kVp in terms of image quality deterioration. Conclusions: For the investigated CBCT model, the most optimal contrast at a fixed dose was found at the highest available kVp setting. There is great potential for dose reduction through mA with a minimal loss in image quality. PMID:24708447

  10. Relationship between Fidelity and Dose of Human Patient Simulation, Critical Thinking Skills, and Knowledge in an Associate Degree Nursing Program

    ERIC Educational Resources Information Center

    Beebe, Rosella I.

    2012-01-01

    This study examined the relationship between human patient simulation (HPS), critical thinking skills, and knowledge acquisition after HPS was integrated across the curriculum of an associate degree nursing program to determine if differences existed in critical thinking and knowledge of students based on the fidelity of HPS used and amount of…

  11. SU-F-T-130: [18F]-FDG Uptake Dose Response in Lung Correlates Linearly with Proton Therapy Dose

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, D; Titt, U; Mirkovic, D

    2016-06-15

    Purpose: Analysis of clinical outcomes in lung cancer patients treated with protons using 18F-FDG uptake in lung as a measure of dose response. Methods: A test case lung cancer patient was selected in an unbiased way. The test patient’s treatment planning and post treatment positron emission tomography (PET) were collected from picture archiving and communication system at the UT M.D. Anderson Cancer Center. Average computerized tomography scan was registered with post PET/CT through both rigid and deformable registrations for selected region of interest (ROI) via VelocityAI imaging informatics software. For the voxels in the ROI, a system that extracts themore » Standard Uptake Value (SUV) from PET was developed, and the corresponding relative biological effectiveness (RBE) weighted (both variable and constant) dose was computed using the Monte Carlo (MC) methods. The treatment planning system (TPS) dose was also obtained. Using histogram analysis, the voxel average normalized SUV vs. 3 different doses was obtained and linear regression fit was performed. Results: From the registration process, there were some regions that showed significant artifacts near the diaphragm and heart region, which yielded poor r-squared values when the linear regression fit was performed on normalized SUV vs. dose. Excluding these values, TPS fit yielded mean r-squared value of 0.79 (range 0.61–0.95), constant RBE fit yielded 0.79 (range 0.52–0.94), and variable RBE fit yielded 0.80 (range 0.52–0.94). Conclusion: A system that extracts SUV from PET to correlate between normalized SUV and various dose calculations was developed. A linear relation between normalized SUV and all three different doses was found.« less

  12. Organ dose conversion coefficients for voxel models of the reference male and female from idealized photon exposures

    NASA Astrophysics Data System (ADS)

    Schlattl, H.; Zankl, M.; Petoussi-Henss, N.

    2007-04-01

    A new series of organ equivalent dose conversion coefficients for whole body external photon exposure is presented for a standardized couple of human voxel models, called Rex and Regina. Irradiations from broad parallel beams in antero-posterior, postero-anterior, left- and right-side lateral directions as well as from a 360° rotational source have been performed numerically by the Monte Carlo transport code EGSnrc. Dose conversion coefficients from an isotropically distributed source were computed, too. The voxel models Rex and Regina originating from real patient CT data comply in body and organ dimensions with the currently valid reference values given by the International Commission on Radiological Protection (ICRP) for the average Caucasian man and woman, respectively. While the equivalent dose conversion coefficients of many organs are in quite good agreement with the reference values of ICRP Publication 74, for some organs and certain geometries the discrepancies amount to 30% or more. Differences between the sexes are of the same order with mostly higher dose conversion coefficients in the smaller female model. However, much smaller deviations from the ICRP values are observed for the resulting effective dose conversion coefficients. With the still valid definition for the effective dose (ICRP Publication 60), the greatest change appears in lateral exposures with a decrease in the new models of at most 9%. However, when the modified definition of the effective dose as suggested by an ICRP draft is applied, the largest deviation from the current reference values is obtained in postero-anterior geometry with a reduction of the effective dose conversion coefficient by at most 12%.

  13. Prediction of obliteration after gamma knife surgery for cerebral arteriovenous malformations.

    PubMed

    Karlsson, B; Lindquist, C; Steiner, L

    1997-03-01

    To define the factors of importance for the obliteration of cerebral arteriovenous malformations (AVMs), thus making a prediction of the probability for obliteration possible. In 945 AVMs of a series of 1319 patients treated with the gamma knife during 1970 to 1990, the relationship between patient, AVMs, and treatment parameters on the one hand and the obliteration of the nidus on the other was analyzed. The obliteration rate increased both with increased minimum (lowest periphery) and average dose and decreased with increased AVM volume. The minimum dose to the AVMs was the decisive dose factor for the treatment result. The higher the minimum dose, the higher the chance for total obliteration. The curve illustrating this relation increased logarithmically to a value of 87%. A higher average dose shortened the latency to AVM obliteration. For the obliterated cases, the larger the malformation, the lower the minimum dose used. This prompted us to relate the obliteration rate to the product minimum dose (AVM volume)1/3 (K index). The obliteration rate increased linearly with the K index up to a value of approximately 27, and for higher K values, the obliteration rate had a constant value of approximately 80%. For the group of 273 cases treated with a minimum dose of at least 25 Gy, the obliteration rate at the study end point (defined as 2-yr latency) was 80% (95% confidence interval = 75-85%). If obliterations that occurred beyond the end point are included, the obliteration rate increased to 85% (81-89%). The probability of obliteration of AVMs after gamma knife surgery is related both to the lowest dose to the AVMs and the AVM volume, and it can be predicted using the K index.

  14. Organ dose conversion coefficients for pediatric reference computational phantoms in external photon radiation fields

    NASA Astrophysics Data System (ADS)

    Chang, Lienard A.

    In the event of a radiological accident or attack, it is important to estimate the organ doses to those exposed. In general, it is difficult to measure organ dose directly in the field and therefore dose conversion coefficients (DCC) are needed to convert measurable values such as air kerma to organ dose. Previous work on these coefficients has been conducted mainly for adults with a focus on radiation protection workers. Hence, there is a large gap in the literature for pediatric values. This study coupled a Monte Carlo N-Particle eXtended (MCNPX) code with International Council of Radiological Protection (ICRP)-adopted University of Florida and National Cancer Institute pediatric reference phantoms to calculate a comprehensive list of dose conversion coefficients (mGy/mGy) to convert air-kerma to organ dose. Parameters included ten phantoms (newborn, 1-year, 5-year, 10-year, 15-year old male and female), 28 organs over 33 energies between 0.01 and 20 MeV in six (6) irradiation geometries relevant to a child who might be exposed to a radiological release: anterior-posterior (AP), posterior-anterior (PA), right-lateral (RLAT), left-lateral (LLAT), rotational (ROT), and isotropic (ISO). Dose conversion coefficients to the red bone marrow over 36 skeletal sites were also calculated. It was hypothesized that the pediatric organ dose conversion coefficients would follow similar trends to the published adult values as dictated by human anatomy, but be of a higher magnitude. It was found that while the pediatric coefficients did yield similar patterns to that of the adult coefficients, depending on the organ and irradiation geometry, the pediatric values could be lower or higher than that of the adult coefficients.

  15. [An investigation of ionizing radiation dose in a manufacturing enterprise of ion-absorbing type rare earth ore].

    PubMed

    Zhang, W F; Tang, S H; Tan, Q; Liu, Y M

    2016-08-20

    Objective: To investigate radioactive source term dose monitoring and estimation results in a manufacturing enterprise of ion-absorbing type rare earth ore and the possible ionizing radiation dose received by its workers. Methods: Ionizing radiation monitoring data of the posts in the control area and supervised area of workplace were collected, and the annual average effective dose directly estimated or estimated using formulas was evaluated and analyzed. Results: In the control area and supervised area of the workplace for this rare earth ore, α surface contamination activity had a maximum value of 0.35 Bq/cm 2 and a minimum value of 0.01 Bq/cm 2 ; β radioactive surface contamination activity had a maximum value of 18.8 Bq/cm 2 and a minimum value of 0.22 Bq/cm 2 . In 14 monitoring points in the workplace, the maximum value of the annual average effective dose of occupational exposure was 1.641 mSv/a, which did not exceed the authorized limit for workers (5 mSv/a) , but exceeded the authorized limit for general personnel (0.25 mSv/a) . The radionuclide specific activity of ionic mixed rare earth oxides was determined to be 0.9. Conclusion: The annual average effective dose of occupational exposure in this enterprise does not exceed the authorized limit for workers, but it exceeds the authorized limit for general personnel. We should pay attention to the focus of the radiation process, especially for public works radiation.

  16. Measuring the incentive value of escalating doses of heroin in heroin-dependent Fischer rats during acute spontaneous withdrawal

    PubMed Central

    Reed, Brian; Ho, Ann; Kreek, Mary Jeanne

    2011-01-01

    Rationale/objectives Although continued heroin use and relapse are thought to be motivated, in part, by the positive incentive-motivational value attributed to heroin, little is understood about heroin’s incentive value during the relapse-prone state of withdrawal. This study uses place preference to measure the incentive value attributed to escalating-dose heroin in the context of heroin dependence. Methods Male Fischer rats were exposed chronically to escalating doses of heroin in the homecage and during place preference conditioning sessions. Conditioned preference for the context paired with escalating-dose heroin was tested after homecage exposure was discontinued and rats entered acute spontaneous withdrawal. Individuals’ behavioral and locomotor responses to heroin and somatic withdrawal signs were recorded. Results Conditioned preference for the heroin-paired context was strong in rats that received chronic homecage exposure to escalating-dose heroin and were tested in acute withdrawal. Behavioral responses to heroin (e.g., stereotypy) varied widely across individuals, with rats that expressed stronger heroin preference also expressing stronger behavioral activation in response to heroin. Individual differences in preference were also related to locomotor responses to heroin but not to overt somatic withdrawal signs. Conclusions Escalating doses of heroin evoked place preference in rats, suggesting that positive incentive-motivational value is attributed to this clinically relevant pattern of drug exposure. This study offers an improved preclinical model for studying dependence and withdrawal and provides insight into individual vulnerabilities to addiction-like behavior. PMID:21748254

  17. [Impact of exposure dose reduction of radiation treatment planning CT using low tube voltage technique].

    PubMed

    Kouno, Takuya; Kuga, Noriyuki; Enzaki, Masahiro; Yamashita, Yuuki; Kitazato, Yumiko; Shimotabira, Haruhiko; Jinnouchi, Takashi; Kusuhara, Kazuo; Kawamura, Shinji

    2015-04-01

    The aim of this study was to reduce the exposed dose of radiotherapy treatment planning computed tomography (CT) by using low tube voltage technique. We used tube voltages of 80 kV, 100 kV, and 120 kV, respectively. First, we evaluated exposure dose with CT dose index (CTDI) for each voltage. Second, we compared image quality indexes such as modulation transfer function (MTF), noise power spectrum (NPS), and contrast to noise ratio (CNR) of phantom images with each voltage. Third, CT to electron density tables were measured in three voltages and monitor unit value was calculated along with clinical cases. Finally, CT surface exposed dose of chest skin was measured by thermoluminescent dosimeter (TLD). In image evaluation MTF and NPS were approximately equal; CNR slightly decreased, 2.0% for 100 kV. We performed check radiation dose accuracy for each tube voltage with each model phantom. As a result, the difference of MU value was not accepted. Finally, compared with 120 kV, CTDIvol and TLD value showed markedly decreased radiation dose, 60% for 80 kV and 30% for 100 kV. Using a technique with low tube voltages, especially 100 kV, is useful in radiotherapy treatment planning to obtain 20% dose reduction without compromising 120 kV image quality.

  18. Accounting for neutron exposure in the Japanese atomic bomb survivors.

    PubMed

    Cullings, Harry M; Pierce, Donald A; Kellerer, Albrecht M

    2014-12-01

    The Japanese atomic bomb survivors that were directly exposed to both γ rays and neutrons have been followed by the Radiation Effects Research Foundation (RERF). The estimation of the γ-ray risks requires some adjustment for the greater biological effect of the neutrons per unit dose. Because the small neutron doses and the predominant γ-ray doses are highly correlated, the neutron relative biological effectiveness (RBE) cannot be reliably estimated from the survivors' data and information from radiobiology must be invoked. As data became available on neutron doses, RERF has used a constant neutron RBE value of 10, even though radiobiological studies indicate that the RBE values appear to have considerably larger values at low doses. The approximation RBE = 10 assumes that if the RBE is variable it takes roughly this value in the range of total dose most relevant for linear risk estimation, namely about 1 Gy. We consider some possible RBE functions to explain the correct use and the impact of a dose-dependent RBE. However, we do not advocate any particular choice or even that a variable RBE be employed. Rather we show that the assumed neutron RBE, within a wide range of choices, is far less important to the outcome of risk assessment of the RERF data than generally believed. Some of these misperceptions have been related to the consideration of variable RBE functions, and without due attention to the fact that in the case of the A-bomb survivors' data, the mixed field of neutrons and γ rays must be considered. Therefore, the RBE value of neutrons is much lower than the RBE in pure neutron fields that are used in radiobiological experiments. Thus, applying the pure neutron field RBE to the mixed-field A-bomb radiation can lead to an overestimation of the actual neutron RBE for moderate total dose levels of 1 Gy by a factor of more than four. While in a pure neutron exposure the RBE depends on the neutron dose, in the mixed field it depends on both components of exposure, and in particular, we show that in the RERF setting the RBE depends mainly on the accompanying γ-ray dose.

  19. Glandular radiation dose in tomosynthesis of the breast using tungsten targets.

    PubMed

    Sechopoulos, Ioannis; D'Orsi, Carl J

    2008-10-24

    With the advent of new detector technology, digital tomosynthesis imaging of the breast has, in the past few years, become a technique intensely investigated as a replacement for planar mammography. As with all other x-ray-based imaging methods, radiation dose is of utmost concern in the development of this new imaging technology. For virtually all development and optimization studies, knowledge of the radiation dose involved in an imaging protocol is necessary. A previous study characterized the normalized glandular dose in tomosynthesis imaging and its variation with various breast and imaging system parameters. This characterization was performed with x-ray spectra generated by molybdenum and rhodium targets. In the recent past, many preliminary patient studies of tomosynthesis imaging have been reported in which the x-ray spectra were generated with x-ray tubes with tungsten targets. The differences in x-ray distribution among spectra from these target materials make the computation of new normalized glandular dose values for tungsten target spectra necessary. In this study we used previously obtained monochromatic normalized glandular dose results to obtain spectral results for twelve different tungsten target x-ray spectra. For each imaging condition, two separate values were computed: the normalized glandular dose for the zero degree projection angle (DgN0), and the ratio of the glandular dose for non-zero projection angles to the glandular dose for the zero degree projection (the relative glandular dose, RGD(alpha)). It was found that DgN0 is higher for tungsten target x-ray spectra when compared with DgN0 values for molybdenum and rhodium target spectra of both equivalent tube voltage and first half value layer. Therefore, the DgN0 for the twelve tungsten target x-ray spectra and different breast compositions and compressed breast thicknesses simulated are reported. The RGD(alpha) values for the tungsten spectra vary with the parameters studied in a similar manner to that found for the molybdenum and rhodium target spectra. The surface fit equations and the fit coefficients for RGD(alpha) included in the previous study were also found to be appropriate for the tungsten spectra.

  20. SU-E-T-44: Angular Dependence of Surface Dose Enhancement Measured On Several Inhomogeneities Using Radiochromic EBT3 Films

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jansen, A; Schoenfeld, A; Poppinga, D

    Purpose: The quantification of the relative surface dose enhancement in dependence on the angle of incidence and the atomic number Z of the surface material. Methods: Experiments were performed with slabs made of aluminum, titanium, copper, silver, dental gold and lead. The metal slabs with equal sizes of 1.0×8.0×8.8mm{sup 3} were embedded in an Octavius 4D phantom (PTW Freiburg, Germany). Radiochromic EBT3 films were used to measure the surface dose for angles of incidence ranging from 0° to 90°. The setup with the metals slabs at the isocenter was irradiated with acceleration voltages of 6MV and 10MV. Water reference measurementsmore » were taken under equal conditions. Results: The surface dose enhancement is highest for angles of incidence below 30° and drops significantly for higher. The surface dose enhancement produced by lead and dental gold at 6MV showed a peak of 65%. At 90°, the surface dose enhancement dropped to 15% for both materials. The surface dose enhancements for silver, copper, titanium and aluminum were 45%, 32%, 22% and 12% at 0°, respectively. At an angle of incidence of 80°, the values dropped to 22%, 18%, 12% und 6%. The values for 10MV were very similar. Lead and dental gold showed peaks of 65% und 60%. Their values dropped to 18% at an angle of 90°. The surface dose enhancements for silver, copper, titanium and aluminum were 45%, 30%, 20% and 8% at 0°. At 80° the values dropped to 30%, 20%, 12% and 5%. A dependence of the magnitude of the surface dose enhancement on the atomic number of the surface material can be seen, which is in consistence with literature. Conclusion: The results show that the surface dose enhancements near implant materials with high Z-values should be taken into consideration in radio therapy, even when the angle of incidence is flat.« less

  1. Estimated human absorbed dose of a new (153)Sm bone seeking agent based on biodistribution data in mice: Comparison with (153)Sm-EDTMP.

    PubMed

    Yousefnia, Hassan; Zolghadri, Samaneh

    2015-11-01

    The main goal in radiotherapy is to deliver the absorbed dose within the target organs in highest possible amount, while the absorbed dose of the other organs, especially the critical organs, should be kept as low as possible. In this work, the absorbed dose to human organs for a new (153)Sm bone-seeking agent was investigated. (153)Sm-(4-{[(bis(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid ((153)Sm-BPAMD) complex was successfully prepared. The biodistribution of the complex was investigated in male Syrian mice up to 48 h post injection. The human absorbed dose of the complex was estimated based on the biodistribution data of the mice by radiation absorbed dose assessment resource (RADAR) method. The target to non-target absorbed dose ratios for (153)Sm-BPAMD were compared with these ratios for (153)Sm-EDTMP. The highest absorbed dose for (153)Sm-BPAMD was observed in bone surface with 5.828 mGy/MBq. The dose ratios of the bone surface to the red marrow and to the total body for (153)Sm-BPAMD were 5.3 and 20.0, respectively, while these ratios for (153)Sm-EDTMP were 4.4 and 18.3, respectively. This means, for a given dose to the bone surface as the target organ, the red marrow (as the main critical organ) and the total body would receive lesser absorbed dose in the case of (153)Sm-BPAMD. Generally, the human absorbed dose estimation of (153)Sm-BPAMD indicated that all other tissues approximately received insignificant absorbed dose in comparison with bone surface and therefore can be regarded as a new potential agent for bone pain palliation therapy. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  2. Dose additive effects of simvastatin and dipentyl phthalate on ...

    EPA Pesticide Factsheets

    Sex differentiation of the mammalian reproductive tract is a highly regulated process that is driven, in part, by fetal testosterone (T) production. In utero exposure to phthalate esters (PE) during sex differentiation can cause reproductive tract malformations in rats. PE alter the expression of genes associated with steroid synthesis/transport and cholesterol biosynthesis. Simvastatin (SMV) is a cholesterol-lowering drug that inhibits HMG-CoA reductase. As cholesterol is a precursor for steroid biosynthesis, we proposed that maternal exposure to SMV during the critical period of sex differentiation would lower fetal T and result in corresponding alterations in cholesterol- and androgenmediated gene expression. Timed pregnant SD rats were dosed orally with SMV from GD14-GD18. T production on GD18 was measured by RIA, and changes in gene expression in maternal and fetal tissues were assessed by quantitative rt-PCR. Circulating lipids were also measured in dams and fetuses. SMV lowered fetal T production, altered several genes involved in cholesterol biosynthesis in the maternal liver, and lowered lipids in the fetus but not in the dam. Unlike PE, SMV did not alter genes associated with sex differentiation. In a second experiment, dams were dosed with SMV, dipentyl phthalate (DPeP, a PE), or both. SMV and DPeP alone reduced fetal T production to 44.3 and 37.5% of control values, respectively, but the mixture reduced T production to 19.9% of control. These studies

  3. Assessments of Sequential Intensity Modulated Radiation Therapy Boost (SqIB) Treatments Using HART

    NASA Astrophysics Data System (ADS)

    Pyakuryal, Anil

    2009-05-01

    A retrospective study was pursued to evaluate the SqIB treatments performed on ten head and neck cancer patients(n=10).Average prescription doses (PDs) of 39 Gy,15Gy and 17.8Gy were delivered consecutively from larger to smaller planning target volumes(ptvs) in three different treatment plans using 6 MV X-ray photon beams from a Linear accelerator (SLA Linac, Elekta) on BID weak on-weak off schedules. These plans were statistically evaluated on basis of plan indices (PIs),dose response of targets and critical structures, and dose tolerance(DT) of various organs utilizing the DVH analysis automated software known as Histogram Analysis in Radiation Therapy-HART(S.Jang et al., 2008, Med Phys 35, p.2812). Mean SqIB PIs were found consistent with the reported values for varying radio-surgical systems.The 95.5%(n=10)of each ptvs and the gross tumor volume also received 95% (n=10)of PDs in treatments. The average volume of ten organs (N=10) affected by each PDs shrank with decreasing size of ptvs in above plans.A largest volume of Oropharynx (79%,n=10,N=10) irradiated at PD, but the largest volume of Larynx (98%, n=10, N=10) was vulnerable to DT of structure (TD50).Thus, we have demonstrated the efficiency and accuracy of HART in the assessment of Linac based plans in radiation therapy treatments of cancer.

  4. Use of short-term toxicity data for prediction of long-term health effects

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hartley, W.R.; Ohanian, E.V.

    1988-01-01

    Under the Safe Drinking Water Act Amendments of 1986, the US Environmental Protection Agency determines Maximum Contaminant Level Goals (MCLGs) and enforceable Maximum Contaminant Levels (MCLs) or provides lifetime health advisories (HAs) in the absence of regulatory standards. The critical value for calculation of the lifetime level is the reference dose (RfD). The RfD is an estimate of a lifetime dose which is likely to be without significant risk to human populations. The RfD is determined by dividing the no-observed-adverse-effect level (NOAEL) or the lowest-observed-adverse-effect level (LOAEL) by an uncertainty factor (UF). The NOAEL or LOAEL is determined from toxicologicalmore » or epidemiological studies. For many chemicals, human toxicological or epidemiological data are not available. Chronic mammalian studies are sometimes unavailable. Faced with the need for providing guidance for the increasing number of chemicals threatening our drinking water sources, this paper considers the possibility of providing provisional RfDs using data from toxicological studies of less than ninety days duration. The current UF approach is reviewed along with some proposed mathematical models for extrapolation of NOAELs from dose-response data. The current UF approach to developing the RfD is protective and conservative. More research is needed on the relationship of short- and long-term toxicity data to improve our current approach.« less

  5. Radiation exposure of contrast-enhanced spectral mammography compared with full-field digital mammography.

    PubMed

    Jeukens, Cécile R L P N; Lalji, Ulrich C; Meijer, Eduard; Bakija, Betina; Theunissen, Robin; Wildberger, Joachim E; Lobbes, Marc B I

    2014-10-01

    Contrast-enhanced spectral mammography (CESM) shows promising initial results but comes at the cost of increased dose as compared with full-field digital mammography (FFDM). We aimed to quantitatively assess the dose increase of CESM in comparison with FFDM. Radiation exposure-related data (such as kilovoltage, compressed breast thickness, glandularity, entrance skin air kerma (ESAK), and average glandular dose (AGD) were retrieved for 47 CESM and 715 FFDM patients. All examinations were performed on 1 mammography unit. Radiation dose values reported by the unit were validated by phantom measurements. Descriptive statistics of the patient data were generated using a statistical software package. Dose values reported by the mammography unit were in good qualitative agreement with those of phantom measurements. Mean ESAK was 10.5 mGy for a CESM exposure and 7.46 mGy for an FFDM exposure. Mean AGD for a CESM exposure was 2.80 mGy and 1.55 mGy for an FFDM exposure. Compared with our institutional FFDM, the AGD of a single CESM exposure is increased by 1.25 mGy (+81%), whereas ESAK is increased by 3.07 mGy (+41%). Dose values of both techniques meet the recommendations for maximum dose in mammography.

  6. Determining Cutoff Point of Ensemble Trees Based on Sample Size in Predicting Clinical Dose with DNA Microarray Data.

    PubMed

    Yılmaz Isıkhan, Selen; Karabulut, Erdem; Alpar, Celal Reha

    2016-01-01

    Background/Aim . Evaluating the success of dose prediction based on genetic or clinical data has substantially advanced recently. The aim of this study is to predict various clinical dose values from DNA gene expression datasets using data mining techniques. Materials and Methods . Eleven real gene expression datasets containing dose values were included. First, important genes for dose prediction were selected using iterative sure independence screening. Then, the performances of regression trees (RTs), support vector regression (SVR), RT bagging, SVR bagging, and RT boosting were examined. Results . The results demonstrated that a regression-based feature selection method substantially reduced the number of irrelevant genes from raw datasets. Overall, the best prediction performance in nine of 11 datasets was achieved using SVR; the second most accurate performance was provided using a gradient-boosting machine (GBM). Conclusion . Analysis of various dose values based on microarray gene expression data identified common genes found in our study and the referenced studies. According to our findings, SVR and GBM can be good predictors of dose-gene datasets. Another result of the study was to identify the sample size of n = 25 as a cutoff point for RT bagging to outperform a single RT.

  7. Poster — Thur Eve — 15: Improvements in the stability of the tomotherapy imaging beam

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Belec, J

    2014-08-15

    Use of helical TomoTherapy based MVCT imaging for adaptive planning requires the image values (HU) to remain stable over the course of treatment. In the past, the image value stability was suboptimal, which required frequent change to the image value to density calibration curve to avoid dose errors on the order of 2–4%. The stability of the image values at our center was recently improved by stabilizing the dose rate of the machine (dose control servo) and performing daily MVCT calibration corrections. In this work, we quantify the stability of the image values over treatment time by comparing patient treatmentmore » image density derived using MVCT and KVCT. The analysis includes 1) MVCT - KVCT density difference histogram, 2) MVCT vs KVCT density spectrum, 3) multiple average profile density comparison and 4) density difference in homogeneous locations. Over two months, the imaging beam stability was compromised several times due to a combination of target wobbling, spectral calibration, target change and magnetron issues. The stability of the image values were analyzed over the same period. Results show that the impact on the patient dose calculation is 0.7% +− 0.6%.« less

  8. A new way of thinking: hydrocortisone in traumatic brain-injured patients.

    PubMed

    Roquilly, Antoine; Vourc'h, Mickael; Cinotti, Raphael; Asehnoune, Karim

    2013-12-04

    Data suggest that treatment of critical illness-related corticosteroid insufficiency after traumatic brain injury (TBI) with a stress dose of hydrocortisone may improve the neurological outcome and the mortality rate. The mineralocorticoid properties of hydrocortisone may reduce the rate of hyponatremia and of brain swelling. The exaggerated inflammatory response may cause critical illness-related corticosteroid insufficiency by altering the function of the hypothalamic-pituitary-adrenal axis, and hydrocortisone is able to restore a balanced inflammatory response rather than inducing immunosuppression. Hydrocortisone could also prevent neuronal apoptosis. Considering side effects, corticosteroids are not equal; when a high dose of synthetic corticosteroids seems detrimental, a strategy using a stress dose of hydrocortisone seems attractive. Finally, results from a large multicenter study are needed to close the debate regarding the use of hydrocortisone in TBI patients.

  9. Dose conversion coefficients for photon exposure of the human eye lens.

    PubMed

    Behrens, R; Dietze, G

    2011-01-21

    In recent years, several papers dealing with the eye lens dose have been published, because epidemiological studies implied that the induction of cataracts occurs even at eye lens doses of less than 500 mGy. Different questions were addressed: Which personal dose equivalent quantity is appropriate for monitoring the dose to the eye lens? Is a new definition of the dose quantity H(p)(3) based on a cylinder phantom to represent the human head necessary? Are current conversion coefficients from fluence to equivalent dose to the lens sufficiently accurate? To investigate the latter question, a realistic model of the eye including the inner structure of the lens was developed. Using this eye model, conversion coefficients for electrons have already been presented. In this paper, the same eye model-with the addition of the whole body-was used to calculate conversion coefficients from fluence (and air kerma) to equivalent dose to the lens for photon radiation from 5 keV to 10 MeV. Compared to the values adopted in 1996 by the International Commission on Radiological Protection (ICRP), the new values are similar between 40 keV and 1 MeV and lower by up to a factor of 5 and 7 for photon energies at about 10 keV and 10 MeV, respectively. Above 1 MeV, the new values (calculated without kerma approximation) should be applied in pure photon radiation fields, while the values adopted by the ICRP in 1996 (calculated with kerma approximation) should be applied in case a significant contribution from secondary electrons originating outside the body is present.

  10. Dose conversion coefficients for photon exposure of the human eye lens

    NASA Astrophysics Data System (ADS)

    Behrens, R.; Dietze, G.

    2011-01-01

    In recent years, several papers dealing with the eye lens dose have been published, because epidemiological studies implied that the induction of cataracts occurs even at eye lens doses of less than 500 mGy. Different questions were addressed: Which personal dose equivalent quantity is appropriate for monitoring the dose to the eye lens? Is a new definition of the dose quantity Hp(3) based on a cylinder phantom to represent the human head necessary? Are current conversion coefficients from fluence to equivalent dose to the lens sufficiently accurate? To investigate the latter question, a realistic model of the eye including the inner structure of the lens was developed. Using this eye model, conversion coefficients for electrons have already been presented. In this paper, the same eye model—with the addition of the whole body—was used to calculate conversion coefficients from fluence (and air kerma) to equivalent dose to the lens for photon radiation from 5 keV to 10 MeV. Compared to the values adopted in 1996 by the International Commission on Radiological Protection (ICRP), the new values are similar between 40 keV and 1 MeV and lower by up to a factor of 5 and 7 for photon energies at about 10 keV and 10 MeV, respectively. Above 1 MeV, the new values (calculated without kerma approximation) should be applied in pure photon radiation fields, while the values adopted by the ICRP in 1996 (calculated with kerma approximation) should be applied in case a significant contribution from secondary electrons originating outside the body is present.

  11. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gopishankar, N; Agarwal, Priyanka; Bisht, Raj Kishor

    Purpose: To evaluate forward and inverse planning methods for acoustic neuroma cases treated in Gamma Knife Perfexion. Methods: Five patients with acoustic neuroma tumour abutting brainstem were planned twice in LGP TPS (Version 10.1) using TMR10 algorithm. First plan was entirely based on forward planning (FP) in which each shot was chosen manually. Second plan was generated using inverse planning (IP) for which planning parameters like coverage, selectivity, gradient index (GI) and beam-on time threshold were set. Number of shots in IP was automatically selected by objective function using iterative process. In both planning methods MRI MPRAGE sequence images weremore » used for tumour localization and planning. A planning dose of 12Gy at 50% isodose level was chosen. Results and Discussion: Number of shots used in FP was greater than IP and beam-on time in FP was in average 1.4 times more than IP. One advantage of FP was that the brainstem volume subjected to 6Gy dose (25% isodose) was less in FP than IP. Our results showed use of more number of shots as in FP results in GI less than or equal to 2.55 which is close to its lower limit. Dose homogeneity index (DHI) analysis of FP and IP showed average values of 0.59 and 0.67 respectively. General trend in GK for planning in acoustic neuroma cases is to use small collimator shots to avoid dose to adjacent critical structures. More number of shots and prolonged treatment time causes inconvenience to the patients. Similarly overuse of automatic shot shaping as in IP results in increased scatter dose. A compromise is required in shot selection for these cases. Conclusion: IP method could be used in acoustic neuroma cases to decrease treatment time provided the source sector openings near brainstem are shielded or adjusted appropriately to reduce brainstem dose.« less

  12. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kuo, C

    Purpose: To analyze and compare the characteristics of dose distributions between Gamma Knife (GK) and CyberKnife (CK), in treating arteriovenous malformations (AVMs), and evaluate the influences on their clinical applications. Methods: Twenty four patients with AVMs treated with CK of prescribed dose (PD) of 16–25 Gy in single fraction were selected. Each patient’s CT images used for CK treatment planning with contours of targets and critical organs were exported and then loaded into the GK planning system. GK treatment plan with the same PD used in CK was generated for each patient. The metrics for dose comparison between GK andmore » CK included conformity index (CI), gradient index (GI) of 75%, 50% and 25% of the PD, heterogeneity index (HI), volume of brain tissues covered by 10 Gy and 12 Gy, maximum dose to brainstem and beam-on time. Paired Samples t-test was used to analyze these metrics for significance (p value). Results: The CI were 0.744 ± 0.075 (GK) and 0.768 ± 0.086 (CK), p = 0.281. The GI75%, GI50%, and GI25% in GK and CK were 1.735 ± 0.100 and 2.439 ± 0.338 (p < 0.001), 3.169 ± 0.265 and 4.972 ± 0.852 (p < 0.001), and 8.650 ± 0.914 and 14.261 ± 2.476 (p < 0.001). The HI were 0.728 ± 0.072 (GK) and 0.313 ± 0.069 (CK), p < 0.001. There were significant differences both for volume of brain tissues covered by 10 Gy and 12 Gy in GK and CK (p < 0.001). GK had smaller maximum dose to brainstem. CK had shorter beam-on time. Conclusion: GK has similar dose conformity as CK, and has better normal tissue sparing but is less efficient than CK.« less

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wan, H; Tseung, Chan; Beltran, C

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

  14. Sex differences in nicotine self-administration in rats during progressive unit dose reduction: Implications for nicotine regulation policy

    PubMed Central

    Grebenstein, Patricia; Burroughs, Danielle; Zhang, Yan; LeSage, Mark G.

    2013-01-01

    Reducing the nicotine content in tobacco products is being considered by the FDA as a policy to reduce the addictiveness of tobacco products. Understanding individual differences in response to nicotine reduction will be critical to developing safe and effective policy. Animal and human research demonstrating sex differences in the reinforcing effects of nicotine suggests that males and females may respond differently to nicotine-reduction policies. However, no studies have directly examined sex differences in the effects of nicotine unit-dose reduction on nicotine self-administration (NSA) in animals. The purpose of the present study was to examine this issue in a rodent self-administration model. Male and female rats were trained to self-administer nicotine (0.06 mg/kg) under an FR 3 schedule during daily 23 h sessions. Rats were then exposed to saline extinction and reacquisition of NSA, followed by weekly reductions in the unit dose (0.03 to 0.00025 mg/kg) until extinction levels of responding were achieved. Males and females were compared with respect to baseline levels of intake, resistance to extinction, degree of compensatory increases in responding during dose reduction, and the threshold reinforcing unit dose of nicotine. Exponential demand-curve analysis was also conducted to compare the sensitivity of males and females to increases in the unit price (FR/unit dose) of nicotine (i.e., elasticity of demand or reinforcing efficacy). Females exhibited significantly higher baseline intake and less compensation than males. However, there were no sex differences in the reinforcement threshold or elasticity of demand. Dose–response relationships were very well described by the exponential demand function (r2 values > 0.96 for individual subjects). These findings suggest that females may exhibit less compensatory smoking in response to nicotine reduction policies, even though their nicotine reinforcement threshold and elasticity of demand may not differ from males. PMID:24201048

  15. Y-12 PLANT NUCLEAR SAFETY HANDBOOK

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wachter, J.W. ed.; Bailey, M.L.; Cagle, T.J.

    1963-03-27

    Information needed to solve nuclear safety problems is condensed into a reference book for use by persons familiar with the field. Included are a glossary of terms; useful tables; nuclear constants; criticality calculations; basic nuclear safety limits; solution geometries and critical values; metal critical values; criticality values for intermediate, heterogeneous, and interacting systems; miscellaneous and related information; and report number, author, and subject indexes. (C.H.)

  16. Prediction model of critical weight loss in cancer patients during particle therapy.

    PubMed

    Zhang, Zhihong; Zhu, Yu; Zhang, Lijuan; Wang, Ziying; Wan, Hongwei

    2018-01-01

    The objective of this study is to investigate the predictors of critical weight loss in cancer patients receiving particle therapy, and build a prediction model based on its predictive factors. Patients receiving particle therapy were enroled between June 2015 and June 2016. Body weight was measured at the start and end of particle therapy. Association between critical weight loss (defined as >5%) during particle therapy and patients' demographic, clinical characteristic, pre-therapeutic nutrition risk screening (NRS 2002) and BMI were evaluated by logistic regression and decision tree analysis. Finally, 375 cancer patients receiving particle therapy were included. Mean weight loss was 0.55 kg, and 11.5% of patients experienced critical weight loss during particle therapy. The main predictors of critical weight loss during particle therapy were head and neck tumour location, total radiation dose ≥70 Gy on the primary tumour, and without post-surgery, as indicated by both logistic regression and decision tree analysis. Prediction model that includes tumour locations, total radiation dose and post-surgery had a good predictive ability, with the area under receiver operating characteristic curve 0.79 (95% CI: 0.71-0.88) and 0.78 (95% CI: 0.69-0.86) for decision tree and logistic regression model, respectively. Cancer patients with head and neck tumour location, total radiation dose ≥70 Gy and without post-surgery were at higher risk of critical weight loss during particle therapy, and early intensive nutrition counselling or intervention should be target at this population. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  17. Evaluation of Enhanced Low Dose Rate Sensitivity in Discrete Bipolar Junction Transistors

    NASA Technical Reports Server (NTRS)

    Chen, Dakai; Ladbury Raymond; LaBel, Kenneth; Topper, Alyson; Ladbury, Raymond; Triggs, Brian; Kazmakites, Tony

    2012-01-01

    We evaluate the low dose rate sensitivity in several families of discrete bipolar transistors across device parameter, quality assurance level, and irradiation bias configuration. The 2N2222 showed the most significant low dose rate sensitivity, with low dose rate enhancement factor of 3.91 after 100 krad(Si). The 2N2907 also showed critical degradation levels. The devices irradiated at 10 mrad(Si)/s exceeded specifications after 40 and 50 krad(Si) for the 2N2222 and 2N2907 devices, respectively.

  18. An organ-based approach to dose calculation in the assessment of dose-dependent biological effects of ionising radiation in Arabidopsis thaliana.

    PubMed

    Biermans, Geert; Horemans, Nele; Vanhoudt, Nathalie; Vandenhove, Hildegarde; Saenen, Eline; Van Hees, May; Wannijn, Jean; Vives i Batlle, Jordi; Cuypers, Ann

    2014-07-01

    There is a need for a better understanding of biological effects of radiation exposure in non-human biota. Correct description of these effects requires a more detailed model of dosimetry than that available in current risk assessment tools, particularly for plants. In this paper, we propose a simple model for dose calculations in roots and shoots of Arabidopsis thaliana seedlings exposed to radionuclides in a hydroponic exposure setup. This model is used to compare absorbed doses for three radionuclides, (241)Am (α-radiation), (90)Sr (β-radiation) and (133)Ba (γ radiation). Using established dosimetric calculation methods, dose conversion coefficient values were determined for each organ separately based on uptake data from the different plant organs. These calculations were then compared to the DCC values obtained with the ERICA tool under equivalent geometry assumptions. When comparing with our new method, the ERICA tool appears to overestimate internal doses and underestimate external doses in the roots for all three radionuclides, though each to a different extent. These observations might help to refine dose-response relationships. The DCC values for (90)Sr in roots are shown to deviate the most. A dose-effect curve for (90)Sr β-radiation has been established on biomass and photosynthesis endpoints, but no significant dose-dependent effects are observed. This indicates the need for use of endpoints at the molecular and physiological scale. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Comparison of 3DCRT,VMAT and IMRT techniques in metastatic vertebra radiotherapy: A phantom Study

    NASA Astrophysics Data System (ADS)

    Gedik, Sonay; Tunc, Sema; Kahraman, Arda; Kahraman Cetintas, Sibel; Kurt, Meral

    2017-09-01

    Vertebra metastases can be seen during the prognosis of cancer patients. Treatment ways of the metastasis are radiotherapy, chemotherapy and surgery. Three-dimensional conformal therapy (3D-CRT) is widely used in the treatment of vertebra metastases. Also, Intensity Modulated Radiotherapy (IMRT) and Volumetric Arc Therapy (VMAT) are used too. The aim of this study is to examine the advantages and disadvantages of the different radiotherapy techniques. In the aspect of this goal, it is studied with a randophantom in Uludag University Medicine Faculty, Radiation Oncology Department. By using a computerized tomography image of the phantom, one 3DCRT plan, two VMAT and three IMRT plans for servical vertebra and three different 3DCRT plans, two VMAT and two IMRT plans for lomber vertebra are calculated. To calculate 3DCRT plans, CMS XiO Treatment System is used and to calculate VMAT and IMRT plans Monaco Treatment Planning System is used in the department. The study concludes with the dosimetric comparison of the treatment plans in the spect of critical organ doses, homogeneity and conformity index. As a result of this study, all critical organ doses are suitable for QUANTEC Dose Limit Report and critical organ doses depend on the techniques which used in radiotherapy. According to homogeneity and conformity indices, VMAT and IMRT plans are better than one in 3DCRT plans in servical and lomber vertebra radiotherapy plans.

  20. Management of background pain and anxiety in critically burned children requiring protracted mechanical ventilation.

    PubMed

    Sheridan, R; Stoddard, F; Querzoli, E

    2001-01-01

    Optimal control of pain and anxiety is an elusive but important goal in children with protracted critical illness. This review represents an effort to document the doses of background medication required to achieve this goal in a group of children managed under a pain and anxiety protocol that adjusts background infusions to comfort. The course of children with wounds involving at least 10% of the body surface and coincident respiratory failure requiring mechanical ventilation for more than 7 days managed 1 Jan 97 to 31 Dec 98 was reviewed. A pain and anxiety protocol was used, including background infusions of morphine and midazolam adjusted to comfort. These 28 children had a mean (+/- standard deviation) age of 5.3 +/- 4.6 years, wound size of 48.3 +/- 28.4%, and were intubated for 25.0 +/- 23.9 days. Neuromuscular blocking drugs were administered for 65 of 447 (14.5%) ventilator days. To maintain comfort, drugs were required at doses substantially above standard dosing schemes. The highest daily background infusion of morphine sulfate averaged 0.40 mg/kg/hr +/- 0.24 mg/kg/hr (usual starting dose was 0.05 to 0.1 mg/kg/hr) and was reached 14.1 +/- 12.8 days after admission. The highest daily background infusion of midazolam averaged 0.15 +/- 0.07 mg/kg/hr (usual starting dose was 0.04 mg/kg/hr) and was reached 14.0 +/- 3.8 days after admission. Morphine infusions at extubation averaged 0.22 +/- 0.17 mg/kg/hr and midazolam infusions 0.10 +/- 0.12 mg/kg/hr. All children survived to discharge and there was no perceived morbidity related to these high doses of medication. Children with serious burns and respiratory failure will require high doses of background opiates and benzodiazepines to remain comfortable, because they develop drug tolerance during protracted critical illness. Infusions can be continued at a reduced dose through extubation, do not result in addiction or other apparent morbidity if adjusted to desired level of comfort, and may contribute to a reduced incidence of treatment-related stress disorders.

  1. Study on the Dose Uncertainties in the Lung during Passive Proton Irradiation with a Proton Beam Range Compensator

    NASA Astrophysics Data System (ADS)

    Yoo, Seung Hoon; Son, Jae Man; Yoon, Myonggeun; Park, Sung Yong; Shin, Dongho; Min, Byung Jun

    2018-06-01

    A moving phantom is manufactured for mimicking lung model to study the dose uncertainty from CT number-stopping power conversion and dose calculation in the soft tissue, light lung tissue and bone regions during passive proton irradiation with compensator smearing value. The phantom is scanned with a CT system, and a proton beam irradiation plan is carried out with the use of a treatment planning system (Eclipse). In the case of the moving phantom, a RPM system is used for respiratory gating. The uncertainties in the dose distribution between the measured data and the planned data are investigated by a gamma analysis with 3%-3 mm acceptance criteria. To investigate smearing effect, three smearing values (0.3 cm, 0.7 cm, 1.2 cm) are used to for fixed and moving phantom system. For both fixed and moving phantom, uncertainties in the light lung tissue are severe than those in soft tissue region in which the dose uncertainties are within clinically tolerable ranges. As the smearing value increases, the uncertainty in the proton dose distribution decreases.

  2. UVER and UV index at high altitude in Northwestern Argentina.

    PubMed

    Utrillas, M P; Marín, M J; Esteve, A R; Salazar, G; Suarez, H; Castillo, J; Martínez-Lozano, J A

    2016-10-01

    Measurements of ultraviolet erythemal radiation (UVER) made during two years at three sites located at altitudes over 1000ma.s.l. in Northwestern Argentina (Salta, San Carlos, and El Rosal) have been used to estimate and analyze the UV Index (UVI) and the cumulative doses at these locations. For the UVER irradiance, data of January (maximum values) and June (minimum values) have been analyzed as representative of the year for all locations. The UVI reaches extreme (>11) values in >20% of the analyzed days in Salta (1190ma.s.l.), while these are reached in San Carlos (1611ma.s.l.) and El Rosal (3355ma.s.l.) in >40% of the analyzed days. Finally, the cumulative doses over an average year have also been studied for each location. The doses received during austral summer and autumn are of the same order, and represent one third of the annual dose, while the doses received during austral winter and spring represent one sixth of the annual dose approximately. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. ASSESSING CHILDREN'S EXPOSURES TO PESTICIDES: AN IMPORTANT APPLICATION OF THE STOCHASTIC HUMAN EXPOSURE AND DOSE SIMULATION MODEL (SHEDS)

    EPA Science Inventory

    Accurately quantifying human exposures and doses of various populations to environmental pollutants is critical for the Agency to assess and manage human health risks. For example, the Food Quality Protection Act of 1996 (FQPA) requires EPA to consider aggregate human exposure ...

  4. Chiral Pesticides in Chiral Biological Enciroments: Do We Need to Move Beyond our Achiral Perspective.

    EPA Science Inventory

    When a chemical stressor crosses the body barrier it becomes an internal dose. In the context of risk assessment, this internal dose provides a critical linkage between exposure and effects. Pharmacokinetic processes (i.e., what the body does to the chemical) such as absorption, ...

  5. Internal dose assessment of 210Po using biokinetic modeling and urinary excretion measurement.

    PubMed

    Li, Wei Bo; Gerstmann, Udo; Giussani, Augusto; Oeh, Uwe; Paretzke, Herwig G

    2008-02-01

    The mysterious death of Mr. Alexander Litvinenko who was most possibly poisoned by Polonium-210 ((210)Po) in November 2006 in London attracted the attention of the public to the kinetics, dosimetry and the risk of this high radiotoxic isotope in the human body. In the present paper, the urinary excretion of seven persons who were possibly exposed to traces of (210)Po was monitored. The values measured in the GSF Radioanalytical Laboratory are in the range of natural background concentration. To assess the effective dose received by those persons, the time-dependence of the organ equivalent dose and the effective dose after acute ingestion and inhalation of (210)Po were calculated using the biokinetic model for polonium (Po) recommended by the International Commission on Radiological Protection (ICRP) and the one recently published by Leggett and Eckerman (L&E). The daily urinary excretion to effective dose conversion factors for ingestion and inhalation were evaluated based on the ICRP and L&E models for members of the public. The ingestion (inhalation) effective dose per unit intake integrated over one day is 1.7 x 10(-8) (1.4 x 10(-7)) Sv Bq(-1), 2.0 x 10(-7) (9.6 x 10(-7)) Sv Bq(-1) over 10 days, 5.2 x 10(-7) (2.0 x 10(-6)) Sv Bq(-1) over 30 days and 1.0 x 10(-6) (3.0 x 10(-6)) Sv Bq(-1) over 100 days. The daily urinary excretions after acute ingestion (inhalation) of 1 Bq of (210)Po are 1.1 x 10(-3) (1.0 x 10(-4)) on day 1, 2.0 x 10(-3) (1.9 x 10(-4)) on day 10, 1.3 x 10(-3) (1.7 x 10(-4)) on day 30 and 3.6 x 10(-4) (8.3 x 10(-5)) Bq d(-1) on day 100, respectively. The resulting committed effective doses range from 2.1 x 10(-3) to 1.7 x 10(-2) mSv by an assumption of ingestion and from 5.5 x 10(-2) to 4.5 x 10(-1) mSv by inhalation. For the case of Mr. Litvinenko, the mean organ absorbed dose as a function of time was calculated using both the above stated models. The red bone marrow, the kidneys and the liver were considered as the critical organs. Assuming a value of lethal absorbed dose of 5 Gy to the bone marrow, 6 Gy to the kidneys and 8 Gy to the liver, the amount of (210)Po which Mr. Litvinenko might have ingested is therefore estimated to range from 27 to 1,408 MBq, i.e 0.2-8.5 microg, depending on the modality of intake and on different assumptions about blood absorption.

  6. Case study on the utility of hepatic global gene expression profiling in the risk assessment of the carcinogen furan

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Jackson, Anna Francina, E-mail: Francina.Jackson@hc-sc.gc.ca; Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa K1S 5B6; Williams, Andrew, E-mail: Andrew.Williams@hc-sc.gc.ca

    2014-01-01

    Furan is a chemical hepatocarcinogen in mice and rats. Its previously postulated cancer mode of action (MOA) is chronic cytotoxicity followed by sustained regenerative proliferation; however, its molecular basis is unknown. To this end, we conducted toxicogenomic analysis of B3C6F1 mouse livers following three week exposures to non-carcinogenic (0, 1, 2 mg/kg bw) or carcinogenic (4 and 8 mg/kg bw) doses of furan. We saw enrichment for pathways responsible for cytotoxicity: stress-activated protein kinase (SAPK) and death receptor (DR5 and TNF-alpha) signaling, and proliferation: extracellular signal-regulated kinases (ERKs) and TNF-alpha. We also noted the involvement of NF-kappaB and c-Jun inmore » response to furan, which are genes that are known to be required for liver regeneration. Furan metabolism by CYP2E1 produces cis-2-butene-1,4-dial (BDA), which is required for ensuing cytotoxicity and oxidative stress. NRF2 is a master regulator of gene expression during oxidative stress and we suggest that chronic NFR2 activity and chronic inflammation may represent critical transition events between the adaptive (regeneration) and adverse (cancer) outcomes. Another objective of this study was to demonstrate the applicability of toxicogenomics data in quantitative risk assessment. We modeled benchmark doses for our transcriptional data and previously published cancer data, and observed consistency between the two. Margin of exposure values for both transcriptional and cancer endpoints were also similar. In conclusion, using furan as a case study we have demonstrated the value of toxicogenomics data in elucidating dose-dependent MOA transitions and in quantitative risk assessment. - Highlights: • Global gene expression changes in furan-exposed mouse livers were analyzed. • A molecular mode of action for furan-induced hepatocarcinogenesis is proposed. • Key pathways include NRF2, SAPK, ERK and death receptor signaling. • Important roles for TNF-alpha, c-Jun, and NF-κB in tumorigenesis are proposed. • BMD and MoE values from transcriptional and apical data are compared.« less

  7. Micronucleus induction in Vicia faba roots. Part 2. Biological effects of neutrons below 1 cGy.

    PubMed

    Marshall, I; Bianchi, M

    1983-08-01

    A dose-effect relationship has been established for high-energy neutrons (maximum energy 600 MeV) within a dose range of 0.2 to 80 cGy and for low-energy neutrons produced by a 252Cf source (mean energy 2.35 MeV) for doses between 0.2 and 5 cGy. The frequency of micronuclei was found to increase linearly with dose. The relative biological effectiveness (r.b.e) values calculated using 60Co radiation as a reference were, in the high-dose region, 4.7 +/- 0.4 and 11.8 +/- 1.3 for the high- and low-energy neutrons, respectively. At doses below 1 cGy constant values of 25.4 +/- 4.4 and 63.7 +/- 12 were reached for the respective neutron energies.

  8. SU-F-207-01: Comparison of Beam Characteristics and Organ Dose From Four Commercial Multidetector Computed Tomography Scanners

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ohno, T; Araki, F

    2015-06-15

    Purpose: To compare dosimetric properties and patient organ doses from four commercial multidetector CT (MDCT) using Monte Carlo (MC) simulation based on the absorbed dose measured using a Farmer chamber and cylindrical water phantoms according to AAPM TG-111. Methods: Four commercial MDCT were modeled using the GMctdospp (IMPS, Germany) based on the EGSnrc user code. The incident photon spectrum and bowtie filter for MC simulations were determined so that calculated values of aluminum half-value layer (Al-HVL) and off-center ratio (OCR) profile in air agreed with measured values. The MC dose was calibrated from absorbed dose measurements using a Farmer chambermore » and cylindrical water phantoms. The dose distributions of head, chest, and abdominal scan were calculated using patient CT images and mean organ doses were evaluated from dose volume histograms. Results: The HVLs at 120 kVp of Brilliance, LightSpeed, Aquilion, and SOMATOM were 9.1, 7.5, 7.2, and 8.7 mm, respectively. The calculated Al-HVLs agreed with measurements within 0.3%. The calculated and measured OCR profiles agreed within 5%. For adult head scans, mean doses for eye lens from Brilliance, LightSpeed, Aquilion, and SOMATOM were 21.7, 38.5, 47.2 and 28.4 mGy, respectively. For chest scans, mean doses for lung from Brilliance, LightSpeed, Aquilion, and SOMATOM were 21.1, 26.1, 35.3 and 24.0 mGy, respectively. For adult abdominal scans, the mean doses for liver from Brilliance, LightSpeed, Aquilion, and SOMATOM were 16.5, 21.3, 22.7, and 18.0 mGy, respectively. The absorbed doses increased with decreasing Al-HVL. The organ doses from Aquilion were two greater than those from Brilliance in head scan. Conclusion: MC dose distributions based on absorbed dose measurement in cylindrical water phantom are useful to evaluate individual patient organ doses.« less

  9. Comparison of warfarin therapy clinical outcomes following implementation of an automated mobile phone-based critical laboratory value text alert system.

    PubMed

    Lin, Shu-Wen; Kang, Wen-Yi; Lin, Dong-Tsamn; Lee, James; Wu, Fe-Lin; Chen, Chuen-Liang; Tseng, Yufeng J

    2014-01-01

    Computerized alert and reminder systems have been widely accepted and applied to various patient care settings, with increasing numbers of clinical laboratories communicating critical laboratory test values to professionals via either manual notification or automated alerting systems/computerized reminders. Warfarin, an oral anticoagulant, exhibits narrow therapeutic range between treatment response and adverse events. It requires close monitoring of prothrombin time (PT)/international normalized ratio (INR) to ensure patient safety. This study was aimed to evaluate clinical outcomes of patients on warfarin therapy following implementation of a Personal Handy-phone System-based (PHS) alert system capable of generating and delivering text messages to communicate critical PT/INR laboratory results to practitioners' mobile phones in a large tertiary teaching hospital. A retrospective analysis was performed comparing patient clinical outcomes and physician prescribing behavior following conversion from a manual laboratory result alert system to an automated system. Clinical outcomes and practitioner responses to both alert systems were compared. Complications to warfarin therapy, warfarin utilization, and PT/INR results were evaluated for both systems, as well as clinician time to read alert messages, time to warfarin therapy modification, and monitoring frequency. No significant differences were detected in major hemorrhage and thromboembolism, warfarin prescribing patterns, PT/INR results, warfarin therapy modification, or monitoring frequency following implementation of the PHS text alert system. In both study periods, approximately 80% of critical results led to warfarin discontinuation or dose reduction. Senior physicians' follow-up response time to critical results was significantly decreased in the PHS alert study period (46.3% responded within 1 day) compared to the manual notification study period (24.7%; P = 0.015). No difference in follow-up response time was detected for junior physicians. Implementation of an automated PHS-based text alert system did not adversely impact clinical or safety outcomes of patients on warfarin therapy. Approximately 80% immediate recognition of text alerts was achieved. The potential benefits of an automated PHS alert for senior physicians were demonstrated.

  10. [Diagnostic reference levels in interventional radiology].

    PubMed

    Vañó Carruana, E; Fernández Soto, J M; Sánchez Casanueva, R M; Ten Morón, J I

    2013-12-01

    This article discusses the diagnostic reference levels for radiation exposure proposed by the International Commission on Radiological Protection (ICRP) to facilitate the application of the optimization criteria in diagnostic imaging and interventional procedures. These levels are normally established as the third quartile of the dose distributions to patients in an ample sample of centers and are supposed to be representative of good practice regarding patient exposure. In determining these levels, it is important to evaluate image quality as well to ensure that it is sufficient for diagnostic purposes. When the values for the dose received by patients are systematically higher or much lower than the reference levels, an investigation should determine whether corrective measures need to be applied. The European and Spanish regulations require the use of these reference values in quality assurance programs. For interventional procedures, the dose area product (or kerma area product) values are usually used as reference values together with the time under fluoroscopy and the total number of images acquired. The most modern imaging devices allow the value of the accumulated dose at the entrance to the patient to be calculated to optimize the distribution of the dose on the skin. The ICRP recommends that the complexity of interventional procedures be taken into account when establishing reference levels. In the future, diagnostic imaging departments will have automatic systems to manage patient dosimetric data; these systems will enable continuous dosage auditing and alerts about individual procedures that might involve doses several times above the reference values. This article also discusses aspects that need to be clarified to take better advantage of the reference levels in interventional procedures. Copyright © 2013 SERAM. Published by Elsevier Espana. All rights reserved.

  11. Simultaneous determination of nine β-lactam antibiotics in human plasma by an ultrafast hydrophilic-interaction chromatography-tandem mass spectrometry.

    PubMed

    Abdulla, Alan; Bahmany, Soma; Wijma, Rixt A; van der Nagel, Bart C H; Koch, Birgit C P

    2017-08-15

    Contemporary β-lactam antibiotic dosing is debatable in severely ill patients, since the occurrence of pathophysiological changes in critical illness can result in great inter-individual variability. Therapeutic drug monitoring (TDM) is a commonly used dosing strategy to optimize exposure and thereby minimize toxicity and maximize the efficacy. Currently, TDM of β-lactam antibiotics is rarely performed, due to poor availability in clinical practice. We describe an ultrafast Hydrophilic-Interaction Chromatography (HILIC) based UPLC-MS/MS method for the determination of amoxicillin, benzylpenicillin, cefotaxime, cefuroxime, ceftazidime, flucloxacillin, imipenem, meropenem and piperacillin in human plasma. This method involves simple sample preparation steps and was comprehensively validated according to standard FDA guidelines. For all analytes, mean accuracy and precision values were within the acceptance value. The lower and upper limits of quantification were found to be sufficient to cover the therapeutic range for all antibiotics. Finally, the method was successfully applied in a large pharmacokinetic study performed in the intensive care setting, and the feasibility of the analytical procedure was demonstrated in routine clinical practice. To the best of our knowledge, we report here the first HILIC-based UPLC-MS/MS assay for the determination of β-lactam antibiotics in human plasma. This simple, sensitive and ultrafast assay requires small-volume samples and can easily be implemented in clinical laboratories to promote the TDM of β-lactam antibiotics. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Technical note: estimating absorbed doses to the thyroid in CT.

    PubMed

    Huda, Walter; Magill, Dennise; Spampinato, Maria V

    2011-06-01

    To describe a method for estimating absorbed doses to the thyroid in patients undergoing neck CT examinations. Thyroid doses in anthropomorphic phantoms were obtained for all 23 scanner dosimetry data sets in the ImPACT CT patient dosimetry calculator. Values of relative thyroid dose [R(thy)(L)], defined as the thyroid dose for a given scan length (L) divided by the corresponding thyroid dose for a whole body scan, were determined for neck CT scans. Ratios of the maximum thyroid dose to the corresponding CTDI(vol) and [D'(thy)], were obtained for two phantom diameters. The mass-equivalent water cylinder of any patient can be derived from the neck cross-sectional area and the corresponding average Hounsfield Unit, and compared to the 16.5-cm diameter water cylinder that models the ImPACT anthropomorphic phantom neck. Published values of relative doses in water cylinders of varying diameter were used to adjust thyroid doses in the anthropomorphic phantom to those of any sized patient. Relative thyroid doses R(thy)(L) increase to unity with increasing scan length and with very small difference between scanners. A 10-cm scan centered on the thyroid would result in a dose that is, nearly 90% of the thyroid dose from a whole body scan when performed using the constant radiographic techniques. At 120 kV, the average value of D'(thy) for the 16-cm diameter was 1.17 +/- 0.05 and was independent of CT vendor and year of CT scanner, and choice of x-ray tube voltage. The corresponding average value of D'(thy) in the 32-cm diameter phantom was 2.28 +/- 0.22 and showed marked variations depending on vendor, year of introduction into clinical practice as well as x-ray tube voltage. At 120 kV, a neck equivalent to a 10-cm diameter cylinder of water would have thyroid doses 36% higher than those in the ImPACT phantom, whereas a neck equivalent to a 25-cm cylinder diameter would have thyroid doses 35% lower. Patient thyroid doses can be estimated by taking into account the amount of radiation used to perform the CT examination (CTDI(vol)) and accounting for scan length and patient anatomy (i.e., neck diameter) at the thyroid location.

  13. Therapeutic benefits in grid irradiation on Tomotherapy for bulky, radiation-resistant tumors.

    PubMed

    Narayanasamy, Ganesh; Zhang, Xin; Meigooni, Ali; Paudel, Nava; Morrill, Steven; Maraboyina, Sanjay; Peacock, Loverd; Penagaricano, Jose

    2017-08-01

    Spatially fractionated radiation therapy (SFRT or grid therapy) has proven to be effective in management of bulky tumors. The aim of this project is to study the therapeutic ratio (TR) of helical Tomotherapy (HT)-based grid therapy using linear-quadratic cell survival model. HT-based grid (or HT-GRID) plan was generated using a patient-specific virtual grid pattern of high-dose cylindrical regions using MLCs. TR was defined as the ratio of normal tissue surviving fraction (SF) under HT-GRID irradiation to an open debulking field of an equivalent dose that result in the same tumor cell SF. TR was estimated from DVH data on ten HT-GRID patient plans with deep seated, bulky tumor. Dependence of the TR values on radiosensitivity of the tumor cells and prescription dose was analyzed. The mean ± standard deviation (SD) of TR was 4.0 ± 0.7 (range: 3.1-5.5) for the 10 patients with single fraction maximum dose of 20 Gy to GTV assuming a tumor cell SF at 2 Gy (SF2 t ) value of 0·5. In addition, the mean ± SD of TR values for SF2 t values of 0.3 and 0.7 were found to be 1 ± 0.1 and 18.0 ± 5.1, respectively. Reducing the prescription dose to 15 and 10 Gy lowered the respective TR values to 2.0 ± 0.2 and 1.2 ± 0.04 for a SF2 t value of 0.5. HT-GRID therapy demonstrates a significant therapeutic advantage over uniform dose from an open field irradiation for the same tumor cell kill. TR increases with the radioresistance of the tumor cells and with prescription dose.

  14. Safety and efficacy of saxagliptin for glycemic control in non-critically ill hospitalized patients.

    PubMed

    Garg, Rajesh; Schuman, Brooke; Hurwitz, Shelley; Metzger, Cheyenne; Bhandari, Shreya

    2017-01-01

    To evaluate whether saxagliptin is non-inferior to basal-bolus insulin therapy for glycemic control in patients with controlled type 2 diabetes mellitus (T2DM) admitted to hospital with non-critical illnesses. This was an open-label, randomized controlled clinical trial. Patients received either saxagliptin or basal-bolus insulin, both with correctional insulin doses. The main study outcome was the mean daily blood glucose (BG) after the first day of randomization. Of 66 patients completing the study, 33 (age 69±10 years, 40% men) were randomized to saxagliptin and 33 (age 67±10 years, 52% men) to basal-bolus insulin therapy. The mean daily BG was 149.8±22.0 mg/dL in the saxagliptin group and 146.9±30.5 mg/dL in the insulin group (p=0.59). With an observed group difference of 2.9 mg/dL and an a priori margin of 20 mg/dL, inferiority of saxagliptin was rejected in favor of non-inferiority (p=0.007). There was no significant difference in the percentage of high or low BG values. The insulin group received a higher number of insulin injections (2.3±1.7/day vs 1.2±1.9/day; p<0.001) as well as a higher daily insulin dose (13.3±12.9 units/day vs 2.4±3.3 units/day; p<0.001) than did the saxagliptin group. Continuous BG monitoring showed that glycemic variability was lower in the saxagliptin group as compared to the insulin group. Patient satisfaction scores were similar in the two groups. We conclude that saxagliptin use is non-inferior to basal-bolus insulin in non-critically ill hospitalized patients with T2DM controlled on 0-2 oral agents without insulin. Saxagliptin use may decrease glycemic variability in these patients. NCT02182895.

  15. Effects of caffeine on fractional flow reserve values measured using intravenous adenosine triphosphate.

    PubMed

    Nakayama, Masafumi; Chikamori, Taishiro; Uchiyama, Takashi; Kimura, Yo; Hijikata, Nobuhiro; Ito, Ryosuke; Yuhara, Mikio; Sato, Hideaki; Kobori, Yuichi; Yamashina, Akira

    2018-04-01

    We investigated the effects of caffeine intake on fractional flow reserve (FFR) values measured using intravenous adenosine triphosphate (ATP) before cardiac catheterization. Caffeine is a competitive antagonist for adenosine receptors; however, it is unclear whether this antagonism affects FFR values. Patients were evenly randomized into 2 groups preceding the FFR study. In the caffeine group (n = 15), participants were given coffee containing 222 mg of caffeine 2 h before the catheterization. In the non-caffeine group (n = 15), participants were instructed not to take any caffeine-containing drinks or foods for at least 12 h before the catheterization. FFR was performed in patients with more than intermediate coronary stenosis using the intravenous infusion of ATP at 140 μg/kg/min (normal dose) and 170 μg/kg/min (high dose), and the intracoronary infusion of papaverine. FFR was followed for 30 s after maximal hyperemia. In the non-caffeine group, the FFR values measured with ATP infusion were not significantly different from those measured with papaverine infusion. However, in the caffeine group, the FFR values were significantly higher after ATP infusion than after papaverine infusion (P = 0.002 and P = 0.007, at normal and high dose ATP vs. papaverine, respectively). FFR values with ATP infusion were significantly increased 30 s after maximal hyperemia (P = 0.001 and P < 0.001 for normal and high dose ATP, respectively). The stability of the FFR values using papaverine showed no significant difference between the 2 groups. Caffeine intake before the FFR study affected FFR values and their stability. These effects could not be reversed by an increased ATP dose.

  16. Lens of the eye dose calculation for neuro-interventional procedures and CBCT scans of the head

    NASA Astrophysics Data System (ADS)

    Xiong, Zhenyu; Vijayan, Sarath; Rana, Vijay; Jain, Amit; Rudin, Stephen; Bednarek, Daniel R.

    2016-03-01

    The aim of this work is to develop a method to calculate lens dose for fluoroscopically-guided neuro-interventional procedures and for CBCT scans of the head. EGSnrc Monte Carlo software is used to determine the dose to the lens of the eye for the projection geometry and exposure parameters used in these procedures. This information is provided by a digital CAN bus on the Toshiba Infinix C-Arm system which is saved in a log file by the real-time skin-dose tracking system (DTS) we previously developed. The x-ray beam spectra on this machine were simulated using BEAMnrc. These spectra were compared to those determined by SpekCalc and validated through measured percent-depth-dose (PDD) curves and half-value-layer (HVL) measurements. We simulated CBCT procedures in DOSXYZnrc for a CTDI head phantom and compared the surface dose distribution with that measured with Gafchromic film, and also for an SK150 head phantom and compared the lens dose with that measured with an ionization chamber. Both methods demonstrated good agreement. Organ dose calculated for a simulated neuro-interventional-procedure using DOSXYZnrc with the Zubal CT voxel phantom agreed within 10% with that calculated by PCXMC code for most organs. To calculate the lens dose in a neuro-interventional procedure, we developed a library of normalized lens dose values for different projection angles and kVp's. The total lens dose is then calculated by summing the values over all beam projections and can be included on the DTS report at the end of the procedure.

  17. Cranial CT with adaptive statistical iterative reconstruction: improved image quality with concomitant radiation dose reduction.

    PubMed

    Rapalino, O; Kamalian, Shervin; Kamalian, Shahmir; Payabvash, S; Souza, L C S; Zhang, D; Mukta, J; Sahani, D V; Lev, M H; Pomerantz, S R

    2012-04-01

    To safeguard patient health, there is great interest in CT radiation-dose reduction. The purpose of this study was to evaluate the impact of an iterative-reconstruction algorithm, ASIR, on image-quality measures in reduced-dose head CT scans for adult patients. Using a 64-section scanner, we analyzed 100 reduced-dose adult head CT scans at 6 predefined levels of ASIR blended with FBP reconstruction. These scans were compared with 50 CT scans previously obtained at a higher routine dose without ASIR reconstruction. SNR and CNR were computed from Hounsfield unit measurements of normal GM and WM of brain parenchyma. A blinded qualitative analysis was performed in 10 lower-dose CT datasets compared with higher-dose ones without ASIR. Phantom data analysis was also performed. Lower-dose scans without ASIR had significantly lower mean GM and WM SNR (P = .003) and similar GM-WM CNR values compared with higher routine-dose scans. However, at ASIR levels of 20%-40%, there was no statistically significant difference in SNR, and at ASIR levels of ≥60%, the SNR values of the reduced-dose scans were significantly higher (P < .01). CNR values were also significantly higher at ASIR levels of ≥40% (P < .01). Blinded qualitative review demonstrated significant improvements in perceived image noise, artifacts, and GM-WM differentiation at ASIR levels ≥60% (P < .01). These results demonstrate that the use of ASIR in adult head CT scans reduces image noise and increases low-contrast resolution, while allowing lower radiation doses without affecting spatial resolution.

  18. Experimental verification of a commercial Monte Carlo-based dose calculation module for high-energy photon beams.

    PubMed

    Künzler, Thomas; Fotina, Irina; Stock, Markus; Georg, Dietmar

    2009-12-21

    The dosimetric performance of a Monte Carlo algorithm as implemented in a commercial treatment planning system (iPlan, BrainLAB) was investigated. After commissioning and basic beam data tests in homogenous phantoms, a variety of single regular beams and clinical field arrangements were tested in heterogeneous conditions (conformal therapy, arc therapy and intensity-modulated radiotherapy including simultaneous integrated boosts). More specifically, a cork phantom containing a concave-shaped target was designed to challenge the Monte Carlo algorithm in more complex treatment cases. All test irradiations were performed on an Elekta linac providing 6, 10 and 18 MV photon beams. Absolute and relative dose measurements were performed with ion chambers and near tissue equivalent radiochromic films which were placed within a transverse plane of the cork phantom. For simple fields, a 1D gamma (gamma) procedure with a 2% dose difference and a 2 mm distance to agreement (DTA) was applied to depth dose curves, as well as to inplane and crossplane profiles. The average gamma value was 0.21 for all energies of simple test cases. For depth dose curves in asymmetric beams similar gamma results as for symmetric beams were obtained. Simple regular fields showed excellent absolute dosimetric agreement to measurement values with a dose difference of 0.1% +/- 0.9% (1 standard deviation) at the dose prescription point. A more detailed analysis at tissue interfaces revealed dose discrepancies of 2.9% for an 18 MV energy 10 x 10 cm(2) field at the first density interface from tissue to lung equivalent material. Small fields (2 x 2 cm(2)) have their largest discrepancy in the re-build-up at the second interface (from lung to tissue equivalent material), with a local dose difference of about 9% and a DTA of 1.1 mm for 18 MV. Conformal field arrangements, arc therapy, as well as IMRT beams and simultaneous integrated boosts were in good agreement with absolute dose measurements in the heterogeneous phantom. For the clinical test cases, the average dose discrepancy was 0.5% +/- 1.1%. Relative dose investigations of the transverse plane for clinical beam arrangements were performed with a 2D gamma-evaluation procedure. For 3% dose difference and 3 mm DTA criteria, the average value for gamma(>1) was 4.7% +/- 3.7%, the average gamma(1%) value was 1.19 +/- 0.16 and the mean 2D gamma-value was 0.44 +/- 0.07 in the heterogeneous phantom. The iPlan MC algorithm leads to accurate dosimetric results under clinical test conditions.

  19. Inpatient Management Of Diabetes Mellitus Among Noncritically Ill Patients At The University Hospital Of Puerto Rico

    PubMed Central

    Allende-Vigo, Myriam Zaydee; González-Rosario, Rafael A.; González, Loida; Sánchez, Viviana; Vega, Mónica A.; Alvarado, Milliette; Ramón, Raul O.

    2014-01-01

    OBJECTIVE To describe the state of glycemic control in non-critically ill diabetic patients admitted to the PR University Hospital, and the adherence to current standard of care guidelines for the treatment of diabetes. METHODS This was a retrospective study of patients admitted to a General Medicine ward with Diabetes Mellitus as a secondary diagnosis. Clinical data was analyzed for the first 5 days and the last 24 hours of admission. RESULTS One hundred and forty-seven (147) non-critically ill diabetic patients were evaluated. The rate of hyperglycemia and hypoglycemia was 56.7% and 2.8%, respectively. Nearly 60% of patients were hyperglycemic during the first 24 hrs of admission and 54.2% during the last 24 hrs. Mean last glucose value before discharge was 189.6 ± 73 mg/dL. Most patients were treated with subcutaneous insulin with basal insulin alone used as the most common regimen. The proportion of patients classified as uncontrolled receiving basal-bolus therapy increased from 54.3% on day 1 to 60.0% on day 5, with still 40.0% receiving only basal insulin. Most of the uncontrolled patients had their insulin dose increased (70.1%), however, a substantial portion had no change (23.7%) or even had a decrease (6.2%) in their insulin dose. CONCLUSIONS Even though there are areas of improvement in the management of hospitalized diabetic patients, it is still suboptimal, probably due to clinical inertia. A comprehensive educational diabetes management program, along with standardized insulin orders should be implemented to improve the care of these patients. PMID:24325996

  20. Proceedings of the 2016 Clinical Nutrition Week Research Workshop-The Optimal Dose of Protein Provided to Critically Ill Patients.

    PubMed

    Heyland, Daren K; Rooyakers, Olav; Mourtzakis, Marina; Stapleton, Renee D

    2017-02-01

    Recent literature has created considerable confusion about the optimal amount of protein/amino acids that should be provided to the critically ill patient. In fact, the evidentiary basis that directly tries to answer this question is relatively small. As a clinical nutrition research community, there is an urgent need to develop the optimal methods to assess the impact of exogenous protein/amino acid administration in the intensive care unit setting. That assessment can be conducted at various levels: (1) impact on stress response pathways, (2) impact on muscle synthesis and protein balance, (3) impact on muscle mass and function, and (4) impact on the patient's recovery. The objective of this research workshop was to review current literature relating to protein/amino acid administration for the critically ill patient and clinical outcomes and to discuss the key measurement and methodological features of future studies that should be done to inform the optimal protein/amino acid dose provided to critically ill patients.

  1. Influence of source batch S{sub K} dispersion on dosimetry for prostate cancer treatment with permanent implants

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Nuñez-Cumplido, E., E-mail: ejnc-mccg@hotmail.com; Hernandez-Armas, J.; Perez-Calatayud, J.

    2015-08-15

    Purpose: In clinical practice, specific air kerma strength (S{sub K}) value is used in treatment planning system (TPS) permanent brachytherapy implant calculations with {sup 125}I and {sup 103}Pd sources; in fact, commercial TPS provide only one S{sub K} input value for all implanted sources and the certified shipment average is typically used. However, the value for S{sub K} is dispersed: this dispersion is not only due to the manufacturing process and variation between different source batches but also due to the classification of sources into different classes according to their S{sub K} values. The purpose of this work is tomore » examine the impact of S{sub K} dispersion on typical implant parameters that are used to evaluate the dose volume histogram (DVH) for both planning target volume (PTV) and organs at risk (OARs). Methods: The authors have developed a new algorithm to compute dose distributions with different S{sub K} values for each source. Three different prostate volumes (20, 30, and 40 cm{sup 3}) were considered and two typical commercial sources of different radionuclides were used. Using a conventional TPS, clinically accepted calculations were made for {sup 125}I sources; for the palladium, typical implants were simulated. To assess the many different possible S{sub K} values for each source belonging to a class, the authors assigned an S{sub K} value to each source in a randomized process 1000 times for each source and volume. All the dose distributions generated for each set of simulations were assessed through the DVH distributions comparing with dose distributions obtained using a uniform S{sub K} value for all the implanted sources. The authors analyzed several dose coverage (V{sub 100} and D{sub 90}) and overdosage parameters for prostate and PTV and also the limiting and overdosage parameters for OARs, urethra and rectum. Results: The parameters analyzed followed a Gaussian distribution for the entire set of computed dosimetries. PTV and prostate V{sub 100} and D{sub 90} variations ranged between 0.2% and 1.78% for both sources. Variations for the overdosage parameters V{sub 150} and V{sub 200} compared to dose coverage parameters were observed and, in general, variations were larger for parameters related to {sup 125}I sources than {sup 103}Pd sources. For OAR dosimetry, variations with respect to the reference D{sub 0.1cm{sup 3}} were observed for rectum values, ranging from 2% to 3%, compared with urethra values, which ranged from 1% to 2%. Conclusions: Dose coverage for prostate and PTV was practically unaffected by S{sub K} dispersion, as was the maximum dose deposited in the urethra due to the implant technique geometry. However, the authors observed larger variations for the PTV V{sub 150}, rectum V{sub 100}, and rectum D{sub 0.1cm{sup 3}} values. The variations in rectum parameters were caused by the specific location of sources with S{sub K} value that differed from the average in the vicinity. Finally, on comparing the two sources, variations were larger for {sup 125}I than for {sup 103}Pd. This is because for {sup 103}Pd, a greater number of sources were used to obtain a valid dose distribution than for {sup 125}I, resulting in a lower variation for each S{sub K} value for each source (because the variations become averaged out statistically speaking)« less

  2. Dose profile variation with voltage in head CT scans using radiochromic films

    NASA Astrophysics Data System (ADS)

    Mourão, A. P.; Alonso, T. C.; DaSilva, T. A.

    2014-02-01

    The voltage source used in an X-ray tube is an important part of defining the generated beam spectrum energy profile. The X-ray spectrum energy defines the X-ray beam absorption as well as the characteristics of the energy deposition in an irradiated object. Although CT scanners allow one to choose between four different voltage values, most of them employ a voltage of 120 kV in their scanning protocols, regardless of the patient characteristics. Based on this fact, this work investigated the deposited dose in a polymethyl methacrylate (PMMA) cylindrical head phantom. The entire volume was irradiated twice. Two CT scanning protocols were used with two different voltage values: 100 and 120 kV. The phantom volume was irradiated, and radiochromic films were employed to record dose profiles. Measurements were conducted with a calibrated pencil ionization chamber, which was positioned in the center and in four peripheral bores of the head PMMA phantom, to calibrate the radiochromic films. The central slice was then irradiated. This procedure allowed us to find the conversion factors necessary to obtain dose values recorded in the films. The data obtained allowed us to observe the dose variation profile inside the phantom head as well as in the peripheral and central regions. The peripheral region showed higher dose values than those of the central region for scans using both voltage values: approximately 31% higher for scanning with 120 kV and 25% higher with 100 kV. Doses recorded with the highest voltage are significantly higher, approximately 50% higher in the peripheral region and 40% higher in the central region. A longitudinal variation could be observed, and the maximum dose was recorded at the peripheral region, at the midpoint of the longitudinal axis. The obtained results will most likely contribute to the dissemination of proper procedure as well as to optimize dosimetry and tests of quality control in CT because the choice of protocols with different voltage values can be a way to optimize the CT scans.

  3. Critical Values for Lawshe's Content Validity Ratio: Revisiting the Original Methods of Calculation

    ERIC Educational Resources Information Center

    Ayre, Colin; Scally, Andrew John

    2014-01-01

    The content validity ratio originally proposed by Lawshe is widely used to quantify content validity and yet methods used to calculate the original critical values were never reported. Methods for original calculation of critical values are suggested along with tables of exact binomial probabilities.

  4. Critical Value Reporting in Transfusion Medicine: A Survey of Communication Practices in US Facilities.

    PubMed

    Reese, Erika M; Nelson, Randin C; Flegel, Willy A; Byrne, Karen M; Booth, Garrett S

    2017-05-01

    While critical value procedures have been adopted in most areas of the clinical laboratory, their use in transfusion medicine has not been reviewed in detail. The results of this study present a comprehensive overview of critical value reporting and communication practices in transfusion medicine in the United States. A web-based survey was developed to collect data on the prevalence of critical value procedures and practices of communicating results. The survey was distributed via email to US hospital-based blood banks. Of 123 facilities surveyed, 84 (68.3%) blood banks had a critical value procedure. From a panel of 23 common blood bank results, nine results were selected by more than 70% of facilities as either a critical value or requiring rapid communication as defined by an alternate procedure. There was overlap among results communicated by facilities with and without a critical value procedure. The most frequently communicated results, such as incompatible crossmatch for RBC units issued uncrossmatched, delay in finding compatible blood due to a clinically significant antibody, and transfusion reaction evaluation suggestive of a serious adverse event, addressed scenarios associated with the leading reported causes of transfusion-related fatalities. American Society for Clinical Pathology, 2017. This work is written by US Government employees and is in the public domain in the US.

  5. EPA and EFSA approaches for Benchmark Dose modeling

    EPA Science Inventory

    Benchmark dose (BMD) modeling has become the preferred approach in the analysis of toxicological dose-response data for the purpose of deriving human health toxicity values. The software packages most often used are Benchmark Dose Software (BMDS, developed by EPA) and PROAST (de...

  6. Genetic Polymorphisms in Host Antiviral Genes: Associations with Humoral and Cellular Immunity to Measles Vaccine

    PubMed Central

    Haralambieva, Iana H.; Ovsyannikova, Inna G.; Umlauf, Benjamin J.; Vierkant, Robert A.; Pankratz, V. Shane; Jacobson, Robert M.; Poland, Gregory A.

    2014-01-01

    Host antiviral genes are important regulators of antiviral immunity and plausible genetic determinants of immune response heterogeneity after vaccination. We genotyped and analyzed 307 common candidate tagSNPs from 12 antiviral genes in a cohort of 745 schoolchildren immunized with two doses of measles-mumps-rubella vaccine. Associations between SNPs/haplotypes and measles virus-specific immune outcomes were assessed using linear regression methodologies in Caucasians and African-Americans. Genetic variants within the DDX58/RIG-I gene, including a coding polymorphism (rs3205166/Val800Val), were associated as single-SNPs (p≤0.017; although these SNPs did not remain significant after correction for false discovery rate/FDR) and in haplotype-level analysis, with measles-specific antibody variations in Caucasians (haplotype allele p-value=0.021; haplotype global p-value=0.076). Four DDX58 polymorphisms, in high LD, demonstrated also associations (after correction for FDR) with variations in both measles-specific IFN-γ and IL-2 secretion in Caucasians (p≤0.001, q=0.193). Two intronic OAS1 polymorphisms, including the functional OAS1 SNP rs10774671 (p=0.003), demonstrated evidence of association with a significant allele-dose-related increase in neutralizing antibody levels in African-Americans. Genotype and haplotype-level associations demonstrated the role of ADAR genetic variants, including a non-synonymous SNP (rs2229857/Arg384Lys; p=0.01), in regulating measles virus-specific IFN-γ Elispot responses in Caucasians (haplotype global p-value=0.017). After correction FDR, 15 single-SNP associations (11 SNPs in Caucasians and 4 SNPs in African-Americans) still remained significant at the q-value<0.20. In conclusion, our findings strongly point to genetic variants/genes, involved in antiviral sensing and antiviral control, as critical determinants, differentially modulating the adaptive immune responses to live attenuated measles vaccine in Caucasians and African-Americans. PMID:21939710

  7. [Radiation effect on cosmonauts during extravehicular activities in 2008-2009].

    PubMed

    Mitrikas, V G

    2010-01-01

    The geometrical model of suited cosmonaut's phantom was used in mathematical modeling of EVAs performed by cosmonauts with consideration of changes in the ISS Russian segment configuration during 2008-2009 and the dependence of space radiation absorbed dose on EVA scene. Influence of spatial position of cosmonaut on absorbed dose value was evaluated with the EVA dosimeter model reproducing the actually determined weight and dimension. Calculated absorbed dose values are in good agreement with experimental data. Absorbed doses imparted to body organs (skin, lens, hemopoietic system, gastrointestinal tract, central nervous system, gonads) were determined for specific EVA events.

  8. SU-G-BRC-16: Theory and Clinical Implications of the Constant Dosimetric Leaf Gap (DLG) Approximation

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kumaraswamy, L; Xu, Z; Podgorsak, M

    Purpose: Commercial dose calculation algorithms incorporate a single DLG value for a given beam energy that is applied across an entire treatment field. However, the physical processes associated with beam generation and dose delivery suggest that the DLG is not constant. The aim of this study is to evaluate the variation of DLG among all leaf pairs, to quantify how this variation impacts delivered dose, and to establish a novel method to correct dose distributions calculated using the approximation of constant DLG. Methods: A 2D diode array was used to measure the DLG for all 60 leaf pairs at severalmore » points along each leaf pair travel direction. This approach was validated by comparison to DLG values measured at select points using a 0.6 cc ion chamber with the standard formalism. In-house software was developed to enable incorporation of position dependent DLG values into dose distribution optimization and calculation. The accuracy of beam delivery of both the corrected and uncorrected treatment plans was studied through gamma pass rate evaluation. A comparison of DVH statistics in corrected and uncorrected treatment plans was made. Results: The outer 20 MLC leaf pairs (1.0 cm width) have DLG values that are 0.32 mm (mean) to 0.65 mm (maximum) lower than the central leaf-pair. VMAT plans using a large number of 1 cm wide leaves were more accurately delivered (gamma pass rate increased by 5%) and dose coverage was higher (D100 increased by 3%) when the 2D DLG was modeled. Conclusion: Using a constant DLG value for a given beam energy will result in dose optimization, dose calculation and treatment delivery inaccuracies that become significant for treatment plans with high modulation complexity scores delivered with 1 cm wide leaves.« less

  9. Correlation between Colon Transit Time Test Value and Initial Maintenance Dose of Laxative in Children with Chronic Functional Constipation

    PubMed Central

    Kim, Mock Ryeon; Park, Hye Won; Son, Jae Sung; Lee, Ran

    2016-01-01

    Purpose To evaluate the correlation between colon transit time (CTT) test value and initial maintenance dose of polyethylene glycol (PEG) 4000 or lactulose. Methods Of 415 children with chronic functional constipation, 190 were enrolled based on exclusion criteria using the CTT test, defecation diary, and clinical chart. The CTT test was performed with prior disimpaction. The laxative dose for maintenance was determined on the basis of the defecation diary and clinical chart. The Shapiro-Wilk test and Pearson's and Spearman's correlations were used for statistical analysis. Results The overall group median value and interquartile range of the CTT test was 43.8 (31.8) hours. The average PEG 4000 dose for maintenance in the overall group was 0.68±0.18 g/kg/d; according to age, the dose was 0.73±0.16 g/kg/d (<8 years), 0.53±0.12 g/kg/d (8 to <12 years), and 0.36±0.05 g/kg/d (12 to 15 years). The dose of lactulose was 1.99±0.43 mL/kg/d (<8 years) or 1.26±0.25 mL/kg/d (8 to <12 years). There was no significant correlation between CTT test value and initial dose of laxative, irrespective of the subgroup (encopresis, abnormal CTT test subtype) for either laxative. Even in the largest group (overall, n=109, younger than 8 years and on PEG 4000), the correlation was weak (Pearson's correlation coefficient [R]=0.268, p=0.005). Within the abnormal transit group, subgroup (n=73, younger than 8 years and on PEG 4000) correlation was weak (R=0.267, p=0.022). Conclusion CTT test value cannot predict the initial maintenance dose of PEG 4000 or lactulose with linear correlation. PMID:27738600

  10. Analytical probabilistic modeling of RBE-weighted dose for ion therapy.

    PubMed

    Wieser, H P; Hennig, P; Wahl, N; Bangert, M

    2017-11-10

    Particle therapy is especially prone to uncertainties. This issue is usually addressed with uncertainty quantification and minimization techniques based on scenario sampling. For proton therapy, however, it was recently shown that it is also possible to use closed-form computations based on analytical probabilistic modeling (APM) for this purpose. APM yields unique features compared to sampling-based approaches, motivating further research in this context. This paper demonstrates the application of APM for intensity-modulated carbon ion therapy to quantify the influence of setup and range uncertainties on the RBE-weighted dose. In particular, we derive analytical forms for the nonlinear computations of the expectation value and variance of the RBE-weighted dose by propagating linearly correlated Gaussian input uncertainties through a pencil beam dose calculation algorithm. Both exact and approximation formulas are presented for the expectation value and variance of the RBE-weighted dose and are subsequently studied in-depth for a one-dimensional carbon ion spread-out Bragg peak. With V and B being the number of voxels and pencil beams, respectively, the proposed approximations induce only a marginal loss of accuracy while lowering the computational complexity from order [Formula: see text] to [Formula: see text] for the expectation value and from [Formula: see text] to [Formula: see text] for the variance of the RBE-weighted dose. Moreover, we evaluated the approximated calculation of the expectation value and standard deviation of the RBE-weighted dose in combination with a probabilistic effect-based optimization on three patient cases considering carbon ions as radiation modality against sampled references. The resulting global γ-pass rates (2 mm,2%) are [Formula: see text]99.15% for the expectation value and [Formula: see text]94.95% for the standard deviation of the RBE-weighted dose, respectively. We applied the derived analytical model to carbon ion treatment planning, although the concept is in general applicable to other ion species considering a variable RBE.

  11. Thermally assisted OSL application for equivalent dose estimation; comparison of multiple equivalent dose values as well as saturation levels determined by luminescence and ESR techniques for a sedimentary sample collected from a fault gouge

    NASA Astrophysics Data System (ADS)

    Şahiner, Eren; Meriç, Niyazi; Polymeris, George S.

    2017-02-01

    Equivalent dose estimation (De) constitutes the most important part of either trap-charge dating techniques or dosimetry applications. In the present work, multiple, independent equivalent dose estimation approaches were adopted, using both luminescence and ESR techniques; two different minerals were studied, namely quartz as well as feldspathic polymineral samples. The work is divided into three independent parts, depending on the type of signal employed. Firstly, different De estimation approaches were carried out on both polymineral and contaminated quartz, using single aliquot regenerative dose protocols employing conventional OSL and IRSL signals, acquired at different temperatures. Secondly, ESR equivalent dose estimations using the additive dose procedure both at room temperature and at 90 K were discussed. Lastly, for the first time in the literature, a single aliquot regenerative protocol employing a thermally assisted OSL signal originating from Very Deep Traps was applied for natural minerals. Rejection criteria such as recycling and recovery ratios are also presented. The SAR protocol, whenever applied, provided with compatible De estimations with great accuracy, independent on either the type of mineral or the stimulation temperature. Low temperature ESR signals resulting from Al and Ti centers indicate very large De values due to bleaching in-ability, associated with large uncertainty values. Additionally, dose saturation of different approaches was investigated. For the signal arising from Very Deep Traps in quartz saturation is extended almost by one order of magnitude. It is interesting that most of De values yielded using different luminescence signals agree with each other and ESR Ge center has very large D0 values. The results presented above highly support the argument that the stability and the initial ESR signal of the Ge center is highly sample-dependent, without any instability problems for the cases of quartz resulting from fault gouge.

  12. Analytical probabilistic modeling of RBE-weighted dose for ion therapy

    NASA Astrophysics Data System (ADS)

    Wieser, H. P.; Hennig, P.; Wahl, N.; Bangert, M.

    2017-12-01

    Particle therapy is especially prone to uncertainties. This issue is usually addressed with uncertainty quantification and minimization techniques based on scenario sampling. For proton therapy, however, it was recently shown that it is also possible to use closed-form computations based on analytical probabilistic modeling (APM) for this purpose. APM yields unique features compared to sampling-based approaches, motivating further research in this context. This paper demonstrates the application of APM for intensity-modulated carbon ion therapy to quantify the influence of setup and range uncertainties on the RBE-weighted dose. In particular, we derive analytical forms for the nonlinear computations of the expectation value and variance of the RBE-weighted dose by propagating linearly correlated Gaussian input uncertainties through a pencil beam dose calculation algorithm. Both exact and approximation formulas are presented for the expectation value and variance of the RBE-weighted dose and are subsequently studied in-depth for a one-dimensional carbon ion spread-out Bragg peak. With V and B being the number of voxels and pencil beams, respectively, the proposed approximations induce only a marginal loss of accuracy while lowering the computational complexity from order O(V × B^2) to O(V × B) for the expectation value and from O(V × B^4) to O(V × B^2) for the variance of the RBE-weighted dose. Moreover, we evaluated the approximated calculation of the expectation value and standard deviation of the RBE-weighted dose in combination with a probabilistic effect-based optimization on three patient cases considering carbon ions as radiation modality against sampled references. The resulting global γ-pass rates (2 mm,2%) are > 99.15% for the expectation value and > 94.95% for the standard deviation of the RBE-weighted dose, respectively. We applied the derived analytical model to carbon ion treatment planning, although the concept is in general applicable to other ion species considering a variable RBE.

  13. Altered operant responding for motor reinforcement and the determination of benchmark doses following perinatal exposure to low-level 2,3,7,8-tetrachlorodibenzo-p-dioxin.

    PubMed

    Markowski, V P; Zareba, G; Stern, S; Cox, C; Weiss, B

    2001-06-01

    Pregnant Holtzman rats were exposed to a single oral dose of 0, 20, 60, or 180 ng/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the 18th day of gestation. Their adult female offspring were trained to respond on a lever for brief opportunities to run in specially designed running wheels. Once they had begun responding on a fixed-ratio 1 (FR1) schedule of reinforcement, the fixed-ratio requirement for lever pressing was increased at five-session intervals to values of FR2, FR5, FR10, FR20, and FR30. We examined vaginal cytology after each behavior session to track estrous cyclicity. Under each of the FR values, perinatal TCDD exposure produced a significant dose-related reduction in the number of earned opportunities to run, the lever response rate, and the total number of revolutions in the wheel. Estrous cyclicity was not affected. Because of the consistent dose-response relationship at all FR values, we used the behavioral data to calculate benchmark doses based on displacements from modeled zero-dose performance of 1% (ED(01)) and 10% (ED(10)), as determined by a quadratic fit to the dose-response function. The mean ED(10) benchmark dose for earned run opportunities was 10.13 ng/kg with a 95% lower bound of 5.77 ng/kg. The corresponding ED(01) was 0.98 ng/kg with a 95% lower bound of 0.83 ng/kg. The mean ED(10) for total wheel revolutions was calculated as 7.32 ng/kg with a 95% lower bound of 5.41 ng/kg. The corresponding ED(01) was 0.71 ng/kg with a 95% lower bound of 0.60. These values should be viewed from the perspective of current human body burdens, whose average value, based on TCDD toxic equivalents, has been calculated as 13 ng/kg.

  14. SU-F-T-51: Investigating the Effect of Eye Size and Eccentricity On Normal Tissue Doses From Eye Plaque Brachytherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Polsdofer, E; Crilly, R

    Purpose: This study investigates the effect of eye size and eccentricity on doses to critical tissues by simulating doses in the Plaque Simulator (v. 6.3.1) software. Present OHSU plaque brachytherapy treatment focuses on delivering radiation to the tumor measured with ocular ultrasound plus a small margin and assumes the orbit has the dimensions of a “standard eye.” Accurately modeling the dimensions of the orbit requires a high resolution ocular CT. This study quantifies how standard differences in equatorial diameters and eccentricity affect calculated doses to critical structures in order to query the justification of the additional CT scan to themore » treatment planning process. Methods: Tumors of 10 mm × 10 mm × 5 mm were modeled at the 12:00:00 hour with a latitude of 45 degrees. Right eyes were modeled at a number of equatorial diameters from 17.5 to 28 mm for each of the standard non-notched COMS plaques with silastic inserts. The COMS plaques were fully loaded with uniform activity, centered on the tumor, and prescribed to a common tumor dose (85 Gy/100 hours). Variations in the calculated doses to normal structures were examined to see if the changes were significant. Results: The calculated dose to normal structures show a marked dependence on eye geometry. This is exemplified by fovea dose which more than doubled in the smaller eyes and nearly halved in the larger model. Additional significant dependence was found in plaque size on the calculated dose in spite of all plaques giving the same dose to the prescription point. Conclusion: The variation in dose with eye dimension fully justifies the addition of a high resolution ocular CT to the planning technique. Additional attention must be made to plaque size beyond simply covering the tumor when considering normal tissue dose.« less

  15. TH-A-9A-04: Incorporating Liver Functionality in Radiation Therapy Treatment Planning

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, V; Epelman, M; Feng, M

    2014-06-15

    Purpose: Liver SBRT patients have both variable pretreatment liver function (e.g., due to degree of cirrhosis and/or prior treatments) and sensitivity to radiation, leading to high variability in potential liver toxicity with similar doses. This work aims to explicitly incorporate liver perfusion into treatment planning to redistribute dose to preserve well-functioning areas without compromising target coverage. Methods: Voxel-based liver perfusion, a measure of functionality, was computed from dynamic contrast-enhanced MRI. Two optimization models with different cost functions subject to the same dose constraints (e.g., minimum target EUD and maximum critical structure EUDs) were compared. The cost functions minimized were EUDmore » (standard model) and functionality-weighted EUD (functional model) to the liver. The resulting treatment plans delivering the same target EUD were compared with respect to their DVHs, their dose wash difference, the average dose delivered to voxels of a particular perfusion level, and change in number of high-/low-functioning voxels receiving a particular dose. Two-dimensional synthetic and three-dimensional clinical examples were studied. Results: The DVHs of all structures of plans from each model were comparable. In contrast, in plans obtained with the functional model, the average dose delivered to high-/low-functioning voxels was lower/higher than in plans obtained with its standard counterpart. The number of high-/low-functioning voxels receiving high/low dose was lower in the plans that considered perfusion in the cost function than in the plans that did not. Redistribution of dose can be observed in the dose wash differences. Conclusion: Liver perfusion can be used during treatment planning potentially to minimize the risk of toxicity during liver SBRT, resulting in better global liver function. The functional model redistributes dose in the standard model from higher to lower functioning voxels, while achieving the same target EUD and satisfying dose limits to critical structures. This project is funded by MCubed and grant R01-CA132834.« less

  16. Particle-related exposure, dose and lung cancer risk of primary school children in two European countries.

    PubMed

    Pacitto, A; Stabile, L; Viana, M; Scungio, M; Reche, C; Querol, X; Alastuey, A; Rivas, I; Álvarez-Pedrerol, M; Sunyer, J; van Drooge, B L; Grimalt, J O; Sozzi, R; Vigo, P; Buonanno, G

    2018-03-01

    Schools represent a critical microenvironment in terms of air quality due to the proximity to outdoor particle sources and the frequent lack of proper ventilation and filtering systems. Moreover, the population exposed in schools (i.e. children) represents a susceptible population due to their age. Air quality-based studies involving students' exposure at schools are still scarce and often limited to mass-based particle metrics and may thus underestimate the possible effect of sub-micron particles and particle toxicity. To this purpose, the present paper aims to evaluate the exposure to different airborne particle metrics (including both sub- and super-micron particles) and attached carcinogenic compounds. Measurements in terms of particle number, lung-deposited surface area, and PM fraction concentrations were measured inside and outside schools in Barcelona (Spain) and Cassino (Italy). Simultaneously, PM samples were collected and chemically analysed to obtain mass fractions of carcinogenic compounds. School time airborne particle doses received by students in classrooms were evaluated as well as their excess lung cancer risk due to a five-year primary school period. Median surface area dose received by students during school time in Barcelona and Cassino resulted equal to 110mm 2 and 303mm 2 , respectively. The risk related to the five-year primary school period was estimated as about 2.9×10 -5 and 1.4×10 -4 for students of Barcelona and Cassino, respectively. The risk in Barcelona is slightly higher with respect to the maximum tolerable value (10 -5 , according to the U.S. Environmental Protection Agency), mainly due to toxic compounds on particles generated from anthropogenic emissions (mainly industry). On the other hand, the excess lung cancer risk in Cassino is cause of concern, being one order of magnitude higher than the above-mentioned threshold value due to the presence of biomass burning heating systems and winter thermal inversion that cause larger doses and great amount of toxic compounds on particles. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Convolutional auto-encoder for image denoising of ultra-low-dose CT.

    PubMed

    Nishio, Mizuho; Nagashima, Chihiro; Hirabayashi, Saori; Ohnishi, Akinori; Sasaki, Kaori; Sagawa, Tomoyuki; Hamada, Masayuki; Yamashita, Tatsuo

    2017-08-01

    The purpose of this study was to validate a patch-based image denoising method for ultra-low-dose CT images. Neural network with convolutional auto-encoder and pairs of standard-dose CT and ultra-low-dose CT image patches were used for image denoising. The performance of the proposed method was measured by using a chest phantom. Standard-dose and ultra-low-dose CT images of the chest phantom were acquired. The tube currents for standard-dose and ultra-low-dose CT were 300 and 10 mA, respectively. Ultra-low-dose CT images were denoised with our proposed method using neural network, large-scale nonlocal mean, and block-matching and 3D filtering. Five radiologists and three technologists assessed the denoised ultra-low-dose CT images visually and recorded their subjective impressions of streak artifacts, noise other than streak artifacts, visualization of pulmonary vessels, and overall image quality. For the streak artifacts, noise other than streak artifacts, and visualization of pulmonary vessels, the results of our proposed method were statistically better than those of block-matching and 3D filtering (p-values < 0.05). On the other hand, the difference in the overall image quality between our proposed method and block-matching and 3D filtering was not statistically significant (p-value = 0.07272). The p-values obtained between our proposed method and large-scale nonlocal mean were all less than 0.05. Neural network with convolutional auto-encoder could be trained using pairs of standard-dose and ultra-low-dose CT image patches. According to the visual assessment by radiologists and technologists, the performance of our proposed method was superior to that of large-scale nonlocal mean and block-matching and 3D filtering.

  18. Bolus-dependent dosimetric effect of positioning errors for tangential scalp radiotherapy with helical tomotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lobb, Eric, E-mail: eclobb2@gmail.com

    2014-04-01

    The dosimetric effect of errors in patient position is studied on-phantom as a function of simulated bolus thickness to assess the need for bolus utilization in scalp radiotherapy with tomotherapy. A treatment plan is generated on a cylindrical phantom, mimicking a radiotherapy technique for the scalp utilizing primarily tangential beamlets. A planning target volume with embedded scalplike clinical target volumes (CTVs) is planned to a uniform dose of 200 cGy. Translational errors in phantom position are introduced in 1-mm increments and dose is recomputed from the original sinogram. For each error the maximum dose, minimum dose, clinical target dose homogeneitymore » index (HI), and dose-volume histogram (DVH) are presented for simulated bolus thicknesses from 0 to 10 mm. Baseline HI values for all bolus thicknesses were in the 5.5 to 7.0 range, increasing to a maximum of 18.0 to 30.5 for the largest positioning errors when 0 to 2 mm of bolus is used. Utilizing 5 mm of bolus resulted in a maximum HI value of 9.5 for the largest positioning errors. Using 0 to 2 mm of bolus resulted in minimum and maximum dose values of 85% to 94% and 118% to 125% of the prescription dose, respectively. When using 5 mm of bolus these values were 98.5% and 109.5%. DVHs showed minimal changes in CTV dose coverage when using 5 mm of bolus, even for the largest positioning errors. CTV dose homogeneity becomes increasingly sensitive to errors in patient position as bolus thickness decreases when treating the scalp with primarily tangential beamlets. Performing a radial expansion of the scalp CTV into 5 mm of bolus material minimizes dosimetric sensitivity to errors in patient position as large as 5 mm and is therefore recommended.« less

  19. High Atomic Number Contrast Media Offer Potential for Radiation Dose Reduction in Contrast-Enhanced Computed Tomography.

    PubMed

    Roessler, Ann-Christin; Hupfer, Martin; Kolditz, Daniel; Jost, Gregor; Pietsch, Hubertus; Kalender, Willi A

    2016-04-01

    Spectral optimization of x-ray computed tomography (CT) has led to substantial radiation dose reduction in contrast-enhanced CT studies using standard iodinated contrast media. The purpose of this study was to analyze the potential for further dose reduction using high-atomic-number elements such as hafnium and tungsten. As in previous studies, spectra were determined for which the patient dose necessary to provide a given contrast-to-noise ratio (CNR) is minimized. We used 2 different quasi-anthropomorphic phantoms representing the liver cross-section of a normal adult and an obese adult patient with the lateral widths of 360 and 460 mm and anterior-posterior heights of 200 and 300 mm, respectively. We simulated and measured on 2 different scanners with x-ray spectra from 80 to 140 kV and from 70 to 150 kV, respectively. We determined the contrast for iodine-, hafnium-, and tungsten-based contrast media, the noise, and 3-dimensional dose distributions at all available tube voltages by measurements and by simulations. The dose-weighted CNR was determined as optimization parameter. Simulations and measurements were in good agreement regarding their dependence on energy for all parameters investigated. Hafnium provided the best performance for normal and for obese patient phantoms, indicating a dose reduction potential of 30% for normal and 50% for obese patients at 120 kV compared with iodine; this advantage increased further with higher kV values. Dose-weighted CNR values for tungsten were always slightly below the hafnium results. Iodine proved to be the superior choice at voltage values of 80 kV and below. Hafnium and tungsten both seem to be candidates for contrast-medium-enhanced CT of normal and obese adult patients with strongly reduced radiation dose at unimpaired image quality. Computed tomography examinations of obese patients will decrease in dose for higher kV values.

  20. SU-E-T-56: A Novel Approach to Computing Expected Value and Variance of Point Dose From Non-Gated Radiotherapy Delivery

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhou, S; Zhu, X; Zhang, M

    Purpose: Randomness in patient internal organ motion phase at the beginning of non-gated radiotherapy delivery may introduce uncertainty to dose received by the patient. Concerns of this dose deviation from the planned one has motivated many researchers to study this phenomenon although unified theoretical framework for computing it is still missing. This study was conducted to develop such framework for analyzing the effect. Methods: Two reasonable assumptions were made: a) patient internal organ motion is stationary and periodic; b) no special arrangement is made to start a non -gated radiotherapy delivery at any specific phase of patient internal organ motion.more » A statistical ensemble was formed consisting of patient’s non-gated radiotherapy deliveries at all equally possible initial organ motion phases. To characterize the patient received dose, statistical ensemble average method is employed to derive formulae for two variables: expected value and variance of dose received by a patient internal point from a non-gated radiotherapy delivery. Fourier Series was utilized to facilitate our analysis. Results: According to our formulae, the two variables can be computed from non-gated radiotherapy generated dose rate time sequences at the point’s corresponding locations on fixed phase 3D CT images sampled evenly in time over one patient internal organ motion period. The expected value of point dose is simply the average of the doses to the point’s corresponding locations on the fixed phase CT images. The variance can be determined by time integration in terms of Fourier Series coefficients of the dose rate time sequences on the same fixed phase 3D CT images. Conclusion: Given a non-gated radiotherapy delivery plan and patient’s 4D CT study, our novel approach can predict the expected value and variance of patient radiation dose. We expect it to play a significant role in determining both quality and robustness of patient non-gated radiotherapy plan.« less

  1. SU-F-T-02: Estimation of Radiobiological Doses (BED and EQD2) of Single Fraction Electronic Brachytherapy That Equivalent to I-125 Eye Plaque: By Using Linear-Quadratic and Universal Survival Curve Models

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kim, Y; Waldron, T; Pennington, E

    Purpose: To test the radiobiological impact of hypofractionated choroidal melanoma brachytherapy, we calculated single fraction equivalent doses (SFED) of the tumor that equivalent to 85 Gy of I125-BT for 20 patients. Corresponding organs-at-risks (OARs) doses were estimated. Methods: Twenty patients treated with I125-BT were retrospectively examined. The tumor SFED values were calculated from tumor BED using a conventional linear-quadratic (L-Q) model and an universal survival curve (USC). The opposite retina (α/β = 2.58), macula (2.58), optic disc (1.75), and lens (1.2) were examined. The % doses of OARs over tumor doses were assumed to be the same as for amore » single fraction delivery. The OAR SFED values were converted into BED and equivalent dose in 2 Gy fraction (EQD2) by using both L-Q and USC models, then compared to I125-BT. Results: The USC-based BED and EQD2 doses of the macula, optic disc, and the lens were on average 118 ± 46% (p < 0.0527), 126 ± 43% (p < 0.0354), and 112 ± 32% (p < 0.0265) higher than those of I125-BT, respectively. The BED and EQD2 doses of the opposite retina were 52 ± 9% lower than I125-BT. The tumor SFED values were 25.2 ± 3.3 Gy and 29.1 ± 2.5 Gy when using USC and LQ models which can be delivered within 1 hour. All BED and EQD2 values using L-Q model were significantly larger when compared to the USC model (p < 0.0274) due to its large single fraction size (> 14 Gy). Conclusion: The estimated single fraction doses were feasible to be delivered within 1 hour using a high dose rate source such as electronic brachytherapy (eBT). However, the estimated OAR doses using eBT were 112 ∼ 118% higher than when using the I125-BT technique. Continued exploration of alternative dose rate or fractionation schedules should be followed.« less

  2. SU-F-T-124: Radiation Biological Equivalent Presentations OfLEM-1 and MKM Approaches in the Carbon-Ion Radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hsi, W; Jiang, G; Sheng, Y

    Purpose: To study the correlations of the radiation biological equivalent doses (BED) along depth and lateral distance between LEM-1 and MKM approaches. Methods: In NIRS-MKM (Microdosimetric Kinetic Model) approach, the prescribed BED, referred as C-Eq, doses aims to present the relative biological effectiveness (RBE) for different energies of carbon-ions on a fixed 10% survival value of HCG cell with respect to convention X-ray. Instead of a fixed 10% survival, the BED doses of LEM-1 (Local Effect Model) approach, referred as X-Eq, aims to present the RBE over the whole survival curve of chordoma-like cell with alpha/beta ratio of 2.0. Themore » relationship of physical doses as a function of C-Eq and X-Eq doses were investigated along depth and lateral distance for various sizes of cubic targets in water irradiated by carbon-ions. Results: At the center of each cubic target, the trends between physical and C-Eq or X-Eq doses can be described by a linear and 2nd order polynomial functions, respectively. Using fit functions can then calculate a scaling factor between C-Eq and X-Eq doses to have similar physical doses. With equalized C-Eq and X-Eq doses at the depth of target center, over- and under-estimated X-Eq to C-Eq are seen for depths before and after the target center, respectively. Near the distal edge along depth, sharp rising of RBE value is observed for X-Eq, but sharp dropping of RBE value is observed for C-Eq. For lateral locations near and just outside 50% dose level, sharp raising of RBE value is also seen for X-Eq, while only minor increasing with fast dropping for C-Eq. Conclusion: An analytical function to model the differences between the CEq and X-Eq doses along depth and lateral distance need to further investigated to explain varied clinic outcome of specific cancers using two different approaches to calculated BED doses.« less

  3. Computer simulations and models for the performance characteristics of spectrally equivalent X-ray beams in medical diagnostic radiology

    PubMed Central

    Okunade, Akintunde A.

    2007-01-01

    In order to achieve uniformity in radiological imaging, it is recommended that the concept of equivalence in shape (quality) and size (quantity) of clinical Xray beams should be used for carrying out the comparative evaluation of image and patient dose. When used under the same irradiation geometry, X-ray beams that are strictly or relatively equivalent in terms of shape and size will produce identical or relatively identical image quality and patient dose. Simple mathematical models and software program EQSPECT.FOR were developed for the comparative evaluation of the performance characteristics in terms of contrast (C), contrast to noise ratio (CNR) and figure-of-merit (FOM = CNR2/DOSE) for spectrally equivalent beams transmitted through filter materials referred to as conventional and k-edged. At the same value of operating potential (kVp), results show that spectrally equivalent beam transmitted through conventional filter with higher atomic number (Z-value) in comparison with that transmitted through conventional filter with lower Z-value resulted in the same value of C and FOM. However, in comparison with the spectrally equivalent beam transmitted through filter of lower Z-value, the beam through filter of higher Z-value produced higher value of CNR and DOSE at equal tube loading (mAs) and kVp. Under the condition of equivalence of spectrum, at scaled (or reduced) tube loading and same kVp, filter materials of higher Z-value can produce the same values of C, CNR, DOSE and FOM as filter materials of lower Z-value. Unlike the case of comparison of spectrally equivalent beam transmitted through one conventional filter and that through another conventional filter, it is not possible to derive simple mathematical formulations for the relative performance of spectrally equivalent beam transmitted through a given conventional filter material and that through kedge filter material. PMID:21224928

  4. Characterization of Relative Biological Effectiveness for Proton Therapy in Human Cancer Cell Lines

    NASA Astrophysics Data System (ADS)

    Howard, Michelle Erin

    Purpose: Relative biological effectiveness (RBE) is utilized to account for the differences in biological effect from different radiation types. The RBE for proton therapy remains uncertain as it has been shown to vary from the clinically used value of 1.1. The purpose of this thesis was to investigate the RBE of protons as compared to X-rays and correlate the biological differences with the underlying physics. Methods: Three cell lines were irradiated (CHO, Chinese hamster ovary; A549, human lung adenocarcinoma; and T98, human glioma) and assessed for cell survival using clonogenic assay. Cells were irradiated with 71 and 160 MeV protons at depths along the Bragg curve and 6 MV X-rays to various doses. To correlate the underlying physics to RBE, both the dose averaged lineal energy (y¯D) and dose averaged LET (LETd) investigated. The microdosimetric quantity y¯D was measured under similar conditions as the cells using a solid state microdosimeter and LETd calculated using Monte Carlo (MC) simulations. Survival data were fit using the linear quadratic model. RBE values were calculated by comparing the physical dose (D6MV/Dp) that results in 50% (RBE0.5), 10% (RBE0.1) cell survival, and survival after 2Gy (RBE2 Gy).. Results: For 10% and 50% survival, the RBE for all three cell lines increased with decreasing proton energy (or increased depth). The RBE at 2Gy also increased with a decrease in proton energy in all cases, within experimental error. Results also showed the experimental end point proved to influence the measured proton RBE as well with larger values corresponding to 50% cell survival. Cell type had the least influence on proton RBE compared to proton energy and end point. Results from this study showed an increase in RBE corresponded to an increase in both LETd and y¯ D. Additionally, the measured y¯D and calculated LET d values did not match for all the points of measurement along the curve for the 71 and 160 MeV proton beams. Conclusion: Proton RBE depends on proton energy, cell type and LET. Cellular response to radiation is varied and can be seen in the data from CHO, A549 and T98 cell lines irradiated with 71 MeV protons. Both A549 and T98 cells generally had higher RBE values, indicating a greater biological response to protons. The RBE values in this study vary from 0.89- 2.40, indicating the clinical value of 1.1 may not be suitable in all cases. Innovation/impact: The rare but devastating complication of brainstem necrosis has occurred recently in pediatric patients treated with proton therapy (PT). Many believe these effects are due to the uncertainty in the RBE of PT, which may be underestimating the biological dose near critical structures. An increased confidence in RBE for PT can lead to a decrease in toxicity to normal tissues and therefore a decrease in secondary or recurrent cancer and better overall patient outcomes. This study is one of the first to consider the intricacies of proton RBE dependence on parameters such as cell type, proton energy and LET. The broader implications of understanding RBE variations in a cell-specific manner will allow for biologically optimized treatment planning and an overall decrease in PT uncertainty which may lead to improved patient outcomes. Further, this was the first study, to our knowledge, to measure y¯D with a solid state detector for the comparison with measured RBE values.

  5. Effect of improved TLD dosimetry on the determination of dose rate constants for {sup 125}I and {sup 103}Pd brachytherapy seeds

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rodriguez, M., E-mail: manuel.rodriguez@rmp.uhn.ca; Rogers, D. W. O.

    Purpose: To more accurately account for the relative intrinsic energy dependence and relative absorbed-dose energy dependence of TLDs when used to measure dose rate constants (DRCs) for {sup 125}I and {sup 103}Pd brachytherapy seeds, to thereby establish revised “measured values” for all seeds and compare the revised values with Monte Carlo and consensus values. Methods: The relative absorbed-dose energy dependence, f{sup rel}, for TLDs and the phantom correction, P{sub phant}, are calculated for {sup 125}I and {sup 103}Pd seeds using the EGSnrc BrachyDose and DOSXYZnrc codes. The original energy dependence and phantom corrections applied to DRC measurements are replaced bymore » calculated (f{sup rel}){sup −1} and P{sub phant} values for 24 different seed models. By comparing the modified measured DRCs to the MC values, an appropriate relative intrinsic energy dependence, k{sub bq}{sup rel}, is determined. The new P{sub phant} values and relative absorbed-dose sensitivities, S{sub AD}{sup rel}, calculated as the product of (f{sup rel}){sup −1} and (k{sub bq}{sup rel}){sup −1}, are used to individually revise the measured DRCs for comparison with Monte Carlo calculated values and TG-43U1 or TG-43U1S1 consensus values. Results: In general, f{sup rel} is sensitive to the energy spectra and models of the brachytherapy seeds. Values may vary up to 8.4% among {sup 125}I and {sup 103}Pd seed models and common TLD shapes. P{sub phant} values depend primarily on the isotope used. Deduced (k{sub bq}{sup rel}){sup −1} values are 1.074 ± 0.015 and 1.084 ± 0.026 for {sup 125}I and {sup 103}Pd seeds, respectively. For (1 mm){sup 3} chips, this implies an overall absorbed-dose sensitivity relative to {sup 60}Co or 6 MV calibrations of 1.51 ± 1% and 1.47 ± 2% for {sup 125}I and {sup 103}Pd seeds, respectively, as opposed to the widely used value of 1.41. Values of P{sub phant} calculated here have much lower statistical uncertainties than literature values, but systematic uncertainties from density and composition uncertainties are significant. Using these revised values with the literature’s DRC measurements, the average discrepancies between revised measured values and Monte Carlo values are 1.2% and 0.2% for {sup 125}I and {sup 103}Pd seeds, respectively, compared to average discrepancies for the original measured values of 4.8%. On average, the revised measured values are 4.3% and 5.9% lower than the original measured values for {sup 103}Pd and {sup 125}I seeds, respectively. The average of revised DRCs and Monte Carlo values is 3.8% and 2.8% lower for {sup 125}I and {sup 103}Pd seeds, respectively, than the consensus values in TG-43U1 or TG-43U1S1. Conclusions: This work shows that f{sup rel} is TLD shape and seed model dependent suggesting a need to update the generalized energy response dependence, i.e., relative absorbed-dose sensitivity, measured 25 years ago and applied often to DRC measurements of {sup 125}I and {sup 103}Pd brachytherapy seeds. The intrinsic energy dependence for LiF TLDs deduced here is consistent with previous dosimetry studies and emphasizes the need to revise the DRC consensus values reported by TG-43U1 or TG-43U1S1.« less

  6. Analytical model for out-of-field dose in photon craniospinal irradiation

    NASA Astrophysics Data System (ADS)

    Taddei, Phillip J.; Jalbout, Wassim; Howell, Rebecca M.; Khater, Nabil; Geara, Fady; Homann, Kenneth; Newhauser, Wayne D.

    2013-11-01

    The prediction of late effects after radiotherapy in organs outside a treatment field requires accurate estimations of out-of-field dose. However, out-of-field dose is not calculated accurately by commercial treatment planning systems (TPSs). The purpose of this study was to develop and test an analytical model for out-of-field dose during craniospinal irradiation (CSI) from photon beams produced by a linear accelerator. In two separate evaluations of the model, we measured absorbed dose for a 6 MV CSI using thermoluminescent dosimeters placed throughout an anthropomorphic phantom and fit the measured data to an analytical model of absorbed dose versus distance outside of the composite field edge. These measurements were performed in two separate clinics—the University of Texas MD Anderson Cancer Center (MD Anderson) and the American University of Beirut Medical Center (AUBMC)—using the same phantom but different linear accelerators and TPSs commissioned for patient treatments. The measurement at AUBMC also included in-field locations. Measured dose values were compared to those predicted by TPSs and parameters were fit to the model in each setting. In each clinic, 95% of the measured data were contained within a factor of 0.2 and one root mean square deviation of the model-based values. The root mean square deviations of the mathematical model were 0.91 cGy Gy-1 and 1.67 cGy Gy-1 in the MD Anderson and AUBMC clinics, respectively. The TPS predictions agreed poorly with measurements in regions of sharp dose gradient, e.g., near the field edge. At distances greater than 1 cm from the field edge, the TPS underestimated the dose by an average of 14% ± 24% and 44% ± 19% in the MD Anderson and AUBMC clinics, respectively. The in-field measured dose values of the measurement at AUBMC matched the dose values calculated by the TPS to within 2%. Dose algorithms in TPSs systematically underestimated the actual out-of-field dose. Therefore, it is important to use an improved model based on measurements when estimating out-of-field dose. The model proposed in this study performed well for this purpose in two clinics and may be applicable in other clinics with similar treatment field configurations.

  7. Electron intensity modulation for mixed-beam radiation therapy with an x-ray multi-leaf collimator

    NASA Astrophysics Data System (ADS)

    Weinberg, Rebecca

    The current standard treatment for head and neck cancer at our institution uses intensity-modulated x-ray therapy (IMRT), which improves target coverage and sparing of critical structures by delivering complex fluence patterns from a variety of beam directions to conform dose distributions to the shape of the target volume. The standard treatment for breast patients is field-in-field forward-planned IMRT, with initial tangential fields and additional reduced-weight tangents with blocking to minimize hot spots. For these treatment sites, the addition of electrons has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. In this work, the use of mixed-beam therapy (MBT), i.e., combined intensity-modulated electron and x-ray beams using the x-ray multi-leaf collimator (MLC), was explored. The hypothesis of this study was that addition of intensity-modulated electron beams to existing clinical IMRT plans would produce MBT plans that were superior to the original IMRT plans for at least 50% of selected head and neck and 50% of breast cases. Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods. An automation system was created to facilitate communication between the dose calculation engine and the treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2x2-cm2 beamlets, which were then beam-weight optimized along with intensity-modulated x-ray beams. Treatment plans were optimized to obtain equivalent target dose coverage, and then compared with the original treatment plans. MBT treatment plans were evaluated by participating physicians with respect to target coverage, normal structure dose, and overall plan quality in comparison with original clinical plans. The physician evaluations did not support the hypothesis for either site, with MBT selected as superior in 1 out of the 15 head and neck cases (p=1) and 6 out of 18 breast cases (p=0.95). While MBT was not shown to be superior to IMRT, reductions were observed in doses to critical structures distal to the target along the electron beam direction and to non-target tissues, at the expense of target coverage and dose homogeneity.

  8. VMAT linear accelerator commissioning and quality assurance: dose control and gantry speed tests

    PubMed Central

    Rowshanfarzad, Pejman; Greer, Peter B.

    2016-01-01

    In VMAT treatment delivery the ability of the linear accelerator (linac) to accurately control dose versus gantry angle is critical to delivering the plan correctly. A new VMAT test delivery was developed to specifically test the dose versus gantry angle with the full range of allowed gantry speeds and dose rates. The gantry‐mounted IBA MatriXX with attached inclinometer was used in movie mode to measure the instantaneous relative dose versus gantry angle during the plan every 0.54 s. The results were compared to the expected relative dose at each gantry angle calculated from the plan. The same dataset was also used to compare the instantaneous gantry speeds throughout the delivery compared to the expected gantry speeds from the plan. Measurements performed across four linacs generally show agreement between measurement and plan to within 1.5% in the constant dose rate regions and dose rate modulation within 0.1 s of the plan. Instantaneous gantry speed was measured to be within 0.11∘/s of the plan (1 SD). An error in one linac was detected in that the nominal gantry speed was incorrectly calibrated. This test provides a practical method to quality‐assure critical aspects of VMAT delivery including dose versus gantry angle and gantry speed control. The method can be performed with any detector that can acquire time‐resolved dosimetric information that can be synchronized with a measurement of gantry angle. The test fulfils several of the aims of the recent Netherlands Commission on Radiation Dosimetry (NCS) Report 24, which provides recommendations for comprehensive VMAT quality assurance. PACS number(s): 87.55.Qr PMID:27167282

  9. SU-F-T-538: CyberKnife with MLC for Treatment of Large Volume Tumors: A Feasibility Study

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bichay, T; Mayville, A

    2016-06-15

    Purpose: CyberKnife is a well-documented modality for SRS and SBRT treatments. Typical tumors are small and 1–5 fractions are usually used. We determined the feasibility of using CyberKnife, with an InCise multileaf collimator option, for larger tumors undergoing standard dose and fractionation. The intent was to understand the limitation of using this modality for other external beam radiation treatments. Methods: Five tumors from different anatomical sites with volumes from 127.8 cc to 1,320.5 cc were contoured and planned on a Multiplan V5.1 workstation. The target average diameter ranged from 7 cm to 13 cm. The dose fractionation was 1.8–2.0 Gy/fractionmore » and 25–45 fractions for total doses of 45–81 Gy. The sites planned were: pancreas, head and neck, prostate, anal, and esophagus. The plans were optimized to meet conventional dose constraints based on various RTOG protocols for conventional fractionation. Results: The Multiplan treatment planning system successfully generated clinically acceptable plans for all sites studied. The resulting dose distributions achieved reasonable target coverage, all greater than 95%, and satisfactory normal tissue sparing. Treatment times ranged from 9 minutes to 38 minutes, the longest being a head and neck plan with dual targets receiving different doses and with multiple adjacent critical structures. Conclusion: CyberKnife, with the InCise multileaf collimation option, can achieve acceptable dose distributions in large volume tumors treated with conventional dose and fractionation. Although treatment times are greater than conventional accelerator time; target coverage and dose to critical structures can be kept within a clinically acceptable range. While time limitations exist, when necessary CyberKnife can provide an alternative to traditional treatment modalities for large volume tumors.« less

  10. Comparison between beta radiation dose distribution due to LDR and HDR ocular brachytherapy applicators using GATE Monte Carlo platform.

    PubMed

    Mostafa, Laoues; Rachid, Khelifi; Ahmed, Sidi Moussa

    2016-08-01

    Eye applicators with 90Sr/90Y and 106Ru/106Rh beta-ray sources are generally used in brachytherapy for the treatment of eye diseases as uveal melanoma. Whenever, radiation is used in treatment, dosimetry is essential. However, knowledge of the exact dose distribution is a critical decision-making to the outcome of the treatment. The Monte Carlo technique provides a powerful tool for calculation of the dose and dose distributions which helps to predict and determine the doses from different shapes of various types of eye applicators more accurately. The aim of this work consisted in using the Monte Carlo GATE platform to calculate the 3D dose distribution on a mathematical model of the human eye according to international recommendations. Mathematical models were developed for four ophthalmic applicators, two HDR 90Sr applicators SIA.20 and SIA.6, and two LDR 106Ru applicators, a concave CCB model and a flat CCB model. In present work, considering a heterogeneous eye phantom and the chosen tumor, obtained results with the use of GATE for mean doses distributions in a phantom and according to international recommendations show a discrepancy with respect to those specified by the manufacturers. The QC of dosimetric parameters shows that contrarily to the other applicators, the SIA.20 applicator is consistent with recommendations. The GATE platform show that the SIA.20 applicator present better results, namely the dose delivered to critical structures were lower compared to those obtained for the other applicators, and the SIA.6 applicator, simulated with MCNPX generates higher lens doses than those generated by GATE. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  11. A fixed-jaw method to protect critical organs during intensity-modulated radiotherapy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Chen, Jiayun; Chen, Xinyuan; Huang, Manni, E-mail: dai_jianrong@163.com

    2014-01-01

    Intensity-modulated radiotherapy (IMRT) plays an important role in cancer radiotherapy. For some patients being treated with IMRT, the extremely low tolerances of critical organs (such as lens, ovaries, and testicles) cannot be met during treatment planning. The aim of this article is to introduce a new planning method to overcome that problem. In current planning practice, jaw positions are automatically set to cover all target volumes by the planning system (e.g., Pinnacle{sup 3} system). Because of such settings, critical organs may be fully blocked by the multileaf collimator (MLC), but they still sit in the field that is shaped bymore » collimator jaws. These critical organs receive doses from the transmission and leakage of MLC leaves. We manually fixed jaw positions to block them to further reduce such doses. This method has been used for different treatment sites in our clinic, and it was thoroughly evaluated in patients with radical hysterectomy plus ovarian transposition after surgery. For each patient, 2 treatment plans were designed with the same optimization parameters: the original plan with automatically chosen jaw positions (called O-plan) and the plan with fixed-jaw positions (named F-plan). In the F-plan, the jaws were manually fixed to block the ovaries. For target coverage, the mean conformity index (CI) of the F-plan (1.28 ± 0.02) was remarkably lower than that of the O-plan (1.53 ± 0.09) (p < 0.05). The F-plan and the O-plan performed similarly in target dose homogeneity. Meanwhile, for the critical organ sparing, the mean dose of both ovaries were much lower in the F-plan than that in the O-plan (p < 0.05). The V{sub 20}, V{sub 30}, and V{sub 40} of bladder were also lower in the F-plan (93.57 ± 1.98, 73.99 ± 5.76, and 42.33 ± 3.7, respectively) than those in the O-plan (97.98 ± 1.11, 85.07 ± 4.04, and 49.71 ± 3.63, respectively) (p < 0.05). The maximum dose to the spinal cord planning organ at risk (OAR) volume (PRV) in the O-plan (3940.24 ± 102.8) was higher than that in the F-plan (3628.18 ± 131.45) with significant differences (p < 0.01). For other OARs, there were no significant differences in doses between these 2 plans except that the high-dose regions of the rectum were higher for V{sub 40} in the O-plan than that in the F-plan (p < 0.01). But the monitor units (MUs) in the F-plan were 1.4 times as much as that in the O-plan. Thus the treatment time could be longer by using the F-plan. As it results in more MUs in spite of better plan quality, it is recommended to be used only in situations in which clinical requirements to critical organs cannot be met with the regular method.« less

  12. Measurement of dose given by Co-60 in radiotherapy with TLD-500

    NASA Astrophysics Data System (ADS)

    Tanır, Güneş; Cengiz, Ferhat; Hicabi Bölükdemir, M.

    2012-04-01

    The uses of dosimeters based on optically stimulated luminescence technique have become widespread in clinical applications. In the present study, the dose values given by Cobalt-60 radiotherapy machine were measured with optically stimulated luminescence (OSL) technique using TLD-500 and compared with those of commonly used ionization chamber dosimeter system. The percentage depth dose (DD%) values and graphs were formed. OSL system with TLD-500 can be reliably used as medical and personal dosimeter.

  13. Retrospective analysis of factors that affect the success of single-dose methotrexate treatment in ectopic pregnancy

    PubMed Central

    Var, Altan; Özyurt, Ramazan; Şık, Bulat Aytek; Kumbasar, Serkan; Sever, Erman; Deveci, Mustafa; Çöt, Özgür; Salman, Süleyman; Güzel, Yılmaz

    2015-01-01

    Objective: Detection of factors that affect the success of single-dose methotrexate treatment in ectopic pregnancy. Materials and Methods: We investigated 99 patients who had been treated with single-dose methotrexate for ectopic pregnancy in our clinic between January 2009 and June 2014. Demographic, clinical, and laboratory results of possible factors that affect treatment success were retrospectively analyzed. Successfully and unsuccessfully treated patients were compared based on their pre-treatment results. Results: The success rate of single-dose methotrexate treatment was found to be 70.7%. No significant difference was found between succesfully and unsuccessfully treated patients before treatment in terms of factors such as gestational weeks, mass size, presence of yolk sac, and presence of free fluid (p=0.224, p=0.201, p=0.200, p=0.200). Serum β-hCG values in patients whose treatment was unsuccessful was found to be higher compared with the successfully treated group (mean β-hCG value of unsuccessful group: 4412±3501 mIU/mL; mean β-hCG value of successful group: 1079±942 mIU/mL; p<0.001). Conclusion: Single-dose methotrexate treatment is an effective and reliable method in the treatment of ectopic pregnancy. Elevation of serum β-hCG value stands as the main prognostic factor that affects the success of single-dose methotrexate treatment. PMID:28913072

  14. Image perception by expert readers as a function of patient skin entrance dose levels in digital radiography

    NASA Astrophysics Data System (ADS)

    Lehnert, T.; Korkusuz, H.; Khan, F.; Vogl, T. J.; Mack, M. G.

    2008-03-01

    In this study, image quality was based on required clinical criteria, in order to investigate to what degree entrance dose could be lowered and what kind of added filtration can be used without impinging on radiologist confidence levels in diagnosing. Images were taken of extremities from a cadaver using stepwise decreasing dose levels and variation of added filtration (no filtration, aluminum, aluminum/copper) under digital projection radiography (Kodak DirectView DR7500). The starting point dose level for all body parts imaged was the current x-ray technique. Two experienced and two resident radiologists were presented the images in a blinded fashion and rated each with an image quality score from 1 to 9 indicated very satisfied and 1 as very unsatisfied indicating loss of diagnostic value. The readers were not aware of which dose level and added filtration corresponded to which image. Dose levels considered were 100%, 75%, 50% and 25% of the normal and customary x-ray techniques used for the particular body part and projection. Images were reviewed on a clinical diagnostic workstation with no time limits imposed. Readers were also able to change the image presentation by adjusting the window width and level. Without added filtration image quality mean score was rated with 6.3 (dose level 100%), 6.2 (dose level 75%), 5.3 (dose level 50%) and with 4.4 (dose level 25%). An added aluminum filtration induced an image quality mean score of 6.3 (dose level 100%), 6.0 (dose level 75%), 5.1 (dose level 50%) and of 4.2 (dose level 25%). Using aluminum/copper filtration image quality mean score was rated with 6.0 (dose level 100%), 6.1 (dose level 75%), 5.0 (dose level 50%) and with 3.8 (dose level 25%). Regardless of the added filtration a differentiation between dose levels 100% and 75% was possible in 38.9%, between dose levels 75% and 50% in 66.7%, and between dose levels 50% and 25% in 70.0% of the cases. It is possible, in the case of extremities, to lower entrance doses up to 75 % of the normal value, a reduction of 25% in dose, under simultaneous use of added aluminum or aluminum/copper filtration, without comprising the diagnostic value required.

  15. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bogen, K.T.; Conrado, C.L.; Robison, W.L.

    A detailed analysis of uncertainty and interindividual variability in estimated doses was conducted for a rehabilitation scenario for Bikini Island at Bikini Atoll, in which the top 40 cm of soil would be removed in the housing and village area, and the rest of the island is treated with potassium fertilizer, prior to an assumed resettlement date of 1999. Predicted doses were considered for the following fallout-related exposure pathways: ingested Cesium-137 and Strontium-90, external gamma exposure, and inhalation and ingestion of Americium-241 + Plutonium-239+240. Two dietary scenarios were considered: (1) imported foods are available (IA), and (2) imported foods aremore » unavailable (only local foods are consumed) (IUA). Corresponding calculations of uncertainty in estimated population-average dose showed that after {approximately}5 y of residence on Bikini, the upper and lower 95% confidence limits with respect to uncertainty in this dose are estimated to be approximately 2-fold higher and lower than its population-average value, respectively (under both IA and IUA assumptions). Corresponding calculations of interindividual variability in the expected value of dose with respect to uncertainty showed that after {approximately}5 y of residence on Bikini, the upper and lower 95% confidence limits with respect to interindividual variability in this dose are estimated to be approximately 2-fold higher and lower than its expected value, respectively (under both IA and IUA assumptions). For reference, the expected values of population-average dose at age 70 were estimated to be 1.6 and 5.2 cSv under the IA and IUA dietary assumptions, respectively. Assuming that 200 Bikini resettlers would be exposed to local foods (under both IA and IUA assumptions), the maximum 1-y dose received by any Bikini resident is most likely to be approximately 2 and 8 mSv under the IA and IUA assumptions, respectively.« less

  16. External beam radiotherapy for palliation of painful bone metastases: pooled data bioeffect dose response analysis of dose fractionation

    NASA Astrophysics Data System (ADS)

    Naveen, T.; Supe, Sanjay S.; Ganesh, K. M.; Samuel, Jacob

    2009-01-01

    Bone metastases develop in up to 70% of newly diagnosed cancer patients and result in immobility, anxiety, and depression, severely diminishing the patients quality of life. Radiotherapy is a frequently used modality for bone metastasis and has been shown to be effective in reducing metastatic bone pain and in some instances, causing tumor shrinkage or growth inhibition. There is controversy surrounding the optimal fractionation schedule and total dose of external beam radiotherapy, despite many randomized trials and overviews addressing the issue. This study was undertaken to apply BED to clinical fractionation data of radiotherapeutic management of bone metastases in order to arrive at optimum BED values for acceptable level of response rate. A computerised literature search was conducted to identify all prospective clinical studies that addressed the issue of fractionation for the treatment of bone metastasis. The results of these studies were pooled together to form the database for the analysis. A total of 4111 number of patients received radiation dose ranging from 4 to 40.5 Gy in 1 to 15 fractions with dose per fraction ranging from 2 to 10 Gy. Single fraction treatments were delivered in 2013 patients and the dose varied from 4 to 10 Gy. Multifraction treatments were delivered in 2098 patients and the dose varied from 15 to 40.5 Gy. The biological effective dose (BED) was evaluated for each fractionation schedule using the linear quadratic model and an α/β value of 10 Gy. Response rate increased significantly beyond a BED value of 14.4 Gy (p < 0.01). Based on our analysis and indications from the literature about higher retreatment and fracture rate of single fraction treatments, minimum BED value of 14.4 Gy is recommended.

  17. Estimation of the initial slope of the cell survival curve after irradiation from micronucleus frequency in cytokinesis-blocked cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ono, K.; Masunaga, S.; Akaboshi, M.

    1994-04-01

    We have already reported that the {alpha}/{beta} ratio of the cell survival curve could be estimated from the micronucleus frequency in cytokinesis-blocked cells treated with cytochalasin-B after irradiation. In this paper, we investigate the direct relationship between the {alpha} value and the appearance of micronuclei. Cells of the SCCVII, RIF-1, EMT6, V-79, CHO, HeLa and human esophageal cancer cell lines were used for the study. Low-dose-rate irradiation was used to determine the {alpha} component of the relationship between dose and micronucleus frequency according to the linear-quadratic (LQ) model. A reduction of the dose rate from 3.09 to 0.0142 Gy/min correspondinglymore » decreased the micronucleus frequency; however, the fraction of binucleate cells without micronuclei was not affected in SCCVII and RIF-1 cells. When this fraction was defined as the normal nuclear division fraction, it decreased exponentially as a function of radiation dose. Then dose vs normal nuclear division fraction (NNDF) was fitted as follows: -In NNDF = aD + C, where D is radiation dose in grays and C is constant. The slope of the dose vs normal nuclear division fraction was not affected by dose rate. The correlation was also explored between the slope (a) and the {alpha} value of the cell survival curve determined by the colony formation assay in cells of eight cell lines. These two values showed extremely high agreement: {alpha} = 1.01a + 0.00795 (r = 0.99, P < 0.01). This assay was applied to estimate the {alpha} value of the cell survival curve of human esophageal cancer cell lines established from surgical specimens. 13 refs., 5 figs.« less

  18. Real Time Radiation Monitoring Using Nanotechnology

    NASA Technical Reports Server (NTRS)

    Li, Jing (Inventor); Hanratty, James J. (Inventor); Wilkins, Richard T. (Inventor); Lu, Yijiang (Inventor)

    2016-01-01

    System and method for monitoring receipt and estimating flux value, in real time, of incident radiation, using two or more nanostructures (NSs) and associated terminals to provide closed electrical paths and to measure one or more electrical property change values .DELTA.EPV, associated with irradiated NSs, during a sequence of irradiation time intervals. Effects of irradiation, without healing and with healing, of the NSs, are separately modeled for first order and second order healing. Change values.DELTA.EPV are related to flux, to cumulative dose received by NSs, and to radiation and healing effectivity parameters and/or.mu., associated with the NS material and to the flux. Flux and/or dose are estimated in real time, based on EPV change values, using measured .DELTA.EPV values. Threshold dose for specified changes of biological origin (usually undesired) can be estimated. Effects of time-dependent radiation flux are analyzed in pre-healing and healing regimes.

  19. Patient dose, gray level and exposure index with a computed radiography system

    NASA Astrophysics Data System (ADS)

    Silva, T. R.; Yoshimura, E. M.

    2014-02-01

    Computed radiography (CR) is gradually replacing conventional screen-film system in Brazil. To assess image quality, manufactures provide the calculation of an exposure index through the acquisition software of the CR system. The objective of this study is to verify if the CR image can be used as an evaluator of patient absorbed dose too, through a relationship between the entrance skin dose and the exposure index or the gray level values obtained in the image. The CR system used for this study (Agfa model 30-X with NX acquisition software) calculates an exposure index called Log of the Median (lgM), related to the absorbed dose to the IP. The lgM value depends on the average gray level (called Scan Average Level (SAL)) of the segmented pixel value histogram of the whole image. A Rando male phantom was used to simulate a human body (chest and head), and was irradiated with an X-ray equipment, using usual radiologic techniques for chest exams. Thermoluminescent dosimeters (LiF, TLD100) were used to evaluate entrance skin dose and exit dose. The results showed a logarithm relation between entrance dose and SAL in the image center, regardless of the beam filtration. The exposure index varies linearly with the entrance dose, but the angular coefficient is beam quality dependent. We conclude that, with an adequate calibration, the CR system can be used to evaluate the patient absorbed dose.

  20. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Seals, Kevin F., E-mail: KSeals@mednet.ucla.edu; Lee, Edward W., E-mail: EdwardLee@mednet.ucla.edu; Cagnon, Christopher H., E-mail: CCagnon@mednet.ucla.edu

    Extensive research supports an association between radiation exposure and cataractogenesis. New data suggests that radiation-induced cataracts may form stochastically, without a threshold and at low radiation doses. We first review data linking cataractogenesis with interventional work. We then analyze the lens dose typical of various procedures, factors modulating dose, and predicted annual dosages. We conclude by critically evaluating the literature describing techniques for lens protection, finding that leaded eyeglasses may offer inadequate protection and exploring the available data on alternative strategies for cataract prevention.

  1. ASSESSING ASTHMATIC CHILDREN'S EXPOSURES TO TOXIC AIR POLLUTANTS AND THE POTENTIAL INHALED DOSES USING TIME ACTIVITY INFORMATION AND ENERGY EXPENDITURE DATA

    EPA Science Inventory

    Accurately quantifying human exposures and the potential doses of various populations to environmental pollutants is critical for the U.S. Environmental Protection Agency to assess and manage human health risks. The Tampa Asthmatic Children's Study (TACS) was a pilot research stu...

  2. Effect of a single dose of dextromethorphan on psychomotor performance and working memory capacity.

    PubMed

    Al-Kuraishy, Hayder M; Al-Gareeb, Ali I; Ashor, Ammar Waham

    2012-04-01

    Previous studies show that the prolonged use of dextromethorphan produces cognitive deterioration in humans. The aim of this study was to investigate the effect of a single dose of dextroemthrophan on psychomotor performance and working memory capacity. This is a randomized, double-blind, controlled, and prospective study. Thirty-six (17 women, 19 men) medical students enrolled in the study; half of them (7 women, 11 men) were given placebo, while the other half (10 women, 8 men) received dextromethorphan. The choice reaction time, critical flicker fusion threshold, and N-back working memory task were measured before and after 2 h of taking the drugs. Dextromethorphan showed a significant deterioration in the 3-back working memory task (P<0.05). No significant changes were seen as regards the choice reaction time components (total, recognition, motor) and critical flicker fusion threshold (P>0.05). On the other hand, placebo showed no significant changes as regards the choice reaction time, critical flicker fusion threshold, and N-back working memory task (P>0.05). A single dose of dextromethorphan has no effect on attention and arousal but may significantly impair the working memory capacity.

  3. Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia.

    PubMed

    Elefritz, Jessica L; Bauer, Karri A; Jones, Christian; Mangino, Julie E; Porter, Kyle; Murphy, Claire V

    2017-09-01

    Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

  4. Optimising drug dosing in patients receiving extracorporeal membrane oxygenation.

    PubMed

    Cheng, Vesa; Abdul-Aziz, Mohd-Hafiz; Roberts, Jason A; Shekar, Kiran

    2018-03-01

    Optimal pharmacological management during extracorporeal membrane oxygenation (ECMO) involves more than administering drugs to reverse underlying disease. ECMO is a complex therapy that should be administered in a goal-directed manner to achieve therapeutic endpoints that allow reversal of disease and ECMO wean, minimisation of complications (treatment of complications when they do occur), early interruption of sedation and rehabilitation, maximising patient comfort and minimising risks of delirium. ECMO can alter both the pharmacokinetics (PK) and pharmacodynamics (PD) of administered drugs and our understanding of these alterations is still evolving. Based on available data it appears that modern ECMO circuitry probably has a less significant impact on PK when compared with critical illness itself. However, these findings need further confirmation in clinical population PK studies and such studies are underway. The altered PD associated with ECMO is less understood and more research is indicated. Until robust dosing guidelines become available, clinicians will have to rely on the principles of drug dosing in critically ill and known PK alterations induced by ECMO itself. This article summarises the PK alterations and makes preliminary recommendations on possible dosing approaches.

  5. Metallic artifact mitigation and organ-constrained tissue assignment for Monte Carlo calculations of permanent implant lung brachytherapy.

    PubMed

    Sutherland, J G H; Miksys, N; Furutani, K M; Thomson, R M

    2014-01-01

    To investigate methods of generating accurate patient-specific computational phantoms for the Monte Carlo calculation of lung brachytherapy patient dose distributions. Four metallic artifact mitigation methods are applied to six lung brachytherapy patient computed tomography (CT) images: simple threshold replacement (STR) identifies high CT values in the vicinity of the seeds and replaces them with estimated true values; fan beam virtual sinogram replaces artifact-affected values in a virtual sinogram and performs a filtered back-projection to generate a corrected image; 3D median filter replaces voxel values that differ from the median value in a region of interest surrounding the voxel and then applies a second filter to reduce noise; and a combination of fan beam virtual sinogram and STR. Computational phantoms are generated from artifact-corrected and uncorrected images using several tissue assignment schemes: both lung-contour constrained and unconstrained global schemes are considered. Voxel mass densities are assigned based on voxel CT number or using the nominal tissue mass densities. Dose distributions are calculated using the EGSnrc user-code BrachyDose for (125)I, (103)Pd, and (131)Cs seeds and are compared directly as well as through dose volume histograms and dose metrics for target volumes surrounding surgical sutures. Metallic artifact mitigation techniques vary in ability to reduce artifacts while preserving tissue detail. Notably, images corrected with the fan beam virtual sinogram have reduced artifacts but residual artifacts near sources remain requiring additional use of STR; the 3D median filter removes artifacts but simultaneously removes detail in lung and bone. Doses vary considerably between computational phantoms with the largest differences arising from artifact-affected voxels assigned to bone in the vicinity of the seeds. Consequently, when metallic artifact reduction and constrained tissue assignment within lung contours are employed in generated phantoms, this erroneous assignment is reduced, generally resulting in higher doses. Lung-constrained tissue assignment also results in increased doses in regions of interest due to a reduction in the erroneous assignment of adipose to voxels within lung contours. Differences in dose metrics calculated for different computational phantoms are sensitive to radionuclide photon spectra with the largest differences for (103)Pd seeds and smallest but still considerable differences for (131)Cs seeds. Despite producing differences in CT images, dose metrics calculated using the STR, fan beam + STR, and 3D median filter techniques produce similar dose metrics. Results suggest that the accuracy of dose distributions for permanent implant lung brachytherapy is improved by applying lung-constrained tissue assignment schemes to metallic artifact corrected images.

  6. Fractionation in normal tissues: the (α/β)eff concept can account for dose heterogeneity and volume effects.

    PubMed

    Hoffmann, Aswin L; Nahum, Alan E

    2013-10-07

    The simple Linear-Quadratic (LQ)-based Withers iso-effect formula (WIF) is widely used in external-beam radiotherapy to derive a new tumour dose prescription such that there is normal-tissue (NT) iso-effect when changing the fraction size and/or number. However, as conventionally applied, the WIF is invalid unless the normal-tissue response is solely determined by the tumour dose. We propose a generalized WIF (gWIF) which retains the tumour prescription dose, but replaces the intrinsic fractionation sensitivity measure (α/β) by a new concept, the normal-tissue effective fractionation sensitivity, [Formula: see text], which takes into account both the dose heterogeneity in, and the volume effect of, the late-responding normal-tissue in question. Closed-form analytical expressions for [Formula: see text] ensuring exact normal-tissue iso-effect are derived for: (i) uniform dose, and (ii) arbitrary dose distributions with volume-effect parameter n = 1 from the normal-tissue dose-volume histogram. For arbitrary dose distributions and arbitrary n, a numerical solution for [Formula: see text] exhibits a weak dependence on the number of fractions. As n is increased, [Formula: see text] increases from its intrinsic value at n = 0 (100% serial normal-tissue) to values close to or even exceeding the tumour (α/β) at n = 1 (100% parallel normal-tissue), with the highest values of [Formula: see text] corresponding to the most conformal dose distributions. Applications of this new concept to inverse planning and to highly conformal modalities are discussed, as is the effect of possible deviations from LQ behaviour at large fraction sizes.

  7. It's All Relative: A Validation of Radiation Quality Comparison Metrics

    NASA Technical Reports Server (NTRS)

    Chappell, Lori J.; Milder, Caitlin M.; Elgart, S. Robin; Semones, Edward J.

    2017-01-01

    The difference between high-LET and low-LET radiation is quantified by a measure called relative biological effectiveness (RBE). RBE is defined as the ratio of the dose of a reference radiation to that of a test radiation to achieve the same effect level, and thus, is described either as an iso-effector dose-to-dose ratio. A single dose point is not sufficient to calculate an RBE value; therefore, studies with only one dose point usually calculate an effect-to-effect ratio. While not formally used in radiation protection, these iso-dose values may still be informative. Shuryak, et al 2017 investigated the use of an iso-dose metric termed "radiation effects ratio" (RER) and used both RBE and RER to estimate high-LET risks. To apply RBE or RER to risk prediction, the selected metric must be uniquely defined. That is, the calculated value must be consistent within a model given a constant set of constraints and assumptions, regardless of how effects are defined using statistical transformations from raw endpoint data. We first test the RBE and the RER to determine whether they are uniquely defined using transformations applied to raw data. Then, we test whether both metrics can predict heavy ion response data after simulated effect size scaling between human populations or when converting animal to human endpoints.

  8. Role of the standard deviation in the estimation of benchmark doses with continuous data.

    PubMed

    Gaylor, David W; Slikker, William

    2004-12-01

    For continuous data, risk is defined here as the proportion of animals with values above a large percentile, e.g., the 99th percentile or below the 1st percentile, for the distribution of values among control animals. It is known that reducing the standard deviation of measurements through improved experimental techniques will result in less stringent (higher) doses for the lower confidence limit on the benchmark dose that is estimated to produce a specified risk of animals with abnormal levels for a biological effect. Thus, a somewhat larger (less stringent) lower confidence limit is obtained that may be used as a point of departure for low-dose risk assessment. It is shown in this article that it is important for the benchmark dose to be based primarily on the standard deviation among animals, s(a), apart from the standard deviation of measurement errors, s(m), within animals. If the benchmark dose is incorrectly based on the overall standard deviation among average values for animals, which includes measurement error variation, the benchmark dose will be overestimated and the risk will be underestimated. The bias increases as s(m) increases relative to s(a). The bias is relatively small if s(m) is less than one-third of s(a), a condition achieved in most experimental designs.

  9. Validation of Monte Carlo simulation of mammography with TLD measurement and depth dose calculation with a detailed breast model

    NASA Astrophysics Data System (ADS)

    Wang, Wenjing; Qiu, Rui; Ren, Li; Liu, Huan; Wu, Zhen; Li, Chunyan; Li, Junli

    2017-09-01

    Mean glandular dose (MGD) is not only determined by the compressed breast thickness (CBT) and the glandular content, but also by the distribution of glandular tissues in breast. Depth dose inside the breast in mammography has been widely concerned as glandular dose decreases rapidly with increasing depth. In this study, an experiment using thermo luminescent dosimeters (TLDs) was carried out to validate Monte Carlo simulations of mammography. Percent depth doses (PDDs) at different depth values were measured inside simple breast phantoms of different thicknesses. The experimental values were well consistent with the values calculated by Geant4. Then a detailed breast model with a CBT of 4 cm and a glandular content of 50%, which has been constructed in previous work, was used to study the effects of the distribution of glandular tissues in breast with Geant4. The breast model was reversed in direction of compression to get a reverse model with a different distribution of glandular tissues. Depth dose distributions and glandular tissue dose conversion coefficients were calculated. It revealed that the conversion coefficients were about 10% larger when the breast model was reversed, for glandular tissues in the reverse model are concentrated in the upper part of the model.

  10. Assessment of radiation exposure in dental cone-beam computerized tomography with the use of metal-oxide semiconductor field-effect transistor (MOSFET) dosimeters and Monte Carlo simulations.

    PubMed

    Koivisto, J; Kiljunen, T; Tapiovaara, M; Wolff, J; Kortesniemi, M

    2012-09-01

    The aims of this study were to assess the organ and effective dose (International Commission on Radiological Protection (ICRP) 103) resulting from dental cone-beam computerized tomography (CBCT) imaging using a novel metal-oxide semiconductor field-effect transistor (MOSFET) dosimeter device, and to assess the reliability of the MOSFET measurements by comparing the results with Monte Carlo PCXMC simulations. Organ dose measurements were performed using 20 MOSFET dosimeters that were embedded in the 8 most radiosensitive organs in the maxillofacial and neck area. The dose-area product (DAP) values attained from CBCT scans were used for PCXMC simulations. The acquired MOSFET doses were then compared with the Monte Carlo simulations. The effective dose measurements using MOSFET dosimeters yielded, using 0.5-cm steps, a value of 153 μSv and the PCXMC simulations resulted in a value of 136 μSv. The MOSFET dosimeters placed in a head phantom gave results similar to Monte Carlo simulations. Minor vertical changes in the positioning of the phantom had a substantial affect on the overall effective dose. Therefore, the MOSFET dosimeters constitute a feasible method for dose assessment of CBCT units in the maxillofacial region. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Acceleration of intensity-modulated radiotherapy dose calculation by importance sampling of the calculation matrices.

    PubMed

    Thieke, Christian; Nill, Simeon; Oelfke, Uwe; Bortfeld, Thomas

    2002-05-01

    In inverse planning for intensity-modulated radiotherapy, the dose calculation is a crucial element limiting both the maximum achievable plan quality and the speed of the optimization process. One way to integrate accurate dose calculation algorithms into inverse planning is to precalculate the dose contribution of each beam element to each voxel for unit fluence. These precalculated values are stored in a big dose calculation matrix. Then the dose calculation during the iterative optimization process consists merely of matrix look-up and multiplication with the actual fluence values. However, because the dose calculation matrix can become very large, this ansatz requires a lot of computer memory and is still very time consuming, making it not practical for clinical routine without further modifications. In this work we present a new method to significantly reduce the number of entries in the dose calculation matrix. The method utilizes the fact that a photon pencil beam has a rapid radial dose falloff, and has very small dose values for the most part. In this low-dose part of the pencil beam, the dose contribution to a voxel is only integrated into the dose calculation matrix with a certain probability. Normalization with the reciprocal of this probability preserves the total energy, even though many matrix elements are omitted. Three probability distributions were tested to find the most accurate one for a given memory size. The sampling method is compared with the use of a fully filled matrix and with the well-known method of just cutting off the pencil beam at a certain lateral distance. A clinical example of a head and neck case is presented. It turns out that a sampled dose calculation matrix with only 1/3 of the entries of the fully filled matrix does not sacrifice the quality of the resulting plans, whereby the cutoff method results in a suboptimal treatment plan.

  12. TU-F-17A-08: The Relative Accuracy of 4D Dose Accumulation for Lung Radiotherapy Using Rigid Dose Projection Versus Dose Recalculation On Every Breathing Phase

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lamb, J; Lee, C; Tee, S

    2014-06-15

    Purpose: To investigate the accuracy of 4D dose accumulation using projection of dose calculated on the end-exhalation, mid-ventilation, or average intensity breathing phase CT scan, versus dose accumulation performed using full Monte Carlo dose recalculation on every breathing phase. Methods: Radiotherapy plans were analyzed for 10 patients with stage I-II lung cancer planned using 4D-CT. SBRT plans were optimized using the dose calculated by a commercially-available Monte Carlo algorithm on the end-exhalation 4D-CT phase. 4D dose accumulations using deformable registration were performed with a commercially available tool that projected the planned dose onto every breathing phase without recalculation, as wellmore » as with a Monte Carlo recalculation of the dose on all breathing phases. The 3D planned dose (3D-EX), the 3D dose calculated on the average intensity image (3D-AVE), and the 4D accumulations of the dose calculated on the end-exhalation phase CT (4D-PR-EX), the mid-ventilation phase CT (4D-PR-MID), and the average intensity image (4D-PR-AVE), respectively, were compared against the accumulation of the Monte Carlo dose recalculated on every phase. Plan evaluation metrics relating to target volumes and critical structures relevant for lung SBRT were analyzed. Results: Plan evaluation metrics tabulated using 4D-PR-EX, 4D-PR-MID, and 4D-PR-AVE differed from those tabulated using Monte Carlo recalculation on every phase by an average of 0.14±0.70 Gy, - 0.11±0.51 Gy, and 0.00±0.62 Gy, respectively. Deviations of between 8 and 13 Gy were observed between the 4D-MC calculations and both 3D methods for the proximal bronchial trees of 3 patients. Conclusions: 4D dose accumulation using projection without re-calculation may be sufficiently accurate compared to 4D dose accumulated from Monte Carlo recalculation on every phase, depending on institutional protocols. Use of 4D dose accumulation should be considered when evaluating normal tissue complication probabilities as well as in clinical situations where target volumes are directly inferior to mobile critical structures.« less

  13. In vivo diode dosimetry vs. computerized tomography and digitally reconstructed radiographs for critical organ dose calculation in high-dose-rate brachytherapy of cervical cancer.

    PubMed

    Hassouna, Ashraf H; Bahadur, Yasir A; Constantinescu, Camelia; El Sayed, Mohamed E; Naseem, Hussain; Naga, Adly F

    2011-01-01

    To investigate the correlation between the dose predicted by the treatment planning system using digitally reconstructed radiographs or three-dimensional (3D)-reconstructed CT images and the dose measured by semiconductor detectors, under clinical conditions of high-dose-rate brachytherapy of the cervix uteri. Thirty-two intracavitary brachytherapy applications were performed for 12 patients with cancer of the cervix uteri. The prescribed dose to Point A was 7 Gy. Dose was calculated for both International Commissioning on Radiation Units and Measurements (ICRU) bladder and rectal points based on digitally reconstructed radiographs and for 3D CT images-based volumetric calculation of the bladder and rectum. In vivo diode dosimetry was performed for the bladder and rectum. The ICRU reference point and the volumes of 1, 2, and 5cm(3) received 3.6±0.9, 5.6±2.0, 5.1±1.7, 4.3±1.4 and 5.0±1.2, 5.3±1.3, 4.9±1.1, and 4.2±0.9 Gy for the bladder and rectum, respectively. The ratio of the 1cm(3) and the ICRU reference point dose to the diode dose was 1.8±0.7 and 1.2±0.5 for the bladder and 1.9±0.6 and 1.7±0.5 for the rectum, respectively. 3D image-based dose calculation is the most accurate and reliable method to evaluate the dose given to critical organs. In vivo diode dosimetry is an important method of quality assurance, but clinical decisions should be made based on 3D-reconstructed CT image calculations. Copyright © 2011 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  14. Monte Carlo study of out-of-field exposure in carbon-ion radiotherapy with a passive beam: Organ doses in prostate cancer treatment.

    PubMed

    Yonai, Shunsuke; Matsufuji, Naruhiro; Akahane, Keiichi

    2018-04-23

    The aim of this work was to estimate typical dose equivalents to out-of-field organs during carbon-ion radiotherapy (CIRT) with a passive beam for prostate cancer treatment. Additionally, sensitivity analyses of organ doses for various beam parameters and phantom sizes were performed. Because the CIRT out-of-field dose depends on the beam parameters, the typical values of those parameters were determined from statistical data on the target properties of patients who received CIRT at the Heavy-Ion Medical Accelerator in Chiba (HIMAC). Using these typical beam-parameter values, out-of-field organ dose equivalents during CIRT for typical prostate treatment were estimated by Monte Carlo simulations using the Particle and Heavy-Ion Transport Code System (PHITS) and the ICRP reference phantom. The results showed that the dose decreased with distance from the target, ranging from 116 mSv in the testes to 7 mSv in the brain. The organ dose equivalents per treatment dose were lower than those either in 6-MV intensity-modulated radiotherapy or in brachytherapy with an Ir-192 source for organs within 40 cm of the target. Sensitivity analyses established that the differences from typical values were within ∼30% for all organs, except the sigmoid colon. The typical out-of-field organ dose equivalents during passive-beam CIRT were shown. The low sensitivity of the dose equivalent in organs farther than 20 cm from the target indicated that individual dose assessments required for retrospective epidemiological studies may be limited to organs around the target in cases of passive-beam CIRT for prostate cancer. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  15. Transatlantic Comparison of CT Radiation Doses in the Era of Radiation Dose-Tracking Software.

    PubMed

    Parakh, Anushri; Euler, Andre; Szucs-Farkas, Zsolt; Schindera, Sebastian T

    2017-12-01

    The purpose of this study is to compare diagnostic reference levels from a local European CT dose registry, using radiation-tracking software from a large patient sample, with preexisting European and North American diagnostic reference levels. Data (n = 43,761 CT scans obtained over the course of 2 years) for the European local CT dose registry were obtained from eight CT scanners at six institutions. Means, medians, and interquartile ranges of volumetric CT dose index (CTDI vol ), dose-length product (DLP), size-specific dose estimate, and effective dose values for CT examinations of the head, paranasal sinuses, thorax, pulmonary angiogram, abdomen-pelvis, renal-colic, thorax-abdomen-pelvis, and thoracoabdominal angiogram were obtained using radiation-tracking software. Metrics from this registry were compared with diagnostic reference levels from Canada and California (published in 2015), the American College of Radiology (ACR) dose index registry (2015), and national diagnostic reference levels from local CT dose registries in Switzerland (2010), the United Kingdom (2011), and Portugal (2015). Our local registry had a lower 75th percentile CTDI vol for all protocols than did the individual internationally sourced data. Compared with our study, the ACR dose index registry had higher 75th percentile CTDI vol values by 55% for head, 240% for thorax, 28% for abdomen-pelvis, 42% for thorax-abdomen-pelvis, 128% for pulmonary angiogram, 138% for renal-colic, and 58% for paranasal sinus studies. Our local registry had lower diagnostic reference level values than did existing European and North American diagnostic reference levels. Automated radiation-tracking software could be used to establish and update existing diagnostic reference levels because they are capable of analyzing large datasets meaningfully.

  16. Radiation Tests of the Extravehicular Mobility Unit Space Suit for the International Space Station Using Energetic Protons. Chapter 3

    NASA Technical Reports Server (NTRS)

    Zeitlin, C.; Heilbronn, L.; Miller, J.; Shavers, M.

    2003-01-01

    Measurements using silicon detectors to characterize the radiation transmitted through the EMU space suit and a human phantom have been performed using 155 and 250 MeV proton beams at LLUMC. The beams simulate radiation encountered in space, where trapped protons having kinetic energies on the order of 100 MeV are copious. Protons with 100 MeV kinetic energy and above can penetrate many centimeters of water or other light materials, so that astronauts exposed to such energetic particles will receive doses to their internal organs. This dose can be enhanced or reduced by shielding - either from the space suit or the self-shielding of the body - but minimization of the risk depends on details of the incident particle flux (in particular the energy spectrum) and on the dose responses of the various critical organs. Data were taken to characterize the beams and to calibrate the detectors using the beam in a treatment room at LLUPTF, in preparation for an experiment with the same beams incident on detectors placed in a human phantom within the EMU suit. Nuclear interactions of high-energy protons in various materials produce a small flux of highly ionizing, low-energy secondary radiation. Secondaries are of interest for their biological effects, since they cause doses and especially dose-equivalents to increase relative to the values expected simply from ionization energy loss along the Bragg curve. Because many secondaries have very short ranges, they are best measured in passive track detectors such as CR-39. The silicon detector data presented here are intended to supplement the CR-39 data in regions where silicon has greater sensitivity, in particular the portion of the LET spectrum below 5 keV/micron. The results obtained in this study suggest that optimizing the radiation shielding properties of space suits is a formidable task. The naive assumption that adding mass can reduce risk is not supported by the data, which show that reducing the dose delivered at or near the skin by low-energy particles may increase the dose delivered by energetic particles to points deeper in the body.

  17. Cumulative radiation dose caused by radiologic studies in critically ill trauma patients.

    PubMed

    Kim, Patrick K; Gracias, Vicente H; Maidment, Andrew D A; O'Shea, Michael; Reilly, Patrick M; Schwab, C William

    2004-09-01

    Critically ill trauma patients undergo many radiologic studies, but the cumulative radiation dose is unknown. The purpose of this study was to estimate the cumulative effective dose (CED) of radiation resulting from radiologic studies in critically ill trauma patients. The study group was composed of trauma patients at an urban Level I trauma center with surgical intensive care unit length of stay (LOS) greater than 30 days. The radiology records were reviewed. A typical effective dose per study for each type of plain film radiograph, computed tomographic scan, fluoroscopic study, and nuclear medicine study was used to calculate CED. Forty-six patients met criteria. The mean surgical intensive care unit and hospital LOS were 42.7 +/- 14.0 and 59.5 +/- 28.5 days, respectively. The mean Injury Severity Score was 32.2 +/- 15.0. The mean number of studies per patient was 70.1 +/- 29.0 plain film radiographs, 7.8 +/- 4.1 computed tomographic scans, 2.5 +/- 2.6 fluoroscopic studies, and 0.065 +/- 0.33 nuclear medicine study. The mean CED was 106 +/- 59 mSv per patient (range, 11-289 mSv; median, 104 mSv). Among age, mechanism, Injury Severity Score, and LOS, there was no statistically significant predictor of high CED. The mean CED in the study group was 30 times higher than the average yearly radiation dose from all sources for individuals in the United States. The theoretical additional morbidity attributable to radiologic studies was 0.78%. From a radiobiologic perspective, risk-to-benefit ratios of radiologic studies are favorable, given the importance of medical information obtained. Current practice patterns regarding use of radiologic studies appear to be acceptable.

  18. Influence of jaw tracking in intensity-modulated and volumetric-modulated arc radiotherapy for head and neck cancers: a dosimetric study.

    PubMed

    Mani, Karthick Raj; Upadhayay, Sagar; Das, K J Maria

    2017-03-01

    To Study the dosimetric advantage of the Jaw tracking technique in intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for Head and Neck Cancers. We retrospectively selected 10 previously treated head and neck cancer patients stage (T1/T2, N1, M0) in this study. All the patients were planned for IMRT and VMAT with simultaneous integrated boost technique. IMRT and VMAT plans were performed with jaw tracking (JT) and with static jaw (SJ) technique by keeping the same constraints and priorities for a particular patient. Target conformity, dose to the critical structures and low dose volumes were recorded and analyzed for IMRT and VMAT plans with and without JT for all the patients. The conformity index average of all patients followed by standard deviation ([Formula: see text] ± [Formula: see text]) of the JT-IMRT, SJ-IMRT, JT-VMAT, and SJ-VMAT were 1.72 ± 0.56, 1.67 ± 0.57, 1.83 ± 0.65, and 1.85 ± 0.64, and homogeneity index were 0.059 ± 0.05, 0.064 ± 0.05, 0.064 ± 0.04, and 0.064 ± 0.05. JT-IMRT shows significant mean reduction in right parotid and left parotid shows of 7.64% (p < 0.001) and 7.45% (p < 0.001) compare to SJ-IMRT. JT-IMRT plans also shows considerable dose reduction to thyroid, inferior constrictors, spinal cord and brainstem compared to the SJ-IMRT plans. Significant dose reductions were observed for critical structure in the JT-IMRT compared to SJ-IMRT technique. In JT-VMAT plans dose reduction to the critical structure were not significant compared to the SJ-IMRT due to relatively lesser monitor units.

  19. Vitamin C revisited.

    PubMed

    Oudemans-van Straaten, Heleen M; Spoelstra-de Man, Angelique Me; de Waard, Monique C

    2014-08-06

    This narrative review summarizes the role of vitamin C in mitigating oxidative injury-induced microcirculatory impairment and associated organ failure in ischemia/reperfusion or sepsis. Preclinical studies show that high-dose vitamin C can prevent or restore microcirculatory flow impairment by inhibiting activation of nicotinamide adenine dinucleotide phosphate-oxidase and inducible nitric oxide synthase, augmenting tetrahydrobiopterin, preventing uncoupling of oxidative phosphorylation, and decreasing the formation of superoxide and peroxynitrite, and by directly scavenging superoxide. Vitamin C can additionally restore vascular responsiveness to vasoconstrictors, preserve endothelial barrier by maintaining cyclic guanylate phosphatase and occludin phosphorylation and preventing apoptosis. Finally, high-dose vitamin C can augment antibacterial defense. These protective effects against overwhelming oxidative stress due to ischemia/reperfusion, sepsis or burn seems to mitigate organ injury and dysfunction, and promote recovery after cardiac revascularization and in critically ill patients, in the latter partially in combination with other antioxidants. Of note, several questions remain to be solved, including optimal dose, timing and combination of vitamin C with other antioxidants. The combination obviously offers a synergistic effect and seems reasonable during sustained critical illness. High-dose vitamin C, however, provides a cheap, strong and multifaceted antioxidant, especially robust for resuscitation of the circulation. Vitamin C given as early as possible after the injurious event, or before if feasible, seems most effective. The latter could be considered at the start of cardiac surgery, organ transplant or major gastrointestinal surgery. Preoperative supplementation should consider the inhibiting effect of vitamin C on ischemic preconditioning. In critically ill patients, future research should focus on the use of short-term high-dose intravenous vitamin C as a resuscitation drug, to intervene as early as possible in the oxidant cascade in order to optimize macrocirculation and microcirculation and limit cellular injury.

  20. Limitations of the planning organ at risk volume (PRV) concept.

    PubMed

    Stroom, Joep C; Heijmen, Ben J M

    2006-09-01

    Previously, we determined a planning target volume (PTV) margin recipe for geometrical errors in radiotherapy equal to M(T) = 2 Sigma + 0.7 sigma, with Sigma and sigma standard deviations describing systematic and random errors, respectively. In this paper, we investigated margins for organs at risk (OAR), yielding the so-called planning organ at risk volume (PRV). For critical organs with a maximum dose (D(max)) constraint, we calculated margins such that D(max) in the PRV is equal to the motion averaged D(max) in the (moving) clinical target volume (CTV). We studied margins for the spinal cord in 10 head-and-neck cases and 10 lung cases, each with two different clinical plans. For critical organs with a dose-volume constraint, we also investigated whether a margin recipe was feasible. For the 20 spinal cords considered, the average margin recipe found was: M(R) = 1.6 Sigma + 0.2 sigma with variations for systematic and random errors of 1.2 Sigma to 1.8 Sigma and -0.2 sigma to 0.6 sigma, respectively. The variations were due to differences in shape and position of the dose distributions with respect to the cords. The recipe also depended significantly on the volume definition of D(max). For critical organs with a dose-volume constraint, the PRV concept appears even less useful because a margin around, e.g., the rectum changes the volume in such a manner that dose-volume constraints stop making sense. The concept of PRV for planning of radiotherapy is of limited use. Therefore, alternative ways should be developed to include geometric uncertainties of OARs in radiotherapy planning.

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