Limiting CT radiation dose in children with craniosynostosis: phantom study using model-based iterative reconstruction.

PubMed

Kaasalainen, Touko; Palmu, Kirsi; Lampinen, Anniina; Reijonen, Vappu; Leikola, Junnu; Kivisaari, Riku; Kortesniemi, Mika

2015-09-01

Medical professionals need to exercise particular caution when developing CT scanning protocols for children who require multiple CT studies, such as those with craniosynostosis. To evaluate the utility of ultra-low-dose CT protocols with model-based iterative reconstruction techniques for craniosynostosis imaging. We scanned two pediatric anthropomorphic phantoms with a 64-slice CT scanner using different low-dose protocols for craniosynostosis. We measured organ doses in the head region with metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters. Numerical simulations served to estimate organ and effective doses. We objectively and subjectively evaluated the quality of images produced by adaptive statistical iterative reconstruction (ASiR) 30%, ASiR 50% and Veo (all by GE Healthcare, Waukesha, WI). Image noise and contrast were determined for different tissues. Mean organ dose with the newborn phantom was decreased up to 83% compared to the routine protocol when using ultra-low-dose scanning settings. Similarly, for the 5-year phantom the greatest radiation dose reduction was 88%. The numerical simulations supported the findings with MOSFET measurements. The image quality remained adequate with Veo reconstruction, even at the lowest dose level. Craniosynostosis CT with model-based iterative reconstruction could be performed with a 20-μSv effective dose, corresponding to the radiation exposure of plain skull radiography, without compromising required image quality.

Evidence for Dose-Additive Effects of Pyrethroids on Motor Activity in Rats

PubMed Central

Wolansky, Marcelo J.; Gennings, Chris; DeVito, Michael J.; Crofton, Kevin M.

2009-01-01

Background Pyrethroids are neurotoxic insecticides used in a variety of indoor and outdoor applications. Previous research characterized the acute dose–effect functions for 11 pyrethroids administered orally in corn oil (1 mL/kg) based on assessment of motor activity. Objectives We used a mixture of these 11 pyrethroids and the same testing paradigm used in single-compound assays to test the hypothesis that cumulative neurotoxic effects of pyrethroid mixtures can be predicted using the default dose–addition theory. Methods Mixing ratios of the 11 pyrethroids in the tested mixture were based on the ED30 (effective dose that produces a 30% decrease in response) of the individual chemical (i.e., the mixture comprised equipotent amounts of each pyrethroid). The highest concentration of each individual chemical in the mixture was less than the threshold for inducing behavioral effects. Adult male rats received acute oral exposure to corn oil (control) or dilutions of the stock mixture solution. The mixture of 11 pyrethroids was administered either simultaneously (2 hr before testing) or after a sequence based on times of peak effect for the individual chemicals (4, 2, and 1 hr before testing). A threshold additivity model was fit to the single-chemical data to predict the theoretical dose–effect relationship for the mixture under the assumption of dose additivity. Results When subthreshold doses of individual chemicals were combined in the mixtures, we found significant dose-related decreases in motor activity. Further, we found no departure from the predicted dose-additive curve regardless of the mixture dosing protocol used. Conclusion In this article we present the first in vivo evidence on pyrethroid cumulative effects supporting the default assumption of dose addition. PMID:20019907

SU-E-T-109: An Investigation of Including Variable Relative Biological Effectiveness in Intensity Modulated Proton Therapy Planning Optimization for Head and Neck Cancer Patients

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

Cao, W; Zaghian, M; Lim, G

2015-06-15

Purpose: The current practice of considering the relative biological effectiveness (RBE) of protons in intensity modulated proton therapy (IMPT) planning is to use a generic RBE value of 1.1. However, RBE is indeed a variable depending on the dose per fraction, the linear energy transfer, tissue parameters, etc. In this study, we investigate the impact of using variable RBE based optimization (vRBE-OPT) on IMPT dose distributions compared by conventional fixed RBE based optimization (fRBE-OPT). Methods: Proton plans of three head and neck cancer patients were included for our study. In order to calculate variable RBE, tissue specific parameters were obtainedmore » from the literature and dose averaged LET values were calculated by Monte Carlo simulations. Biological effects were calculated using the linear quadratic model and they were utilized in the variable RBE based optimization. We used a Polak-Ribiere conjugate gradient algorithm to solve the model. In fixed RBE based optimization, we used conventional physical dose optimization to optimize doses weighted by 1.1. IMPT plans for each patient were optimized by both methods (vRBE-OPT and fRBE-OPT). Both variable and fixed RBE weighted dose distributions were calculated for both methods and compared by dosimetric measures. Results: The variable RBE weighted dose distributions were more homogenous within the targets, compared with the fixed RBE weighted dose distributions for the plans created by vRBE-OPT. We observed that there were noticeable deviations between variable and fixed RBE weighted dose distributions if the plan were optimized by fRBE-OPT. For organs at risk sparing, dose distributions from both methods were comparable. Conclusion: Biological dose based optimization rather than conventional physical dose based optimization in IMPT planning may bring benefit in improved tumor control when evaluating biologically equivalent dose, without sacrificing OAR sparing, for head and neck cancer patients. The research is supported in part by National Institutes of Health Grant No. 2U19CA021239-35.« less

Fluence-to-dose conversion coefficients for heavy ions calculated using the PHITS code and the ICRP/ICRU adult reference computational phantoms.

PubMed

Sato, Tatsuhiko; Endo, Akira; Niita, Koji

2010-04-21

The fluence to organ-absorbed-dose and effective-dose conversion coefficients for heavy ions with atomic numbers up to 28 and energies from 1 MeV/nucleon to 100 GeV/nucleon were calculated using the PHITS code coupled to the ICRP/ICRU adult reference computational phantoms, following the instruction given in ICRP Publication 103 (2007 (Oxford: Pergamon)). The conversion coefficients for effective dose equivalents derived using the radiation quality factors of both Q(L) and Q(y) relationships were also estimated, utilizing the functions for calculating the probability densities of absorbed dose in terms of LET (L) and lineal energy (y), respectively, implemented in PHITS. The calculation results indicate that the effective dose can generally give a conservative estimation of the effective dose equivalent for heavy-ion exposure, although it is occasionally too conservative especially for high-energy lighter-ion irradiations. It is also found from the calculation that the conversion coefficients for the Q(y)-based effective dose equivalents are generally smaller than the corresponding Q(L)-based values because of the conceptual difference between LET and y as well as the numerical incompatibility between the Q(L) and Q(y) relationships. The calculated data of these dose conversion coefficients are very useful for the dose estimation of astronauts due to cosmic-ray exposure.

Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies.

PubMed

Silva-Rodríguez, Jesús; Aguiar, Pablo; Sánchez, Manuel; Mosquera, Javier; Luna-Vega, Víctor; Cortés, Julia; Garrido, Miguel; Pombar, Miguel; Ruibal, Alvaro

2014-05-01

Current procedure guidelines for whole body [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) state that studies with visible dose extravasations should be rejected for quantification protocols. Our work is focused on the development and validation of methods for estimating extravasated doses in order to correct standard uptake value (SUV) values for this effect in clinical routine. One thousand three hundred sixty-seven consecutive whole body FDG-PET studies were visually inspected looking for extravasation cases. Two methods for estimating the extravasated dose were proposed and validated in different scenarios using Monte Carlo simulations. All visible extravasations were retrospectively evaluated using a manual ROI based method. In addition, the 50 patients with higher extravasated doses were also evaluated using a threshold-based method. Simulation studies showed that the proposed methods for estimating extravasated doses allow us to compensate the impact of extravasations on SUV values with an error below 5%. The quantitative evaluation of patient studies revealed that paravenous injection is a relatively frequent effect (18%) with a small fraction of patients presenting considerable extravasations ranging from 1% to a maximum of 22% of the injected dose. A criterion based on the extravasated volume and maximum concentration was established in order to identify this fraction of patients that might be corrected for paravenous injection effect. The authors propose the use of a manual ROI based method for estimating the effectively administered FDG dose and then correct SUV quantification in those patients fulfilling the proposed criterion.

Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies

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

Silva-Rodríguez, Jesús, E-mail: jesus.silva.rodriguez@sergas.es; Aguiar, Pablo, E-mail: pablo.aguiar.fernandez@sergas.es; Servicio de Medicina Nuclear, Complexo Hospitalario Universidade de Santiago de Compostela

Purpose: Current procedure guidelines for whole body [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) state that studies with visible dose extravasations should be rejected for quantification protocols. Our work is focused on the development and validation of methods for estimating extravasated doses in order to correct standard uptake value (SUV) values for this effect in clinical routine. Methods: One thousand three hundred sixty-seven consecutive whole body FDG-PET studies were visually inspected looking for extravasation cases. Two methods for estimating the extravasated dose were proposed and validated in different scenarios using Monte Carlo simulations. All visible extravasations were retrospectively evaluated using a manualmore » ROI based method. In addition, the 50 patients with higher extravasated doses were also evaluated using a threshold-based method. Results: Simulation studies showed that the proposed methods for estimating extravasated doses allow us to compensate the impact of extravasations on SUV values with an error below 5%. The quantitative evaluation of patient studies revealed that paravenous injection is a relatively frequent effect (18%) with a small fraction of patients presenting considerable extravasations ranging from 1% to a maximum of 22% of the injected dose. A criterion based on the extravasated volume and maximum concentration was established in order to identify this fraction of patients that might be corrected for paravenous injection effect. Conclusions: The authors propose the use of a manual ROI based method for estimating the effectively administered FDG dose and then correct SUV quantification in those patients fulfilling the proposed criterion.« less

New approach to CT pixel-based photon dose calculations in heterogeneous media

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

Wong, J.W.; Henkelman, R.M.

The effects of small cavities on dose in water and the dose in a homogeneous nonunit density medium illustrate that inhomogeneities do not act independently in photon dose perturbation, and serve as two constraints which should be satisfied by approximate methods of computed tomography (CT) pixel-based dose calculations. Current methods at best satisfy only one of the two constraints and show inadequacies in some intermediate geometries. We have developed an approximate method that satisfies both these constraints and treats much of the synergistic effect of multiple inhomogeneities correctly. The method calculates primary and first-scatter doses by first-order ray tracing withmore » the first-scatter contribution augmented by a component of second scatter that behaves like first scatter. Multiple-scatter dose perturbation values extracted from small cavity experiments are used in a function which approximates the small residual multiple-scatter dose. For a wide range of geometries tested, our method agrees very well with measurements. The average deviation is less than 2% with a maximum of 3%. In comparison, calculations based on existing methods can have errors larger than 10%.« less

Dose Relations between Goal Setting, Theory-Based Correlates of Goal Setting and Increases in Physical Activity during a Workplace Trial

ERIC Educational Resources Information Center

Dishman, Rod K.; Vandenberg, Robert J.; Motl, Robert W.; Wilson, Mark G.; DeJoy, David M.

2010-01-01

The effectiveness of an intervention depends on its dose and on moderators of dose, which usually are not studied. The purpose of the study is to determine whether goal setting and theory-based moderators of goal setting had dose relations with increases in goal-related physical activity during a successful workplace intervention. A…

Current Status and Future Challenges in Risk-Based Radiation Engineering

NASA Technical Reports Server (NTRS)

Pellish, Jonathan A.

2017-01-01

This presentation covers the basis and challenges for radiation effects in electronic systems. The three main types of radiation effects in electronics are: 1) total ionizing dose (TID), 2) total non-ionizing dose (TNID) / displacement damage dose (DDD), and 3) single-event effect (SEE). Some content on relevant examples of effects, current concerns, and possible environmental model-driven solutions are also included.

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.

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.

Comparison of 2-Dose and 3-Dose 9-Valent Human Papillomavirus Vaccine Schedules in the United States: A Cost-effectiveness Analysis.

PubMed

Laprise, Jean-François; Markowitz, Lauri E; Chesson, Harrell W; Drolet, Mélanie; Brisson, Marc

2016-09-01

A recent clinical trial using the 9-valent human papillomavirus virus (HPV) vaccine has shown that antibody responses after 2 doses are noninferior to those after 3 doses, suggesting that 2 and 3 doses may have comparable vaccine efficacy. We used an individual-based transmission-dynamic model to compare the population-level effectiveness and cost-effectiveness of 2- and 3-dose schedules of 9-valent HPV vaccine in the United States. Our model predicts that if 2 doses of 9-valent vaccine protect for ≥20 years, the additional benefits of a 3-dose schedule are small as compared to those of 2-dose schedules, and 2-dose schedules are likely much more cost-efficient than 3-dose schedules. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Dose-dependent EEG effects of zolpidem provide evidence for GABA(A) receptor subtype selectivity in vivo.

PubMed

Visser, S A G; Wolters, F L C; van der Graaf, P H; Peletier, L A; Danhof, M

2003-03-01

Zolpidem is a nonbenzodiazepine GABA(A) receptor modulator that binds in vitro with high affinity to GABA(A) receptors expressing alpha(1) subunits but with relatively low affinity to receptors expressing alpha(2), alpha(3), and alpha(5) subunits. In the present study, it was investigated whether this subtype selectivity could be detected and quantified in vivo. Three doses (1.25, 5, and 25 mg) of zolpidem were administered to rats in an intravenous infusion over 5 min. The time course of the plasma concentrations was determined in conjunction with the change in the beta-frequency range of the EEG as pharmacodynamic endpoint. The concentration-effect relationship of the three doses showed a dose-dependent maximum effect and a dose-dependent potency. The data were analyzed for one- or two-site binding using two pharmacodynamic models based on 1) the descriptive model and 2) a novel mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for GABA(A) receptor modulators that aims to separates drug- and system-specific properties, thereby allowing the estimation of in vivo affinity and efficacy. The application of two-site models significantly improved the fits compared with one-site models. Furthermore, in contrast to the descriptive model, the mechanism-based PK/PD model yielded dose-independent estimates for affinity (97 +/- 40 and 33,100 +/- 14,800 ng x ml(-1)). In conclusion, the mechanism-based PK/PD model is able to describe and explain the observed dose-dependent EEG effects of zolpidem and suggests the subtype selectivity of zolpidem in vivo.

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

ERIC Educational Resources Information Center

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

2009-01-01

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

SU-F-T-372: Surface and Peripheral Dose in Compensator-Based FFF Beam IMRT

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

Zhang, D; Feygelman, V; Moros, E

2016-06-15

Purpose: Flattening filter free (FFF) beams produce higher dose rates. Combined with compensator IMRT techniques, the dose delivery for each beam can be much shorter compared to the flattened beam MLC-based or compensator-based IMRT. This ‘snap shot’ IMRT delivery is beneficial to patients for tumor motion management. Due to softer energy, surface doses in FFF beam treatment are usually higher than those from flattened beams. Because of less scattering due to no flattening filter, peripheral doses are usually lower in FFF beam treatment. However, in compensator-based IMRT using FFF beams, the compensator is in the beam pathway. Does it introducemore » beam hardening effects and scattering such that the surface dose is lower and peripheral dose is higher compared to FFF beam MLC-based IMRT? Methods: This study applied Monte Carlo techniques to investigate the surface and peripheral doses in compensator-based IMRT using FFF beams and compared it to the MLC-based IMRT using FFF beams and flattened beams. Besides various thicknesses of copper slabs to simulate various thicknesses of compensators, a simple cone-shaped compensator was simulated to mimic a clinical application. The dose distribution in water phantom by the cone-shaped compensator was then simulated by multiple MLC defined FFF and flattened beams with various openings. After normalized to Dmax, the surface and peripheral dose was compared between the FFF beam compensator-based IMRT and FFF/flattened beam MLC-based IMRT. Results: The surface dose at the central 0.5mm depth was close between the compensator and 6FFF MLC dose distributions, and about 8% (of Dmax) higher than the flattened 6MV MLC dose. At 8cm off axis at dmax, the peripheral dose between the 6FFF and flattened 6MV MLC demonstrated similar doses, while the compensator dose was about 1% higher. Conclusion: Compensator does not reduce the surface doses but slightly increases the peripheral doses due to scatter inside compensator.« less

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

NASA Astrophysics Data System (ADS)

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

2003-08-01

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

Hybrid dose calculation: a dose calculation algorithm for microbeam radiation therapy

NASA Astrophysics Data System (ADS)

Donzelli, Mattia; Bräuer-Krisch, Elke; Oelfke, Uwe; Wilkens, Jan J.; Bartzsch, Stefan

2018-02-01

Microbeam radiation therapy (MRT) is still a preclinical approach in radiation oncology that uses planar micrometre wide beamlets with extremely high peak doses, separated by a few hundred micrometre wide low dose regions. Abundant preclinical evidence demonstrates that MRT spares normal tissue more effectively than conventional radiation therapy, at equivalent tumour control. In order to launch first clinical trials, accurate and efficient dose calculation methods are an inevitable prerequisite. In this work a hybrid dose calculation approach is presented that is based on a combination of Monte Carlo and kernel based dose calculation. In various examples the performance of the algorithm is compared to purely Monte Carlo and purely kernel based dose calculations. The accuracy of the developed algorithm is comparable to conventional pure Monte Carlo calculations. In particular for inhomogeneous materials the hybrid dose calculation algorithm out-performs purely convolution based dose calculation approaches. It is demonstrated that the hybrid algorithm can efficiently calculate even complicated pencil beam and cross firing beam geometries. The required calculation times are substantially lower than for pure Monte Carlo calculations.

Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs.

PubMed Central

Brouwer, A; Longnecker, M P; Birnbaum, L S; Cogliano, J; Kostyniak, P; Moore, J; Schantz, S; Winneke, G

1999-01-01

This article addresses issues related to the characterization of endocrine-related health effects resulting from low-level exposures to polychlorinated biphenyls (PCBs). It is not intended to be a comprehensive review of the literature but reflects workshop discussions. "The Characterizing the Effects of Endocrine Disruptors on Human Health at Environmental Exposure Levels," workshop provided a forum to discuss the methods and data needed to improve risk assessments of endocrine disruptors. This article contains an overview of endocrine-related (estrogen and thyroid system) interactions and other low-dose effects of PCBs. The data set on endocrine effects includes results obtained from mechanistic methods/ and models (receptor based, metabolism based, and transport protein based), as well as from (italic)in vivo(/italic) models, including studies with experimental animals and wildlife species. Other low-dose effects induced by PCBs, such as neurodevelopmental and reproductive effects and endocrine-sensitive tumors, have been evaluated with respect to a possible causative linkage with PCB-induced alterations in endocrine systems. In addition, studies of low-dose exposure and effects in human populations are presented and critically evaluated. A list of conclusions and recommendations is included. PMID:10421775

TEMIS UV product validation using NILU-UV ground-based measurements in Thessaloniki, Greece

NASA Astrophysics Data System (ADS)

Zempila, Melina-Maria; van Geffen, Jos H. G. M.; Taylor, Michael; Fountoulakis, Ilias; Koukouli, Maria-Elissavet; van Weele, Michiel; van der A, Ronald J.; Bais, Alkiviadis; Meleti, Charikleia; Balis, Dimitrios

2017-06-01

This study aims to cross-validate ground-based and satellite-based models of three photobiological UV effective dose products: the Commission Internationale de l'Éclairage (CIE) erythemal UV, the production of vitamin D in the skin, and DNA damage, using high-temporal-resolution surface-based measurements of solar UV spectral irradiances from a synergy of instruments and models. The satellite-based Tropospheric Emission Monitoring Internet Service (TEMIS; version 1.4) UV daily dose data products were evaluated over the period 2009 to 2014 with ground-based data from a Norsk Institutt for Luftforskning (NILU)-UV multifilter radiometer located at the northern midlatitude super-site of the Laboratory of Atmospheric Physics, Aristotle University of Thessaloniki (LAP/AUTh), in Greece. For the NILU-UV effective dose rates retrieval algorithm, a neural network (NN) was trained to learn the nonlinear functional relation between NILU-UV irradiances and collocated Brewer-based photobiological effective dose products. Then the algorithm was subjected to sensitivity analysis and validation. The correlation of the NN estimates with target outputs was high (r = 0. 988 to 0.990) and with a very low bias (0.000 to 0.011 in absolute units) proving the robustness of the NN algorithm. For further evaluation of the NILU NN-derived products, retrievals of the vitamin D and DNA-damage effective doses from a collocated Yankee Environmental Systems (YES) UVB-1 pyranometer were used. For cloud-free days, differences in the derived UV doses are better than 2 % for all UV dose products, revealing the reference quality of the ground-based UV doses at Thessaloniki from the NILU-UV NN retrievals. The TEMIS UV doses used in this study are derived from ozone measurements by the SCIAMACHY/Envisat and GOME2/MetOp-A satellite instruments, over the European domain in combination with SEVIRI/Meteosat-based diurnal cycle of the cloud cover fraction per 0. 5° × 0. 5° (lat × long) grid cells. TEMIS UV doses were found to be ˜ 12.5 % higher than the NILU NN estimates but, despite the presence of a visually apparent seasonal pattern, the R2 values were found to be robustly high and equal to 0.92-0.93 for 1588 all-sky coincidences. These results significantly improve when limiting the dataset to cloud-free days with differences of 0.57 % for the erythemal doses, 1.22 % for the vitamin D doses, and 1.18 % for the DNA-damage doses, with standard deviations of the order of 11-13 %. The improvement of the comparative statistics under cloud-free cases further testifies to the importance of the appropriate consideration of the contribution of clouds in the UV radiation reaching the Earth's surface. For the urban area of Thessaloniki, with highly variable aerosol, the weakness of the implicit aerosol information introduced to the TEMIS UV dose algorithm was revealed by comparison of the datasets to aerosol optical depths at 340 nm as reported by a collocated CIMEL sun photometer, operating in Thessaloniki at LAP/AUTh as part of the NASA Aerosol Robotic Network.

Contrast enema as a guide for senna-based laxatives in managing overflow retentive stool incontinence in pediatrics.

PubMed

Radwan, Ahmed Bassiuony; El-Debeiky, Mohammed Soliman; Abdel-Hay, Sameh

2015-08-01

Overflow retentive stool incontinence (ORSI) is secondary to constipation and fecal loading. In our study, the dose and duration of senna-based laxatives (SBL) treatment to achieve full defecatory control will be examined for possible correlation with new parameters measured from the initial contrast enema. Initially, an observational study was conducted prospectively on a group of patient with ORSI to define the optimum dose of SBL to achieve full defecatory control with measurement of six parameters in the initial contrast enema (level of colonic dilatation, recto-anal angle, ratio of maximal diameter of dilated colon to last lumbar spine, ratio of maximum diameter of dilated colon to normal descending colon, immediate and after 24-h post-evacuation residual contrast). The result was analyzed statistically to reach a correlation between the radiological data and prescribed dose. Over 2 and half years, 72 patients were included in the study; their mean age was 6.3 ± 3.33 years. The mean effective starting dose of SBL was 57 ± 18.13 mg/day and the mean effective ending dose was 75 ± 31.68 mg/day. Time lapsed till full defecatory control ranged from 1 to 16 weeks. Statistical correlation revealed that mean effective ending dose of SBL treatment significantly increased with higher levels of colonic dilatation. A weak positive correlation was found for both the mean effective starting and ending doses with the ratio of maximum colonic diameter to last lumbar spine and descending colonic diameters ratio. Senna-based laxatives are effective treatment for overflow retentive stool incontinence and their doses can be adjusted initially depending on the analysis of the radiological data.

Radiation-Induced Carcinogenesis: Mechanistically Based Differences between Gamma-Rays and Neutrons, and Interactions with DMBA

PubMed Central

Shuryak, Igor; Brenner, David J.; Ullrich, Robert L.

2011-01-01

Different types of ionizing radiation produce different dependences of cancer risk on radiation dose/dose rate. Sparsely ionizing radiation (e.g. γ-rays) generally produces linear or upwardly curving dose responses at low doses, and the risk decreases when the dose rate is reduced (direct dose rate effect). Densely ionizing radiation (e.g. neutrons) often produces downwardly curving dose responses, where the risk initially grows with dose, but eventually stabilizes or decreases. When the dose rate is reduced, the risk increases (inverse dose rate effect). These qualitative differences suggest qualitative differences in carcinogenesis mechanisms. We hypothesize that the dominant mechanism for induction of many solid cancers by sparsely ionizing radiation is initiation of stem cells to a pre-malignant state, but for densely ionizing radiation the dominant mechanism is radiation-bystander-effect mediated promotion of already pre-malignant cell clone growth. Here we present a mathematical model based on these assumptions and test it using data on the incidence of dysplastic growths and tumors in the mammary glands of mice exposed to high or low dose rates of γ-rays and neutrons, either with or without pre-treatment with the chemical carcinogen 7,12-dimethylbenz-alpha-anthracene (DMBA). The model provides a mechanistic and quantitative explanation which is consistent with the data and may provide useful insight into human carcinogenesis. PMID:22194850

Proteomic and Epigenetic Analysis of Rice after Seed Spaceflight and Ground-Base Ion Radiations

NASA Astrophysics Data System (ADS)

Wang, Wei; Sun, Yeqing; Peng, Yuming; Zhao, Qian; Wen, Bin; Yang, Jun

Highly ionizing radiation (HZE) in space is considered as main factor causing biological effects to plant seeds. In previous work, we compared the proteomic profiles of rice plants growing after seed spaceflights to ground controls by two-dimensional difference gel electrophoresis (2-D DIGE) with mass spectrometry and found that the protein expression profiles were changed and differentially expressed proteins participated in most of the biological processes of rice. To further evaluate the dosage effects of space radiation and compare between low- and high-dose ion effects, we carried out three independent ground-base ionizing radiation experiments with different cumulative doses (low-dose range: 2~1000mGy, high-dose range: 2000~20000mGy) to rice seeds and performed proteomic analysis of seedlings. We found that protein expression profiles showed obvious boundaries between low- and high-dose radiation groups. Rates of differentially expressed proteins presented a dose-dependent effect, it reached the highest value at 2000mGy dosage point in all three radiation experiments coincidently; while proteins responded to low-dose radiations preferred to change their expressions at the minimum dosage (2mGy). Proteins participating in rice biological processes also responded differently between low- and high-dose radiations: proteins involved in energy metabolism and photosynthesis tended to be regulated after low-dose radiations while stress responding, protein folding and cell redox homeostasis related proteins preferred to change their expressions after high-dose radiations. By comparing the proteomic profiles between ground-base radiations and spaceflights, it was worth noting that ground-base low-dose ion radiation effects shared similar biological effects as space environment. In addition, we discovered that protein nucleoside diphosphate kinase 1 (NDPK1) showed obvious increased regulation after spaceflights and ion radiations. NDPK1 catalyzes nucleotide metabolism and is reported to be involved in DNA repair process. Its expression sensitivity and specificity were confirmed by RT-PCR and western blot analysis, indicating its potential to be used as space radiation biomarker. Space radiations might induce epigenetic effects on rice plants, especially changes of DNA methylation. Early results suggested that there were correlations between DNA methylation polymorphic and genomic mutation rates. In addition, the 5-methylcytosine located in coding gene’s promoter and exon regions could regulate gene expressions thus influence protein expressions. So whether there is correlation between genome DNA methylation changes and protein expression profile alterations caused by space radiation is worth for further investigation. Therefore we used the same rice samples treated by carbon ion radiation with different doses (0, 10, 20,100, 200, 1000, 2000, 5000, 20000mGy) and applied methylation sensitive amplification polymorphism (MSAP) for scanning genome DNA methylation changes. Interestingly, DNA methylation polymorphism rates also presented a dose-dependent effect and showed the same changing trend as rates of differentially expressed proteins. Whether there are correlations between epigenetic and proteomic effects of space radiation is worth for further investigation.

A test-based strategy is more cost effective than empiric dose escalation for patients with Crohn's disease who lose responsiveness to infliximab.

PubMed

Velayos, Fernando S; Kahn, James G; Sandborn, William J; Feagan, Brian G

2013-06-01

Patients with Crohn's disease who become unresponsive to therapy with tumor necrosis factor antagonists are managed initially with either empiric dose escalation or testing-based strategies. The comparative cost effectiveness of these 2 strategies is unknown. We investigated whether a testing-based strategy is more cost effective than an empiric dose-escalation strategy. A decision analytic model that simulated 2 cohorts of patients with Crohn's disease compared outcomes for the 2 strategies over a 1-year time period. The incremental cost-effectiveness ratio of the empiric strategy was expressed as cost per quality-adjusted life-year (QALY) gained, compared with the testing-based strategy. We performed 1-way, probabilistic, and prespecified secondary analyses. The testing strategy yielded similar QALYs compared with the empiric strategy (0.801 vs 0.800, respectively) but was less expensive ($31,870 vs $37,266, respectively). In sensitivity analyses, the incremental cost-effectiveness ratio of the empiric strategy ranged from $500,000 to more than $5 million per QALY gained. Similar rates of remission (63% vs 66%) and response (28% vs 26%) were achieved through differential use of available interventions. The testing-based strategy resulted in a higher percentage of surgeries (48% vs 34%) and lower percentage use of high-dose biological therapy (41% vs 54%). A testing-based strategy is a cost-effective alternative to the current strategy of empiric dose escalation for managing patients with Crohn's disease who have lost responsiveness to infliximab. The basis for this difference is lower cost at similar outcomes. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

Effective Dose of CT- and Fluoroscopy-Guided Perineural/Epidural Injections of the Lumbar Spine: A Comparative Study

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

Schmid, Gebhard; Schmitz, Alexander; Borchardt, Dieter

The objective of this study was to compare the effective radiation dose of perineural and epidural injections of the lumbar spine under computed tomography (CT) or fluoroscopic guidance with respect to dose-reduced protocols. We assessed the radiation dose with an Alderson Rando phantom at the lumbar segment L4/5 using 29 thermoluminescence dosimeters. Based on our clinical experience, 4-10 CT scans and 1-min fluoroscopy are appropriate. Effective doses were calculated for CT for a routine lumbar spine protocol and for maximum dose reduction; as well as for fluoroscopy in a continuous and a pulsed mode (3-15 pulses/s). Effective doses under CTmore » guidance were 1.51 mSv for 4 scans and 3.53 mSv for 10 scans using a standard protocol and 0.22 mSv and 0.43 mSv for the low-dose protocol. In continuous mode, the effective doses ranged from 0.43 to 1.25 mSv for 1-3 min of fluoroscopy. Using 1 min of pulsed fluoroscopy, the effective dose was less than 0.1 mSv for 3 pulses/s. A consequent low-dose CT protocol reduces the effective dose compared to a standard lumbar spine protocol by more than 85%. The latter dose might be expected when applying about 1 min of continuous fluoroscopy for guidance. A pulsed mode further reduces the effective dose of fluoroscopy by 80-90%.« less

Low dose radiation effects on the brain - from mechanisms and behavioral outcomes to mitigation strategies.

PubMed

Kovalchuk, Anna; Kolb, Bryan

2017-07-03

Based on the most recent estimates by the Canadian Cancer Society, 2 in 5 Canadians will develop cancer in their lifetimes. More than half of all cancer patients receive some type of radiation therapy, and all patients undergo radiation-based diagnostics. While radiation is one of the most important diagnostic and treatments modalities, high-dose cranial radiation therapy causes numerous central nervous system side-effects, including declines in cognitive function, memory, and attention. While the mechanisms of these effects have been studies, they still need to be further elucidated. On the other hand, the effects of low dose radiation as well as indirect radiation bystander effects on the brain remain elusive. We pioneered analysis of the molecular and cellular effects of low dose direct, bystander and scatter radiation on the brain. Using a rat model, we showed that low dose radiation exposures cause molecular and cellular changes in the brain and impacts animal behavior. Here we reflect upon our recent findings and current state of knowledge in the field, and suggest novel radiation effect biomarkers and means of prevention. We propose strategies and interventions to prevent and mitigate radiation effects on the brain.

Assessment of an organ-based tube current modulation in thoracic computed tomography.

PubMed

Matsubara, Kosuke; Sugai, Mai; Toyoda, Asami; Koshida, Haruka; Sakuta, Keita; Takata, Tadanori; Koshida, Kichiro; Iida, Hiroji; Matsui, Osamu

2012-03-08

Recently, specific computed tomography (CT) scanners have been equipped with organ-based tube current modulation (TCM) technology. It is possible that organ-based TCM will replace the conventional dose-reduction technique of reducing the effective milliampere-second. The aim of this study was to determine if organ-based TCM could reduce radiation exposure to the breasts without compromising the image uniformity and beam hardening effect in thoracic CT examinations. Breast and skin radiation doses and the absorbed radiation dose distribution within a single section were measured with an anthropomorphic phantom and radiophotoluminescent glass dosimeters using four approaches to thoracic CT (reference, organ-based TCM, copper shielding, and the combination of the above two techniques, hereafter referred to as the combination technique). The CT value and noise level were measured using the same calibration phantom. Organ-based TCM and copper shielding reduced radiation doses to the breast by 23.7% and 21.8%, respectively. However, the CT value increased, especially in the anterior region, using copper shielding. In contrast, the CT value and noise level barely increased using organ-based TCM. The combination technique reduced the radiation dose to the breast by 38.2%, but greatly increased the absorbed radiation dose from the central to the posterior regions. Moreover, the CT value increased in the anterior region and the noise level increased by more than 10% in the entire region. Therefore, organ-based TCM can reduce radiation doses to breasts with only small increases in noise levels, making it preferable for specific groups of patients, such as children and young women.

EVALUATION OF EYE LENS DOSE TO WORKERS IN THE STEAM GENERATOR AT THE KOREAN OPTIMIZED POWER REACTOR 1000.

PubMed

Maeng, Sung Jun; Kim, Jinhwan; Cho, Gyuseong

2018-03-15

ICRP (2011) revised the dose limit to the eye lens to 20 mSv/y based on a recent epidemiological study of radiation-induced cataracts. Maintenance of steam generators at nuclear power plants is one of the highest radiation-associated tasks within a non-uniform radiation field. This study aims to evaluate eye lens doses in the steam generators of the Korean OPR1000 design. The source term was characterized based on the CRUD-specific activity, and both the eye lens dose and organ dose were simulated using MCNP6 combined with an ICRP voxel phantom and a mesh phantom, respectively. The eye lens dose was determined to be 5.39E-02-9.43E-02 Sv/h, with a negligible effect by beta particles. As the effective dose was found to be 0.81-1.21 times the lens equivalent dose depending on the phantom angles, the former can be used to estimate the lens dose in the SG of the OPR1000 for radiation monitoring purposes.

The internal dosimetry of Rubidium-82 based on dynamic PET/CT imaging in humans

NASA Astrophysics Data System (ADS)

Hunter, Chad R.

Rubidium-82 (Rb-82) is a useful blood flow tracer, and has become important in recent years due to the shutdown of the Chalk River reactor. Published effective dose estimates for Rb-82 vary widely, and as yet no comprehensive study in man has been conducted with PET/CT, and no effective dose estimates for Rb-82 during pharmacological stress testing has been published. 30 subjects were recruited for rest, and 25 subjects were recruited for stress. The subjects consisted of both cardiac patients and normal subjects. For rest, a total of 283 organs were measured across 60 scans. For stress, a total of 171 organs were measured across 25 scans. Effective dose estimates were calculated using the ICRP 60, 80, and 103 tissue weighting factors. Relative differences between this study and the published in-vivo estimates showed agreement for the lungs. Relative differences between this study and the blood flow models showed differences> 5 times in the thyroid contribution to the effective dose demonstrating a limitation in these models. Comparisons between rest and stress effective dose estimates revealed no significant difference. The average 'adult' effective dose for Rb-82 was found to be 0.00084+/-0.00018 mSv/MBq. The highest dose organs were the lungs, kidneys and stomach wall. These dose estimates for Rb-82 are the first to be measured directly with PET/CT in humans, and are 4 times lower than previous ICRP 60 values based on a theoretical blood flow model. The total adult effective dose from a typical Rb-82 study including CT for attenuation correction and potential Sr-85 breakthrough is 1.5 +/- 0.4 mSv.

Point-of-use chlorination of turbid water: results from a field study in Tanzania.

PubMed

Mohamed, Hussein; Brown, Joe; Njee, Robert M; Clasen, Thomas; Malebo, Hamisi M; Mbuligwe, Steven

2015-06-01

Household-based chlorine disinfection is widely effective against waterborne bacteria and viruses, and may be among the most inexpensive and accessible options for household water treatment. The microbiological effectiveness of chlorine is limited, however, by turbidity. In Tanzania, there are no guidelines on water chlorination at household level, and limited data on whether dosing guidelines for higher turbidity waters are sufficient to produce potable water. This study was designed to assess the effectiveness of chlorination across a range of turbidities found in rural water sources, following local dosing guidelines that recommend a 'double dose' for water that is visibly turbid. We chlorinated water from 43 sources representing a range of turbidities using two locally available chlorine-based disinfectants: WaterGuard and Aquatabs. We determined free available chlorine at 30 min and 24 h contact time. Our data suggest that water chlorination with WaterGuard or Aquatabs can be effective using both single and double doses up to 20 nephelometric turbidity units (NTU), or using a double dose of Aquatabs up to 100 NTU, but neither was effective at turbidities greater than 100 NTU.

Evaluation of radiation dose of triple rule-out coronary angiography protocols with different scan length using 256-slice CT

NASA Astrophysics Data System (ADS)

Tsai, Chia-Jung; Lee, Jason J. S.; Chen, Liang-Kuang; Mok, Greta S. P.; Hsu, Shih-Ming; Wu, Tung-Hsin

2011-10-01

Triple rule-out coronary CT angiography (TRO-CTA) is a new approach for providing noninvasive visualization of coronary arteries with simultaneous evaluation of pulmonary arteries, thoracic aorta and other intrathoracic structures. The increasing use of TRO-CTA examination with longer scan length is associated with the concerns about radiation dose and their corresponding cancer risk. The purpose of this study is to evaluate organ dose and effective dose for the TRO-CTA examination with 2 scan lengths: TRO std and TRO ext, using 256-slice CT. TRO-CTA examinations were performed on a 256-slice CT scanner without ECG-based tube current modulation. Absorbed organ doses were measured using an anthropomorphic phantom and thermal-luminance dosimeters (TLDs). Effective dose was determined by taking a sum of the measured absorbed organ doses multiplied with the tissue weighting factor based on ICRP-103, and compared to that calculated using the dose-length product (DLP) method. We obtained high organ doses in the thyroid, esophagus, breast, heart and lung in both TRO-CTA protocols. Effective doses of the TRO std and TRO ext protocols with the phantom method were 26.37 and 42.49 mSv, while those with the DLP method were 19.68 and 38.96 mSv, respectively. Our quantitative dose information establishes a relationship between radiation dose and scanning length, and can provide a practical guidance to best clinical practice.

Estimation of effective dose and lifetime attributable risk from multiple head CT scans in ventriculoperitoneal shunted children.

PubMed

Aw-Zoretic, J; Seth, D; Katzman, G; Sammet, S

2014-10-01

The purpose of this review is to determine the averaged effective dose and lifetime attributable risk factor from multiple head computed tomography (CT) dose data on children with ventriculoperitoneal shunts (VPS). A total of 422 paediatric head CT exams were found between October 2008 and January 2011 and retrospectively reviewed. The CT dose data was weighted with the latest IRCP 103 conversion factor to obtain the effective dose per study and the averaged effective dose was calculated. Estimates of the lifetime attributable risk were also calculated from the averaged effective dose using a conversion factor from the latest BEIR VII report. Our study found the highest effective doses in neonates and the lowest effective doses were observed in the 10-18 years age group. We estimated a 0.007% potential increase risk in neonates and 0.001% potential increased risk in teenagers over the base risk. Multiple head CTs in children equates to a slight potential increase risk in lifetime attributable risk over the baseline risk for cancer, slightly higher in neonates relative to teenagers. The potential risks versus clinical benefit must be assessed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Characterization and prediction of monomer-based dose rate effects in electron-beam polymerization

NASA Astrophysics Data System (ADS)

Schissel, Sage M.; Lapin, Stephen C.; Jessop, Julie L. P.

2017-12-01

Properties of some materials produced by electron-beam (EB) induced polymerization appear dependent upon the rate at which the initiating dose was delivered. However, the magnitude of these dose rate effects (DREs) can vary greatly with different monomer formulations, suggesting DREs are dependent on chemical structure. The relationship among dose, dose rate, conversion, and the glass transition temperature (Tg) of the cured material was explored for an acrylate monomer series. A strong correlation was determined between the DRE magnitude and monomer size, and this correlation may be attributed to chain transfer. Using the Tg shift caused by changes in dose, a preliminary predictive relationship was developed to estimate the magnitude of the Tg DRE, enabling scale-up of process variables for polymers prone to dose rate effects.

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

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

Sahbaee, Pooyan, E-mail: psahbae@ncsu.edu; Segars, W. Paul; Samei, Ehsan

2014-07-15

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

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique.

PubMed

Gandhi, Diksha; Crotty, Dominic J; Stevens, Grant M; Schmidt, Taly Gilat

2015-11-01

This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings. Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%-20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.

Reducing radiation dose to the female breast during conventional and dedicated breast computed tomography

NASA Astrophysics Data System (ADS)

Rupcich, Franco John

The purpose of this study was to quantify the effectiveness of techniques intended to reduce dose to the breast during CT coronary angiography (CTCA) scans with respect to task-based image quality, and to evaluate the effectiveness of optimal energy weighting in improving contrast-to-noise ratio (CNR), and thus the potential for reducing breast dose, during energy-resolved dedicated breast CT. A database quantifying organ dose for several radiosensitive organs irradiated during CTCA, including the breast, was generated using Monte Carlo simulations. This database facilitates estimation of organ-specific dose deposited during CTCA protocols using arbitrary x-ray spectra or tube-current modulation schemes without the need to run Monte Carlo simulations. The database was used to estimate breast dose for simulated CT images acquired for a reference protocol and five protocols intended to reduce breast dose. For each protocol, the performance of two tasks (detection of signals with unknown locations) was compared over a range of breast dose levels using a task-based, signal-detectability metric: the estimator of the area under the exponential free-response relative operating characteristic curve, AFE. For large-diameter/medium-contrast signals, when maintaining equivalent AFE, the 80 kV partial, 80 kV, 120 kV partial, and 120 kV tube-current modulated protocols reduced breast dose by 85%, 81%, 18%, and 6%, respectively, while the shielded protocol increased breast dose by 68%. Results for the small-diameter/high-contrast signal followed similar trends, but with smaller magnitude of the percent changes in dose. The 80 kV protocols demonstrated the greatest reduction to breast dose, however, the subsequent increase in noise may be clinically unacceptable. Tube output for these protocols can be adjusted to achieve more desirable noise levels with lesser dose reduction. The improvement in CNR of optimally projection-based and image-based weighted images relative to photon-counting was investigated for six different energy bin combinations using a bench-top energy-resolving CT system with a cadmium zinc telluride (CZT) detector. The non-ideal spectral response reduced the CNR for the projection-based weighted images, while image-based weighting improved CNR for five out of the six investigated bin combinations, despite this non-ideal response, indicating potential for image-based weighting to reduce breast dose during dedicated breast CT.

The mass-action law based algorithms for quantitative econo-green bio-research.

PubMed

Chou, Ting-Chao

2011-05-01

The relationship between dose and effect is not random, but rather governed by the unified theory based on the median-effect equation (MEE) of the mass-action law. Rearrangement of MEE yields the mathematical form of the Michaelis-Menten, Hill, Henderson-Hasselbalch and Scatchard equations of biochemistry and biophysics, and the median-effect plot allows linearization of all dose-effect curves regardless of potency and shape. The "median" is the universal common-link and reference-point for the 1st-order to higher-order dynamics, and from single-entities to multiple-entities and thus, it allows the all for one and one for all unity theory to "integrate" simple and complex systems. Its applications include the construction of a dose-effect curve with a theoretical minimum of only two data points if they are accurately determined; quantification of synergism or antagonism at all dose and effect levels; the low-dose risk assessment for carcinogens, toxic substances or radiation; and the determination of competitiveness and exclusivity for receptor binding. Since the MEE algorithm allows the reduced requirement of the number of data points for small size experimentation, and yields quantitative bioinformatics, it points to the deterministic, efficient, low-cost biomedical research and drug discovery, and ethical planning for clinical trials. It is concluded that the contemporary biomedical sciences would greatly benefit from the mass-action law based "Green Revolution".

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

Sugano, Yasutaka; Mizuta, Masahiro; Takao, Seishin

Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of themore » tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.« less

NUNDO: a numerical model of a human torso phantom and its application to effective dose equivalent calculations for astronauts at the ISS.

PubMed

Puchalska, Monika; Bilski, Pawel; Berger, Thomas; Hajek, Michael; Horwacik, Tomasz; Körner, Christine; Olko, Pawel; Shurshakov, Vyacheslav; Reitz, Günther

2014-11-01

The health effects of cosmic radiation on astronauts need to be precisely quantified and controlled. This task is important not only in perspective of the increasing human presence at the International Space Station (ISS), but also for the preparation of safe human missions beyond low earth orbit. From a radiation protection point of view, the baseline quantity for radiation risk assessment in space is the effective dose equivalent. The present work reports the first successful attempt of the experimental determination of the effective dose equivalent in space, both for extra-vehicular activity (EVA) and intra-vehicular activity (IVA). This was achieved using the anthropomorphic torso phantom RANDO(®) equipped with more than 6,000 passive thermoluminescent detectors and plastic nuclear track detectors, which have been exposed to cosmic radiation inside the European Space Agency MATROSHKA facility both outside and inside the ISS. In order to calculate the effective dose equivalent, a numerical model of the RANDO(®) phantom, based on computer tomography scans of the actual phantom, was developed. It was found that the effective dose equivalent rate during an EVA approaches 700 μSv/d, while during an IVA about 20 % lower values were observed. It is shown that the individual dose based on a personal dosimeter reading for an astronaut during IVA results in an overestimate of the effective dose equivalent of about 15 %, whereas under an EVA conditions the overestimate is more than 200 %. A personal dosemeter can therefore deliver quite good exposure records during IVA, but may overestimate the effective dose equivalent received during an EVA considerably.

Optimization of the scan protocols for CT-based material extraction in small animal PET/CT studies

NASA Astrophysics Data System (ADS)

Yang, Ching-Ching; Yu, Jhih-An; Yang, Bang-Hung; Wu, Tung-Hsin

2013-12-01

We investigated the effects of scan protocols on CT-based material extraction to minimize radiation dose while maintaining sufficient image information in small animal studies. The phantom simulation experiments were performed with the high dose (HD), medium dose (MD) and low dose (LD) protocols at 50, 70 and 80 kVp with varying mA s. The reconstructed CT images were segmented based on Hounsfield unit (HU)-physical density (ρ) calibration curves and the dual-energy CT-based (DECT) method. Compared to the (HU;ρ) method performed on CT images acquired with the 80 kVp HD protocol, a 2-fold improvement in segmentation accuracy and a 7.5-fold reduction in radiation dose were observed when the DECT method was performed on CT images acquired with the 50/80 kVp LD protocol, showing the possibility to reduce radiation dose while achieving high segmentation accuracy.

Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer

NASA Astrophysics Data System (ADS)

González, S. J.; Pozzi, E. C. C.; Monti Hughes, A.; Provenzano, L.; Koivunoro, H.; Carando, D. G.; Thorp, S. I.; Casal, M. R.; Bortolussi, S.; Trivillin, V. A.; Garabalino, M. A.; Curotto, P.; Heber, E. M.; Santa Cruz, G. A.; Kankaanranta, L.; Joensuu, H.; Schwint, A. E.

2017-10-01

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson’s correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed model are compatible with the observed clinical outcome. The extension of the photon iso-effective dose model has allowed, for the first time, the determination of the photon iso-effective dose for unacceptable complications in the dose-limiting normal tissue. Finally, the formalism developed in this work to compute photon-equivalent doses can be applied to other therapies that combine mixed radiation fields, such as hadron therapy.

Photon iso-effective dose for cancer treatment with mixed field radiation based on dose-response assessment from human and an animal model: clinical application to boron neutron capture therapy for head and neck cancer.

PubMed

González, S J; Pozzi, E C C; Monti Hughes, A; Provenzano, L; Koivunoro, H; Carando, D G; Thorp, S I; Casal, M R; Bortolussi, S; Trivillin, V A; Garabalino, M A; Curotto, P; Heber, E M; Santa Cruz, G A; Kankaanranta, L; Joensuu, H; Schwint, A E

2017-10-03

Boron neutron capture therapy (BNCT) is a treatment modality that combines different radiation qualities. Since the severity of biological damage following irradiation depends on the radiation type, a quantity different from absorbed dose is required to explain the effects observed in the clinical BNCT in terms of outcome compared with conventional photon radiation therapy. A new approach for calculating photon iso-effective doses in BNCT was introduced previously. The present work extends this model to include information from dose-response assessments in animal models and humans. Parameters of the model were determined for tumour and precancerous tissue using dose-response curves obtained from BNCT and photon studies performed in the hamster cheek pouch in vivo models of oral cancer and/or pre-cancer, and from head and neck cancer radiotherapy data with photons. To this end, suitable expressions of the dose-limiting Normal Tissue Complication and Tumour Control Probabilities for the reference radiation and for the mixed field BNCT radiation were developed. Pearson's correlation coefficients and p-values showed that TCP and NTCP models agreed with experimental data (with r  >  0.87 and p-values  >0.57). The photon iso-effective dose model was applied retrospectively to evaluate the dosimetry in tumours and mucosa for head and neck cancer patients treated with BNCT in Finland. Photon iso-effective doses in tumour were lower than those obtained with the standard RBE-weighted model (between 10% to 45%). The results also suggested that the probabilities of tumour control derived from photon iso-effective doses are more adequate to explain the clinical responses than those obtained with the RBE-weighted values. The dosimetry in the mucosa revealed that the photon iso-effective doses were about 30% to 50% higher than the corresponding RBE-weighted values. While the RBE-weighted doses are unable to predict mucosa toxicity, predictions based on the proposed model are compatible with the observed clinical outcome. The extension of the photon iso-effective dose model has allowed, for the first time, the determination of the photon iso-effective dose for unacceptable complications in the dose-limiting normal tissue. Finally, the formalism developed in this work to compute photon-equivalent doses can be applied to other therapies that combine mixed radiation fields, such as hadron therapy.

Task-based measures of image quality and their relation to radiation dose and patient risk

PubMed Central

Barrett, Harrison H.; Myers, Kyle J.; Hoeschen, Christoph; Kupinski, Matthew A.; Little, Mark P.

2015-01-01

The theory of task-based assessment of image quality is reviewed in the context of imaging with ionizing radiation, and objective figures of merit (FOMs) for image quality are summarized. The variation of the FOMs with the task, the observer and especially with the mean number of photons recorded in the image is discussed. Then various standard methods for specifying radiation dose are reviewed and related to the mean number of photons in the image and hence to image quality. Current knowledge of the relation between local radiation dose and the risk of various adverse effects is summarized, and some graphical depictions of the tradeoffs between image quality and risk are introduced. Then various dose-reduction strategies are discussed in terms of their effect on task-based measures of image quality. PMID:25564960

Quantifying annual internal effective 137Cesium dose utilizing direct body-burden measurement and ecological dose modeling.

PubMed

Jelin, Benjamin A; Sun, Wenjie; Kravets, Alexandra; Naboka, Maryna; Stepanova, Eugenia I; Vdovenko, Vitaliy Y; Karmaus, Wilfried J; Lichosherstov, Alex; Svendsen, Erik R

2016-11-01

The Chernobyl Nuclear Power Plant (CNPP) accident represents one of the most significant civilian releases of 137 Cesium ( 137 Cs, radiocesium) in human history. In the Chernobyl-affected region, radiocesium is considered to be the greatest on-going environmental hazard to human health by radiobiologists and public health scientists. The goal of this study was to characterize dosimetric patterns and predictive factors for whole-body count (WBC)-derived radiocesium internal dose estimations in a CNPP-affected children's cohort, and cross-validate these estimations with a soil-based ecological dose estimation model. WBC data were used to estimate the internal effective dose using the International Commission on Radiological Protection (ICRP) 67 dose conversion coefficient for 137 Cs and MONDAL Version 3.01 software. Geometric mean dose estimates from each model were compared utilizing paired t-tests and intra-class correlation coefficients. Additionally, we developed predictive models for WBC-derived dose estimation in order to determine the appropriateness of EMARC to estimate dose for this population. The two WBC-derived dose predictive models identified 137 Cs soil concentration (P<0.0001) as the strongest predictor of annual internal effective dose from radiocesium validating the use of the soil-based EMARC model. The geometric mean internal effective dose estimate of the EMARC model (0.183 mSv/y) was the highest followed by the ICRP 67 dose estimates (0.165 mSv/y) and the MONDAL model estimates (0.149 mSv/y). All three models yielded significantly different geometric mean dose (P<0.05) estimates for this cohort when stratified by sex, age at time of exam and season of exam, except for the mean MONDAL and EMARC estimates for 15- and 16-year olds and mean ICRP and MONDAL estimates for children examined in Winter. Further prospective and retrospective radio-epidemiological studies utilizing refined WBC measurements and ecological model dose estimations, in conjunction with findings from animal toxicological studies, should help elucidate possible deterministic radiogenic health effects associated with chronic low-dose internal exposure to 137 Cs.

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

PubMed

Chiu, Weihsueh A; Slob, Wout

2015-12-01

When chemical health hazards have been identified, probabilistic dose-response assessment ("hazard characterization") quantifies uncertainty and/or variability in toxicity as a function of human exposure. Existing probabilistic approaches differ for different types of endpoints or modes-of-action, lacking a unifying framework. We developed a unified framework for probabilistic dose-response assessment. We established a framework based on four principles: a) individual and population dose responses are distinct; b) dose-response relationships for all (including quantal) endpoints can be recast as relating to an underlying continuous measure of response at the individual level; c) for effects relevant to humans, "effect metrics" can be specified to define "toxicologically equivalent" sizes for this underlying individual response; and d) dose-response assessment requires making adjustments and accounting for uncertainty and variability. We then derived a step-by-step probabilistic approach for dose-response assessment of animal toxicology data similar to how nonprobabilistic reference doses are derived, illustrating the approach with example non-cancer and cancer datasets. Probabilistically derived exposure limits are based on estimating a "target human dose" (HDMI), which requires risk management-informed choices for the magnitude (M) of individual effect being protected against, the remaining incidence (I) of individuals with effects ≥ M in the population, and the percent confidence. In the example datasets, probabilistically derived 90% confidence intervals for HDMI values span a 40- to 60-fold range, where I = 1% of the population experiences ≥ M = 1%-10% effect sizes. Although some implementation challenges remain, this unified probabilistic framework can provide substantially more complete and transparent characterization of chemical hazards and support better-informed risk management decisions.

Genotoxic effects of high dose rate X-ray and low dose rate gamma radiation in ApcMin/+ mice.

PubMed

Graupner, Anne; Eide, Dag M; Brede, Dag A; Ellender, Michele; Lindbo Hansen, Elisabeth; Oughton, Deborah H; Bouffler, Simon D; Brunborg, Gunnar; Olsen, Ann Karin

2017-10-01

Risk estimates for radiation-induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc +/+ (wild type) and Apc Min/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60 Co-γ-rays at a LDR (2.2 mGy h -1 ) or acutely exposed to 2.6 Gy HDR X-rays (1.3 Gy min -1 ). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig-a gene mutation assay), and levels of DNA lesions (Comet assay, single-strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3- and 10-fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The Apc Min/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560-569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.

Genotoxic effects of high dose rate X‐ray and low dose rate gamma radiation in ApcMin/+ mice

PubMed Central

Eide, Dag M.; Brede, Dag A.; Ellender, Michele; Lindbo Hansen, Elisabeth; Oughton, Deborah H.; Bouffler, Simon D.; Brunborg, Gunnar; Olsen, Ann Karin

2017-01-01

Risk estimates for radiation‐induced cancer in humans are based on epidemiological data largely drawn from the Japanese atomic bomb survivor studies, which received an acute high dose rate (HDR) ionising radiation. Limited knowledge exists about the effects of chronic low dose rate (LDR) exposure, particularly with respect to the application of the dose and dose rate effectiveness factor. As part of a study to investigate the development of colon cancer following chronic LDR vs. acute HDR radiation, this study presents the results of genotoxic effects in blood of exposed mice. CBAB6 F1 Apc+/+ (wild type) and ApcMin/+ mice were chronically exposed to estimated whole body absorbed doses of 1.7 or 3.2 Gy 60Co‐γ‐rays at a LDR (2.2 mGy h−1) or acutely exposed to 2.6 Gy HDR X‐rays (1.3 Gy min−1). Genotoxic endpoints assessed in blood included chromosomal damage (flow cytometry based micronuclei (MN) assay), mutation analyses (Pig‐a gene mutation assay), and levels of DNA lesions (Comet assay, single‐strand breaks (ssb), alkali labile sites (als), oxidized DNA bases). Ionising radiation (ca. 3 Gy) induced genotoxic effects dependent on the dose rate. Chromosomal aberrations (MN assay) increased 3‐ and 10‐fold after chronic LDR and acute HDR, respectively. Phenotypic mutation frequencies as well as DNA lesions (ssb/als) were modulated after acute HDR but not after chronic LDR. The ApcMin/+ genotype did not influence the outcome in any of the investigated endpoints. The results herein will add to the scant data available on genotoxic effects following chronic LDR of ionising radiation. Environ. Mol. Mutagen. 58:560–569, 2017. © 2017 The Authors Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society PMID:28856770

Experimental and Monte Carlo evaluation of Eclipse treatment planning system for effects on dose distribution of the hip prostheses

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

Çatlı, Serap, E-mail: serapcatli@hotmail.com; Tanır, Güneş

2013-10-01

The present study aimed to investigate the effects of titanium, titanium alloy, and stainless steel hip prostheses on dose distribution based on the Monte Carlo simulation method, as well as the accuracy of the Eclipse treatment planning system (TPS) at 6 and 18 MV photon energies. In the present study the pencil beam convolution (PBC) method implemented in the Eclipse TPS was compared to the Monte Carlo method and ionization chamber measurements. The present findings show that if high-Z material is used in prosthesis, large dose changes can occur due to scattering. The variance in dose observed in the presentmore » study was dependent on material type, density, and atomic number, as well as photon energy; as photon energy increased back scattering decreased. The dose perturbation effect of hip prostheses was significant and could not be predicted accurately by the PBC method for hip prostheses. The findings show that for accurate dose calculation the Monte Carlo-based TPS should be used in patients with hip prostheses.« less

Effect of electron beam irradiation on thermal and mechanical properties of aluminum based epoxy composites

NASA Astrophysics Data System (ADS)

Visakh, P. M.; Nazarenko, O. B.; Sarath Chandran, C.; Melnikova, T. V.; Nazarenko, S. Yu.; Kim, J.-C.

2017-07-01

The epoxy resins are widely used in nuclear and aerospace industries. The certain properties of epoxy resins as well as the resistance to radiation can be improved by the incorporation of different fillers. This study examines the effect of electron beam irradiation on the thermal and mechanical properties of the epoxy composites filled with aluminum nanoparticles at percentage of 0.35 wt%. The epoxy composites were exposed to the irradiation doses of 30, 100 and 300 kGy using electron beam generated by the linear electron accelerator ELU-4. The effects of the doses on thermal and mechanical properties of the aluminum based epoxy composites were investigated by the methods of thermal gravimetric analysis, tensile test, and dynamic mechanical analysis. The results revealed that the studied epoxy composites showed good radiation resistance. The thermal and mechanical properties of the aluminum based epoxy composites increased with increasing the irradiation dose up to 100 kGy and decreased with further increasing the dose.

A cost effectiveness analysis of thiopurine methyltransferase testing for guiding 6-mercaptopurine dosing in children with acute lymphoblastic leukemia.

PubMed

Donnan, Jennifer R; Ungar, Wendy J; Mathews, Maria; Hancock-Howard, Rebecca L; Rahman, Proton

2011-08-01

An increased understanding of the genetic basis of disease creates a demand for personalized medicine and more genetic testing for diagnosis and treatment. The objective was to assess the incremental cost-effectiveness per life-month gained of thiopurine methyltransferase (TPMT) genotyping to guide doses of 6-mercaptopurine (6-MP) in children with acute lymphoblastic leukemia (ALL) compared to enzymatic testing and standard weight-based dosing. A cost-effectiveness analysis was conducted from a health care system perspective comparing costs and consequences over 3 months. Decision analysis was used to evaluate the impact of TPMT tests on preventing myelosuppression and improving survival in ALL patients receiving 6-MP. Direct medical costs included laboratory tests, medications, physician services, pharmacy and inpatient care. Probabilities were derived from published evidence. Survival was measured in life-months. The robustness of the results to variable uncertainty was tested in one-way sensitivity analyses. Probabilistic sensitivity analysis examined the impact of parameter uncertainty and generated confidence intervals around point estimates. Neither of the testing interventions showed a benefit in survival compared to weight-based dosing. Both test strategies were more costly compared to weight-based dosing. Incremental costs per child (95% confidence interval) were $277 ($112, $442) and $298 ($392, $421) for the genotyping and phenotyping strategies, respectively, compared to weight-based dosing. The present analysis suggests that screening for TPMT mutations using either genotype or enzymatic laboratory tests prior to the administration of 6-MP in pediatric ALL patients is not cost-effective. Copyright © 2011 Wiley-Liss, Inc.

SU-F-I-09: Improvement of Image Registration Using Total-Variation Based Noise Reduction Algorithms for Low-Dose CBCT

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

Mukherjee, S; Farr, J; Merchant, T

Purpose: To study the effect of total-variation based noise reduction algorithms to improve the image registration of low-dose CBCT for patient positioning in radiation therapy. Methods: In low-dose CBCT, the reconstructed image is degraded by excessive quantum noise. In this study, we developed a total-variation based noise reduction algorithm and studied the effect of the algorithm on noise reduction and image registration accuracy. To study the effect of noise reduction, we have calculated the peak signal-to-noise ratio (PSNR). To study the improvement of image registration, we performed image registration between volumetric CT and MV- CBCT images of different head-and-neck patientsmore » and calculated the mutual information (MI) and Pearson correlation coefficient (PCC) as a similarity metric. The PSNR, MI and PCC were calculated for both the noisy and noise-reduced CBCT images. Results: The algorithms were shown to be effective in reducing the noise level and improving the MI and PCC for the low-dose CBCT images tested. For the different head-and-neck patients, a maximum improvement of PSNR of 10 dB with respect to the noisy image was calculated. The improvement of MI and PCC was 9% and 2% respectively. Conclusion: Total-variation based noise reduction algorithm was studied to improve the image registration between CT and low-dose CBCT. The algorithm had shown promising results in reducing the noise from low-dose CBCT images and improving the similarity metric in terms of MI and PCC.« less

High-intensity corneal collagen crosslinking with riboflavin and UVA in rat cornea.

PubMed

Zhu, Yirui; Reinach, Peter S; Zhu, Hanlei; Tan, Qiufan; Zheng, Qinxiang; Qu, Jia; Chen, Wei

2017-01-01

Corneal collagen cross-linking (CXL) halts human corneal ectasias progression by increasing stromal mechanical stiffness. Although some reports describe that this procedure is effective in dealing with some infectious and immunologic corneal thinning diseases, there is a need for more animal models whose corneal thickness more closely resemble those occurring in these patients. To meet this need, we describe here high-intensity protocols that are safe and effective for obtaining CXL in rat corneas. Initially, a range of potentially effective UVA doses were evaluated based on their effectiveness in increasing tissue enzymatic resistance to dissolution. At UVA doses higher than a threshold level of 0.54 J/cm2, resistance to enzymatic digestion increased relative to that in non-irradiated corneas. Based on the theoretical threshold CXL dose, a CXL regimen was established in which the UVA tissue irradiance was 9 mW/cm2, which was delivered at doses of either 2.16, 2.7 or 3.24 J/cm2. Their dose dependent effects were evaluated on ocular surface morphological integrity, keratocyte apoptotic frequency, tissue thickness and endothelial cell layer density. Doses of 2.16 and 2.7 J/cm2 transiently decreased normal corneal transparency and increased thickness. These effects were fully reversed after 14 days. In contrast, 3.24 J/cm2 had more irreversible side effects. Three days after treatment, apoptotic frequency in the CXL-2.16 group was lower than that at higher doses. Endothelial cell losses remained evident only in the CXL-3.24 group at 42 days posttreatment. Stromal fiber thickening was evident in all the CXL-treated groups. We determined both the threshold UVA dose using the high-intensity CXL procedure and identified an effective dose range that provides optimal CXL with minimal transient side effects in the rat cornea. These results may help to provide insight into how to improve the CXL outcome in patients afflicted with a severe corneal thinning disease.

TH-AB-207A-06: The Use of Realistic Phantoms to Predict CT Dose to Pediatric Patients

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

Carver, D; Kost, S; Fraser, N

Purpose: To predict pediatric patient dose from diagnostic CT scans using Monte Carlo simulation of realistic reference phantoms of various ages, weights, and heights. Methods: A series of deformable pediatric reference phantoms using Non-Uniform Rational B-Splines (NURBS) was developed for a large range of ages, percentiles, and reference anatomy. Individual bones were modeled using age-dependent factors, and red marrow was modeled as functions of age and spatial distribution based on Cristy1. Organ and effective doses for the phantom series were calculated using Monte Carlo simulation of chest, abdominopelvic, and chest-abdomen-pelvis CT exams. Non-linear regression was performed to determine the relationshipmore » between dose-length-product (DLP)-normalized organ and effective doses and phantom diameter. Patient-specific voxel computational phantoms were also created by manual segmentation of previously acquired CT images for 40 pediatric patients (0.7 to 17 years). Organ and effective doses were determined by Monte Carlo simulation of these patient-specific phantoms. Each patient was matched to the closest pediatric reference phantom based primarily on age and diameter for all major organs within the torso. Results: A total of 80 NURBS phantoms were created ranging from newborn to 15 years with height/weight percentiles from 10 to 90%. Organ and effective dose normalized by DLP correlated strongly with exponentially decreasing average phantom diameter (R{sup 2} > 0.95 for most organs). A similar relationship was determined for the patient-specific voxel phantoms. Differences between patient-phantom matched organ-dose values ranged from 0.37 to 2.39 mGy (2.87% to 22.1%). Conclusion: Dose estimation using NURBS-based pediatric reference phantoms offers the ability to predict patient dose before and after CT examinations, and physicians and scientists can use this information in their analysis of dose prescriptions for particular subjects and study types. This may lead to practices that minimize radiation dose while still achieving high quality images and, ultimately, improved patient care. NIH/NCI 1 R01 CA155400-01A1.« less

A dose-finding, cross-over study to evaluate the effect of a Nestorone®/Estradiol transdermal gel delivery on ovulation suppression in normal ovulating women.

PubMed

Brache, Vivian; Merkatz, Ruth; Kumar, Narender; Jesam, Cristian; Sussman, Heather; Hoskin, Elena; Roberts, Kevin; Alami, Mohcine; Taylor, Deshawn; Jorge, Aidelis; Croxatto, Horacio; Lorange, Ellen; Mishell, Daniel R; Sitruk-Ware, Regine

2015-10-01

This study aims to determine the lowest effective of three Nestorone (NES)/estradiol (E2) transdermal gel doses to ensure ovulation suppression in 90-95% of cycles. This was a randomized, open-label, three-treatment-period cross-over study to evaluate the effects of NES/E2 transdermal gel on ovulation inhibition, suppression of follicular growth and pharmacokinetic parameters. The doses were low (1.5 mg NES/0.5 mg E2), medium (3.0 mg NES/1.0 mg E2) and high (4.5 mg NES/1.5 mg E2). Participants applied gel daily to a fixed area on the abdomen for 21 consecutive days. They were interviewed regarding their experiences using the gel. Eighteen participants were randomized; 16 completed the study. Median NES C(max) values for low, medium and high dose groups at day 21 were 318.6 pmol/L, 783.0 pmol/L and 1063.8 pmol/L, respectively. Median maximum follicular diameter was higher with the lowest dose with 16.2 mm versus 10.0 and 10.4 mm with the medium and high doses, respectively. Among adherent participants, ovulation was inhibited in all dose groups, except for one participant in the medium dose (6.7%) that had luteal activity and an ultrasound image suggestive of a luteinized unruptured follicle. There were few reports of unscheduled bleeding, with more episodes reported for the lower dose. Adverse events were mild, and no skin irritation was reported from gel application. While all three doses blocked ovulation effectively and were evaluated as safe and acceptable, the medium dose was considered the lowest effective dose based on a more adequate suppression of follicular development. Further development of this novel contraceptive delivering NES and E2 is warranted and has potential for improved safety compared to ethinyl-estradiol-based methods. Copyright © 2015 Elsevier Inc. All rights reserved.

Probabilistic Analysis of Radiation Doses for Shore-Based Individuals in Operation Tomodachi

DTIC Science & Technology

2013-05-01

Based Upon Oxygen Consumption Rates. EPA/600/R-06/129F, U.S. Environmental Protection Agency, Washington, D.C. May. USEPA (U.S. Environmental...pascal (Pa) pound-force per square inch (psi) 6.894 757 × 103 pascal (Pa) Angle/ Temperature /Time hour (h) 3.6 × 103 second (s) degree of arc (o...equivalent and effective dose is the sievert (Sv). (1 Sv = 1 J kg–1). 1 DTRA-TR-12-002: Probabilistic Analysis of Radiation Doses for Shore-Based

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.

Rationale for recommending a lower dose of primaquine as a Plasmodium falciparum gametocytocide in populations where G6PD deficiency is common

PubMed Central

2012-01-01

In areas of low malaria transmission, it is currently recommended that a single dose of primaquine (0.75 mg base/kg; 45 mg adult dose) be added to artemisinin combination treatment (ACT) in acute falciparum malaria to block malaria transmission. Review of studies of transmission-blocking activity based on the infectivity of patients or volunteers to anopheline mosquitoes, and of haemolytic toxicity in glucose 6-dehydrogenase (G6PD) deficient subjects, suggests that a lower primaquine dose (0.25 mg base/kg) would be safer and equally effective. This lower dose could be deployed together with ACTs without G6PD testing wherever use of a specific gametocytocide is indicated. PMID:23237606

Rationale for recommending a lower dose of primaquine as a Plasmodium falciparum gametocytocide in populations where G6PD deficiency is common.

PubMed

White, Nicholas J; Qiao, Li Guo; Qi, Gao; Luzzatto, Lucio

2012-12-14

In areas of low malaria transmission, it is currently recommended that a single dose of primaquine (0.75 mg base/kg; 45 mg adult dose) be added to artemisinin combination treatment (ACT) in acute falciparum malaria to block malaria transmission. Review of studies of transmission-blocking activity based on the infectivity of patients or volunteers to anopheline mosquitoes, and of haemolytic toxicity in glucose 6-dehydrogenase (G6PD) deficient subjects, suggests that a lower primaquine dose (0.25 mg base/kg) would be safer and equally effective. This lower dose could be deployed together with ACTs without G6PD testing wherever use of a specific gametocytocide is indicated.

Using translational medicine to understand clinical differences between botulinum toxin formulations.

PubMed

Aoki, K R; Ranoux, D; Wissel, J

2006-12-01

When using botulinum toxin-based products, the physician must decide the optimal location and dose required to alleviate symptoms and improve the patient's quality of life. To deliver effective treatment, the physician needs to understand the importance of accurate target muscle selection and localization and the implications of each product's migration properties when diluted in different volumes. Pre-clinical mouse models of efficacy and safety have been utilized to compare local and distal muscle relaxation effects following defined intramuscular administration. Data from the model allow the products to be ranked based on their propensity for local efficacy versus their distal migration properties. Using standardized dilutions, the non-parallel dose-response curves for the various formulations demonstrate that they have different efficacy profiles. Distal effects were also noted at different treatment doses, which are reflected in the different safety and/or therapeutic margins. Based on these pre-clinical data, the safety and therapeutic margin rankings are ordered, largest to smallest, as BOTOX, Dysport and Myobloc. The results of subsequent clinical trials are variable and dose comparisons are inconclusive, thus supporting the regulatory position that the dose units of the individual preparations are unique and cannot be simply converted between products.

Pharmacokinetic/Pharmacodynamic Modeling and Simulation of Cefiderocol, a Parenteral Siderophore Cephalosporin, for Dose Adjustment Based on Renal Function.

PubMed

Katsube, Takayuki; Wajima, Toshihiro; Ishibashi, Toru; Arjona Ferreira, Juan Camilo; Echols, Roger

2017-01-01

Cefiderocol, a novel parenteral siderophore cephalosporin, exhibits potent efficacy against most Gram-negative bacteria, including carbapenem-resistant strains. Since cefiderocol is excreted primarily via the kidneys, this study was conducted to develop a population pharmacokinetics (PK) model to determine dose adjustment based on renal function. Population PK models were developed based on data for cefiderocol concentrations in plasma, urine, and dialysate with a nonlinear mixed-effects model approach. Monte-Carlo simulations were conducted to calculate the probability of target attainment (PTA) of fraction of time during the dosing interval where the free drug concentration in plasma exceeds the MIC (T f >MIC ) for an MIC range of 0.25 to 16 μg/ml. For the simulations, dose regimens were selected to compare cefiderocol exposure among groups with different levels of renal function. The developed models well described the PK of cefiderocol for each renal function group. A dose of 2 g every 8 h with 3-h infusions provided >90% PTA for 75% T f >MIC for an MIC of ≤4 μg/ml for patients with normal renal function, while a more frequent dose (every 6 h) could be used for patients with augmented renal function. A reduced dose and/or extended dosing interval was selected for patients with impaired renal function. A supplemental dose immediately after intermittent hemodialysis was proposed for patients requiring intermittent hemodialysis. The PK of cefiderocol could be adequately modeled, and the modeling-and-simulation approach suggested dose regimens based on renal function, ensuring drug exposure with adequate bactericidal effect. Copyright © 2016 American Society for Microbiology.

Appropriate Use of Effective Dose in Radiation Protection and Risk Assessment.

PubMed

Fisher, Darrell R; Fahey, Frederic H

2017-08-01

Effective dose was introduced by the ICRP for the single, over-arching purpose of setting limits for radiation protection. Effective dose is a derived quantity or mathematical construct and not a physical, measurable quantity. The formula for calculating effective dose to a reference model incorporates terms to account for all radiation types, organ and tissue radiosensitivities, population groups, and multiple biological endpoints. The properties and appropriate applications of effective dose are not well understood by many within and outside the health physics profession; no other quantity in radiation protection has been more confusing or misunderstood. According to ICRP Publication 103, effective dose is to be used for "prospective dose assessment for planning and optimization in radiological protection, and retrospective demonstration of compliance for regulatory purposes." In practice, effective dose has been applied incorrectly to predict cancer risk among exposed persons. The concept of effective dose applies generally to reference models only and not to individual subjects. While conceived to represent a measure of cancer risk or heritable detrimental effects, effective dose is not predictive of future cancer risk. The formula for calculating effective dose incorporates committee-selected weighting factors for radiation quality and organ sensitivity; however, the organ weighting factors are averaged across all ages and both genders and thus do not apply to any specific individual or radiosensitive subpopulations such as children and young women. Further, it is not appropriate to apply effective dose to individual medical patients because patient-specific parameters may vary substantially from the assumptions used in generalized models. Also, effective dose is not applicable to therapeutic uses of radiation, as its mathematical underpinnings pertain only to observed late (stochastic) effects of radiation exposure and do not account for short-term adverse tissue reactions. The weighting factors incorporate substantial uncertainties, and linearity of the dose-response function at low dose is uncertain and highly disputed. Since effective dose is not predictive of future cancer incidence, it follows that effective dose should never be used to estimate future cancer risk from specific sources of radiation exposure. Instead, individual assessments of potential detriment should only be based on organ or tissue radiation absorbed dose, together with best scientific understanding of the corresponding dose-response relationships.

Radiation dosimetry with fiber Bragg gratings

NASA Astrophysics Data System (ADS)

Avino, S.; D'Avino, V.; Giorgini, A.; Pacelli, R.; Liuzzi, R.; Cella, L.; Gagliardi, G.; De Natale, P.

2014-05-01

The measurement and monitoring of radiation dose delivered in patient tissues is a critical aspect in radiation therapy. Various dosimeters have proven effective in measuring radiations at low doses. However, there is a growing demand for new dosimeters based on small, non-invasive and high resolution devices. Here we report on a miniature dosimeter based on an optical fiber cavity. We demonstrate an ultimate detection limit of 160 mGy with an effective interaction region of 6 x 10-4 mm3. Due to its reliability, compactness and biomedical dose level sensitivity, our system shows itself suitable for applications in radiation therapy dosimetry.

SimDoseCT: dose reporting software based on Monte Carlo simulation for a 320 detector-row cone-beam CT scanner and ICRP computational adult phantoms

NASA Astrophysics Data System (ADS)

Cros, Maria; Joemai, Raoul M. S.; Geleijns, Jacob; Molina, Diego; Salvadó, Marçal

2017-08-01

This study aims to develop and test software for assessing and reporting doses for standard patients undergoing computed tomography (CT) examinations in a 320 detector-row cone-beam scanner. The software, called SimDoseCT, is based on the Monte Carlo (MC) simulation code, which was developed to calculate organ doses and effective doses in ICRP anthropomorphic adult reference computational phantoms for acquisitions with the Aquilion ONE CT scanner (Toshiba). MC simulation was validated by comparing CTDI measurements within standard CT dose phantoms with results from simulation under the same conditions. SimDoseCT consists of a graphical user interface connected to a MySQL database, which contains the look-up-tables that were generated with MC simulations for volumetric acquisitions at different scan positions along the phantom using any tube voltage, bow tie filter, focal spot and nine different beam widths. Two different methods were developed to estimate organ doses and effective doses from acquisitions using other available beam widths in the scanner. A correction factor was used to estimate doses in helical acquisitions. Hence, the user can select any available protocol in the Aquilion ONE scanner for a standard adult male or female and obtain the dose results through the software interface. Agreement within 9% between CTDI measurements and simulations allowed the validation of the MC program. Additionally, the algorithm for dose reporting in SimDoseCT was validated by comparing dose results from this tool with those obtained from MC simulations for three volumetric acquisitions (head, thorax and abdomen). The comparison was repeated using eight different collimations and also for another collimation in a helical abdomen examination. The results showed differences of 0.1 mSv or less for absolute dose in most organs and also in the effective dose calculation. The software provides a suitable tool for dose assessment in standard adult patients undergoing CT examinations in a 320 detector-row cone-beam scanner.

SimDoseCT: dose reporting software based on Monte Carlo simulation for a 320 detector-row cone-beam CT scanner and ICRP computational adult phantoms.

PubMed

Cros, Maria; Joemai, Raoul M S; Geleijns, Jacob; Molina, Diego; Salvadó, Marçal

2017-07-17

This study aims to develop and test software for assessing and reporting doses for standard patients undergoing computed tomography (CT) examinations in a 320 detector-row cone-beam scanner. The software, called SimDoseCT, is based on the Monte Carlo (MC) simulation code, which was developed to calculate organ doses and effective doses in ICRP anthropomorphic adult reference computational phantoms for acquisitions with the Aquilion ONE CT scanner (Toshiba). MC simulation was validated by comparing CTDI measurements within standard CT dose phantoms with results from simulation under the same conditions. SimDoseCT consists of a graphical user interface connected to a MySQL database, which contains the look-up-tables that were generated with MC simulations for volumetric acquisitions at different scan positions along the phantom using any tube voltage, bow tie filter, focal spot and nine different beam widths. Two different methods were developed to estimate organ doses and effective doses from acquisitions using other available beam widths in the scanner. A correction factor was used to estimate doses in helical acquisitions. Hence, the user can select any available protocol in the Aquilion ONE scanner for a standard adult male or female and obtain the dose results through the software interface. Agreement within 9% between CTDI measurements and simulations allowed the validation of the MC program. Additionally, the algorithm for dose reporting in SimDoseCT was validated by comparing dose results from this tool with those obtained from MC simulations for three volumetric acquisitions (head, thorax and abdomen). The comparison was repeated using eight different collimations and also for another collimation in a helical abdomen examination. The results showed differences of 0.1 mSv or less for absolute dose in most organs and also in the effective dose calculation. The software provides a suitable tool for dose assessment in standard adult patients undergoing CT examinations in a 320 detector-row cone-beam scanner.

Optimization of equivalent uniform dose using the L-curve criterion.

PubMed

Chvetsov, Alexei V; Dempsey, James F; Palta, Jatinder R

2007-10-07

Optimization of equivalent uniform dose (EUD) in inverse planning for intensity-modulated radiation therapy (IMRT) prevents variation in radiobiological effect between different radiotherapy treatment plans, which is due to variation in the pattern of dose nonuniformity. For instance, the survival fraction of clonogens would be consistent with the prescription when the optimized EUD is equal to the prescribed EUD. One of the problems in the practical implementation of this approach is that the spatial dose distribution in EUD-based inverse planning would be underdetermined because an unlimited number of nonuniform dose distributions can be computed for a prescribed value of EUD. Together with ill-posedness of the underlying integral equation, this may significantly increase the dose nonuniformity. To optimize EUD and keep dose nonuniformity within reasonable limits, we implemented into an EUD-based objective function an additional criterion which ensures the smoothness of beam intensity functions. This approach is similar to the variational regularization technique which was previously studied for the dose-based least-squares optimization. We show that the variational regularization together with the L-curve criterion for the regularization parameter can significantly reduce dose nonuniformity in EUD-based inverse planning.

The Radiobiology of Proton Therapy: Challenges and Opportunities Around Relative Biological Effectiveness.

PubMed

Jones, B; McMahon, S J; Prise, K M

2018-05-01

With the current UK expansion of proton therapy there is a great opportunity for clinical oncologists to develop a translational interest in the associated scientific base and clinical results. In particular, the underpinning controversy regarding the conversion of photon dose to proton dose by the relative biological effectiveness (RBE) must be understood, including its important implications. At the present time, the proton prescribed dose includes an RBE of 1.1 regardless of tissue, tumour and dose fractionation. A body of data has emerged against this pragmatic approach, including a critique of the existing evidence base, due to choice of dose, use of only acute-reacting in vivo assays, analysis methods and the reference radiations used to determine the RBE. Modelling systems, based on the best available scientific evidence, and which include the clinically useful biological effective dose (BED) concept, have also been developed to estimate proton RBEs for different dose and linear energy transfer (LET) values. The latter reflect ionisation density, which progressively increases along each proton track. Late-reacting tissues, such as the brain, where α/β = 2 Gy, show a higher RBE than 1.1 at a low dose per fraction (1.2-1.8 Gy) at LET values used to cover conventional target volumes and can be much higher. RBE changes with tissue depth seem to vary depending on the method of beam delivery used. To reduce unexpected toxicity, which does occasionally follow proton therapy, a more rational approach to RBE allocation, using a variable RBE that depends on dose per fraction and the tissue and tumour radiobiological characteristics such as α/β, is proposed. Copyright © 2018. Published by Elsevier Ltd.

Low-dose right unilateral electroconvulsive therapy (ECT): effectiveness of the first treatment.

PubMed

Lapidus, Kyle A B; Shin, Joseph S W; Pasculli, Rosa M; Briggs, Mimi C; Popeo, Dennis M; Kellner, Charles H

2013-06-01

Electroconvulsive therapy (ECT) is a widely used, highly effective antidepressant treatment. Except for the most severely ill patients, right unilateral (RUL) electrode placement is the most frequent initial treatment choice. In current practice, RUL ECT is administered at several multiples of seizure threshold (ST) based on reports that lower stimulus intensity results in lower response/remission rates. Many patients, as part of an initial dose titration to determine ST, will receive a single treatment with low-dose RUL ECT and subsequent treatments with a stimulus at a multiple of ST. To assess response to the first ECT. A retrospective analysis of charts from clinical practice at Mount Sinai Medical Center was performed. A single treatment with low-dose (presumably near ST) RUL ECT had a significant and immediate antidepressant effect in our sample of patients with major depression. We determined that this response is similar to that of patients receiving a single initial treatment with high-dose RUL ECT (at a multiple of ST). These data suggest, contrary to commonly held belief, that RUL ECT may be effective at a low stimulus dose. This argues against restimulating at 6 times ST in the initial session, based on the belief that the near-threshold seizure has no antidepressant efficacy. Our findings suggest a need for further investigation of cases in which low-dose RUL ECT may be an effective antidepressant treatment. Further prospective studies, including larger numbers of patients who receive randomized treatment with low- or high-dose RUL with longer follow-up, are indicated.

SU-E-T-378: Evaluation of An Analytical Model for the Inter-Seed Attenuation Effect in 103-Pd Multi-Seed Implant Brachytherapy

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

Safigholi, H; Soliman, A; Song, W

Purpose: Brachytherapy treatment planning systems based on TG-43 protocol calculate the dose in water and neglects the heterogeneity effect of seeds in multi-seed implant brachytherapy. In this research, the accuracy of a novel analytical model that we propose for the inter-seed attenuation effect (ISA) for 103-Pd seed model is evaluated. Methods: In the analytical model, dose perturbation due to the ISA effect for each seed in an LDR multi-seed implant for 103-Pd is calculated by assuming that the seed of interest is active and the other surrounding seeds are inactive. The cumulative dosimetric effect of all seeds is then summedmore » using the superposition principle. The model is based on pre Monte Carlo (MC) simulated 3D kernels of the dose perturbations caused by the ISA effect. The cumulative ISA effect due to multiple surrounding seeds is obtained by a simple multiplication of the individual ISA effect by each seed, the effect of which is determined by the distance from the seed of interest. This novel algorithm is then compared with full MC water-based simulations (FMCW). Results: The results show that the dose perturbation model we propose is in excellent agreement with the FMCW values for a case with three seeds separated by 1 cm. The average difference of the model and the FMCW simulations was less than 8%±2%. Conclusion: Using the proposed novel analytical ISA effect model, one could expedite the corrections due to the ISA dose perturbation effects during permanent seed 103-Pd brachytherapy planning with minimal increase in time since the model is based on multiplications and superposition. This model can be applied, in principle, to any other brachytherapy seeds. Further work is necessary to validate this model on a more complicated geometry as well.« less

SU-E-J-181: Effect of Prostate Motion On Combined Brachytherapy and External Beam Dose Based On Daily Motion of the Prostate

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

Narayana, V; McLaughlin, P; University of Michigan, Ann Arbor, MI

2015-06-15

Purpose: In this study, the adequacy of target expansions on the combined external beam and implant dose was examined based on the measured daily motion of the prostate. Methods: Thirty patients received an I–125 prostate implant prescribed to dose of 90Gy. This was followed by external beam to deliver a dose of 90Gyeq (external beam equivalent) to the prostate over 25 to 30 fractions. An ideal IMRT plan was developed by optimizing the external beam dose based on the delivered implant dose. The implant dose was converted to an equivalent external beam dose using the linear quadratic model. Patients weremore » set up on the treatment table by daily orthogonal imaging and aligning the marker seeds in the prostate. Orthogonal images were obtained at the end of treatment to assess prostate intrafraction motion. Based on the observed motion of the markers between the initial and final images, 5 individual plans showing the actual dose delivered to the patient were calculated. A final true dose distribution was established based on summing the implant dose and the 5 external beam plans. Dose to the prostate, seminal vesicles, lymphnodes and normal tissues, rectal wall, urethra and lower sphincter were calculated and compared to ideal. On 18 patients who were sexually active, dose to the corpus cavernosum and internal pudendal artery was also calculated. Results: The average prostate motion in 3 orthogonal directions was less than 1 mm with a standard deviation of less than +2 mm. Dose and volume parameters showed that there was no decrease in dose to the targets and a marginal decrease in dose to in normal tissues. Conclusion: Dose delivered by seed implant moves with the prostate, decreasing the impact of intrafractions dose movement on actual dose delivered. Combined brachytherapy and external beam dose delivered to the prostate was not sensitive to prostate motion.« less

Technical Note: Phantom study to evaluate the dose and image quality effects of a computed tomography organ-based tube current modulation technique

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

Gandhi, Diksha; Schmidt, Taly Gilat, E-mail: taly.gilat-schmidt@marquette.edu; Crotty, Dominic J.

Purpose: This technical note quantifies the dose and image quality performance of a clinically available organ-dose-based tube current modulation (ODM) technique, using experimental and simulation phantom studies. The investigated ODM implementation reduces the tube current for the anterior source positions, without increasing current for posterior positions, although such an approach was also evaluated for comparison. Methods: Axial CT scans at 120 kV were performed on head and chest phantoms on an ODM-equipped scanner (Optima CT660, GE Healthcare, Chalfont St. Giles, England). Dosimeters quantified dose to breast, lung, heart, spine, eye lens, and brain regions for ODM and 3D-modulation (SmartmA) settings.more » Monte Carlo simulations, validated with experimental data, were performed on 28 voxelized head phantoms and 10 chest phantoms to quantify organ dose and noise standard deviation. The dose and noise effects of increasing the posterior tube current were also investigated. Results: ODM reduced the dose for all experimental dosimeters with respect to SmartmA, with average dose reductions across dosimeters of 31% (breast), 21% (lung), 24% (heart), 6% (spine), 19% (eye lens), and 11% (brain), with similar results for the simulation validation study. In the phantom library study, the average dose reduction across all phantoms was 34% (breast), 20% (lung), 8% (spine), 20% (eye lens), and 8% (brain). ODM increased the noise standard deviation in reconstructed images by 6%–20%, with generally greater noise increases in anterior regions. Increasing the posterior tube current provided similar dose reduction as ODM for breast and eye lens, increased dose to the spine, with noise effects ranging from 2% noise reduction to 16% noise increase. At noise equal to SmartmA, ODM increased the estimated effective dose by 4% and 8% for chest and head scans, respectively. Increasing the posterior tube current further increased the effective dose by 15% (chest) and 18% (head) relative to SmartmA. Conclusions: ODM reduced dose in all experimental and simulation studies over a range of phantoms, while increasing noise. The results suggest a net dose/noise benefit for breast and eye lens for all studied phantoms, negligible lung dose effects for two phantoms, increased lung dose and/or noise for eight phantoms, and increased dose and/or noise for brain and spine for all studied phantoms compared to the reference protocol.« less

BODY SIZE-SPECIFIC EFFECTIVE DOSE CONVERSION COEFFICIENTS FOR CT SCANS.

PubMed

Romanyukha, Anna; Folio, Les; Lamart, Stephanie; Simon, Steven L; Lee, Choonsik

2016-12-01

Effective dose from computed tomography (CT) examinations is usually estimated using the scanner-provided dose-length product and using conversion factors, also known as k-factors, which correspond to scan regions and differ by age according to five categories: 0, 1, 5, 10 y and adult. However, patients often deviate from the standard body size on which the conversion factor is based. In this study, a method for deriving body size-specific k-factors is presented, which can be determined from a simple regression curve based on patient diameter at the centre of the scan range. Using the International Commission on Radiological Protection reference paediatric and adult computational phantoms paired with Monte Carlo simulation of CT X-ray beams, the authors derived a regression-based k-factor model for the following CT scan types: head-neck, head, neck, chest, abdomen, pelvis, abdomen-pelvis (AP) and chest-abdomen-pelvis (CAP). The resulting regression functions were applied to a total of 105 paediatric and 279 adult CT scans randomly sampled from patients who underwent chest, AP and CAP scans at the National Institutes of Health Clinical Center. The authors have calculated and compared the effective doses derived from the conventional age-specific k-factors with the values computed using their body size-specific k-factor. They found that by using the age-specific k-factor, paediatric patients tend to have underestimates (up to 3-fold) of effective dose, while underweight and overweight adult patients tend to have underestimates (up to 2.6-fold) and overestimates (up to 4.6-fold) of effective dose, respectively, compared with the effective dose determined from their body size-dependent factors. The authors present these size-specific k-factors as an alternative to the existing age-specific factors. The body size-specific k-factor will assess effective dose more precisely and on a more individual level than the conventional age-specific k-factors and, hence, improve awareness of the true exposure, which is important for the clinical community to understand. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

SU-E-T-248: An Extended Generalized Equivalent Uniform Dose Accounting for Dose-Range Dependency of Radio-Biological Parameters.

PubMed

Troeller, A; Soehn, M; Yan, D

2012-06-01

Introducing an extended, phenomenological, generalized equivalent uniform dose (eEUD) that incorporates multiple volume-effect parameters for different dose-ranges. The generalized EUD (gEUD) was introduced as an estimate of the EUD that incorporates a single, tissue-specific parameter - the volume-effect-parameter (VEP) 'a'. As a purely phenomenological concept, its radio-biological equivalency to a given inhomogeneous dose distribution is not a priori clear and mechanistic models based on radio-biological parameters are assumed to better resemble the underlying biology. However, for normal organs mechanistic models are hard to derive, since the structural organization of the tissue plays a significant role. Consequently, phenomenological approaches might be especially useful in order to describe dose-response for normal tissues. However, the single parameter used to estimate the gEUD may not suffice in accurately representing more complex biological effects that have been discussed in the literature. For instance, radio-biological parameters and hence the effects of fractionation are known to be dose-range dependent. Therefore, we propose an extended phenomenological eEUD formula that incorporates multiple VEPs accounting for dose-range dependency. The eEUD introduced is a piecewise polynomial expansion of the gEUD formula. In general, it allows for an arbitrary number of VEPs, each valid for a certain dose-range. We proved that the formula fulfills required mathematical and physical criteria such as invertibility of the underlying dose-effect and continuity in dose. Furthermore, it contains the gEUD as a special case, if all VEPs are equal to 'a' from the gEUD model. The eEUD is a concept that expands the gEUD such that it can theoretically represent dose-range dependent effects. Its practicality, however, remains to be shown. As a next step, this will be done by estimating the eEUD from patient data using maximum-likelihood based NTCP modelling in the same way it is commonly done for the gEUD. © 2012 American Association of Physicists in Medicine.

Organ doses for reference pediatric and adolescent patients undergoing computed tomography estimated by Monte Carlo simulation

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

Lee, Choonsik; Kim, Kwang Pyo; Long, Daniel J.

Purpose: To establish an organ dose database for pediatric and adolescent reference individuals undergoing computed tomography (CT) examinations by using Monte Carlo simulation. The data will permit rapid estimates of organ and effective doses for patients of different age, gender, examination type, and CT scanner model. Methods: The Monte Carlo simulation model of a Siemens Sensation 16 CT scanner previously published was employed as a base CT scanner model. A set of absorbed doses for 33 organs/tissues normalized to the product of 100 mAs and CTDI{sub vol} (mGy/100 mAs mGy) was established by coupling the CT scanner model with age-dependentmore » reference pediatric hybrid phantoms. A series of single axial scans from the top of head to the feet of the phantoms was performed at a slice thickness of 10 mm, and at tube potentials of 80, 100, and 120 kVp. Using the established CTDI{sub vol}- and 100 mAs-normalized dose matrix, organ doses for different pediatric phantoms undergoing head, chest, abdomen-pelvis, and chest-abdomen-pelvis (CAP) scans with the Siemens Sensation 16 scanner were estimated and analyzed. The results were then compared with the values obtained from three independent published methods: CT-Expo software, organ dose for abdominal CT scan derived empirically from patient abdominal circumference, and effective dose per dose-length product (DLP). Results: Organ and effective doses were calculated and normalized to 100 mAs and CTDI{sub vol} for different CT examinations. At the same technical setting, dose to the organs, which were entirely included in the CT beam coverage, were higher by from 40 to 80% for newborn phantoms compared to those of 15-year phantoms. An increase of tube potential from 80 to 120 kVp resulted in 2.5-2.9-fold greater brain dose for head scans. The results from this study were compared with three different published studies and/or techniques. First, organ doses were compared to those given by CT-Expo which revealed dose differences up to several-fold when organs were partially included in the scan coverage. Second, selected organ doses from our calculations agreed to within 20% of values derived from empirical formulae based upon measured patient abdominal circumference. Third, the existing DLP-to-effective dose conversion coefficients tended to be smaller than values given in the present study for all examinations except head scans. Conclusions: A comprehensive organ/effective dose database was established to readily calculate doses for given patients undergoing different CT examinations. The comparisons of our results with the existing studies highlight that use of hybrid phantoms with realistic anatomy is important to improve the accuracy of CT organ dosimetry. The comprehensive pediatric dose data developed here are the first organ-specific pediatric CT scan database based on the realistic pediatric hybrid phantoms which are compliant with the reference data from the International Commission on Radiological Protection (ICRP). The organ dose database is being coupled with an adult organ dose database recently published as part of the development of a user-friendly computer program enabling rapid estimates of organ and effective dose doses for patients of any age, gender, examination types, and CT scanner model.« less

Health effects in women exposed to low levels of ionizing radiation

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

Fabrikant, J.I.

1982-06-01

There are three delayed health effects of radiation which appear at the present time to have importance to women in radiation protection. These are: (1) the probability of cancer-induction at low doses and low-dose rates; (2) the consideration of those cancers in women, notably the breast and the thyroid, attributable to radiation exposure; and (3) the probability of induction of developmental abnormalities in the newborn following low-dose exposure in utero. The bases for the concern over these effects are discussed. (ACR)

Radiation Hormesis: Historical Perspective and Implications for Low-Dose Cancer Risk Assessment

PubMed Central

Vaiserman, Alexander M.

2010-01-01

Current guidelines for limiting exposure of humans to ionizing radiation are based on the linear-no-threshold (LNT) hypothesis for radiation carcinogenesis under which cancer risk increases linearly as the radiation dose increases. With the LNT model even a very small dose could cause cancer and the model is used in establishing guidelines for limiting radiation exposure of humans. A slope change at low doses and dose rates is implemented using an empirical dose and dose rate effectiveness factor (DDREF). This imposes usually unacknowledged nonlinearity but not a threshold in the dose-response curve for cancer induction. In contrast, with the hormetic model, low doses of radiation reduce the cancer incidence while it is elevated after high doses. Based on a review of epidemiological and other data for exposure to low radiation doses and dose rates, it was found that the LNT model fails badly. Cancer risk after ordinarily encountered radiation exposure (medical X-rays, natural background radiation, etc.) is much lower than projections based on the LNT model and is often less than the risk for spontaneous cancer (a hormetic response). Understanding the mechanistic basis for hormetic responses will provide new insights about both risks and benefits from low-dose radiation exposure. PMID:20585444

Concordance of Transcriptional and Apical Benchmark Dose Levels for Conazole-Induced Liver Effects in Mice

EPA Science Inventory

ABSTRACT The ability to anchor chemical class-based gene expression changes to phenotypic lesions and to describe these changes as a function of dose and time informs mode of action determinations and improves quantitative risk assessments. Previous transcription-based microarra...

Impact of weight-based ribavirin with peginterferon alfa-2b in African Americans with hepatitis C virus genotype 1.

PubMed

Jacobson, Ira M; Brown, Robert S; McCone, Jonathan; Black, Martin; Albert, Clive; Dragutsky, Michael S; Siddiqui, Firdous A; Hargrave, Thomas; Kwo, Paul Y; Lambiase, Louis; Galler, Greg W; Araya, Victor; Freilich, Bradley; Harvey, Joann; Griffel, Louis H; Brass, Clifford A

2007-10-01

WIN-R (Weight-based dosing of pegINterferon alfa-2b and Ribavirin) was a multicenter, randomized, open-label, investigator-initiated trial involving 236 community and academic sites in the United States, comparing response to pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in treatment-naive patients with chronic hepatitis C and compensated liver disease. Patients were randomized to receive PEG-IFN alfa-2b at 1.5 microg/kg/week plus flat-dose (800 mg/day) or weight-based-dose RBV (800 mg/day for weight <65 kg, 1000 mg/day for 65-85 kg, 1200 mg/day for >85-105 kg, or 1400 mg/day for >105-<125 kg). Sustained virologic response (SVR; undetectable [<125 IU/mL] hepatitis C virus [HCV] RNA at end of follow-up) in patients > or =65 kg was the primary end point. Low SVR rates have been reported among African American individuals, in whom there is a preponderance of HCV genotype 1. This subanalysis of WIN-R was conducted to evaluate the efficacy of weight-based dosing among African American individuals with genotype 1 infection enrolled in the trial. Of 362 African American patients in the primary efficacy analysis, 188 received RBV flat dosing and 174 received weight-based dosing. SVR rates were higher (21% versus 10%; P = 0.0006) and relapse rates were lower (22% versus 30%) in the weight-based-dose group than in the flat-dose group. Safety and rates of drug discontinuation were similar between the 2 groups. Weight-based dosing of RBV is more effective than flat dosing in combination with PEG-IFN alfa-2b in African American individuals with HCV genotype 1. Even with weight-based dosing, response rates in African American individuals are lower than reported in other ethnic groups.

Evidence for Dose-Additive Effects of Pyrethroids on Motor Activity in Rats

EPA Science Inventory

BACKGROUND: Pyrethroids are neurotoxic insecticides used in a variety of indoor and outdoor applications. Previous research characterized the acute dose-effect functions for 11 pyrethroids administered orally in corn oil (1 mL/kg) based on assessment of motor activity. OBJECTIVES...

SU-E-T-802: Verification of Implanted Cardiac Pacemaker Doses in Intensity-Modulated Radiation Therapy: Dose Prediction Accuracy and Reduction Effect of a Lead Sheet

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

Lee, J; Chung, J

2015-06-15

Purpose: To verify delivered doses on the implanted cardiac pacemaker, predicted doses with and without dose reduction method were verified using the MOSFET detectors in terms of beam delivery and dose calculation techniques in intensity-modulated radiation therapy (IMRT). Methods: The pacemaker doses for a patient with a tongue cancer were predicted according to the beam delivery methods [step-and-shoot (SS) and sliding window (SW)], intensity levels for dose optimization, and dose calculation algorithms. Dosimetric effects on the pacemaker were calculated three dose engines: pencil-beam convolution (PBC), analytical anisotropic algorithm (AAA), and Acuros-XB. A lead shield of 2 mm thickness was designedmore » for minimizing irradiated doses to the pacemaker. Dose variations affected by the heterogeneous material properties of the pacemaker and effectiveness of the lead shield were predicted by the Acuros-XB. Dose prediction accuracy and the feasibility of the dose reduction strategy were verified based on the measured skin doses right above the pacemaker using mosfet detectors during the radiation treatment. Results: The Acuros-XB showed underestimated skin doses and overestimated doses by the lead-shield effect, even though the lower dose disagreement was observed. It led to improved dose prediction with higher intensity level of dose optimization in IMRT. The dedicated tertiary lead sheet effectively achieved reduction of pacemaker dose up to 60%. Conclusion: The current SS technique could deliver lower scattered doses than recommendation criteria, however, use of the lead sheet contributed to reduce scattered doses.Thin lead plate can be a useful tertiary shielder and it could not acuse malfunction or electrical damage of the implanted pacemaker in IMRT. It is required to estimate more accurate scattered doses of the patient with medical device to design proper dose reduction strategy.« less

Dose Equivalents for Second-Generation Antipsychotic Drugs: The Classical Mean Dose Method

PubMed Central

Leucht, Stefan; Samara, Myrto; Heres, Stephan; Patel, Maxine X.; Furukawa, Toshi; Cipriani, Andrea; Geddes, John; Davis, John M.

2015-01-01

Background: The concept of dose equivalence is important for many purposes. The classical approach published by Davis in 1974 subsequently dominated textbooks for several decades. It was based on the assumption that the mean doses found in flexible-dose trials reflect the average optimum dose which can be used for the calculation of dose equivalence. We are the first to apply the method to second-generation antipsychotics. Methods: We searched for randomized, double-blind, flexible-dose trials in acutely ill patients with schizophrenia that examined 13 oral second-generation antipsychotics, haloperidol, and chlorpromazine (last search June 2014). We calculated the mean doses of each drug weighted by sample size and divided them by the weighted mean olanzapine dose to obtain olanzapine equivalents. Results: We included 75 studies with 16 555 participants. The doses equivalent to 1 mg/d olanzapine were: amisulpride 38.3 mg/d, aripiprazole 1.4 mg/d, asenapine 0.9 mg/d, chlorpromazine 38.9 mg/d, clozapine 30.6 mg/d, haloperidol 0.7 mg/d, quetiapine 32.3mg/d, risperidone 0.4mg/d, sertindole 1.1 mg/d, ziprasidone 7.9 mg/d, zotepine 13.2 mg/d. For iloperidone, lurasidone, and paliperidone no data were available. Conclusions: The classical mean dose method is not reliant on the limited availability of fixed-dose data at the lower end of the effective dose range, which is the major limitation of “minimum effective dose methods” and “dose-response curve methods.” In contrast, the mean doses found by the current approach may have in part depended on the dose ranges chosen for the original trials. Ultimate conclusions on dose equivalence of antipsychotics will need to be based on a review of various methods. PMID:25841041

Improved sulfide mitigation in sewers through on-line control of ferrous salt dosing.

PubMed

Ganigué, Ramon; Jiang, Guangming; Liu, Yiqi; Sharma, Keshab; Wang, Yue-Cong; Gonzalez, José; Nguyen, Tung; Yuan, Zhiguo

2018-05-15

Water utilities worldwide spend annually billions of dollars to control sulfide-induced corrosion in sewers. Iron salts chemically oxidize and/or precipitate dissolved sulfide in sewage and are especially used in medium- and large-size sewers. Iron salt dosing rates are defined ad hoc, ignoring variation in sewage flows and sulfide levels. This often results in iron overdosing or poor sulfide control. Online dosing control can adjust the chemical dosing rates to current (and future) state of the sewer system, allowing high-precision, stable and cost-effective sulfide control. In this paper, we report a novel and robust online control strategy for the dosing of ferrous salt in sewers. The control considers the fluctuation of sewage flow, pH, sulfide levels and also the perturbation from rainfall. Sulfide production in the pipe is predicted using auto-regressive models (AR) based on current flow measurements, which in turn can be used to determine the dose of ferrous salt required for cost-effective sulfide control. Following comprehensive model-based assesment, the control was successfully validated and its effectiveness demonstrated in a 3-week field trial. The online control algorithm controlled sulfide below the target level (0.5 mg S/L) while reducing chemical dosing up to 30%. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Evaluation of effective dose with chest digital tomosynthesis system using Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Kim, Dohyeon; Jo, Byungdu; Lee, Youngjin; Park, Su-Jin; Lee, Dong-Hoon; Kim, Hee-Joung

2015-03-01

Chest digital tomosynthesis (CDT) system has recently been introduced and studied. This system offers the potential to be a substantial improvement over conventional chest radiography for the lung nodule detection and reduces the radiation dose with limited angles. PC-based Monte Carlo program (PCXMC) simulation toolkit (STUK, Helsinki, Finland) is widely used to evaluate radiation dose in CDT system. However, this toolkit has two significant limits. Although PCXMC is not possible to describe a model for every individual patient and does not describe the accurate X-ray beam spectrum, Geant4 Application for Tomographic Emission (GATE) simulation describes the various size of phantom for individual patient and proper X-ray spectrum. However, few studies have been conducted to evaluate effective dose in CDT system with the Monte Carlo simulation toolkit using GATE. The purpose of this study was to evaluate effective dose in virtual infant chest phantom of posterior-anterior (PA) view in CDT system using GATE simulation. We obtained the effective dose at different tube angles by applying dose actor function in GATE simulation which was commonly used to obtain the medical radiation dosimetry. The results indicated that GATE simulation was useful to estimate distribution of absorbed dose. Consequently, we obtained the acceptable distribution of effective dose at each projection. These results indicated that GATE simulation can be alternative method of calculating effective dose in CDT applications.

TU-H-207A-08: Estimating Radiation Dose From Low-Dose Lung Cancer Screening CT Exams Using Tube Current Modulation

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

Hardy, A; Bostani, M; McMillan, K

Purpose: The purpose of this work is to estimate effective and lung doses from a low-dose lung cancer screening CT protocol using Tube Current Modulation (TCM) across patient models of different sizes. Methods: Monte Carlo simulation methods were used to estimate effective and lung doses from a low-dose lung cancer screening protocol for a 64-slice CT (Sensation 64, Siemens Healthcare) that used TCM. Scanning parameters were from the AAPM protocols. Ten GSF voxelized patient models were used and had all radiosensitive organs identified to facilitate estimating both organ and effective doses. Predicted TCM schemes for each patient model were generatedmore » using a validated method wherein tissue attenuation characteristics and scanner limitations were used to determine the TCM output as a function of table position and source angle. The water equivalent diameter (WED) was determined by estimating the attenuation at the center of the scan volume for each patient model. Monte Carlo simulations were performed using the unique TCM scheme for each patient model. Lung doses were tallied and effective doses were estimated using ICRP 103 tissue weighting factors. Effective and lung dose values were normalized by scanspecific 32 cm CTDIvol values based upon the average tube current across the entire simulated scan. Absolute and normalized doses were reported as a function of WED for each patient. Results: For all ten patients modeled, the effective dose using TCM protocols was below 1.5 mSv. Smaller sized patient models experienced lower absolute doses compared to larger sized patients. Normalized effective and lung doses showed some dependence on patient size (R2 = 0.77 and 0.78, respectively). Conclusion: Effective doses for a low-dose lung screening protocol using TCM were below 1.5 mSv for all patient models used in this study. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics.« less

Dose rate mapping of VMAT treatments

NASA Astrophysics Data System (ADS)

Podesta, Mark; Antoniu Popescu, I.; Verhaegen, Frank

2016-06-01

Human tissues exhibit a varying response to radiation dose depending on the dose rate and fractionation scheme used. Dose rate effects have been reported for different radiations, and tissue types. The literature indicates that there is not a significant difference in response for low-LET radiation when using dose rates between 1 Gy min-1 and 12 Gy min-1 but lower dose rates have an observable sparing effect on tissues and a differential effect between tissues. In intensity-modulated radiotherapy such as volumetric modulated arc therapy (VMAT) the dose can be delivered with a wide range of dose rates. In this work we developed a method based on time-resolved Monte Carlo simulations to quantify the dose rate frequency distribution for clinical VMAT treatments for three cancer sites, head and neck, lung, and pelvis within both planning target volumes (PTV) and normal tissues. The results show a wide range of dose rates are used to deliver dose in VMAT and up to 75% of the PTV can have its dose delivered with dose rates  <1 Gy min-1. Pelvic plans on average have a lower mean dose rate within the PTV than lung or head and neck plans but a comparable mean dose rate within the organs at risk. Two VMAT plans that fulfil the same dose objectives and constraints may be delivered with different dose rate distributions, particularly when comparing single arcs to multiple arc plans. It is concluded that for dynamic plans, the dose rate range used varies to a larger degree than previously assumed. The effect of the dose rate range in VMAT on clinical outcome is unknown.

MO-F-CAMPUS-J-01: Effect of Iodine Contrast Agent Concentration On Cerebrovascular Dose for Synchrotron Radiation Microangiography Based On a Simple Mouse Head Model and a Voxel Mouse Head Phantom

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

Lin, H; Jing, J; Xie, C

Purpose: To find effective setting methods to mitigate the irradiation injure in synchrotron radiation microangiography(SRA) by Monte Carlo simulation. Methods: A mouse 1-D head model and a segmented voxel mouse head phantom were simulated by EGSnrc/Dosxyznrc code to investigate the dose enhancement effect of the iodine contrast agent irradiated by a monochromatic synchrotron radiation(SR) source. The influence of, like iodine concentration (IC), vessel width and depth, with and without skull layer protection and the various incident X ray energies, were simulated. The dose enhancement effect and the absolute dose based on the segmented voxel mouse head phantom were evaluated. Results:more » The dose enhancement ratio depends little on the irradiation depth, but strongly on the IC, which is linearly increases with IC. The skull layer protection cannot be ignored in SRA, the 700µm thick skull could decrease 10% of the dose. The incident X-ray energy can significantly affact the dose. E.g. compared to the dose of 33.2keV for 50mgI/ml, the 32.7keV dose decreases 38%, whereas the dose of 33.7 keV increases 69.2%, and the variation will strengthen more with enhanced IC. The segmented voxel mouse head phantom also showed that the average dose enhancement effect and the maximal voxel dose per photon depends little on the iodine voxel volume ratio, but strongly on IC. Conclusion: To decrease dose damage in SRA, the high-Z contrast agent should be used as little as possible, and try to avoid radiating locally the injected position immediately after the contrast agent injection. The fragile vessel containing iodine should avoid closely irradiating. Avoiding irradiating through the no or thin skull region, or appending thin equivalent material from outside to protect is also a better method. As long as SRA image quality is ensured, using incident X-ray energy as low as possible.« less

Radioactivity Risk Assessment of Radon and Gamma Dose at One Uranium Tailings Pond in China

NASA Astrophysics Data System (ADS)

Lou, Yalong; Liu, Yong; Peng, Guowen; Zhao, Guodong; Zhang, Yan; Yang, Zhu

2018-01-01

A year-long monitoring of gamma radiation effective dose rate and radon concentration had been done in the reservoir area of one uranium tailings pond in Hunan province (The monitoring area included indoor and outdoor area of residential buildings and workshops, tailings dam slope). Afterwards, the annual effective radiation dose of the people in that radiation environment had been calculated based on the results of monitoring, as well as a radiation risk assessment. According to the assessment, gamma radiation effective dose rate and radon concentration in the monitoring area were low, and the annual effective radiation dose was far below the international standard (30mSv), which showed that the radiation would not put the people’s health at risk. However, the annual effective radiation dose of gamma was far above that of radon in the area of uranium tailings pond; therefore, it’s advisable to take quarantine measures in in the area of uranium tailings pond to keep the surrounding residents away from unnecessary ionizing radiation.

Effects of Radiation Exposure From Cardiac Imaging: How Good Are the Data?

PubMed Central

Einstein, Andrew J.

2012-01-01

Concerns about medical exposure to ionizing radiation have become heightened in recent years due to rapid growth in procedure volumes and the high radiation doses incurred from some procedures. This article summarizes the evidence base undergirding concerns about radiation exposure in cardiac imaging. After classifying radiation effects, explaining terminology used to quantify the radiation received by patients, and describing typical doses from cardiac imaging procedures, I address the major epidemiological studies having bearing on radiation effects at doses comparable to those received by patients undergoing cardiac imaging. These include studies of atomic bomb survivors, nuclear industry workers, and children exposed in utero to x-rays, all of which have evidenced increased cancer risks at low doses. Additional higher dose epidemiological studies of cohorts exposed to radiation in the context of medical treatment are described and found to be generally compatible with these cardiac-dose-level studies, albeit with exceptions. Using risk projection models developed by the US National Academies that incorporate these data and reflect several evidence-based assumptions, cancer risk from cardiac imaging can be estimated and compared to benefits from imaging. Several ongoing epidemiological studies will provide better understanding of radiation-associated cancer risks. PMID:22300689

Determination of the starting dose in the first-in-human clinical trials with monoclonal antibodies: a systematic review of papers published between 1990 and 2013.

PubMed

Suh, Hoon Young; Peck, Carl C; Yu, Kyung-Sang; Lee, Howard

2016-01-01

A systematic review was performed to evaluate how the maximum recommended starting dose (MRSD) was determined in first-in-human (FIH) studies with monoclonal antibodies (mAbs). Factors associated with the choice of each MRSD determination method were also identified. PubMed was searched for FIH studies with mAbs published in English between January 1, 1990 and December 31, 2013, and the following information was extracted: MRSD determination method, publication year, therapeutic area, antibody type, safety factor, safety assessment results after the first dose, and number of dose escalation steps. Seventy-nine FIH studies with mAbs were identified, 49 of which clearly reported the MRSD determination method. The no observed adverse effects level (NOAEL)-based approach was the most frequently used method, whereas the model-based approach was the least commonly used method (34.7% vs 16.3%). The minimal anticipated biological effect level (MABEL)- or minimum effective dose (MED)-based approach was used more frequently in 2011-2013 than in 1990-2007 (31.6% vs 6.3%, P =0.036), reflecting a slow, but steady acceptance of the European Medicines Agency's guidance on mitigating risks for FIH clinical trials (2007). The median safety factor was much lower for the MABEL- or MED-based approach than for the other MRSD determination methods (10 vs 32.2-53). The number of dose escalation steps was not significantly different among the different MRSD determination methods. The MABEL-based approach appears to be safer and as efficient as the other MRSD determination methods for achieving the objectives of FIH studies with mAbs faster.

Conceptus radiation dose and risk from chest screen-film radiography.

PubMed

Damilakis, John; Perisinakis, Kostas; Prassopoulos, Panos; Dimovasili, Evangelia; Varveris, Haralambos; Gourtsoyiannis, Nicholas

2003-02-01

The objectives of the present study were to (a) estimate the conceptus radiation dose and risks for pregnant women undergoing posteroanterior and anteroposterior (AP) chest radiographs, (b) study the conceptus dose as a function of chest thickness of the patient undergoing chest radiograph, and (c) investigate the possibility of a conceptus to receive a dose of more than 10 mGy, the level above which specific measurements of conceptus doses may be necessary. Thermoluminescent dosimeters were used for dose measurements in anthropomorphic phantoms simulating pregnancy at the three trimesters of gestation. The effect of chest thickness on conceptus dose and risk was studied by adding slabs of lucite on the anterior and posterior surface of the phantom chest. The conceptus risk for radiation-induced childhood fatal cancer and hereditary effects was calculated based on appropriate risk factors. The average AP chest dimension (d(a)) was estimated for 51 women of childbearing age from chest CT examinations. The value of d(a) was estimated to be 22.3 cm (17.4-27.2 cm). The calculated maximum conceptus dose was 107 x 10(-3) mGy for AP chest radiographs performed during the third trimester of pregnancy with maternal chest thickness of 27.2 cm. This calculation was based on dose data obtained from measurements in the phantoms and d(a) estimated from the patient group. The corresponding average excess of childhood cancer was 10.7 per million patients. The risk for hereditary effects was 1.1 per million births. Radiation dose for a conceptus increases exponentially as chest thickness increases. The conceptus dose at the third trimester is higher than that of the second and first trimesters. The results of the current study suggest that chest radiographs carried out in women at any time during gestation will result in a negligible increase in risk of radiation-induced harmful effects to the unborn child. After a properly performed maternal chest X-ray, there is no need for individual conceptus dose estimations.

Patient-specific IMRT verification using independent fluence-based dose calculation software: experimental benchmarking and initial clinical experience.

PubMed

Georg, Dietmar; Stock, Markus; Kroupa, Bernhard; Olofsson, Jörgen; Nyholm, Tufve; Ahnesjö, Anders; Karlsson, Mikael

2007-08-21

Experimental methods are commonly used for patient-specific intensity-modulated radiotherapy (IMRT) verification. The purpose of this study was to investigate the accuracy and performance of independent dose calculation software (denoted as 'MUV' (monitor unit verification)) for patient-specific quality assurance (QA). 52 patients receiving step-and-shoot IMRT were considered. IMRT plans were recalculated by the treatment planning systems (TPS) in a dedicated QA phantom, in which an experimental 1D and 2D verification (0.3 cm(3) ionization chamber; films) was performed. Additionally, an independent dose calculation was performed. The fluence-based algorithm of MUV accounts for collimator transmission, rounded leaf ends, tongue-and-groove effect, backscatter to the monitor chamber and scatter from the flattening filter. The dose calculation utilizes a pencil beam model based on a beam quality index. DICOM RT files from patient plans, exported from the TPS, were directly used as patient-specific input data in MUV. For composite IMRT plans, average deviations in the high dose region between ionization chamber measurements and point dose calculations performed with the TPS and MUV were 1.6 +/- 1.2% and 0.5 +/- 1.1% (1 S.D.). The dose deviations between MUV and TPS slightly depended on the distance from the isocentre position. For individual intensity-modulated beams (total 367), an average deviation of 1.1 +/- 2.9% was determined between calculations performed with the TPS and with MUV, with maximum deviations up to 14%. However, absolute dose deviations were mostly less than 3 cGy. Based on the current results, we aim to apply a confidence limit of 3% (with respect to the prescribed dose) or 6 cGy for routine IMRT verification. For off-axis points at distances larger than 5 cm and for low dose regions, we consider 5% dose deviation or 10 cGy acceptable. The time needed for an independent calculation compares very favourably with the net time for an experimental approach. The physical effects modelled in the dose calculation software MUV allow accurate dose calculations in individual verification points. Independent calculations may be used to replace experimental dose verification once the IMRT programme is mature.

MAMMARY GLAND DEVELOPMENT AS A SENSITIVE END-POINT FOLLOWING ACUTE PERNATAL EXPOSURE TO A LOW DOSE ATRAZINE METABOLITE MIXTURE IN FEMALE LONG EVANS RATS

EPA Science Inventory

In order to characterize the potential developmental effects of atrazine (ATR) metabolites at low doses, an environmentally-based mixture (EBM) of ATR and its metabolites hydroxyatrazine, diaminochlorotriazine, deethylatrazine, and deisopropylatrazine was formulated based on surv...

USE OF EXPOSURE RELATED DOSE ESTIMATING MODEL ( ERDEM ) TO CONSTRUCT A PBPK /MODEL FOR CARBOFURAN WITH THE REPORTED EXPERIMENTAL DATA IN THE RAT

EPA Science Inventory

To better understand the relationships among carbofuran exposure, dose, and effects, a physiologically-based pharmacokinetic and pharmacodynamic (PBPK/PD) model was developed for the rat using the Exposure Related Dose Estimating Model (ERDEM) framework.

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

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

Scott, Bobby, R., Ph.D.

2003-06-27

OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer.more » Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on applications of NEOTRANS2, indicate that nonlinear threshold-type, dose-response relationships for excess stochastic effects (problematic nonlethal mutations, neoplastic transformation) should be expected after exposure to low linear energy transfer (LET) gamma rays or gamma rays in combination with high-LET alpha radiation. Similar thresholds are expected for low-dose-rate low-LET beta irradiation. We attribute the thresholds to low-dose, low-LET radiation induced protection against spontaneous mutations and neoplastic transformations. The protection is presumed mainly to involve selective elimination of problematic cells via apoptosis. Low-dose, low-LET radiation is presumed to trigger wide-area cell signaling, which in turn leads to problematic bystander cells (e.g., mutants, neoplastically transformed cells) selectively undergoing apoptosis. Thus, this protective bystander effect leads to selective elimination of problematic cells (a tissue cleansing process in vivo). However, this protective bystander effects is a different process from low-dose stimulation of the immune system. Low-dose, low-LET radiation stimulation of the immune system may explain why thresholds for inducing excess cancer appear much larger (possibly more than 100-fold larger) than thresholds for inducing excess mutations and neoplastic transformations, when the dose rate is low. For ionizing radiation, the current risk assessment paradigm is such that the relative risk (RR) is always ¡Ý 1, no matter how small the dose. Our research results indicate that for low-dose or low-dose-rate, low-LET irradiation, RR < 1 may be more the rule than the exception. Directly tied to the current RR paradigm are the billion-dollar cleanup costs for radionuclide-contaminated DOE sites. Our research results suggest that continued use of the current RR paradigm for which RR ¡Ý 1 could cause more harm than benefit to society (e.g., by spreading unwarranted fear about phantom excess risks associated with low-dose low-LET radiation). Such phantom risks also may arise from risk assessments conducted for combined exposure to low- and high-LET radiations when based on the LNT or other models that exclude RR < 1. Our results for high-LET radiation are consistent with the LNT hypothesis but only where there is no additional low-LET contribution (e.g., gamma rays) to the total dose. For high-LET neutron sources, gamma rays arise (especially in vivo) for large mammals such as humans from neutron interactions with tissue. The gamma rays might provide some protection from low-dose-related stochastic effects via inducing the protective bystander apoptosis effect that is considered to contribute to tissue cleansing via removal of problematic cells.« less

Determination of effective doses in image-guided radiation therapy system

NASA Astrophysics Data System (ADS)

Pyone, Y. Y.; Suriyapee, S.; Sanghangthum, T.; Oonsiri, S.; Tawonwong, T.

2016-03-01

The organ and effective doses in image-guided radiotherapy system are determined in this study. For 2D imaging, incident air kerma (Ki) was measured by 6cc ionization chamber with Accu-Pro dosimeter. The entrance surface air kerma (ESAK) was calculated by multiplying Ki with backscatter factor. The effective dose was calculated by multiplying ESAK with conversion coefficient. For 3D imaging, computed tomography/cone-beam dose index (CTDI/CBDI) measurements were performed by using 100mm pencil ionization chamber with Accu-Pro dosimeter. The dose index in air and in CTDI phantom from planning CT and cone- beam CT were measured. Then, effective dose was calculated by ImPACT software. The effective doses from 2D conventional simulator for anteroposterior and lateral projections were 01 and 0.02mSv for head, 0.15 and 0.16mSv for thorax, 0.22 and 0.21mSv for pelvis, respectively. The effective doses from 3D, planning CT and CBCT, were 3.3 and 0.1mSv for head, 13 and 2.4mSv for thorax and 7.2 and 4.9mSv for pelvis, respectively. Based on 30 fractions of treatment course, total effective dose (3D CT, 2D setup verification and 6 times CBCT) of head, thorax and pelvis were 3.93, 27.71 and 37.03mSv, respectively. Therefore, IGRT should be administered with significant parameters to reduce the dose.

Addition of High-Dose Cytarabine to Fludarabine-Based Conditioning for Hematopoietic Stem Cell Transplantation for Treating Fanconi Anemia Patients with Advanced Myeloid Malignancy: A Single-Center Experience and Literature Review.

PubMed

Aoki, Takahiro; Koh, Katsuyoshi; Ikeda, Yuhachi; Sekinaka, Yujin; Akiyama, Kosuke; Mori, Makiko; Arakawa, Yuki; Hanada, Ryoji

2016-09-01

The complication of Fanconi anemia (FA) with acute leukemia is rare and challenging to treat because of high relapse rates, despite the improved outcome of hematopoietic stem cell transplantation with fludarabine-based conditioning for treating FA patients with hematological abnormalities. We added high-dose cytarabine to fludarabine-based conditioning to promote an enhanced antitumor effect and successfully subjected 4 patients with FA, including 3 with acute leukemia, to hematopoietic stem cell transplantation. All patients remain alive without treatment-related mortality or evidence of disease. Adding high-dose cytarabine to fludarabine-based conditioning may be tolerable and effective for treating FA patients with acute leukemia. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

A gEUD-based inverse planning technique for HDR prostate brachytherapy: Feasibility study

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

Giantsoudi, D.; Department of Radiation Oncology, Francis H. Burr Proton Therapy Center, Boston, Massachusetts 02114; Baltas, D.

2013-04-15

Purpose: The purpose of this work was to study the feasibility of a new inverse planning technique based on the generalized equivalent uniform dose for image-guided high dose rate (HDR) prostate cancer brachytherapy in comparison to conventional dose-volume based optimization. Methods: The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO (Hybrid Inverse Planning Optimization) is compared with alternative plans, which were produced through inverse planning using the generalized equivalent uniform dose (gEUD). All the common dose-volume indices for the prostate and the organs at risk were considered together with radiobiological measures. The clinical effectiveness of the differentmore » dose distributions was investigated by comparing dose volume histogram and gEUD evaluators. Results: Our results demonstrate the feasibility of gEUD-based inverse planning in HDR brachytherapy implants for prostate. A statistically significant decrease in D{sub 10} or/and final gEUD values for the organs at risk (urethra, bladder, and rectum) was found while improving dose homogeneity or dose conformity of the target volume. Conclusions: Following the promising results of gEUD-based optimization in intensity modulated radiation therapy treatment optimization, as reported in the literature, the implementation of a similar model in HDR brachytherapy treatment plan optimization is suggested by this study. The potential of improved sparing of organs at risk was shown for various gEUD-based optimization parameter protocols, which indicates the ability of this method to adapt to the user's preferences.« less

Assessment of an organ‐based tube current modulation in thoracic computed tomography

PubMed Central

Sugai, Mai; Toyoda, Asami; Koshida, Haruka; Sakuta, Keita; Takata, Tadanori; Koshida, Kichiro; Iida, Hiroji; Matsui, Osamu

2012-01-01

Recently, specific computed tomography (CT) scanners have been equipped with organ‐based tube current modulation (TCM) technology. It is possible that organ‐based TCM will replace the conventional dose‐reduction technique of reducing the effective milliampere‐second. The aim of this study was to determine if organ‐based TCM could reduce radiation exposure to the breasts without compromising the image uniformity and beam hardening effect in thoracic CT examinations. Breast and skin radiation doses and the absorbed radiation dose distribution within a single section were measured with an anthropomorphic phantom and radiophotoluminescent glass dosimeters using four approaches to thoracic CT (reference, organ‐based TCM, copper shielding, and the combination of the above two techniques, hereafter referred to as the combination technique). The CT value and noise level were measured using the same calibration phantom. Organ‐based TCM and copper shielding reduced radiation doses to the breast by 23.7% and 21.8%, respectively. However, the CT value increased, especially in the anterior region, using copper shielding. In contrast, the CT value and noise level barely increased using organ‐based TCM. The combination technique reduced the radiation dose to the breast by 38.2%, but greatly increased the absorbed radiation dose from the central to the posterior regions. Moreover, the CT value increased in the anterior region and the noise level increased by more than 10% in the entire region. Therefore, organ‐based TCM can reduce radiation doses to breasts with only small increases in noise levels, making it preferable for specific groups of patients, such as children and young women. PACS numbers: 87.53.Bn; 87.57.Q‐; 87.57.qp PMID:22402390

The effect of Sinabung volcanic ash and rock phosphate nanoparticle on CEC (cation exchange capacity) base saturation exchange (K, Na, Ca, Mg) and base saturation at Andisol soils Ciater, West Java

NASA Astrophysics Data System (ADS)

Yuniarti, Anni; Arifin, Mahfud; Sofyan, Emma Trinurasi; Natalie, Betty; Sudirja, Rija; Dahliani, Dewi

2018-02-01

Andisol, soil orders which covers an upland area dominantly. The aim of this research is to know the effect between the ameliorant of Sinabung volcanic ashes with the ameliorant of rock phosphatenanoparticle towards CEC and base saturation exchange (K, Na, Ca, Mg) and the base saturation on Ciater's Andisols, West Java. A randomized complete block design (RCBD) factorial with two factors was used in this research. The first factor is the volcanic ash and the second factor is rock phosphate which consists of four levels each amount of 0%, 2.5%, 5%, 7.5% with three replications. The result showed that there was no interaction between volcanic ash and rock phosphate nanoparticle formed in first month and fourth month towards the improvement of CEC and saturation base exchange rate unless magnesium cation exchange increased in fourth month. There was independent effect of volcanic ash formed nanoparticles towards base saturation exchange increased for 5% dose. There was independent effect of rock phosphate formed nanoparticles towards base saturation exchange and increased for 5% dose. The dose combination of volcanic ashes 7.5% with phosphate rock, 5% increased the base saturation in the first month incubation.

Radiation dosimetry estimates of (18)F-alfatide II based on whole-body PET imaging of mice.

PubMed

Wang, Si-Yang; Bao, Xiao; Wang, Ming-Wei; Zhang, Yong-Ping; Zhang, Ying-Jian; Zhang, Jian-Ping

2015-11-01

We estimated the dosimetry of (18)F-alfatide II with the method established by MIRD based on biodistribution data of mice. Six mice (three females and three males) were scanned for 160min on an Inveon MicroPET/CT scanner after injection of (18)F-alfatide II via tail vein. Eight source organs were delineated on the CT images and their residence times calculated. The data was then converted to human using scaling factors based on organ and body weight. The absorbed doses for human and the resulting effective dose were computed by OLINDA 1.1 software. The highest absorbed doses was observed in urinary bladder wall (male 0.102mGy/MBq, female 0.147mGy/MBq); and the lowest one was detected in brain (male 0.0030mGy/MBq, female 0.0036). The total effective doses were 0.0127mSv/MBq for male and 0.0166 mSv/MBq for female, respectively. A 370-MBq injection of (18)F-alfatide II led to an estimated effective dose of 4.70mSv for male and 6.14mSv for female. The potential radiation burden associated with (18)F-alfatide II/PET imaging therefore is comparable to other PET examinations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perfusion CT of the Brain and Liver and of Lung Tumors: Use of Monte Carlo Simulation for Patient Dose Estimation for Examinations With a Cone-Beam 320-MDCT Scanner.

PubMed

Cros, Maria; Geleijns, Jacob; Joemai, Raoul M S; Salvadó, Marçal

2016-01-01

The purpose of this study was to estimate the patient dose from perfusion CT examinations of the brain, lung tumors, and the liver on a cone-beam 320-MDCT scanner using a Monte Carlo simulation and the recommendations of the International Commission on Radiological Protection (ICRP). A Monte Carlo simulation based on the Electron Gamma Shower Version 4 package code was used to calculate organ doses and the effective dose in the reference computational phantoms for an adult man and adult woman as published by the ICRP. Three perfusion CT acquisition protocols--brain, lung tumor, and liver perfusion--were evaluated. Additionally, dose assessments were performed for the skin and for the eye lens. Conversion factors were obtained to estimate effective doses and organ doses from the volume CT dose index and dose-length product. The sex-averaged effective doses were approximately 4 mSv for perfusion CT of the brain and were between 23 and 26 mSv for the perfusion CT body protocols. The eye lens dose from the brain perfusion CT examination was approximately 153 mGy. The sex-averaged peak entrance skin dose (ESD) was 255 mGy for the brain perfusion CT studies, 157 mGy for the lung tumor perfusion CT studies, and 172 mGy for the liver perfusion CT studies. The perfusion CT protocols for imaging the brain, lung tumors, and the liver performed on a 320-MDCT scanner yielded patient doses that are safely below the threshold doses for deterministic effects. The eye lens dose, peak ESD, and effective doses can be estimated for other clinical perfusion CT examinations from the conversion factors that were derived in this study.

The Impact of Disulfiram Treatment on the Reinforcing Effects of Cocaine: A Randomized Clinical Trial

PubMed Central

Haile, Colin N.; De La Garza, Richard; Mahoney, James J.; Nielsen, David A.; Kosten, Thomas R.; Newton, Thomas F.

2012-01-01

Background Clinical trials indicate that disulfiram (250 mg/d) reduces cocaine use, though one study found that treatment with lower doses of disulfiram (62.5 and 125 mg/d) increased cocaine use. We conducted the present study to better understand how disulfiram alters the reinforcing effects of cocaine in cocaine users. Methods Seventeen non-treatment seeking, cocaine-dependent volunteers participated in this double-blind, placebo-controlled, laboratory-based study. A cross-over design was utilized in which participants received placebo in one phase and disulfiram (250 mg/d) in the other. Following three days of study medication participants completed two choice sessions. In one they made 10 choices between receiving an intravenous infusion of saline or money that increased in value (US$ 0.05–16) and in the other cocaine (20 mg) or money. Results Participants chose cocaine more than saline under both disulfiram and placebo conditions (p<0.05). Unexpectedly, disulfiram increased both the number of cocaine and saline infusion choices (p<0.05). We next examined the relationship between disulfiram dose and cocaine choices. Disulfiram dose (mg/kg bodyweight) was negatively correlated with number of choices for cocaine (p<0.05). Disulfiram also enhanced cocaine-induced increases in cardiovascular measures (p's<0.05–0.01). Conclusions Disulfiram's impact on the reinforcing effects of cocaine depends on dose relative to body weight. Our results suggest that the use of weight-based medication doses would produce more reliable effects, consistent with weight-based dosing used in pediatrics and in preclinical research. Trial Registration Clinicaltrials.gov NCT00729300 PMID:23144826

Optimization of the temporal pattern of applied dose for a single fraction of radiation: Implications for radiation therapy

NASA Astrophysics Data System (ADS)

Altman, Michael B.

The increasing prevalence of intensity modulated radiation therapy (IMRT) as a treatment modality has led to a renewed interest in the potential for interaction between prolonged treatment time, as frequently associated with IMRT, and the underlying radiobiology of the irradiated tissue. A particularly relevant aspect of radiobiology is cell repair capacity, which influences cell survival, and thus directly relates to the ability to control tumors and spare normal tissues. For a single fraction of radiation, the linear quadratic (LQ) model is commonly used to relate the radiation dose to the fraction of cells surviving. The LQ model implies a dependence on two time-related factors which correlate to radiobiological effects: the duration of radiation application, and the functional form of how the dose is applied over that time (the "temporal pattern of applied dose"). Although the former has been well studied, the latter has not. Thus, the goal of this research is to investigate the impact of the temporal pattern of applied dose on the survival of human cells and to explore how the manipulation of this temporal dose pattern may be incorporated into an IMRT-based radiation therapy treatment planning scheme. The hypothesis is that the temporal pattern of applied dose in a single fraction of radiation can be optimized to maximize or minimize cell kill. Furthermore, techniques which utilize this effect could have clinical ramifications. In situations where increased cell kill is desirable, such as tumor control, or limiting the degree of cell kill is important, such as the sparing of normal tissue, temporal sequences of dose which maximize or minimize cell kill (temporally "optimized" sequences) may provide greater benefit than current clinically used radiation patterns. In the first part of this work, an LQ-based modeling analysis of effects of the temporal pattern of dose on cell kill is performed. Through this, patterns are identified for maximizing cell kill for a given radiation pattern by concentrating the highest doses in the middle of a fraction (a "Triangle" pattern), or minimizing cell kill by placing the highest doses near the beginning and end (a "V-shaped" pattern). The conditions under which temporal optimization effects are most acute are also identified: irradiation of low alpha/beta tissues, long fraction durations, and high doses/fx. An in vitro study is then performed which verifies that the temporal effects and trends predicted by the modeling study are clearly manifested in human cells. Following this a phantom which could allow similar in vitro radiobiological experiments in a 3-dimensional clinically-based environment is designed, created, and dosimetrically assessed using TLDs, film, and biological assay-based techniques. The phantom is found to be a useful and versatile tool for such experiments. A scheme for utilizing the phantom in a clinical treatment environment is then developed. This includes a demonstration of prototype methods for optimizing the temporal pattern of applied dose in clinical IMRT plans to manipulate tissue-dependent effects. Looking toward future experimental validation of such plans using the phantom, an analysis of the suitability of biological assays for use in phantom-based in vitro experiments is performed. Finally, a discussion is provided about the steps necessary to integrate temporal optimization into in vivo experiments and ultimately into a clinical radiation therapy environment. If temporal optimization is ultimately shown to have impact in vivo, the successful implementation of the methods developed in this study could enhance the efficacy and care of thousands of patients receiving radiotherapy.

An estimation of Canadian population exposure to cosmic rays from air travel.

PubMed

Chen, Jing; Newton, Dustin

2013-03-01

Based on air travel statistics in 1984, it was estimated that less than 4 % of the population dose from cosmic ray exposure would result from air travel. In the present study, cosmic ray doses were calculated for more than 3,000 flights departing from more than 200 Canadian airports using actual flight profiles. Based on currently available air travel statistics, the annual per capita effective dose from air transportation is estimated to be 32 μSv for Canadians, about 10 % of the average cosmic ray dose received at ground level (310 μSv per year).

Model-Based Dose Selection for Intravaginal Ring Formulations Releasing Anastrozole and Levonorgestrel Intended for the Treatment of Endometriosis Symptoms.

PubMed

Reinecke, Isabel; Schultze-Mosgau, Marcus-Hillert; Nave, Rüdiger; Schmitz, Heinz; Ploeger, Bart A

2017-05-01

Pharmacokinetics (PK) of anastrozole (ATZ) and levonorgestrel (LNG) released from an intravaginal ring (IVR) intended to treat endometriosis symptoms were characterized, and the exposure-response relationship focusing on the development of large ovarian follicle-like structures was investigated by modeling and simulation to support dose selection for further studies. A population PK analysis and simulations were performed for ATZ and LNG based on clinical phase 1 study data from 66 healthy women. A PK/PD model was developed to predict the probability of a maximum follicle size ≥30 mm and the potential contribution of ATZ beside the known LNG effects. Population PK models for ATZ and LNG were established where the interaction of LNG with sex hormone-binding globulin (SHBG) as well as a stimulating effect of estradiol on SHBG were considered. Furthermore, simulations showed that doses of 40 μg/d LNG combined with 300, 600, or 1050 μg/d ATZ reached anticipated exposure levels for both drugs, facilitating selection of ATZ and LNG doses in the phase 2 dose-finding study. The main driver for the effect on maximum follicle size appears to be unbound LNG exposure. A 50% probability of maximum follicle size ≥30 mm was estimated for 40 μg/d LNG based on the exposure-response analysis. ATZ in the dose range investigated does not increase the risk for ovarian cysts as occurs with LNG at a dose that does not inhibit ovulation. © 2016, The American College of Clinical Pharmacology.

SU-E-J-240: The Impact On Clinical Dose-Distributions When Using MR-Images Registered with Stereotactic CT-Images in Gamma Knife Radiosurgery

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

Benmakhlouf, H; Kraepelien, T; Forander, P

2014-06-01

Purpose: Most Gamma knife treatments are based solely on MR-images. However, for fractionated treatments and to implement TPS dose calculations that require electron densities, CT image data is essential. The purpose of this work is to assess the dosimetric effects of using MR-images registered with stereotactic CT-images in Gamma knife treatments. Methods: Twelve patients treated for vestibular schwannoma with Gamma Knife Perfexion (Elekta Instruments, Sweden) were selected for this study. The prescribed doses (12 Gy to periphery) were delivered based on the conventional approach of using stereotactic MR-images only. These plans were imported into stereotactic CT-images (by registering MR-images withmore » stereotactic CT-images using the Leksell gamma plan registration software). The dose plans, for each patient, are identical in both cases except for potential rotations and translations resulting from the registration. The impact of the registrations was assessed by an algorithm written in Matlab. The algorithm compares the dose-distributions voxel-by-voxel between the two plans, calculates the full dose coverage of the target (treated in the conventional approach) achieved by the CT-based plan, and calculates the minimum dose delivered to the target (treated in the conventional approach) achieved by the CT-based plan. Results: The mean dose difference between the plans was 0.2 Gy to 0.4 Gy (max 4.5 Gy) whereas between 89% and 97% of the target (treated in the conventional approach) received the prescribed dose, by the CT-plan. The minimum dose to the target (treated in the conventional approach) given by the CT-based plan was between 7.9 Gy and 10.7 Gy (compared to 12 Gy in the conventional treatment). Conclusion: The impact of using MR-images registered with stereotactic CT-images has successfully been compared to conventionally delivered dose plans showing significant differences between the two. Although CTimages have been implemented clinically; the effect of the registration has not been fully investigated.« less

PROPOSALS FOR THE ESTABLISHMENT OF NATIONAL DIAGNOSTIC REFERENCE LEVELS FOR RADIOGRAPHY FOR ADULT PATIENTS BASED ON REGIONAL DOSE SURVEYS IN RUSSIAN FEDERATION.

PubMed

Vodovatov, A V; Balonov, M I; Golikov, V Yu; Shatsky, I G; Chipiga, L A; Bernhardsson, C

2017-04-01

In 2009-2014, dose surveys aimed to collect adult patient data and parameters of most common radiographic examinations were performed in six Russian regions. Typical patient doses were estimated for the selected examinations both in entrance surface dose and in effective dose. 75%-percentiles of typical patient effective dose distributions were proposed as preliminary regional diagnostic reference levels (DRLs) for radiography. Differences between the 75%-percentiles of regional typical patient dose distributions did not exceed 30-50% for the examinations with standardized clinical protocols (skull, chest and thoracic spine) and a factor of 1.5 for other examinations. Two different approaches for establishing national DRLs were evaluated: as a 75%-percentile of a pooled regional sample of patient typical doses (pooled method) and as a median of 75%-percentiles of regional typical patient dose distributions (median method). Differences between pooled and median methods for effective dose did not exceed 20%. It was proposed to establish Russian national DRLs in effective dose using a pooled method. In addition, the local authorities were granted an opportunity to establish regional DRLs if the local radiological practice and typical patient dose distributions are significantly different. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Analysis of dose to patient, spouse/caretaker, and staff, from an implanted trackable radioactive fiducial for use in the radiation treatment of prostate cancer

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

Neustadter, David; Barnea, Gideon; Stokar, Saul

Purpose: A fiducial tracking system based on a novel radioactive tracking technology is being developed for real-time target tracking in radiation therapy. In this study, the authors calculate the radiation dose to the patient, the spouse/caretaker, and the medical staff that would result from a 100 {mu}Ci Ir192 radioactive fiducial marker permanently implanted in the prostate of a radiation therapy patient. Methods: Local tissue dose was calculated by Monte Carlo simulation. The patient's whole body effective dose equivalent was calculated by summing the doses to the sensitive organs. Exposure of the spouse/caretaker was calculated from the NRC guidelines. Exposure ofmore » the medical staff was based on estimates of proximity to and time spent with the patient. Results: The local dose is below 40 Gy at 5 mm from the marker and below 10 Gy at 10 mm from the marker. The whole body effective dose equivalent to the patient is 64 mSv. The dose to the spouse/caretaker is 0.25 mSv. The annual exposures of the medical staff are 0.2 mSv for a doctor performing implantations and 0.34 mSv for a radiation therapist positioning patients for therapy. Conclusions: The local dose is not expected to have any clinically significant effect on the surrounding tissue which is irradiated during therapy. The dose to the patient is small in comparison to the whole body dose received from the therapy itself. The exposure of all other people is well below the recommended limits. The authors conclude that there is no radiation exposure related contraindication for use of this technology in the radiation treatment of prostate cancer.« less

Effect of +-methamphetamine on path integration learning, novel object recognition, and neurotoxicity in rats.

PubMed

Herring, Nicole R; Schaefer, Tori L; Gudelsky, Gary A; Vorhees, Charles V; Williams, Michael T

2008-09-01

Methamphetamine (MA) has been implicated in cognitive deficits in humans after chronic use. Animal models of neurotoxic MA exposure reveal persistent damage to monoaminergic systems but few associated cognitive effects. Since questions have been raised about the typical neurotoxic dosing regimen used in animals and whether it adequately models human cumulative drug exposure, these experiments examined two different dosing regimens. Rats were treated with one of the two regimens: one based on the typical neurotoxic regimen (4 x 10 mg/kg every 2 h) and one based on pharmacokinetic modeling (Cho AK, Melega WP, Kuczenski R, Segal DS Synapse 39:161-166, 2001) designed to better represent accumulating plasma concentrations of MA as seen in human users (24 x 1.67 mg/kg once every 15 min) matched for total daily dose. In two separate experiments, dosing regimens were compared for their effects on markers of neurotoxicity or on behavior. On markers of neurotoxicity, MA showed decreased dopamine (DA) and 5-HT, increased glial fibrillary acidic protein, and increased corticosterone levels regardless of dosing regimen 3 days post-treatment. Behaviorally, MA-treated groups, regardless of dosing regimen, showed hypoactivity, increased initial hyperactivity to a subsequent MA challenge, impaired novel object recognition, impaired learning in a multiple T water maze test of path integration, and no differences on spatial navigation or reference memory in the Morris water maze. After behavioral testing, reductions of DA and 5-HT remained. MA treatment induces an effect on path integration learning not previously reported. Dosing regimen had no differential effects on behavior or neurotoxicity.

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.

A practical method of I-131 thyroid cancer therapy dose optimization using estimated effective renal clearance.

PubMed

Howard, Brandon A; James, Olga G; Perkins, Jennifer M; Pagnanelli, Robert A; Borges-Neto, Salvador; Reiman, Robert E

2017-01-01

In thyroid cancer patients with renal impairment or other complicating factors, it is important to maximize I-131 therapy efficacy while minimizing bone marrow and lung damage. We developed a web-based calculator based on a modified Benua and Leeper method to calculate the maximum I-131 dose to reduce the risk of these toxicities, based on the effective renal clearance of I-123 as measured from two whole-body I-123 scans, performed at 0 and 24 h post-administration.

Organ dose conversion coefficients based on a voxel mouse model and MCNP code for external photon irradiation.

PubMed

Zhang, Xiaomin; Xie, Xiangdong; Cheng, Jie; Ning, Jing; Yuan, Yong; Pan, Jie; Yang, Guoshan

2012-01-01

A set of conversion coefficients from kerma free-in-air to the organ absorbed dose for external photon beams from 10 keV to 10 MeV are presented based on a newly developed voxel mouse model, for the purpose of radiation effect evaluation. The voxel mouse model was developed from colour images of successive cryosections of a normal nude male mouse, in which 14 organs or tissues were segmented manually and filled with different colours, while each colour was tagged by a specific ID number for implementation of mouse model in Monte Carlo N-particle code (MCNP). Monte Carlo simulation with MCNP was carried out to obtain organ dose conversion coefficients for 22 external monoenergetic photon beams between 10 keV and 10 MeV under five different irradiation geometries conditions (left lateral, right lateral, dorsal-ventral, ventral-dorsal, and isotropic). Organ dose conversion coefficients were presented in tables and compared with the published data based on a rat model to investigate the effect of body size and weight on the organ dose. The calculated and comparison results show that the organ dose conversion coefficients varying the photon energy exhibits similar trend for most organs except for the bone and skin, and the organ dose is sensitive to body size and weight at a photon energy approximately <0.1 MeV.

Lens dose in routine head CT: comparison of different optimization methods with anthropomorphic phantoms.

PubMed

Nikupaavo, Ulla; Kaasalainen, Touko; Reijonen, Vappu; Ahonen, Sanna-Mari; Kortesniemi, Mika

2015-01-01

The purpose of this study was to study different optimization methods for reducing eye lens dose in head CT. Two anthropomorphic phantoms were scanned with a routine head CT protocol for evaluation of the brain that included bismuth shielding, gantry tilting, organ-based tube current modulation, or combinations of these techniques. Highsensitivity metal oxide semiconductor field effect transistor dosimeters were used to measure local equivalent doses in the head region. The relative changes in image noise and contrast were determined by ROI analysis. The mean absorbed lens doses varied from 4.9 to 19.7 mGy and from 10.8 to 16.9 mGy in the two phantoms. The most efficient method for reducing lens dose was gantry tilting, which left the lenses outside the primary radiation beam, resulting in an approximately 75% decrease in lens dose. Image noise decreased, especially in the anterior part of the brain. The use of organ-based tube current modulation resulted in an approximately 30% decrease in lens dose. However, image noise increased as much as 30% in the posterior and central parts of the brain. With bismuth shields, it was possible to reduce lens dose as much as 25%. Our results indicate that gantry tilt, when possible, is an effective method for reducing exposure of the eye lenses in CT of the brain without compromising image quality. Measurements in two different phantoms showed how patient geometry affects the optimization. When lenses can only partially be cropped outside the primary beam, organ-based tube current modulation or bismuth shields can be useful in lens dose reduction.

The relationship of body mass index and abdominal fat on the radiation dose received during routine computed tomographic imaging of the abdomen and pelvis.

PubMed

Chan, Victoria O; McDermott, Shaunagh; Buckley, Orla; Allen, Sonya; Casey, Michael; O'Laoide, Risteard; Torreggiani, William C

2012-11-01

To determine the relationship of increasing body mass index (BMI) and abdominal fat on the effective dose acquired from computed tomography (CT) abdomen and pelvis scans. Over 6 months, dose-length product and total milliamp-seconds (mAs) from routine CT abdomen and pelvis scans of 100 patients were recorded. The scans were performed on a 64-slice CT scanner by using an automatic exposure control system. Effective dose (mSv) based on dose-length product, BMI, periumbilical fat thickness, and intra-abdominal fat were documented for each patient. BMI, periumbilical fat thickness, and intra-abdominal fat were compared with effective dose. Thirty-nine men and 61 women were included in the study (mean age, 56.3 years). The mean BMI was 26.2 kg/m(2). The mean effective dose was 10.3 mSv. The mean periumbilical fat thickness was 2.4 cm. Sixty-five patients had a small amount of intra-abdominal fat, and 35 had a large amount of intra-abdominal fat. The effective dose increased with increasing BMI (P < .001) and increasing amounts of intra-abdominal fat (P < .001). For every kilogram of weight, there is a 0.13 mSv increase in effective dose, which is equal to 6.5 chest radiographs per CT examination. For an increase in BMI by 5 kg/m(2), there is a 1.95 mSv increase in effective dose, which is equal to 97.5 chest radiographs per CT examination. Increasing BMI and abdominal fat significantly increases the effective dose received from CT abdomen and pelvis scans. Copyright © 2012 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Dose-Effect Relationships for Individual Pelvic Floor Muscles and Anorectal Complaints After Prostate Radiotherapy

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

Smeenk, Robert Jan, E-mail: r.smeenk@rther.umcn.nl; Hoffmann, Aswin L.; Hopman, Wim P.M.

2012-06-01

Purpose: To delineate the individual pelvic floor muscles considered to be involved in anorectal toxicity and to investigate dose-effect relationships for fecal incontinence-related complaints after prostate radiotherapy (RT). Methods and Materials: In 48 patients treated for localized prostate cancer, the internal anal sphincter (IAS) muscle, the external anal sphincter (EAS) muscle, the puborectalis muscle (PRM), and the levator ani muscles (LAM) in addition to the anal wall (Awall) and rectal wall (Rwall) were retrospectively delineated on planning computed tomography scans. Dose parameters were obtained and compared between patients with and without fecal urgency, incontinence, and frequency. Dose-effect curves were constructed.more » Finally, the effect of an endorectal balloon, which was applied in 28 patients, was investigated. Results: The total volume of the pelvic floor muscles together was about three times that of the Awall. The PRM was exposed to the highest RT dose, whereas the EAS received the lowest dose. Several anal and rectal dose parameters, as well as doses to all separate pelvic floor muscles, were associated with urgency, while incontinence was associated mainly with doses to the EAS and PRM. Based on the dose-effect curves, the following constraints regarding mean doses could be deduced to reduce the risk of urgency: {<=}30 Gy to the IAS; {<=}10 Gy to the EAS; {<=}50 Gy to the PRM; and {<=}40 Gy to the LAM. No dose-effect relationships for frequency were observed. Patients treated with an endorectal balloon reported significantly less urgency and incontinence, while their treatment plans showed significantly lower doses to the Awall, Rwall, and all pelvic floor muscles. Conclusions: Incontinence-related complaints show specific dose-effect relationships to individual pelvic floor muscles. Dose constraints for each muscle can be identified for RT planning. When only the Awall is delineated, substantial components of the continence apparatus are excluded.« less

Dose-effect relationships for individual pelvic floor muscles and anorectal complaints after prostate radiotherapy.

PubMed

Smeenk, Robert Jan; Hoffmann, Aswin L; Hopman, Wim P M; van Lin, Emile N J Th; Kaanders, Johannes H A M

2012-06-01

To delineate the individual pelvic floor muscles considered to be involved in anorectal toxicity and to investigate dose-effect relationships for fecal incontinence-related complaints after prostate radiotherapy (RT). In 48 patients treated for localized prostate cancer, the internal anal sphincter (IAS) muscle, the external anal sphincter (EAS) muscle, the puborectalis muscle (PRM), and the levator ani muscles (LAM) in addition to the anal wall (Awall) and rectal wall (Rwall) were retrospectively delineated on planning computed tomography scans. Dose parameters were obtained and compared between patients with and without fecal urgency, incontinence, and frequency. Dose-effect curves were constructed. Finally, the effect of an endorectal balloon, which was applied in 28 patients, was investigated. The total volume of the pelvic floor muscles together was about three times that of the Awall. The PRM was exposed to the highest RT dose, whereas the EAS received the lowest dose. Several anal and rectal dose parameters, as well as doses to all separate pelvic floor muscles, were associated with urgency, while incontinence was associated mainly with doses to the EAS and PRM. Based on the dose-effect curves, the following constraints regarding mean doses could be deduced to reduce the risk of urgency: ≤ 30 Gy to the IAS; ≤ 10 Gy to the EAS; ≤ 50 Gy to the PRM; and ≤ 40 Gy to the LAM. No dose-effect relationships for frequency were observed. Patients treated with an endorectal balloon reported significantly less urgency and incontinence, while their treatment plans showed significantly lower doses to the Awall, Rwall, and all pelvic floor muscles. Incontinence-related complaints show specific dose-effect relationships to individual pelvic floor muscles. Dose constraints for each muscle can be identified for RT planning. When only the Awall is delineated, substantial components of the continence apparatus are excluded. Copyright © 2012 Elsevier Inc. All rights reserved.

MOVING FROM EXTERNAL EXPOSURE CONCENTRATION TO INTERNAL DOSE: DURATION EXTRAPOLATION BASED ON PHYSIOLOGICALLY-BASED PHARMACOKINETIC-MODEL DERIVED ESTIMATES OF INTERNAL DOSE

EPA Science Inventory

The potential human health risk(s) from exposure to chemicals under conditions for which adequate human or animal data are not available must frequently be assessed. Exposure scenario is particularly important for the acute neurotoxic effects of volatile organic compounds (VOCs)...

Comparison of TG-43 and TG-186 in breast irradiation using a low energy electronic brachytherapy source.

PubMed

White, Shane A; Landry, Guillaume; Fonseca, Gabriel Paiva; Holt, Randy; Rusch, Thomas; Beaulieu, Luc; Verhaegen, Frank; Reniers, Brigitte

2014-06-01

The recently updated guidelines for dosimetry in brachytherapy in TG-186 have recommended the use of model-based dosimetry calculations as a replacement for TG-43. TG-186 highlights shortcomings in the water-based approach in TG-43, particularly for low energy brachytherapy sources. The Xoft Axxent is a low energy (<50 kV) brachytherapy system used in accelerated partial breast irradiation (APBI). Breast tissue is a heterogeneous tissue in terms of density and composition. Dosimetric calculations of seven APBI patients treated with Axxent were made using a model-based Monte Carlo platform for a number of tissue models and dose reporting methods and compared to TG-43 based plans. A model of the Axxent source, the S700, was created and validated against experimental data. CT scans of the patients were used to create realistic multi-tissue/heterogeneous models with breast tissue segmented using a published technique. Alternative water models were used to isolate the influence of tissue heterogeneity and backscatter on the dose distribution. Dose calculations were performed using Geant4 according to the original treatment parameters. The effect of the Axxent balloon applicator used in APBI which could not be modeled in the CT-based model, was modeled using a novel technique that utilizes CAD-based geometries. These techniques were validated experimentally. Results were calculated using two dose reporting methods, dose to water (Dw,m) and dose to medium (Dm,m), for the heterogeneous simulations. All results were compared against TG-43-based dose distributions and evaluated using dose ratio maps and DVH metrics. Changes in skin and PTV dose were highlighted. All simulated heterogeneous models showed a reduced dose to the DVH metrics that is dependent on the method of dose reporting and patient geometry. Based on a prescription dose of 34 Gy, the average D90 to PTV was reduced by between ~4% and ~40%, depending on the scoring method, compared to the TG-43 result. Peak skin dose is also reduced by 10%-15% due to the absence of backscatter not accounted for in TG-43. The balloon applicator also contributed to the reduced dose. Other ROIs showed a difference depending on the method of dose reporting. TG-186-based calculations produce results that are different from TG-43 for the Axxent source. The differences depend strongly on the method of dose reporting. This study highlights the importance of backscatter to peak skin dose. Tissue heterogeneities, applicator, and patient geometries demonstrate the need for a more robust dose calculation method for low energy brachytherapy sources.

Mapping of RBE-Weighted Doses Between HIMAC- and LEM-Based Treatment Planning Systems for Carbon Ion Therapy

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

Steinstraeter, Olaf, E-mail: o.steinstraeter@gsi.de; Gruen, Rebecca; Institut fuer Medizinische Physik und Strahlenschutz, TH-Mittelhessen, Giessen

2012-11-01

Purpose: A method was developed to convert clinically prescribed RBE (Relative Biological Effectiveness)-weighted doses from the approach used at the Heavy-Ion Medical Accelerator (HIMAC) at the National Institute of Radiological Science, Chiba, Japan, to the LEM (Local Effect Model)-based TReatment planning for Particles (TRiP98) approach used in the pilot project at the GSI Helmholtzzentrum, Darmstadt, and the Heidelberg Ion-Beam Therapy Center (HIT). Methods and Materials: The proposed conversion method is based on a simulation of the fixed spread-out Bragg peak (SOBP) depth dose profiles as used for the irradiation at HIMAC by LEM/TRiP98 and a recalculation of the resulting RBE-weightedmore » dose distribution. We present data according to the clinical studies conducted at GSI in the past decade (LEM I), as well as data used in current studies (refined LEM version: LEM IV). Results: We found conversion factors (RBE-weighted dose LEM/RBE-weighted dose HIMAC) reaching from 0.4 to 2.0 for prescribed carbon ion doses from 1 to 60 Gy (RBE) for SOBP extensions ranging from 20 to 120 mm according to the HIMAC approach. A conversion factor of 1.0 was found for approximately 5 Gy (RBE). The conversion factor decreases with increasing prescribed dose. Slightly smaller values for the LEM IV-based data set compared with LEM I were found. A significant dependence of the conversion factor from the SOBP width could be observed in particular for LEM IV, whereas the depth dependence was found to be small. Conclusions: For the interpretation and comparison of clinical trials performed at HIMAC and GSI/HIT, it is of extreme importance to consider these conversion factors because according to the various methods to determine the RBE-weighted dose, similar dose values might not necessarily be related to similar clinical outcomes.« less

The effect of dose enhancement near metal interfaces on synthetic diamond based X-ray dosimeters

NASA Astrophysics Data System (ADS)

Alamoudi, D.; Lohstroh, A.; Albarakaty, H.

2017-11-01

This study investigates the effects of dose enhancement on the photocurrent performance at metallic interfaces in synthetic diamond detectors based X-ray dosimeters as a function of bias voltages. Monte Carlo (MC) simulations with the BEAMnrc code were carried out to simulate the dose enhancement factor (DEF) and compared against the equivalent photocurrent ratio from experimental investigations. The MC simulation results show that the sensitive region for the absorbed dose distribution covers a few micrometers distances from the interface. Experimentally, two single crystals (SC) and one polycrystalline (PC) synthetic diamond samples were fabricated into detectors with carbon based electrodes by boron and carbon ion implantation. Subsequently; the samples were each mounted inside a tissue equivalent encapsulation to minimize unintended fluence perturbation. Dose enhancement was generated by placing copper, lead or gold near the active volume of the detectors using 50 kVp and 100 kVp X-rays relevant for medical dosimetry. The results show enhancement in the detectors' photocurrent performance when different metals are butted up to the diamond bulk as expected. The variation in the photocurrent measurement depends on the type of diamond samples, their electrodes' fabrication and the applied bias voltages indicating that the dose enhancement near the detector may modify their electronic performance.

Efficacy and safety of weight-based insulin glargine dose titration regimen compared with glucose level- and current dose-based regimens in hospitalized patients with type 2 diabetes: a randomized, controlled study.

PubMed

Li, Xiaowei; Du, Tao; Li, Wangen; Zhang, Tong; Liu, Haiyan; Xiong, Yifeng

2014-09-01

Insulin glargine is widely used as basal insulin. However, published dose titration regimens for insulin glargine are complex. This study aimed to compare the efficacy and safety profile of a user-friendly, weight-based insulin glargine dose titration regimen with 2 published regimens. A total of 160 hospitalized patients with hyperglycemia in 3 medical centers were screened. Our inclusion criteria included age 18 to 80 years and being conscious. Exclusion criteria included pregnancy or breast-feeding and hepatic or renal dysfunction. A total of 149 patients were randomly assigned to receive weight-based, glucose level-based, or dose-based insulin glargine dose titration regimen between January 2011 and February 2013. The initial dose of insulin glargine was 0.2 U/kg. In the weight-based regimen (n = 49), the dose was titrated by increments of 0.1 U/kg daily. In the glucose level-based regimen (n = 51), the dose was titrated by 2, 4, 6, or 8 U daily when fasting blood glucose (FBG) was, respectively, between 7.0 and 7.9, 8.0 and 8.9, 9.0 and 9.9, or ≥10 mmol/L. In the current dose-based regimen (n = 49), titration was by daily increments of 20% of the current dose. The target FBG in all groups was ≤7.0 mmol/L. The incidence of hypoglycemia was recorded. One-way ANOVA and χ(2) test were used to compare data between the 3 groups. All but 1 patient who required additional oral antidiabetic medication completed the study. The mean (SD) time to achieve target FBG was 3.2 (1.2) days with the weight-based regimen and 3.7 (1.5) days with the glucose level-based regimen (P = 0.266). These times were both shorter than that achieved with the current dose-based regimen (4.8 [2.8] days; P = 0.0001 and P = 0.005, respectively). The daily doses of insulin glargine at the study end point were 0.43 (0.13) U/kg with the weight-based regimen, 0.50 (0.20) U/kg with the glucose level-based regimen, and 0.47 (0.23) U/kg with the current dose-based regimen (P = 0.184). The incidence of hypoglycemia was 4.1%, 2.0%, and 6.3%, respectively (P = 0.557). The currently proposed weight-based insulin glargine dose titration regimen is effective, tolerable, and user-friendly at achieving FBG target levels in hospitalized patients with hyperglycemia. Copyright © 2014 Elsevier HS Journals, Inc. All rights reserved.

A method to improve the effectiveness of diode in vivo dosimetry.

PubMed

Alecu, R; Alecu, M; Ochran, T G

1998-05-01

A routine diode in vivo dosimetry program based on a combination of entrance and exit dose measurements was clinically implemented in the radiation oncology department of Grace Hospital, Detroit, in January 1995. The delivered dose has been monitored by taking weekly measurements. The calibration of the diodes and the in vivo dosimetry protocol for this new, more effective type of dose verification is presented. The problems encountered within the program are discussed along with our solutions.

The feasibility assessment of radiation dose of movement 3D NIPAM gel by magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Hsieh, Chih-Ming; Leung, Joseph Hang; Ng, Yu-Bun; Cheng, Chih-Wu; Sun, Jung-Chang; Lin, Ping-Chin; Hsieh, Bor-Tsung

2015-11-01

NIPAM dosimeter is widely accepted and recommended for its 3D distribution and accuracy in dose absorption. Up to the moment, most research works on dose measurement are based on a fixed irradiation target without the consideration of the effect from physiological motion. We present a study to construct a respiratory motion simulating patient anatomical and dosimetry model for the study of dosimetic effect of organ motion. The dose on fixed and motion targets was measured by MRI after a dose adminstration of 1, 2, 5, 8, and 10 Gy from linear accelerator. Comparison of two situations is made. The average sensitivity of fixed NIPAM was 0.1356 s-1/Gy with linearity R2=0.998. The average sensitivity of movement NIPAM was 0.1366 s-1/Gy with linearity R2=0.998 both having only 0.001 of the sensitivity difference. The difference between the two based on dose rate dependency, position and depth was not significant. There was thus no apparent impact on NIPAM dosimeter from physiological motion. The high sensitivity, linearity and stability of NIPAM dosimeter proved to be an ideal apparatus in the dose measurement in these circumstances.

Fast method for in-flight estimation of total dose from protons and electrons using RADE Minstrument on JUICE

NASA Astrophysics Data System (ADS)

Hajdas, Wojtek; Mrigakshi, Alankrita; Xiao, Hualin

2017-04-01

The primary concern of the ESA JUICE mission to Jupiter is the harsh particle radiation environment. Ionizing particles introduce radiation damage by total dose effects, displacement damages or single events effects. Therefore, both the total ionizing dose and the displacement damage equivalent fluence must be assessed to alert spacecraft and its payload as well as to quantify radiation levels for the entire mission lifetime. We present a concept and implementations steps for simplified method used to compute in flight a dose rate and total dose caused by protons. We also provide refinement of the method previously developed for electrons. The dose rates values are given for predefined active volumes located behind layers of materials with known thickness. Both methods are based on the electron and proton flux measurements provided by the Electron and Proton Detectors inside the Radiation Hard Electron Monitor (RADEM) located on-board of JUICE. The trade-off between method accuracy and programming limitations for in-flight computations are discussed. More comprehensive and precise dose rate computations based on detailed analysis of all stack detectors will be made during off-line data processing. It will utilize full spectral unfolding from all RADEM detector subsystems.

Organ dose conversion coefficients for tube current modulated CT protocols for an adult population

NASA Astrophysics Data System (ADS)

Fu, Wanyi; Tian, Xiaoyu; Sahbaee, Pooyan; Zhang, Yakun; Segars, William Paul; Samei, Ehsan

2016-03-01

In computed tomography (CT), patient-specific organ dose can be estimated using pre-calculated organ dose conversion coefficients (organ dose normalized by CTDIvol, h factor) database, taking into account patient size and scan coverage. The conversion coefficients have been previously estimated for routine body protocol classes, grouped by scan coverage, across an adult population for fixed tube current modulated CT. The coefficients, however, do not include the widely utilized tube current (mA) modulation scheme, which significantly impacts organ dose. This study aims to extend the h factors and the corresponding dose length product (DLP) to create effective dose conversion coefficients (k factor) database incorporating various tube current modulation strengths. Fifty-eight extended cardiac-torso (XCAT) phantoms were included in this study representing population anatomy variation in clinical practice. Four mA profiles, representing weak to strong mA dependency on body attenuation, were generated for each phantom and protocol class. A validated Monte Carlo program was used to simulate the organ dose. The organ dose and effective dose was further normalized by CTDIvol and DLP to derive the h factors and k factors, respectively. The h factors and k factors were summarized in an exponential regression model as a function of body size. Such a population-based mathematical model can provide a comprehensive organ dose estimation given body size and CTDIvol. The model was integrated into an iPhone app XCATdose version 2, enhancing the 1st version based upon fixed tube current modulation. With the organ dose calculator, physicists, physicians, and patients can conveniently estimate organ dose.

Implementation and Challenges of Direct Acoustic Dosing into Cell-Based Assays.

PubMed

Roberts, Karen; Callis, Rowena; Ikeda, Tim; Paunovic, Amalia; Simpson, Carly; Tang, Eric; Turton, Nick; Walker, Graeme

2016-02-01

Since the adoption of Labcyte Echo Acoustic Droplet Ejection (ADE) technology by AstraZeneca in 2005, ADE has become the preferred method for compound dosing into both biochemical and cell-based assays across AstraZeneca research and development globally. The initial implementation of Echos and the direct dosing workflow provided AstraZeneca with a unique set of challenges. In this article, we outline how direct Echo dosing has evolved over the past decade in AstraZeneca. We describe the practical challenges of applying ADE technology to 96-well, 384-well, and 1536-well assays and how AstraZeneca developed and applied software and robotic solutions to generate fully automated and effective cell-based assay workflows. © 2015 Society for Laboratory Automation and Screening.

Effect of radiation dose reduction and iterative reconstruction on computer-aided detection of pulmonary nodules: Intra-individual comparison.

PubMed

Den Harder, Annemarie M; Willemink, Martin J; van Hamersvelt, Robbert W; Vonken, Evert-Jan P A; Milles, Julien; Schilham, Arnold M R; Lammers, Jan-Willem; de Jong, Pim A; Leiner, Tim; Budde, Ricardo P J

2016-02-01

To evaluate the effect of radiation dose reduction and iterative reconstruction (IR) on the performance of computer-aided detection (CAD) for pulmonary nodules. In this prospective study twenty-five patients were included who were scanned for pulmonary nodule follow-up. Image acquisition was performed at routine dose and three reduced dose levels in a single session by decreasing mAs-values with 45%, 60% and 75%. Tube voltage was fixed at 120 kVp for patients ≥ 80 kg and 100 kVp for patients < 80 kg. Data were reconstructed with filtered back projection (FBP), iDose(4) (levels 1,4,6) and IMR (levels 1-3). All noncalcified solid pulmonary nodules ≥ 4 mm identified by two radiologists in consensus served as the reference standard. Subsequently, nodule volume was measured with CAD software and compared to the reference consensus. The numbers of true-positives, false-positives and missed pulmonary nodules were evaluated as well as the sensitivity. Median effective radiation dose was 2.2 mSv at routine dose and 1.2, 0.9 and 0.6 mSv at respectively 45%, 60% and 75% reduced dose. A total of 28 pulmonary nodules were included. With FBP at routine dose, 89% (25/28) of the nodules were correctly identified by CAD. This was similar at reduced dose levels with FBP, iDose(4) and IMR. CAD resulted in a median number of false-positives findings of 11 per scan with FBP at routine dose (93% of the CAD marks) increasing to 15 per scan with iDose(4) (95% of the CAD marks) and 26 per scan (96% of the CAD marks) with IMR at the lowest dose level. CAD can identify pulmonary nodules at submillisievert dose levels with FBP, hybrid and model-based IR. However, the number of false-positive findings increased using hybrid and especially model-based IR at submillisievert dose while dose reduction did not affect the number of false-positives with FBP. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Clozapine Titration for People in Early Psychosis: A Chart Review and Treatment Guideline.

PubMed

Ballon, Jacob S; Ashfaq, Hera; Noordsy, Douglas L

2018-06-01

The use of clozapine, particularly in young people, is often limited by early treatment-emergent adverse effects including drowsiness and lethargy. Concerns about adverse effects, medication adherence, and the need for blood monitoring often impede the use of clozapine in this population, leading to repeated trials of less effective medications. Current clozapine dosing recommendations are based on people further in the course of their illness and thus reflect different responsiveness and sensitivities to antipsychotic medication. As such, there is a need for evidence-based guidelines for titration and dosing of clozapine among people in early psychosis. We performed a chart review of 14 people treated with clozapine within our early psychosis team. Data regarding dose titration, response, time to discontinuation, symptom severity, weight gain, and other adverse effects were gathered at clozapine initiation, 3 months, and last available visit on clozapine. People treated with slow titration within their first year of psychosis onset achieved sustained response at very low maintenance doses (mean dose = 81 mg/d, mean duration of treatment = 200 weeks) compared with slow titration with longer duration of illness (mean dose = 350 mg/d, mean duration of treatment = 68 weeks) or standard dose titration in early psychosis (mean dose = 112 mg/d, mean duration of treatment = 38 weeks). The most common adverse effects in all groups were weight gain and sedation, with the groups requiring higher mean doses reporting a broader range of adverse effects. There was no apparent difference in the clinical global impression for severity or improvement between the slow titration and standard titration groups in people with early psychosis. These observations are synthesized into a proposed treatment guideline for use of clozapine among people in early psychosis. We describe development of a slow titration approach to initiating clozapine among people in early psychosis. This approach resulted in clinical response at remarkably low maintenance doses of clozapine among people within their first year of illness, but not in those with longer duration of symptoms. Slow titration also led to good tolerability and acceptance of clozapine treatment for some patients.

BENCHMARK DOSE TECHNICAL GUIDANCE DOCUMENT ...

EPA Pesticide Factsheets

The purpose of this document is to provide guidance for the Agency on the application of the benchmark dose approach in determining the point of departure (POD) for health effects data, whether a linear or nonlinear low dose extrapolation is used. The guidance includes discussion on computation of benchmark doses and benchmark concentrations (BMDs and BMCs) and their lower confidence limits, data requirements, dose-response analysis, and reporting requirements. This guidance is based on today's knowledge and understanding, and on experience gained in using this approach.

Increasing the dose of television advertising in a national antismoking media campaign: results from a randomised field trial

PubMed Central

McAfee, Tim; Davis, Kevin C; Shafer, Paul; Patel, Deesha; Alexander, Robert; Bunnell, Rebecca

2017-01-01

Background While antismoking media campaigns have demonstrated effectiveness, less is known about the country-level effects of increased media dosing. The 2012 US Tips From Former Smokers (Tips) campaign generated approximately 1.6 million quit attempts overall; however, the specific dose–response from the campaign was only assessed by self-report. Objective Assess the impact of higher ad exposure during the 2013 Tips campaign on quit-related behaviours and intentions, campaign awareness, communication about campaign, and disease knowledge. Methods A 3-month national media buy was supplemented within 67 (of 190) randomly selected local media markets. Higher-dose markets received media buys 3 times that of standard-dose markets. We compared outcomes of interest using data collected via web-based surveys from nationally representative, address-based probability samples of 5733 cigarette smokers and 2843 non-smokers. Results In higher-dose markets, 87.2% of smokers and 83.9% of non-smokers recalled television campaign exposure versus 75.0% of smokers and 73.9% of non-smokers in standard-dose markets. Among smokers overall, the relative quit attempt rate was 11% higher in higher-dose markets (38.8% vs 34.9%; p<0.04). The higher-dose increase was larger in African-Americans (50.9% vs 31.8%; p<0.01). Smokers in higher-dose markets without a mental health condition, with a chronic health condition, or with only some college education made quit attempts at a higher rate than those in standard-dose markets. Non-smokers in higher-dose markets were more likely to talk with family or friends about smoking dangers (43.1% vs 35.7%; p<0.01) and had greater knowledge of smoking-related diseases. Conclusions The US 2013 Tips antismoking media campaign compared standard and higher doses by randomisation of local media markets. Results demonstrate the effectiveness of a higher dose for engaging non-smokers and further increasing quit attempts among smokers, especially African-Americans. PMID:26678518

Effect of americium-241 alpha-particles on the dose-response of chromosome aberrations in human lymphocytes analysed by fluorescence in situ hybridization.

PubMed

Barquinero, J F; Stephan, G; Schmid, E

2004-02-01

To evaluate by the fluorescent in-situ hybridization (FISH) technique the dose-response and intercellular distribution of alpha-particle-induced chromosome aberrations. In particular, the validity of using the yield of characteristic types of chromosome abnormalities in stable cells as quantitative indicators for retrospective dose reconstruction has been evaluated. Monolayers of human peripheral lymphocytes were exposed at doses from 0.02 to 1 Gy to alpha-particles emitted from a source of americium-241. The most probable energy of the alpha-particles entering the cells was 2.7 MeV. FISH painting was performed using DNA probes for chromosomes 2, 4 and 8 in combination with a pan-centromeric probe. In complete first-division cells, identified by harlequin staining, aberrations involving painted target chromosomal material were recorded as well as aberrations involving only unpainted chromosomal material. In total, the percentage of complex aberrations was about 35% and no dose dependence was observed. When complex-type exchanges were reduced to simple base types, the different cell distributions were clearly over-dispersed, and the linear coefficients of the dose-effect curves for translocations were significantly higher than for dicentrics. For past dose reconstruction, only a few complex aberrations were in stable cells. The linear coefficient obtained for transmissible aberrations in stable cells was more than seven times lower than that obtained in all analysed cells, i.e. including unstable cells. FISH-based analysis of complex rearrangements allows discrimination between partial-body exposures to low-linear energy transfer radiation and high-linear energy transfer exposures. In assessing past or chronic exposure to alpha-particles, the use of a dose-effect curve obtained by FISH-based translocation data, which had not excluded data determined in unstable cells, would underestimate the dose. Insertions are ineffective biomarkers because their frequency is too low.

Impact of the new nuclear decay data of ICRP publication 107 on inhalation dose coefficients for workers

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

Manabe, K.; Endo, Akira; Eckerman, Keith F

2010-03-01

The impact a revision of nuclear decay data had on dose coefficients was studied using data newly published in ICRP Publication 107 (ICRP 107) and existing data from ICRP Publication 38 (ICRP 38). Committed effective dose coefficients for occupational inhalation of radionuclides were calculated using two sets of decay data with the dose and risk calculation software DCAL for 90 elements, 774 nuclides and 1572 cases. The dose coefficients based on ICRP 107 increased by over 10 % compared with those based on ICRP 38 in 98 cases, and decreased by over 10 % in 54 cases. It was foundmore » that the differences in dose coefficients mainly originated from changes in the radiation energy emitted per nuclear transformation. In addition, revisions of the half-lives, radiation types and decay modes also resulted in changes in the dose coefficients.« less

Evaluation of genotype-guided acenocoumarol dosing algorithms in Russian patients.

PubMed

Sychev, Dmitriy Alexeyevich; Rozhkov, Aleksandr Vladimirovich; Ananichuk, Anna Viktorovna; Kazakov, Ruslan Evgenyevich

2017-05-24

Acenocoumarol dose is normally determined via step-by-step adjustment process based on International Normalized Ratio (INR) measurements. During this time, the risk of adverse reactions is especially high. Several genotype-based acenocoumarol dosing algorithms have been created to predict ideal doses at the start of anticoagulant therapy. Nine dosing algorithms were selected through a literature search. These were evaluated using a cohort of 63 patients with atrial fibrillation receiving acenocoumarol therapy. None of the existing algorithms could predict the ideal acenocoumarol dose in 50% of Russian patients. The Wolkanin-Bartnik algorithtm based on European population was the best-performing one with the highest correlation values (r=0.397), mean absolute error (MAE) 0.82 (±0.61). EU-PACT also managed to give an estimate within the ideal range in 43% of the cases. The two least accurate results were yielded by the Indian population-based algorithms. Among patients receiving amiodarone, algorithms by Schie and Tong proved to be the most effective with the MAE of 0.48±0.42 mg/day and 0.56±0.31 mg/day, respectively. Patient ethnicity and amiodarone intake are factors that must be considered when building future algorithms. Further research is required to find the perfect dosing formula of acenocoumarol maintenance doses in Russian patients.

Effects of radiation exposure from cardiac imaging: how good are the data?

PubMed

Einstein, Andrew J

2012-02-07

Concerns about medical exposure to ionizing radiation have become heightened in recent years as a result of rapid growth in procedure volumes and the high radiation doses incurred from some procedures. This paper summarizes the evidence base undergirding concerns about radiation exposure in cardiac imaging. After classifying radiation effects, explaining terminology used to quantify the radiation received by patients, and describing typical doses from cardiac imaging procedures, this paper will address the major epidemiological studies having bearing on radiation effects at doses comparable to those received by patients undergoing cardiac imaging. These include studies of atomic bomb survivors, nuclear industry workers, and children exposed in utero to x-rays, all of which have evidenced increased cancer risks at low doses. Additional higher-dose epidemiological studies of cohorts exposed to radiation in the context of medical treatment are described and found to be generally compatible with these cardiac dose-level studies, albeit with exceptions. Using risk projection models developed by the U.S. National Academies that incorporate these data and reflect several evidence-based assumptions, cancer risk from cardiac imaging can be estimated and compared with the benefits from imaging. Several ongoing epidemiological studies will provide better understanding of radiation-associated cancer risks. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Dose-distance metric that predicts late rectal bleeding in patients receiving radical prostate external-beam radiotherapy

NASA Astrophysics Data System (ADS)

Lee, Richard; Chan, Elisa K.; Kosztyla, Robert; Liu, Mitchell; Moiseenko, Vitali

2012-12-01

The relationship between rectal dose distribution and the incidence of late rectal complications following external-beam radiotherapy has been previously studied using dose-volume histograms or dose-surface histograms. However, they do not account for the spatial dose distribution. This study proposes a metric based on both surface dose and distance that can predict the incidence of rectal bleeding in prostate cancer patients treated with radical radiotherapy. One hundred and forty-four patients treated with radical radiotherapy for prostate cancer were prospectively followed to record the incidence of grade ≥2 rectal bleeding. Radiotherapy plans were used to evaluate a dose-distance metric that accounts for the dose and its spatial distribution on the rectal surface, characterized by a logistic weighting function with slope a and inflection point d0. This was compared to the effective dose obtained from dose-surface histograms, characterized by the parameter n which describes sensitivity to hot spots. The log-rank test was used to determine statistically significant (p < 0.05) cut-off values for the dose-distance metric and effective dose that predict for the occurrence of rectal bleeding. For the dose-distance metric, only d0 = 25 and 30 mm combined with a > 5 led to statistical significant cut-offs. For the effective dose metric, only values of n in the range 0.07-0.35 led to statistically significant cut-offs. The proposed dose-distance metric is a predictor of rectal bleeding in prostate cancer patients treated with radiotherapy. Both the dose-distance metric and the effective dose metric indicate that the incidence of grade ≥2 rectal bleeding is sensitive to localized damage to the rectal surface.

Benchmark Dose Analysis from Multiple Datasets: The Cumulative Risk Assessment for the N-Methyl Carbamate Pesticides

EPA Science Inventory

The US EPA’s N-Methyl Carbamate (NMC) Cumulative Risk assessment was based on the effect on acetylcholine esterase (AChE) activity of exposure to 10 NMC pesticides through dietary, drinking water, and residential exposures, assuming the effects of joint exposure to NMCs is dose-...

SEMICONDUCTOR TECHNOLOGY: An efficient dose-compensation method for proximity effect correction

NASA Astrophysics Data System (ADS)

Ying, Wang; Weihua, Han; Xiang, Yang; Renping, Zhang; Yang, Zhang; Fuhua, Yang

2010-08-01

A novel simple dose-compensation method is developed for proximity effect correction in electron-beam lithography. The sizes of exposed patterns depend on dose factors while other exposure parameters (including accelerate voltage, resist thickness, exposing step size, substrate material, and so on) remain constant. This method is based on two reasonable assumptions in the evaluation of the compensated dose factor: one is that the relation between dose factors and circle-diameters is linear in the range under consideration; the other is that the compensated dose factor is only affected by the nearest neighbors for simplicity. Four-layer-hexagon photonic crystal structures were fabricated as test patterns to demonstrate this method. Compared to the uncorrected structures, the homogeneity of the corrected hole-size in photonic crystal structures was clearly improved.

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.

SU-G-IeP3-05: Effects of Image Receptor Technology and Dose Reduction Software On Radiation Dose Estimates for Fluoroscopically-Guided Interventional (FGI) Procedures

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

Merritt, Z; Dave, J; Eschelman, D

Purpose: To investigate the effects of image receptor technology and dose reduction software on radiation dose estimates for most frequently performed fluoroscopically-guided interventional (FGI) procedures at a tertiary health care center. Methods: IRB approval was obtained for retrospective analysis of FGI procedures performed in the interventional radiology suites between January-2011 and December-2015. This included procedures performed using image-intensifier (II) based systems which were subsequently replaced, flat-panel-detector (FPD) based systems which were later upgraded with ClarityIQ dose reduction software (Philips Healthcare) and relatively new FPD system already equipped with ClarityIQ. Post procedure, technologists entered system-reported cumulative air kerma (CAK) and kerma-areamore » product (KAP; only KAP for II based systems) in RIS; these values were analyzed. Data pre-processing included correcting typographical errors and cross-verifying CAK and KAP. The most frequent high and low dose FGI procedures were identified and corresponding CAK and KAP values were compared. Results: Out of 27,251 procedures within this time period, most frequent high and low dose procedures were chemo/immuno-embolization (n=1967) and abscess drainage (n=1821). Mean KAP for embolization and abscess drainage procedures were 260,657, 310,304 and 94,908 mGycm{sup 2}, and 14,497, 15,040 and 6307 mGycm{sup 2} using II-, FPD- and FPD with ClarityIQ- based systems, respectively. Statistically significant differences were observed in KAP values for embolization procedures with respect to different systems but for abscess drainage procedures significant differences were only noted between systems with FPD and FPD with ClarityIQ (p<0.05). Mean CAK reduced significantly from 823 to 308 mGy and from 43 to 21 mGy for embolization and abscess drainage procedures, respectively, in transitioning to FPD systems with ClarityIQ (p<0.05). Conclusion: While transitioning from II- to FPD- based systems was not associated with dose reduction for the most frequently performed FGI procedures, substantial dose reduction was noted with relatively newer systems and dose reduction software.« less

Comparison of the extent of hippocampal sparing according to the tilt of a patient's head during WBRT using linear accelerator-based IMRT and VMAT.

PubMed

Moon, Sun Young; Yoon, Myonggeun; Chung, Mijoo; Chung, Weon Kuu; Kim, Dong Wook

2016-05-01

In this paper, we report the results of our investigation into whole brain radiotherapy (WBRT) using linear accelerator-based intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) in lung cancer patients with a high risk of metastasis to the brain. Specifically, we assessed the absorbed dose and the rate of adverse effects for several organs at risk (OAR), including the hippocampus, according to the tilt of a patient's head. We arbitrarily selected five cases where measurements were made with the patients' heads tilted forward and five cases without such tilt. We set the entire brain as the planning target volume (PTV), and the hippocampi, the lenses, the eyes, and the cochleae as the main OAR, and formulated new plans for IMRT (coplanar, non-coplanar) and VMAT (coplanar, non-coplanar). Using the dose-volume histogram (DVH), we calculated and compared the effective uniform dose (EUD), normal tissue complication probability (NTCP) of the OAR and the mean and the maximum doses of hippocampus. As a result, if the patient tilted the head forward when receiving the Linac-based treatment, for the same treatment effect in the PTV, we confirmed that a lower dose entered the OAR, such as the hippocampus, eye, lens, and cochlea. Moreover, the damage to the hippocampus was expected to be the least when receiving coplanar VMAT with the head tilted forward. Accordingly, if patients tilt their heads forward when undergoing Linac-based WBRT, we anticipate that a smaller dose would be transmitted to the OAR, resulting in better quality of life following treatment. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Pharmacogenetics-based warfarin dosing algorithm decreases time to stable anticoagulation and the risk of major hemorrhage: an updated meta-analysis of randomized controlled trials.

PubMed

Wang, Zhi-Quan; Zhang, Rui; Zhang, Peng-Pai; Liu, Xiao-Hong; Sun, Jian; Wang, Jun; Feng, Xiang-Fei; Lu, Qiu-Fen; Li, Yi-Gang

2015-04-01

Warfarin is yet the most widely used oral anticoagulant for thromboembolic diseases, despite the recently emerged novel anticoagulants. However, difficulty in maintaining stable dose within the therapeutic range and subsequent serious adverse effects markedly limited its use in clinical practice. Pharmacogenetics-based warfarin dosing algorithm is a recently emerged strategy to predict the initial and maintaining dose of warfarin. However, whether this algorithm is superior over conventional clinically guided dosing algorithm remains controversial. We made a comparison of pharmacogenetics-based versus clinically guided dosing algorithm by an updated meta-analysis. We searched OVID MEDLINE, EMBASE, and the Cochrane Library for relevant citations. The primary outcome was the percentage of time in therapeutic range. The secondary outcomes were time to stable therapeutic dose and the risks of adverse events including all-cause mortality, thromboembolic events, total bleedings, and major bleedings. Eleven randomized controlled trials with 2639 participants were included. Our pooled estimates indicated that pharmacogenetics-based dosing algorithm did not improve percentage of time in therapeutic range [weighted mean difference, 4.26; 95% confidence interval (CI), -0.50 to 9.01; P = 0.08], but it significantly shortened the time to stable therapeutic dose (weighted mean difference, -8.67; 95% CI, -11.86 to -5.49; P < 0.00001). Additionally, pharmacogenetics-based algorithm significantly reduced the risk of major bleedings (odds ratio, 0.48; 95% CI, 0.23 to 0.98; P = 0.04), but it did not reduce the risks of all-cause mortality, total bleedings, or thromboembolic events. Our results suggest that pharmacogenetics-based warfarin dosing algorithm significantly improves the efficiency of International Normalized Ratio correction and reduces the risk of major hemorrhage.

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

NASA Astrophysics Data System (ADS)

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

2016-07-01

Highly ionizing radiation (HZE) in space is considered as main factor causing biological effects. Radiobiological studies during space flights are unrepeatable due to the variable space radiation environment, ground-base ion radiations are usually performed to simulate of the space biological effect. Spaceflights present a low-dose rate (0.1˜~0.3mGy/day) radiation environment inside aerocrafts while ground-base ion radiations present a much higher dose rate (100˜~500mGy/min). Whether ground-base ion radiation can reflect effects of space radiation is worth of evaluation. In this research, we compared the functional proteomic profiles of rice plants between on-ground simulated HZE particle radiation and spaceflight treatments. Three independent ground-base seed ionizing radiation experiments with different cumulative doses (dose range: 2˜~20000mGy) and different liner energy transfer (LET) values (13.3˜~500keV/μμm) and two independent seed spaceflight experiments onboard Chinese 20th satellite and SZ-6 spacecraft were carried out. Alterations in the proteome were analyzed by two-dimensional difference gel electrophoresis (2-D DIGE) with MALDI-TOF/TOF mass spectrometry identifications. 45 and 59 proteins showed significant (p<0.05) and reproducible quantitative differences in ground-base ion radiation and spaceflight experiments respectively. The functions of ground-base radiation and spaceflight proteins were both involved in a wide range of biological processes. Gene Ontology enrichment analysis further revealed that ground-base radiation responsive proteins were mainly involved in removal of superoxide radicals, defense response to stimulus and photosynthesis, while spaceflight responsive proteins mainly participate in nucleoside metabolic process, protein folding and phosphorylation. The results implied that ground-base radiations cannot truly reflect effects of spaceflight radiations, ground-base radiation was a kind of indirect effect to rice causing oxidation and metabolism stresses, but space radiation was a kind of direct effect leading to macromolecule (DNA and protein) damage and signal pathway disorders. This functional proteomic analysis work might provide a new evaluation method for further on-ground simulated HZE radiation experiments.

Using spatial information about recurrence risk for robust optimization of dose-painting prescription functions

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

Bender, Edward T.

Purpose: To develop a robust method for deriving dose-painting prescription functions using spatial information about the risk for disease recurrence. Methods: Spatial distributions of radiobiological model parameters are derived from distributions of recurrence risk after uniform irradiation. These model parameters are then used to derive optimal dose-painting prescription functions given a constant mean biologically effective dose. Results: An estimate for the optimal dose distribution can be derived based on spatial information about recurrence risk. Dose painting based on imaging markers that are moderately or poorly correlated with recurrence risk are predicted to potentially result in inferior disease control when comparedmore » the same mean biologically effective dose delivered uniformly. A robust optimization approach may partially mitigate this issue. Conclusions: The methods described here can be used to derive an estimate for a robust, patient-specific prescription function for use in dose painting. Two approximate scaling relationships were observed: First, the optimal choice for the maximum dose differential when using either a linear or two-compartment prescription function is proportional to R, where R is the Pearson correlation coefficient between a given imaging marker and recurrence risk after uniform irradiation. Second, the predicted maximum possible gain in tumor control probability for any robust optimization technique is nearly proportional to the square of R.« less

Tumor and red bone marrow dosimetry: comparison of methods for prospective treatment planning in pretargeted radioimmunotherapy.

PubMed

Woliner-van der Weg, Wietske; Schoffelen, Rafke; Hobbs, Robert F; Gotthardt, Martin; Goldenberg, David M; Sharkey, Robert M; Slump, Cornelis H; van der Graaf, Winette Ta; Oyen, Wim Jg; Boerman, Otto C; Sgouros, George; Visser, Eric P

2015-12-01

Red bone marrow (RBM) toxicity is dose-limiting in (pretargeted) radioimmunotherapy (RIT). Previous blood-based and two-dimensional (2D) image-based methods have failed to show a clear dose-response relationship. We developed a three-dimensional (3D) image-based RBM dosimetry approach using the Monte Carlo-based 3D radiobiological dosimetry (3D-RD) software and determined its additional value for predicting RBM toxicity. RBM doses were calculated for 13 colorectal cancer patients after pretargeted RIT with the two-step administration of an anti-CEA × anti-HSG bispecific monoclonal antibody and a (177)Lu-labeled di-HSG-peptide. 3D-RD RBM dosimetry was based on the lumbar vertebrae, delineated on single photon emission computed tomography (SPECT) scans acquired directly, 3, 24, and 72 h after (177)Lu administration. RBM doses were correlated to hematologic effects, according to NCI-CTC v3 and compared with conventional 2D cranium-based and blood-based dosimetry results. Tumor doses were calculated with 3D-RD, which has not been possible with 2D dosimetry. Tumor-to-RBM dose ratios were calculated and compared for (177)Lu-based pretargeted RIT and simulated pretargeted RIT with (90)Y. 3D-RD RBM doses of all seven patients who developed thrombocytopenia were higher (range 0.43 to 0.97 Gy) than that of the six patients without thrombocytopenia (range 0.12 to 0.39 Gy), except in one patient (0.47 Gy) without thrombocytopenia but with grade 2 leucopenia. Blood and 2D image-based RBM doses for patients with grade 1 to 2 thrombocytopenia were in the same range as in patients without thrombocytopenia (0.14 to 0.29 and 0.11 to 0.26 Gy, respectively). Blood-based RBM doses for two grade 3 to 4 patients were higher (0.66 and 0.51 Gy, respectively) than the others, and the cranium-based dose of only the grade 4 patient was higher (0.34 Gy). Tumor-to-RBM dose ratios would increase by 25% on average when treating with (90)Y instead of (177)Lu. 3D dosimetry identifies patients at risk of developing any grade of RBM toxicity more accurately than blood- or 2D image-based methods. It has the added value to enable calculation of tumor-to-RBM dose ratios.

Influence of Ultra-Low-Dose and Iterative Reconstructions on the Visualization of Orbital Soft Tissues on Maxillofacial CT.

PubMed

Widmann, G; Juranek, D; Waldenberger, F; Schullian, P; Dennhardt, A; Hoermann, R; Steurer, M; Gassner, E-M; Puelacher, W

2017-08-01

Dose reduction on CT scans for surgical planning and postoperative evaluation of midface and orbital fractures is an important concern. The purpose of this study was to evaluate the variability of various low-dose and iterative reconstruction techniques on the visualization of orbital soft tissues. Contrast-to-noise ratios of the optic nerve and inferior rectus muscle and subjective scores of a human cadaver were calculated from CT with a reference dose protocol (CT dose index volume = 36.69 mGy) and a subsequent series of low-dose protocols (LDPs I-4: CT dose index volume = 4.18, 2.64, 0.99, and 0.53 mGy) with filtered back-projection (FBP) and adaptive statistical iterative reconstruction (ASIR)-50, ASIR-100, and model-based iterative reconstruction. The Dunn Multiple Comparison Test was used to compare each combination of protocols (α = .05). Compared with the reference dose protocol with FBP, the following statistically significant differences in contrast-to-noise ratios were shown (all, P ≤ .012) for the following: 1) optic nerve: LDP-I with FBP; LDP-II with FBP and ASIR-50; LDP-III with FBP, ASIR-50, and ASIR-100; and LDP-IV with FBP, ASIR-50, and ASIR-100; and 2) inferior rectus muscle: LDP-II with FBP, LDP-III with FBP and ASIR-50, and LDP-IV with FBP, ASIR-50, and ASIR-100. Model-based iterative reconstruction showed the best contrast-to-noise ratio in all images and provided similar subjective scores for LDP-II. ASIR-50 had no remarkable effect, and ASIR-100, a small effect on subjective scores. Compared with a reference dose protocol with FBP, model-based iterative reconstruction may show similar diagnostic visibility of orbital soft tissues at a CT dose index volume of 2.64 mGy. Low-dose technology and iterative reconstruction technology may redefine current reference dose levels in maxillofacial CT. © 2017 by American Journal of Neuroradiology.

Estimation of body surface area in the musk shrew ( Suncus murinus): a small animal for testing chemotherapy-induced emesis.

PubMed

Eiseman, Julie L; Sciullo, Michael; Wang, Hong; Beumer, Jan H; Horn, Charles C

2017-10-01

Several cancer chemotherapies cause nausea and vomiting, which can be dose-limiting. Musk shrews are used as preclinical models for chemotherapy-induced emesis and for antiemetic effectiveness. Unlike rats and mice, shrews possess a vomiting reflex and demonstrate an emetic profile similar to humans, including acute and delayed phases. As with most animals, dosing of shrews is based on body weight, while translation of such doses to clinically equivalent exposure requires doses based on body surface area. In the current study body surface area in musk shrews was directly assessed to determine the Meeh constant (K m ) conversion factor (female = 9.97, male = 9.10), allowing estimation of body surface area based on body weight. These parameters can be used to determine dosing strategies for shrew studies that model human drug exposures, particularly for investigating the emetic liability of cancer chemotherapeutic agents.

Pulmonary Nodule Volumetry at Different Low Computed Tomography Radiation Dose Levels With Hybrid and Model-Based Iterative Reconstruction: A Within Patient Analysis.

PubMed

den Harder, Annemarie M; Willemink, Martin J; van Hamersvelt, Robbert W; Vonken, Evertjan P A; Schilham, Arnold M R; Lammers, Jan-Willem J; Luijk, Bart; Budde, Ricardo P J; Leiner, Tim; de Jong, Pim A

2016-01-01

The aim of the study was to determine the effects of dose reduction and iterative reconstruction (IR) on pulmonary nodule volumetry. In this prospective study, 25 patients scheduled for follow-up of pulmonary nodules were included. Computed tomography acquisitions were acquired at 4 dose levels with a median of 2.1, 1.2, 0.8, and 0.6 mSv. Data were reconstructed with filtered back projection (FBP), hybrid IR, and model-based IR. Volumetry was performed using semiautomatic software. At the highest dose level, more than 91% (34/37) of the nodules could be segmented, and at the lowest dose level, this was more than 83%. Thirty-three nodules were included for further analysis. Filtered back projection and hybrid IR did not lead to significant differences, whereas model-based IR resulted in lower volume measurements with a maximum difference of -11% compared with FBP at routine dose. Pulmonary nodule volumetry can be accurately performed at a submillisievert dose with both FBP and hybrid IR.

Patient-specific radiation dose and cancer risk estimation in CT: Part II. Application to patients

PubMed Central

Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Toncheva, Greta; Yoshizumi, Terry T.; Frush, Donald P.

2011-01-01

Purpose: Current methods for estimating and reporting radiation dose from CT examinations are largely patient-generic; the body size and hence dose variation from patient to patient is not reflected. Furthermore, the current protocol designs rely on dose as a surrogate for the risk of cancer incidence, neglecting the strong dependence of risk on age and gender. The purpose of this study was to develop a method for estimating patient-specific radiation dose and cancer risk from CT examinations. Methods: The study included two patients (a 5-week-old female patient and a 12-year-old male patient), who underwent 64-slice CT examinations (LightSpeed VCT, GE Healthcare) of the chest, abdomen, and pelvis at our institution in 2006. For each patient, a nonuniform rational B-spine (NURBS) based full-body computer model was created based on the patient’s clinical CT data. Large organs and structures inside the image volume were individually segmented and modeled. Other organs were created by transforming an existing adult male or female full-body computer model (developed from visible human data) to match the framework defined by the segmented organs, referencing the organ volume and anthropometry data in ICRP Publication 89. A Monte Carlo program previously developed and validated for dose simulation on the LightSpeed VCT scanner was used to estimate patient-specific organ dose, from which effective dose and risks of cancer incidence were derived. Patient-specific organ dose and effective dose were compared with patient-generic CT dose quantities in current clinical use: the volume-weighted CT dose index (CTDIvol) and the effective dose derived from the dose-length product (DLP). Results: The effective dose for the CT examination of the newborn patient (5.7 mSv) was higher but comparable to that for the CT examination of the teenager patient (4.9 mSv) due to the size-based clinical CT protocols at our institution, which employ lower scan techniques for smaller patients. However, the overall risk of cancer incidence attributable to the CT examination was much higher for the newborn (2.4 in 1000) than for the teenager (0.7 in 1000). For the two pediatric-aged patients in our study, CTDIvol underestimated dose to large organs in the scan coverage by 30%–48%. The effective dose derived from DLP using published conversion coefficients differed from that calculated using patient-specific organ dose values by −57% to 13%, when the tissue weighting factors of ICRP 60 were used, and by −63% to 28%, when the tissue weighting factors of ICRP 103 were used. Conclusions: It is possible to estimate patient-specific radiation dose and cancer risk from CT examinations by combining a validated Monte Carlo program with patient-specific anatomical models that are derived from the patients’ clinical CT data and supplemented by transformed models of reference adults. With the construction of a large library of patient-specific computer models encompassing patients of all ages and weight percentiles, dose and risk can be estimated for any patient prior to or after a CT examination. Such information may aid in decisions for image utilization and can further guide the design and optimization of CT technologies and scan protocols. PMID:21361209

Patient-specific radiation dose and cancer risk estimation in CT: Part II. Application to patients

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

Li Xiang; Samei, Ehsan; Segars, W. Paul

2011-01-15

Purpose: Current methods for estimating and reporting radiation dose from CT examinations are largely patient-generic; the body size and hence dose variation from patient to patient is not reflected. Furthermore, the current protocol designs rely on dose as a surrogate for the risk of cancer incidence, neglecting the strong dependence of risk on age and gender. The purpose of this study was to develop a method for estimating patient-specific radiation dose and cancer risk from CT examinations. Methods: The study included two patients (a 5-week-old female patient and a 12-year-old male patient), who underwent 64-slice CT examinations (LightSpeed VCT, GEmore » Healthcare) of the chest, abdomen, and pelvis at our institution in 2006. For each patient, a nonuniform rational B-spine (NURBS) based full-body computer model was created based on the patient's clinical CT data. Large organs and structures inside the image volume were individually segmented and modeled. Other organs were created by transforming an existing adult male or female full-body computer model (developed from visible human data) to match the framework defined by the segmented organs, referencing the organ volume and anthropometry data in ICRP Publication 89. A Monte Carlo program previously developed and validated for dose simulation on the LightSpeed VCT scanner was used to estimate patient-specific organ dose, from which effective dose and risks of cancer incidence were derived. Patient-specific organ dose and effective dose were compared with patient-generic CT dose quantities in current clinical use: the volume-weighted CT dose index (CTDI{sub vol}) and the effective dose derived from the dose-length product (DLP). Results: The effective dose for the CT examination of the newborn patient (5.7 mSv) was higher but comparable to that for the CT examination of the teenager patient (4.9 mSv) due to the size-based clinical CT protocols at our institution, which employ lower scan techniques for smaller patients. However, the overall risk of cancer incidence attributable to the CT examination was much higher for the newborn (2.4 in 1000) than for the teenager (0.7 in 1000). For the two pediatric-aged patients in our study, CTDI{sub vol} underestimated dose to large organs in the scan coverage by 30%-48%. The effective dose derived from DLP using published conversion coefficients differed from that calculated using patient-specific organ dose values by -57% to 13%, when the tissue weighting factors of ICRP 60 were used, and by -63% to 28%, when the tissue weighting factors of ICRP 103 were used. Conclusions: It is possible to estimate patient-specific radiation dose and cancer risk from CT examinations by combining a validated Monte Carlo program with patient-specific anatomical models that are derived from the patients' clinical CT data and supplemented by transformed models of reference adults. With the construction of a large library of patient-specific computer models encompassing patients of all ages and weight percentiles, dose and risk can be estimated for any patient prior to or after a CT examination. Such information may aid in decisions for image utilization and can further guide the design and optimization of CT technologies and scan protocols.« less

Radiation assessment to paediatric with F-18-FDG undergo whole-body PET/CT examination

NASA Astrophysics Data System (ADS)

Dhalisa, H.; Mohamad, A. S.; Rafidah, Z.

2016-01-01

This study was carried out on wholebody radiation dose assessment to paediatrics patient who undergo PET/CT scanner at Institut Kanser Negara. Consist of 68 patients with varies of malignancies and epilepsy disease case covering age between 2 years to 12 years old. This is a retrospective study from 2010-2014. The use of PET/CT scanner as an advanced tool has been proven to give an extra radiation dose to the patient. It is because of the radiation exposure from the combination of both CT and PET scans rather than a single CT or PET scan. Furthermore, a study on radiation dose to paediatric patient undergoing PET/CT is rare in Malaysia. So, the aim of this study is to estimate the wholebody effective dose to paediatric patient in Malaysia. Effective dose from PET scan was calculated based on the activity of F18 FDG and dose coefficient reported in International Commission on Radiological Protection (ICRP) Publication 106. Effective dose from CT was determined using k coefficient as reported in ICRP publication 102 and Dose Length Product (DLP) value. The average effective dose from PET and CT were found to be 7.05mSv and 5.77mSv respectively. The mean wholebody effective dose received by a patient with combined PETCT examination was 12.78mSv. These results could be used as reference for dosimetry of a patient undergoing PETCT examination in Malaysia.

Assessment of serum biomarkers in rats after exposure to pesticides of different chemical classes

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

Moser, Virginia C., E-mail: Moser.ginger@epa.gov; Stewart, Nicholas; Freeborn, Danielle L.

There is increasing emphasis on the use of biomarkers of adverse outcomes in safety assessment and translational research. We evaluated serum biomarkers and targeted metabolite profiles after exposure to pesticides (permethrin, deltamethrin, imidacloprid, carbaryl, triadimefon, fipronil) with different neurotoxic actions. Adult male Long–Evans rats were evaluated after single exposure to vehicle or one of two doses of each pesticide at the time of peak effect. The doses were selected to produce similar magnitude of behavioral effects across chemicals. Serum or plasma was analyzed using commercial cytokine/protein panels and targeted metabolomics. Additional studies of fipronil used lower doses (lacking behavioral effects),more » singly or for 14 days, and included additional markers of exposure and biological activity. Biomarker profiles varied in the number of altered analytes and patterns of change across pesticide classes, and discriminant analysis could separate treatment groups from control. Low doses of fipronil produced greater effects when given for 14 days compared to a single dose. Changes in thyroid hormones and relative amounts of fipronil and its sulfone metabolite also differed between the dosing regimens. Most cytokine changes reflected alterations in inflammatory responses, hormone levels, and products of phospholipid, fatty acid, and amino acid metabolism. These findings demonstrate distinct blood-based analyte profiles across pesticide classes, dose levels, and exposure duration. These results show promise for detailed analyses of these biomarkers and their linkages to biological pathways. - Highlights: • Pesticides typical of different classes produced distinct patterns of change in biomarker panels. • Based on the panels used, alterations suggest impacts on immune, metabolism, and homeostasis functions. • Some changes may reflect actions on neurotransmitter systems involved in immune modulation. • Fipronil effects on thyroid and kinetics differed with acute and repeated administration.« less

The Analgesic Effects of Different Extracts of Aerial Parts of Coriandrum Sativum in Mice

PubMed Central

Fatemeh Kazempor, Seyedeh; Vafadar langehbiz, Shabnam; Hosseini, Mahmoud; Naser Shafei, Mohammad; Ghorbani, Ahmad; Pourganji, Masoomeh

2015-01-01

Regarding the effects of Coriandrum sativum (C. sativum) on central nervous system, in the present study analgesic properties of different extracts of C. sativum aerial partswere investigated. The mice were treated by saline, morphine, three doses (20, 100 and 500 mg/kg) of aqueous, ethanolic, choloroformic extracts of C. sativum and one dose (100 mg/kg) of aqueous, two doses of ethanolic (100 and 500 mg/kg) and one dose of choloroformic (20 mg/kg) extracts of C. sativum pretreated by naloxone. Recording of the hot plate test was performed 10 min before injection of the drugs as a base and it was consequently repeated every 10 minutes after the extracts injection. The maximal percent effect (MPE) in the groups treated by three doses of aqueous, ethanolic and chloroformic extracts were significantly higher than saline group which were comparable to the effect of morphine. The effects of most effective doses of extracts were reversed by naloxone. The results of present study showed analgesic effect of aqueous, ethanolic and chloroformic extracts of C. sativum extract. These effects of the extracts may be mediated by opioid system. However, more investigations are needed to elucidate the exact responsible mechanism(s) and the effective compound(s).

Effects of Home-Based Constraint-Induced Therapy versus Dose-Matched Control Intervention on Functional Outcomes and Caregiver Well-Being in Children with Cerebral Palsy

ERIC Educational Resources Information Center

Lin, Keh-chung; Wang, Tien-ni; Wu, Ching-yi; Chen, Chia-ling; Chang, Kai-chieh; Lin, Yu-chan; Chen, Yi-ju

2011-01-01

This study compared home-based constraint-induced therapy (CIT) with a dose-matched home-based control intervention for children with cerebral palsy (CP). The differences in unilateral and bilateral motor performance, daily functions, and quality of parental well-being (i.e., the stress level of their parents) were evaluated. The study included 21…

Immediate effects of 33 to 180 rad/min (60)Co exposure on performance and blood pressure in monkeys. Topical report

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

Bruner, A.

1976-09-01

Four groups of monkeys received 1000 rads (60)Co at 33, 50, 75, or 180 rad/min wholebody irradiation while performing a delayed matching-to-sample task. Systematic dose rate effects were observed on performance and blood pressure within the initial 20 min postirradiation. The incidence and severity of performance decrement (PD) increased with higher dose rate. The appearance of postirradiation hypotension was systematically delayed and its rate of fall prolonged as dose rate was lower. The hypotension likewise appeared less deep with lower dose rate exposure. Based on the calculated cumulative dose absorbed at the time of symptom appearance two coactive thresholds weremore » proposed to exist: a total dose threshold of approximately 300 rads (midbody measurement), and a dose rate threshold of about 25 rad/min.« less

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.

Cost-effectiveness of hepatitis A vaccination in Indonesia.

PubMed

Suwantika, Auliya A; Beutels, Philippe; Postma, Maarten J

2014-01-01

This study aims to assess the cost-effectiveness of hepatitis A immunization in Indonesia, including an explicit comparison between one-dose and two-dose vaccines. An age-structured cohort model based on a decision tree was developed for the 2012 Indonesia birth cohort. Using the model, we made a comparison on the use of two-dose and one-dose vaccines. The model involved a 70-year time horizon with 1-month cycles for children less than 2 years old and annually thereafter. Monte Carlo simulations were used to examine the economic acceptability and affordability of the hepatitis A vaccination. Vaccination would save US$ 3,795,148 and US$ 2,892,920 from the societal perspective, for the two-dose and one-dose vaccine schedules, respectively, in the context of hepatitis A treatment. It also would save 8917 and 6614 discounted quality-adjusted-life-years (QALYs), respectively. With the vaccine price of US$ 3.21 per dose, the implementation of single dose vaccine would yield an incremental cost-effectiveness ratio (ICER) of US$ 4933 per QALY gained versus no vaccination, whereas the two-dose versus one-dose schedule would cost US$ 14 568 per QALY gained. Considering the 2012 gross-domestic-product (GDP) per capita in Indonesia of US$ 3557, the results indicate that hepatitis A vaccination would be a cost-effective intervention, both for the two-dose and one-dose vaccine schedules in isolation, but two-dose vaccination would no longer be cost-effective if one-dose vaccination is a feasible option. Vaccination would be 100% affordable at budgets of US$ 71,408 000 and US$ 37,690,000 for the implementation of the two-dose and one-dose vaccine schedules, respectively. The implementation of hepatitis A vaccination in Indonesia would be a cost-effective health intervention under the market vaccine price. Given the budget limitations, the use of a one-dose-vaccine schedule would be more realistic to be applied than a two-dose schedule. The vaccine price, mortality rate and discount rate were the most influential parameters impacting the ICERs.

Cost-effectiveness of hepatitis A vaccination in Indonesia

PubMed Central

Suwantika, Auliya A; Beutels, Philippe; Postma, Maarten J

2014-01-01

Objective This study aims to assess the cost-effectiveness of hepatitis A immunization in Indonesia, including an explicit comparison between one-dose and two-dose vaccines. Methods An age-structured cohort model based on a decision tree was developed for the 2012 Indonesia birth cohort. Using the model, we made a comparison on the use of two-dose and one-dose vaccines. The model involved a 70-year time horizon with 1-month cycles for children less than 2 years old and annually thereafter. Monte Carlo simulations were used to examine the economic acceptability and affordability of the hepatitis A vaccination. Results Vaccination would save US$ 3 795 148 and US$ 2 892 920 from the societal perspective, for the two-dose and one-dose vaccine schedules, respectively, in the context of hepatitis A treatment. It also would save 8917 and 6614 discounted quality-adjusted-life-years (QALYs), respectively. With the vaccine price of US$ 3.21 per dose, the implementation of single dose vaccine would yield an incremental cost-effectiveness ratio (ICER) of US$ 4933 per QALY gained versus no vaccination, whereas the two-dose versus one-dose schedule would cost US$ 14 568 per QALY gained. Considering the 2012 gross-domestic-product (GDP) per capita in Indonesia of US$ 3557, the results indicate that hepatitis A vaccination would be a cost-effective intervention, both for the two-dose and one-dose vaccine schedules in isolation, but two-dose vaccination would no longer be cost-effective if one-dose vaccination is a feasible option. Vaccination would be 100% affordable at budgets of US$ 71 408 000 and US$ 37 690 000 for the implementation of the two-dose and one-dose vaccine schedules, respectively. Conclusions The implementation of hepatitis A vaccination in Indonesia would be a cost-effective health intervention under the market vaccine price. Given the budget limitations, the use of a one-dose-vaccine schedule would be more realistic to be applied than a two-dose schedule. The vaccine price, mortality rate and discount rate were the most influential parameters impacting the ICERs. PMID:25424941

MO-F-CAMPUS-I-04: Patient Eye-Lens Dose Reduction in Routine Brain CT Examinations Using Organ-Based Tube Current Modulation and In-Plane Bismuth Shielding

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

Tsai, Hui-Yu; Liao, Ying-Lan; Chang Gung University / Chang Gung Memorial Hospital, Taoyun, Taiwan

Purpose: The purpose of this study is to assess eye-lens dose for patients who underwent brain CT examinations using two dose reduction Methods: organ-based tube current modulation (OBTCM) and in-plane bismuth shielding method. Methods: This study received institutional review board approval; written informed consent to participate was obtained from all patients. Ninety patients who underwent the routine brain CT examination were randomly assigned to three groups, ie. routine, OBTCM, and bismuth shield. The OBTCM technique reduced the tube current when the X-ray tube rotates in front of patients’ eye-lens region. The patients in the bismuth shield group were covered one-plymore » bismuth shield in the eyes’ region. Eye-lens doses were measured using TLD-100H chips and the total effective doses were calculated using CT-Expo according to the CT scanning parameters. The surface doses for patients at off-center positions were assessed to evaluate the off-centering effect. Results: Phantom measurements indicates that OBTCM technique could reduced by 26% to 28% of the surface dose to the eye lens, and increased by 25% of the surface dose at the opposed incident direction at the angle of 180°. Patients’ eye-lens doses were reduced 16.9% and 30.5% dose of bismuth shield scan and OBTCM scan, respectively compared to the routine scan. The eye-lens doses were apparently increased when the table position was lower than isocenter. Conclusion: Reducing the dose to the radiosensitive organs, such as eye lens, during routine brain CT examinations could lower the radiation risks. The OBTCM technique and in-plane bismuth shielding could be used to reduce the eye-lens dose. The eye-lens dose could be effectively reduced using OBTCM scan without interfering the diagnostic image quality. Patient position relative the CT gantry also affects the dose level of the eye lens. This study was supported by the grants from the Ministry of Science and Technology of Taiwan (MOST103-2314-B-182-009-MY2), and Chang Gung Memorial Hospital (CMRPD1C0682)« less

Galactic and solar radiation exposure to aircrew during a solar cycle.

PubMed

Lewis, B J; Bennett, L G I; Green, A R; McCall, M J; Ellaschuk, B; Butler, A; Pierre, M

2002-01-01

An on-going investigation using a tissue-equivalent proportional counter (TEPC) has been carried out to measure the ambient dose equivalent rate of the cosmic radiation exposure of aircrew during a solar cycle. A semi-empirical model has been derived from these data to allow for the interpolation of the dose rate for any global position. The model has been extended to an altitude of up to 32 km with further measurements made on board aircraft and several balloon flights. The effects of changing solar modulation during the solar cycle are characterised by correlating the dose rate data to different solar potential models. Through integration of the dose-rate function over a great circle flight path or between given waypoints, a Predictive Code for Aircrew Radiation Exposure (PCAIRE) has been further developed for estimation of the route dose from galactic cosmic radiation exposure. This estimate is provided in units of ambient dose equivalent as well as effective dose, based on E/H x (10) scaling functions as determined from transport code calculations with LUIN and FLUKA. This experimentally based treatment has also been compared with the CARI-6 and EPCARD codes that are derived solely from theoretical transport calculations. Using TEPC measurements taken aboard the International Space Station, ground based neutron monitoring, GOES satellite data and transport code analysis, an empirical model has been further proposed for estimation of aircrew exposure during solar particle events. This model has been compared to results obtained during recent solar flare events.

Evaluation of the dependence of the exposure dose on the attenuation correction in brain PET/CT scans using 18F-FDG

NASA Astrophysics Data System (ADS)

Choi, Eun-Jin; Jeong, Moon-Taeg; Jang, Seong-Joo; Choi, Nam-Gil; Han, Jae-Bok; Yang, Nam-Hee; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Yun-Jong; Ryu, Young-Hwan; Choi, Sung-Hyun; Seong, Kyeong-Jeong

2014-01-01

This study examined whether scanning could be performed with minimum dose and minimum exposure to the patient after an attenuation correction. A Hoffman 3D Brain Phantom was used in BIO_40 and D_690 PET/CT scanners, and the CT dose for the equipment was classified as a low dose (minimum dose), medium dose (general dose for scanning) and high dose (dose with use of contrast medium) before obtaining the image at a fixed kilo-voltage-peak (kVp) and milliampere (mA) that were adjusted gradually in 17-20 stages. A PET image was then obtained to perform an attenuation correction based on an attenuation map before analyzing the dose difference. Depending on tube current in the range of 33-190 milliampere-second (mAs) when BIO_40 was used, a significant difference in the effective dose was observed between the minimum and the maximum mAs (p < 0.05). According to a Scheffe post-hoc test, the ratio of the minimum to the maximum of the effective dose was increased by approximately 5.26-fold. Depending on the change in the tube current in the range of 10-200 mA when D_690 was used, a significant difference in the effective dose was observed between the minimum and the maximum of mA (p < 0.05). The Scheffe posthoc test revealed a 20.5-fold difference. In conclusion, because effective exposure dose increases with increasing operating current, it is possible to reduce the exposure limit in a brain scan can be reduced if the CT dose can be minimized for a transmission scan.

Degradation of the Bragg peak due to inhomogeneities.

PubMed

Urie, M; Goitein, M; Holley, W R; Chen, G T

1986-01-01

The rapid fall-off of dose at the end of range of heavy charged particle beams has the potential in therapeutic applications of sparing critical structures just distal to the target volume. Here we explored the effects of highly inhomogeneous regions on this desirable depth-dose characteristic. The proton depth-dose distribution behind a lucite-air interface parallel to the beam was bimodal, indicating the presence of two groups of protons with different residual ranges, creating a step-like depth-dose distribution at the end of range. The residual ranges became more spread out as the interface was angled at 3 degrees, and still more at 6 degrees, to the direction of the beam. A second experiment showed little significant effect on the distal depth-dose of protons having passed through a mosaic of teflon and lucite. Anatomic studies demonstrated significant effects of complex fine inhomogeneities on the end of range characteristics. Monoenergetic protons passing through the petrous ridges and mastoid air cells in the base of skull showed a dramatic degradation of the distal Bragg peak. In beams with spread out Bragg peaks passing through regions of the base of skull, the distal fall-off from 90 to 20% dose was increased from its nominal 6 to well over 32 mm. Heavy ions showed a corresponding degradation in their ends of range. In the worst case in the base of skull region, a monoenergetic neon beam showed a broadening of the full width at half maximum of the Bragg peak to over 15 mm (compared with 4 mm in a homogeneous unit density medium). A similar effect was found with carbon ions in the abdomen, where the full width at half maximum of the Bragg peak (nominally 5.5 mm) was found to be greater than 25 mm behind gas-soft-tissue interfaces. We address the implications of these data for dose computation with heavy charged particles.

[Personal dose monitoring of radiation workers in medical institutions at the municipal level and below in a city from 2011 to 2014].

PubMed

Wang, C; Mo, S F; Zhang, J B; Li, J R; Huang, R L; Tan, H Y

2017-08-20

Objective: To determine the personal dose level of radiation workers in medical institutions at the municipal level and below in a city, and to provide a scientific support for strengthening the radiation protection in the city's medical institutions. Methods: Information of the successful applicants for the "Radiation Worker Permit" from 174 medical institutions at the municipal level and below was collected from October 1, 2011 to December 31, 2014. The annual effective dose was calculated based on the personal dose monitoring report, and indicators including sex, permit application time, hospital level, type of occupational radiation, length of radiation work, blood test, and micronucleated lymphocyte rate were analyzed. Results: Of the 1 143 radiation worker permit applications submitted by medical institutions the municipal level and below in this city from 2011 to 2014, 1 123 provided at least one personal dose monitoring report. The annual effective dose of the radiation workers was 0-4.76 mSv (mean 0.31±0.40 mSv) , and the collective annual effective dose was 351.96 mSv. The annual effective dose was significantly different between radiation workers with different times of permit application, hospital levels, and types of occupational radiation ( P <0.05) . Interventional radiology workers had the highest annual effective dose (0.63 mSv) , and annual effective dose was significantly different between interventional radiology workers with different lengths of radiation work ( H =10.812, P <0.05) . Conclusion: The personal radiation dose of radiation workers in medical institutions at the municipal level and below in this city is maintained at a relatively low level, suggesting that the occupational environment is relatively safe for these workers. However, more focus should be placed on clinical interventional radiology workers.

Low-dose environmental radiation, DNA damage, and cancer: the possible contribution of psychological factors.

PubMed

Cwikel, Julie G; Gidron, Yori; Quastel, Michael

2010-01-01

Radiation causes DNA damage, increases risk of cancer, and is associated with psychological stress responses. This article proposes an evidence-based integrative model in which psychological factors could interact with radiation by either augmenting or moderating the adverse effects of radiation on DNA integrity and eventual tumorigenesis. Based on a review of the literature, we demonstrate the following: (1) the effects of low-dose radiation exposures on DNA integrity and on tumorigenesis; (2) the effects of low-dose radiation exposure on psychological distress; (3) the relationship between psychological factors and DNA damage; and (4) the possibility that psychological stress augments and that psychological resource variables moderate radiation-induced DNA damage and risk of cancer. The additional contribution of psychological processes to radiation-DNA damage-cancer relationships needs further study, and if verified, has clinical implications.

A deep convolutional neural network using directional wavelets for low-dose X-ray CT reconstruction.

PubMed

Kang, Eunhee; Min, Junhong; Ye, Jong Chul

2017-10-01

Due to the potential risk of inducing cancer, radiation exposure by X-ray CT devices should be reduced for routine patient scanning. However, in low-dose X-ray CT, severe artifacts typically occur due to photon starvation, beam hardening, and other causes, all of which decrease the reliability of the diagnosis. Thus, a high-quality reconstruction method from low-dose X-ray CT data has become a major research topic in the CT community. Conventional model-based de-noising approaches are, however, computationally very expensive, and image-domain de-noising approaches cannot readily remove CT-specific noise patterns. To tackle these problems, we want to develop a new low-dose X-ray CT algorithm based on a deep-learning approach. We propose an algorithm which uses a deep convolutional neural network (CNN) which is applied to the wavelet transform coefficients of low-dose CT images. More specifically, using a directional wavelet transform to extract the directional component of artifacts and exploit the intra- and inter- band correlations, our deep network can effectively suppress CT-specific noise. In addition, our CNN is designed with a residual learning architecture for faster network training and better performance. Experimental results confirm that the proposed algorithm effectively removes complex noise patterns from CT images derived from a reduced X-ray dose. In addition, we show that the wavelet-domain CNN is efficient when used to remove noise from low-dose CT compared to existing approaches. Our results were rigorously evaluated by several radiologists at the Mayo Clinic and won second place at the 2016 "Low-Dose CT Grand Challenge." To the best of our knowledge, this work is the first deep-learning architecture for low-dose CT reconstruction which has been rigorously evaluated and proven to be effective. In addition, the proposed algorithm, in contrast to existing model-based iterative reconstruction (MBIR) methods, has considerable potential to benefit from large data sets. Therefore, we believe that the proposed algorithm opens a new direction in the area of low-dose CT research. © 2017 American Association of Physicists in Medicine.

Effective Dose in Nuclear Medicine Studies and SPECT/CT: Dosimetry Survey Across Quebec Province.

PubMed

Charest, Mathieu; Asselin, Chantal

2018-06-01

The aims of the current study were to draw a portrait of the delivered dose in selected nuclear medicine studies in Québec province and to assess the degree of change between an earlier survey performed in 2010 and a later survey performed in 2014. Methods: Each surveyed nuclear medicine department had to complete 2 forms: the first, about the administered activity in selected nuclear medicine studies, and the second, about the CT parameters used in SPECT/CT imaging, if available. The administered activities were converted into effective doses using the most recent conversion factors. Diagnostic reference levels were computed for each imaging procedure to obtain a benchmark for comparison. Results: The distributions of administered activity in various nuclear medicine studies, along with the corresponding distribution of the effective doses, were determined. Excluding 131 I for thyroid studies, 67 Ga-citrate for infectious workups, and combined stress and rest myocardial perfusion studies, the remainder of the 99m Tc-based studies delivered average effective doses clustered below 10 mSv. Between the 2010 survey and the 2014 survey, there was a statistically significant decrease in delivered dose from 18.3 to 14.5 mSv. 67 Ga-citrate studies for infectious workups also showed a significant decrease in delivered dose from 31.0 to 26.2 mSv. The standardized CT portion of SPECT/CT studies yielded a mean effective dose 14 times lower than the radiopharmaceutical portion of the study. Conclusion: Between 2010 and 2014, there was a significant decrease in the delivered effective dose in myocardial perfusion and 67 Ga-citrate studies. The CT portions of the surveyed SPECT/CT studies contributed a relatively small fraction of the total delivered effective dose. © 2018 by the Society of Nuclear Medicine and Molecular Imaging.

Cost Effectiveness of Genotype-Guided Warfarin Dosing in Patients with Mechanical Heart Valve Replacement Under the Fee-for-Service System.

PubMed

Kim, Dong-Jin; Kim, Ho-Sook; Oh, Minkyung; Kim, Eun-Young; Shin, Jae-Gook

2017-10-01

Although studies assessing the cost effectiveness of genotype-guided warfarin dosing for the management of atrial fibrillation, deep vein thrombosis, and pulmonary embolism have been reported, no publications have addressed genotype-guided warfarin therapy in mechanical heart valve replacement (MHVR) patients or genotype-guided warfarin therapy under the fee-for-service (FFS) insurance system. The aim of this study was to evaluate the cost effectiveness of genotype-guided warfarin dosing in patients with MHVR under the FFS system from the Korea healthcare sector perspective. A decision-analytic Markov model was developed to evaluate the cost effectiveness of genotype-guided warfarin dosing compared with standard dosing. Estimates of clinical adverse event rates and health state utilities were derived from the published literature. The outcome measure was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were performed to explore the range of plausible results. In a base-case analysis, genotype-guided warfarin dosing was associated with marginally higher QALYs than standard warfarin dosing (6.088 vs. 6.083, respectively), at a slightly higher cost (US$6.8) (year 2016 values). The ICER was US$1356.2 per QALY gained. In probabilistic sensitivity analysis, there was an 82.7% probability that genotype-guided dosing was dominant compared with standard dosing, and a 99.8% probability that it was cost effective at a willingness-to-pay threshold of US$50,000 per QALY gained. Compared with only standard warfarin therapy, genotype-guided warfarin dosing was cost effective in MHVR patients under the FFS insurance system.

Four-Dimensional Patient Dose Reconstruction for Scanned Ion Beam Therapy of Moving Liver Tumors

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

Richter, Daniel; TU Darmstadt, Darmstadt; Saito, Nami

2014-05-01

Purpose: Estimation of the actual delivered 4-dimensional (4D) dose in treatments of patients with mobile hepatocellular cancer with scanned carbon ion beam therapy. Methods and Materials: Six patients were treated with 4 fractions to a total relative biological effectiveness (RBE)–weighted dose of 40 Gy (RBE) using a single field. Respiratory motion was addressed by dedicated margins and abdominal compression (5 patients) or gating (1 patient). 4D treatment dose reconstructions based on the treatment records and the measured motion monitoring data were performed for the single-fraction dose and a total of 17 fractions. To assess the impact of uncertainties in the temporalmore » correlation between motion trajectory and beam delivery sequence, 3 dose distributions for varying temporal correlation were calculated per fraction. For 3 patients, the total treatment dose was formed from the fractional distributions using all possible combinations. Clinical target volume (CTV) coverage was analyzed using the volumes receiving at least 95% (V{sub 95}) and 107% (V{sub 107}) of the planned doses. Results: 4D dose reconstruction based on daily measured data is possible in a clinical setting. V{sub 95} and V{sub 107} values for the single fractions ranged between 72% and 100%, and 0% and 32%, respectively. The estimated total treatment dose to the CTV exhibited improved and more robust dose coverage (mean V{sub 95} > 87%, SD < 3%) and overdose (mean V{sub 107} < 4%, SD < 3%) with respect to the single-fraction dose for all analyzed patients. Conclusions: A considerable impact of interplay effects on the single-fraction CTV dose was found for most of the analyzed patients. However, due to the fractionated treatment, dose heterogeneities were substantially reduced for the total treatment dose. 4D treatment dose reconstruction for scanned ion beam therapy is technically feasible and may evolve into a valuable tool for dose assessment.« less

Assessment of occupational cosmic radiation exposure of flight attendants using questionnaire data.

PubMed

Anderson, Jeri L; Waters, Martha A; Hein, Misty J; Schubauer-Berigan, Mary K; Pinkerton, Lynne E

2011-11-01

Female flight attendants may have a higher risk of breast and other cancers than the general population because of routine exposure to cosmic radiation. As part of a forthcoming study of breast and other cancer incidence, occupational cosmic radiation exposure of a cohort of female flight attendants was estimated. Questionnaire data were collected from living female cohort members who were formerly employed as flight attendants with Pan American World Airways. These data included airline at which the flight attendant was employed, assigned domicile, start and end dates for employment at domicile, and number of block hours and commuter segments flown per month. Questionnaire respondents were assigned daily absorbed and effective doses using a time-weighted dose rate specific to the domicile and/or work history era combined with self-reported work history information. Completed work history questionnaires were received from 5898 living cohort members. Mean employment time as a flight attendant was 7.4 yr at Pan Am and 12 yr in total. Estimated mean annual effective dose from all sources of occupational cosmic radiation exposure was 2.5 +/- 1.0 mSv, with a mean career dose of 30 mSv. Annual effective doses were similar to doses assessed for other flight attendant cohorts; however, questionnaire-based cumulative doses assessed in this study were on average higher than those assessed for other flight attendant cohorts using company-based records. The difference is attributed to the inclusion of dose from work at other airlines and commuter flights, which was made possible by using questionnaire data.

Development and application of a rat PBPK model to elucidate kidney and liver effects induced by ETBE and tert-butanol

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

Salazar, Keith D., E-mail: Salazar.keith@epa.gov; Brinkerhoff, Christopher J., E-mail: Brinkerhoff.Chris@epa.gov; Lee, Janice S., E-mail: Lee.JaniceS@epa.gov

Subchronic and chronic studies in rats of the gasoline oxygenates ethyl tert-butyl ether (ETBE) and tert-butanol (TBA) report similar noncancer kidney and liver effects but differing results with respect to kidney and liver tumors. Because TBA is a major metabolite of ETBE, it is possible that TBA is the active toxic moiety in all these studies, with reported differences due simply to differences in the internal dose. To test this hypothesis, a physiologically-based pharmacokinetic (PBPK) model was developed for ETBE and TBA to calculate internal dosimetrics of TBA following either TBA or ETBE exposure. This model, based on earlier PBPKmore » models of methyl tert-butyl ether (MTBE), was used to evaluate whether kidney and liver effects are consistent across routes of exposure, as well as between ETBE and TBA studies, on the basis of estimated internal dose. The results demonstrate that noncancer kidney effects, including kidney weight changes, urothelial hyperplasia, and chronic progressive nephropathy (CPN), yielded consistent dose–response relationships across routes of exposure and across ETBE and TBA studies using TBA blood concentration as the dose metric. Relative liver weights were also consistent across studies on the basis of TBA metabolism, which is proportional to TBA liver concentrations. However, kidney and liver tumors were not consistent using any dose metric. These results support the hypothesis that TBA mediates the noncancer kidney and liver effects following ETBE administration; however, additional factors besides internal dose are necessary to explain the induction of liver and kidney tumors. - Highlights: • We model two metabolically-related fuel oxygenates to address toxicity data gaps. • Kidney and liver effects are compared on an internal dose basis. • Noncancer kidney effects are consistent using TBA blood concentration. • Liver weight changes are consistent using TBA metabolic rate. • Kidney and liver tumors are not consistent using any internal dose metric.« less

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

External dose assessment in the Ukraine following the Chernobyl accident

NASA Astrophysics Data System (ADS)

Frazier, Remi Jordan Lesartre

While the physiological effects of radiation exposure have been well characterized in general, it remains unclear what the relationship is between large-scale radiological events and psychosocial behavior outcomes in individuals or populations. To investigate this, the National Science Foundation funded a research project in 2008 at the University of Colorado in collaboration with Colorado State University to expand the knowledge of complex interactions between radiation exposure, perception of risk, and psychosocial behavior outcomes by modeling outcomes for a representative sample of the population of the Ukraine which had been exposed to radiocontaminant materials released by the reactor accident at Chernobyl on 26 April 1986. In service of this project, a methodology (based substantially on previously published models specific to the Chernobyl disaster and the Ukrainian population) was developed for daily cumulative effective external dose and dose rate assessment for individuals in the Ukraine for as a result of the Chernobyl disaster. A software platform was designed and produced to estimate effective external dose and dose rate for individuals based on their age, occupation, and location of residence on each day between 26 April 1986 and 31 December 2009. A methodology was developed to transform published 137Cs soil deposition contour maps from the Comprehensive Atlas of Caesium Deposition on Europe after the Chernobyl Accident into a geospatial database to access these data as a radiological source term. Cumulative effective external dose and dose rate were computed for each individual in a 703-member cohort of Ukrainians randomly selected to be representative of the population of the country as a whole. Error was estimated for the resulting individual dose and dose rate values with Monte Carlo simulations. Distributions of input parameters for the dose assessment methodology were compared to computed dose and dose rate estimates to determine which parameters were driving the computed results. The mean external effective dose for all individuals in the cohort due to exposure to radiocontamination from the Chernobyl accident between 26 April 1986 and 31 December 2009 was found to be 1.2 mSv; the geometric mean was 0.84 mSv with a geometric standard deviation of 2.1. The mean value is well below the mean external effective dose expected due to typical background radiation (which in the United States over this time period would be 12.0 mSv). Sensitivity analysis suggests that the greatest driver of the distribution of individual dose estimates is lack of specific information about the daily behavior of each individual, specifically the portion of time each individual spent indoors (and shielded from radionuclides deposited on the soil) versus outdoors (and unshielded).

Estimation Of Organ Doses From Solar Particle Events For Future Space Exploration Missions

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee; Cucinotta, Francis A.

2006-01-01

Radiation protection practices define the effective dose as a weighted sum of equivalent dose over major organ sites for radiation cancer risks. Since a crew personnel dosimeter does not make direct measurement of the effective dose, it has been estimated with skin-dose measurements and radiation transport codes for ISS and STS missions. If sufficient protection is not provided near solar maximum, the radiation risk can be significant due to exposure to sporadic solar particle events (SPEs) as well as to the continuous galactic cosmic radiation (GCR) on future exploratory-class and long-duration missions. For accurate estimates of overall fatal cancer risks from SPEs, the specific doses at various blood forming organs (BFOs) were considered, because proton fluences and doses vary considerably across marrow regions. Previous estimates of BFO doses from SPEs have used an average body-shielding distribution for the bone marrow based on the computerized anatomical man model (CAM). With the development of an 82-point body-shielding distribution at BFOs, the mean and variance of SPE doses in the major active marrow regions (head and neck, chest, abdomen, pelvis and thighs) will be presented. Consideration of the detailed distribution of bone marrow sites is one of many requirements to improve the estimation of effective doses for radiation cancer risks.

Development and application of a rat PBPK model to elucidate kidney and liver effects induced by ETBE and tert-butanol.

PubMed

Salazar, Keith D; Brinkerhoff, Christopher J; Lee, Janice S; Chiu, Weihsueh A

2015-11-01

Subchronic and chronic studies in rats of the gasoline oxygenates ethyl tert-butyl ether (ETBE) and tert-butanol (TBA) report similar noncancer kidney and liver effects but differing results with respect to kidney and liver tumors. Because TBA is a major metabolite of ETBE, it is possible that TBA is the active toxic moiety in all these studies, with reported differences due simply to differences in the internal dose. To test this hypothesis, a physiologically-based pharmacokinetic (PBPK) model was developed for ETBE and TBA to calculate internal dosimetrics of TBA following either TBA or ETBE exposure. This model, based on earlier PBPK models of methyl tert-butyl ether (MTBE), was used to evaluate whether kidney and liver effects are consistent across routes of exposure, as well as between ETBE and TBA studies, on the basis of estimated internal dose. The results demonstrate that noncancer kidney effects, including kidney weight changes, urothelial hyperplasia, and chronic progressive nephropathy (CPN), yielded consistent dose-response relationships across routes of exposure and across ETBE and TBA studies using TBA blood concentration as the dose metric. Relative liver weights were also consistent across studies on the basis of TBA metabolism, which is proportional to TBA liver concentrations. However, kidney and liver tumors were not consistent using any dose metric. These results support the hypothesis that TBA mediates the noncancer kidney and liver effects following ETBE administration; however, additional factors besides internal dose are necessary to explain the induction of liver and kidney tumors. Published by Elsevier Inc.

Single-dose replication-defective VSV-based Nipah virus vaccines provide protection from lethal challenge in Syrian hamsters.

PubMed

Lo, Michael K; Bird, Brian H; Chattopadhyay, Anasuya; Drew, Clifton P; Martin, Brock E; Coleman, Joann D; Rose, John K; Nichol, Stuart T; Spiropoulou, Christina F

2014-01-01

Nipah virus (NiV) continues to cause outbreaks of fatal human encephalitis due to spillover from its bat reservoir. We determined that a single dose of replication-defective vesicular stomatitis virus (VSV)-based vaccine vectors expressing either the NiV fusion (F) or attachment (G) glycoproteins protected hamsters from over 1000 times LD50 NiV challenge. This highly effective single-dose protection coupled with an enhanced safety profile makes these candidates ideal for potential use in livestock and humans. Published by Elsevier B.V.

ESTIMATION OF EFFECTIVE DOSE FROM EXTERNAL EXPOSURE DUE TO SHORT-LIVED NUCLIDES IN THE PREFECTURES SURROUNDING FUKUSHIMA.

PubMed

Miyatake, Hirokazu; Yoshizawa, Nobuaki; Suzuki, Gen

2018-05-11

The Fukushima Daiichi Nuclear Power Plant (FDNPP) accident resulted in a release of radionuclides into the environment. Since the accident, measurements of radiation in the environment such as air dose rate and deposition density of radionuclides have been performed by various organizations and universities. In particular, Japan Atomic Energy Agency (JAEA) has been performing observations of air dose rate using a car-borne survey system continuously over widespread areas. Based on the data measured by JAEA, we estimated effective dose from external exposure in the prefectures surrounding Fukushima. Since car-borne survey started a few months after the accident, the main contribution to measured data comes from 137Cs and 134Cs whose half-lives are relatively long. Using air dose rate of 137Cs and 134Cs and the ratio of deposition density of short-lived nuclides to that of 137Cs and 134Cs, we also estimated contributions to the effective dose from other short-lived nuclides.

The Effect of Compliance on the Impact of Mass Drug Administration for Elimination of Lymphatic Filariasis in Egypt

PubMed Central

El-Setouhy, Maged; Abd Elaziz, Khaled M.; Helmy, Hanan; Farid, Hoda A.; Kamal, Hussein A.; Ramzy, Reda M. R.; Shannon, William D.; Weil, Gary J.

2008-01-01

We studied effects of compliance on the impact of mass drug administration (MDA) with diethylcarbamazine and albendazole for lymphatic filariasis (LF) in an Egyptian village. Baseline microfilaremia (mf) and filarial antigenemia rates were 11.5% and 19.0%, respectively. The MDA compliance rates were excellent (> 85%). However, individual compliance was highly variable; 7.4% of those surveyed after five rounds of MDA denied having ever taken the medications and 52.4% reported that they had taken all five doses. The mf and antigenemia rates were 0.2% and 2.7% in those who reported five doses of MDA and 8.3% and 13.8% in those who reported zero doses. There was no significant difference in residual infection rates among those who had taken two or more doses. These results underscore the importance of compliance for LF elimination programs based on MDA and suggest that two ingested doses of MDA are as effective as five doses for reducing filariasis infection rates. PMID:18165524

Effect of Low-Dose MDCT and Iterative Reconstruction on Trabecular Bone Microstructure Assessment.

PubMed

Kopp, Felix K; Holzapfel, Konstantin; Baum, Thomas; Nasirudin, Radin A; Mei, Kai; Garcia, Eduardo G; Burgkart, Rainer; Rummeny, Ernst J; Kirschke, Jan S; Noël, Peter B

2016-01-01

We investigated the effects of low-dose multi detector computed tomography (MDCT) in combination with statistical iterative reconstruction algorithms on trabecular bone microstructure parameters. Twelve donated vertebrae were scanned with the routine radiation exposure used in our department (standard-dose) and a low-dose protocol. Reconstructions were performed with filtered backprojection (FBP) and maximum-likelihood based statistical iterative reconstruction (SIR). Trabecular bone microstructure parameters were assessed and statistically compared for each reconstruction. Moreover, fracture loads of the vertebrae were biomechanically determined and correlated to the assessed microstructure parameters. Trabecular bone microstructure parameters based on low-dose MDCT and SIR significantly correlated with vertebral bone strength. There was no significant difference between microstructure parameters calculated on low-dose SIR and standard-dose FBP images. However, the results revealed a strong dependency on the regularization strength applied during SIR. It was observed that stronger regularization might corrupt the microstructure analysis, because the trabecular structure is a very small detail that might get lost during the regularization process. As a consequence, the introduction of SIR for trabecular bone microstructure analysis requires a specific optimization of the regularization parameters. Moreover, in comparison to other approaches, superior noise-resolution trade-offs can be found with the proposed methods.

Development and Prospective Federal State-Wide Evaluation of a Device for Height-Based Dose Recommendations in Prehospital Pediatric Emergencies: A Simple Tool to Prevent Most Severe Drug Errors.

PubMed

Kaufmann, Jost; Roth, Bernhard; Engelhardt, Thomas; Lechleuthner, Alex; Laschat, Michael; Hadamitzky, Christoph; Wappler, Frank; Hellmich, Martin

2018-01-01

Drug dosing errors pose a particular threat to children in prehospital emergency care. With the Pediatric emergency ruler (PaedER), we developed a simple height-based dose recommendation system and evaluated its effectiveness in a pre-post interventional trial as the Ethics Committee disapproved randomization due to the expected positive effect of the PaedER on outcome. Pre-interventional data were retrospectively retrieved from the electronic records and medical protocols of the Cologne Emergency Medical Service over a two-year period prior to the introduction of the PaedER. Post-interventional data were collected prospectively over a six-year period in a federal state-wide open trial. The administered doses of either intravenous or intraosseous fentanyl, midazolam, ketamine or epinephrine were recorded. Primary outcome measure was the number and severity of drug dose deviation from recommended dose (DRD) based on the patient's weight. Fifty-nine pre-interventional and 91 post-interventional prehospital drug administrations in children were analyzed. The rate of DRD > 300% overall medications were 22.0% in the pre- and 2.2% in the post-interventional group (p < 0.001). All administrations of epinephrine occurred excessive (DRD > 300%) in pre-interventional and none in post-interventional patients (p < 0.001). The use of the PaedER resulted in a 90% reduction of medication errors (95% CI: 57% to 98%; p < 0.001) and prevented all potentially life-threatening errors associated with epinephrine administration. There is an urgent need to increase the safety of emergency drug dosing in children during emergencies. A simple height-based system can support health care providers and helps to avoid life-threatening medication errors.

Hydroxychloroquine Blood Levels in Systemic Lupus Erythematosus: Clarifying Dosing Controversies and Improving Adherence.

PubMed

Durcan, Laura; Clarke, William A; Magder, Laurence S; Petri, Michelle

2015-11-01

Hydroxychloroquine (HCQ) is used for its effect on systemic lupus erythematosus (SLE) disease activity and longterm benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is disagreement about dosing; rheumatologists recommend weight-based dosing while some other specialists advocate height-based "ideal body weight" dosing. Patients were prescribed HCQ not exceeding 6.5 mg/kg (max 400 mg/day). In hemodialysis, the dose was 200 mg after each session, and in renal insufficiency it was 200 mg/day. Levels were measured at each visit with a therapeutic range of 500-2000 ng/ml. Patients were divided according to baseline blood level. To assess the effect of measurement and counseling on adherence, we compared the proportion of patients with a level of 500 ng/ml or higher based on the number of prior assessments. The proportion of patients with HCQ levels in the therapeutic range differed significantly by age, sex, and Vitamin D level. There was a trend toward lower levels with renal failure. Blood levels were similar regardless of height and ideal body weight. Comparing those with undetectable, subtherapeutic, and therapeutic levels, disease activity decreased (SLE Disease Activity Index 2.92, 2.36, and 2.20, p = 0.04 for trend). At first, 56% were therapeutic, and by the third measurement this increased to 80% (p ≤ 0.0001). There was a trend toward higher disease activity with lower HCQ levels. Renal failure dosing led to suboptimum levels. We show that weight-based dosing (max 400 mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling, and repeated testing can increase adherence rates.

Estimation of Effective Dose from External Exposure in The Six Prefectures adjacent to Fukushima Prefecture

NASA Astrophysics Data System (ADS)

Miyatake, Hirokazu; Yoshizawa, Nobuaki; Hirakawa, Sachiko; Murakami, Kana; Takizawa, Mari; Kawai, Masaki; Sato, Osamu; Takagi, Shunji; Suzuki, Gen

2017-09-01

The Fukushima Daiichi Nuclear Power Plant accident caused a release of radionuclides. Radionuclides were deposited on the ground not only in Fukushima prefecture but also in nearby prefectures. Since the accident, measurement of radiation in environment such as air dose rate and deposition density of radionuclides has been performed by many organizations and universities. In particular, Japan Atomic Energy Agency (JAEA) has been performing observations of air dose rate using a car-borne survey system continuously and over wide areas. In our study, using the data measured by JAEA, we estimated effective dose from external exposure in the six prefectures adjacent to Fukushima prefecture. Since car-borne survey was started a few months later after the accident, measured air dose rate in this method is mainly contributed by 137Cs and 134Cs whose half-lives are relatively long. Therefore, based on air dose rate of 137Cs and 134Cs and the ratio of deposition density of short-half-life nuclides to that of 137Cs and 134Cs, we also estimated effective dose contributed from not only 137Cs and 134Cs but also other short-half-life nuclides. We compared the effective dose estimated by the method above with that of UNSCEAR and measured data using personal dosimeters in some areas.

Web-based scoring of the dicentric assay, a collaborative biodosimetric scoring strategy for population triage in large scale radiation accidents.

PubMed

Romm, H; Ainsbury, E; Bajinskis, A; Barnard, S; Barquinero, J F; Barrios, L; Beinke, C; Puig-Casanovas, R; Deperas-Kaminska, M; Gregoire, E; Oestreicher, U; Lindholm, C; Moquet, J; Rothkamm, K; Sommer, S; Thierens, H; Vral, A; Vandersickel, V; Wojcik, A

2014-05-01

In the case of a large scale radiation accident high throughput methods of biological dosimetry for population triage are needed to identify individuals requiring clinical treatment. The dicentric assay performed in web-based scoring mode may be a very suitable technique. Within the MULTIBIODOSE EU FP7 project a network is being established of 8 laboratories with expertise in dose estimations based on the dicentric assay. Here, the manual dicentric assay was tested in a web-based scoring mode. More than 23,000 high resolution images of metaphase spreads (only first mitosis) were captured by four laboratories and established as image galleries on the internet (cloud). The galleries included images of a complete dose effect curve (0-5.0 Gy) and three types of irradiation scenarios simulating acute whole body, partial body and protracted exposure. The blood samples had been irradiated in vitro with gamma rays at the University of Ghent, Belgium. Two laboratories provided image galleries from Fluorescence plus Giemsa stained slides (3 h colcemid) and the image galleries from the other two laboratories contained images from Giemsa stained preparations (24 h colcemid). Each of the 8 participating laboratories analysed 3 dose points of the dose effect curve (scoring 100 cells for each point) and 3 unknown dose points (50 cells) for each of the 3 simulated irradiation scenarios. At first all analyses were performed in a QuickScan Mode without scoring individual chromosomes, followed by conventional scoring (only complete cells, 46 centromeres). The calibration curves obtained using these two scoring methods were very similar, with no significant difference in the linear-quadratic curve coefficients. Analysis of variance showed a significant effect of dose on the yield of dicentrics, but no significant effect of the laboratories, different methods of slide preparation or different incubation times used for colcemid. The results obtained to date within the MULTIBIODOSE project by a network of 8 collaborating laboratories throughout Europe are very promising. The dicentric assay in the web based scoring mode as a high throughput scoring strategy is a useful application for biodosimetry in the case of a large scale radiation accident.

Cost-effectiveness of the Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults.

PubMed

Le, Phuc; Rothberg, Michael B

2018-02-01

The live attenuated herpes zoster vaccine (ZVL) is recommended for immunocompetent adults 60 years or older, but the efficacy wanes with age and over time. A new adjuvanted herpes zoster subunit vaccine (HZ/su) has higher efficacy but might be more expensive. The choice of vaccines depends on their relative values. To assess the cost-effectiveness of HZ/su. Markov decision model with transition probabilities based on the US medical literature. Participants were immunocompetent adults 60 years or older. Data were derived from participant groups ranging in number from less than 100 to more than 30 000 depending on the variable assessed. The study dates were July 1 to 31, 2017. No vaccination, ZVL (single dose), and HZ/su (2-dose series) vaccine administered at different ages. Total costs and quality-adjusted life-years (QALYs) were estimated. Based on randomized clinical trial data, at a price of $280 per series ($140 per dose), HZ/su was more effective and less expensive than ZVL at all ages. The incremental cost-effectiveness ratios compared with no vaccination ranged from $20 038 to $30 084 per QALY, depending on vaccination age. The finding was insensitive to variations in most model inputs other than the vaccine price and certain combinations of low adherence rate with a second dose and low efficacy of a single dose of HZ/su. At the current ZVL price ($213 per dose), HZ/su had lower overall costs than ZVL up to a price of $350 per 2-dose series. In probabilistic sensitivity analysis, HZ/su had 73% probability of being cost-effective for 60-year-olds at $50 000 per QALY. Under conservative assumptions, at a price of $280 per series ($140 per dose), HZ/su would cost less than ZVL and has a high probability of offering good value.

New Stochastic Annual Limits on Intake for Selected Radionuclides

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

Carbaugh, Eugene H.

Annual limits on intake (ALI) have historically been tabulated by the International Commission on Radiological Protection (e.g., ICRP 1979, 1961) and also by the Environmental Protection Agency (EPA 1988). These compilations have been rendered obsolete by more recent ICRP dosimetry methods, and, rather than provide new ALIs, the ICRP has opted instead to provide committed dose coefficients from which an ALI can be determined by a user for a specific set of conditions. The U.S. Department of Energy historically has referenced compilations of ALIs and has defined their method of calculation in its radiation protection regulation (10 CFDR 835), butmore » has never provided a specific compilation. Under June 2007 amendments to 10 CFR 835, ALIs can be calculated by dividing an appropriate dose limit, either 5-rem (0.05 Sv) effective dose or 50 rem (0.5 Sv) equivalent dose to an individual organ or tissue, by an appropriate committed dose coefficient. When based on effective dose, the ALI is often referred to as a stochastic annual limit on intake (SALI), and when based on the individual organ or tissue equivalent limit, it has often been called a deterministic annual limit on intake (DALI).« less

Increasing the dose of television advertising in a national antismoking media campaign: results from a randomised field trial.

PubMed

McAfee, Tim; Davis, Kevin C; Shafer, Paul; Patel, Deesha; Alexander, Robert; Bunnell, Rebecca

2017-01-01

While antismoking media campaigns have demonstrated effectiveness, less is known about the country-level effects of increased media dosing. The 2012 US Tips From Former Smokers (Tips) campaign generated approximately 1.6 million quit attempts overall; however, the specific dose-response from the campaign was only assessed by self-report. Assess the impact of higher ad exposure during the 2013 Tips campaign on quit-related behaviours and intentions, campaign awareness, communication about campaign, and disease knowledge. A 3-month national media buy was supplemented within 67 (of 190) randomly selected local media markets. Higher-dose markets received media buys 3 times that of standard-dose markets. We compared outcomes of interest using data collected via web-based surveys from nationally representative, address-based probability samples of 5733 cigarette smokers and 2843 non-smokers. In higher-dose markets, 87.2% of smokers and 83.9% of non-smokers recalled television campaign exposure versus 75.0% of smokers and 73.9% of non-smokers in standard-dose markets. Among smokers overall, the relative quit attempt rate was 11% higher in higher-dose markets (38.8% vs 34.9%; p<0.04). The higher-dose increase was larger in African-Americans (50.9% vs 31.8%; p<0.01). Smokers in higher-dose markets without a mental health condition, with a chronic health condition, or with only some college education made quit attempts at a higher rate than those in standard-dose markets. Non-smokers in higher-dose markets were more likely to talk with family or friends about smoking dangers (43.1% vs 35.7%; p<0.01) and had greater knowledge of smoking-related diseases. The US 2013 Tips antismoking media campaign compared standard and higher doses by randomisation of local media markets. Results demonstrate the effectiveness of a higher dose for engaging non-smokers and further increasing quit attempts among smokers, especially African-Americans. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The effective dose result of 18F-FDG PET-CT paediatric patients

NASA Astrophysics Data System (ADS)

Hussin, D.; Said, M. A.; Ali, N. S.; Tajuddin, A. A.; Zainon, R.

2017-05-01

Paediatric patient received high exposure from both CT and PET examination. Automatic Exposure Control (AEC) is important in CT dose reduction. This study aimed to compare the effective dose obtained from PET-CT scanner with and without the use of AEC function. In this study, 68 patients underwent PET-CT examination without the use of AEC function, while 25 patients used the AEC function during the examination. Patients involved in this study were between 2 to 15 years old with varies of malignancies and epilepsy diseases. The effective dose obtained from PET and CT examinations was calculated based on recommendation from International Commission on Radiological Protection (ICRP) Publication 106 and ICRP publication 102. The outcome of this study shows that the radiation dose was reduced up to 20% with the use of AEC function. The mean average of effective dose result obtained from PET and CT examinations without the use of AEC and AEC function were found to be as 6.67 mSv, 6.77 mSv, 6.03mSv and 4.96 mSv respectively. Where total effective dose result of PET-CT with non-AEC and AEC were found to be 13.44 mSv and 10.99 mSv respectively. Conclusion of this study is, the installation of AEC function in PET-CT machine does play important role in CT dose reduction especially for paediatric patient.

RADIANCE: An automated, enterprise-wide solution for archiving and reporting CT radiation dose estimates.

PubMed

Cook, Tessa S; Zimmerman, Stefan L; Steingall, Scott R; Maidment, Andrew D A; Kim, Woojin; Boonn, William W

2011-01-01

There is growing interest in the ability to monitor, track, and report exposure to radiation from medical imaging. Historically, however, dose information has been stored on an image-based dose sheet, an arrangement that precludes widespread indexing. Although scanner manufacturers are beginning to include dose-related parameters in the Digital Imaging and Communications in Medicine (DICOM) headers of imaging studies, there remains a vast repository of retrospective computed tomographic (CT) data with image-based dose sheets. Consequently, it is difficult for imaging centers to monitor their dose estimates or participate in the American College of Radiology (ACR) Dose Index Registry. An automated extraction software pipeline known as Radiation Dose Intelligent Analytics for CT Examinations (RADIANCE) has been designed that quickly and accurately parses CT dose sheets to extract and archive dose-related parameters. Optical character recognition of information in the dose sheet leads to creation of a text file, which along with the DICOM study header is parsed to extract dose-related data. The data are then stored in a relational database that can be queried for dose monitoring and report creation. RADIANCE allows efficient dose analysis of CT examinations and more effective education of technologists, radiologists, and referring physicians regarding patient exposure to radiation at CT. RADIANCE also allows compliance with the ACR's dose reporting guidelines and greater awareness of patient radiation dose, ultimately resulting in improved patient care and treatment.

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.

Optimal dose selection of N-methyl-N-nitrosourea for the rat comet assay to evaluate DNA damage in organs with different susceptibility to cytotoxicity.

PubMed

Kitamoto, Sachiko; Matsuyama, Ryoko; Uematsu, Yasuaki; Ogata, Keiko; Ota, Mika; Yamada, Toru; Miyata, Kaori; Funabashi, Hitoshi; Saito, Koichi

2015-07-01

The in vivo rodent alkaline comet assay (comet assay) is a promising technique to evaluate DNA damage in vivo. However, there is no agreement on a method to evaluate DNA damage in organs where cytotoxicity is observed. As a part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the comet assay, we examined DNA damage in the liver, stomach, and bone marrow of rats given three oral doses of N-methyl-N-nitrosourea (MNU) up to the maximum tolerated dose based on systemic toxicity. MNU significantly increased the % tail DNA in all the organs. Histopathological analysis showed no cytotoxic effect on the liver, indicating clearly that MNU has a genotoxic potential in the liver. In the stomach, however, the cytotoxic effects were very severe at systemically non-toxic doses. Low-dose MNU significantly increased the % tail DNA even at a non-cytotoxic dose, indicating that MNU has a genotoxic potential also in the stomach. Part of the DNA damage at cytotoxic doses was considered to be a secondary effect of severe cell damage. In the bone marrow, both the % tail DNA and incidence of micronucleated polychromatic erythrocytes significantly increased at non-hematotoxic doses, which were different from the non-cytotoxic doses for liver and stomach. These findings indicate that an optimal dose for detecting DNA damage may vary among organs and that careful attention is required to select an optimum dose for the comet assay based on systemic toxicity such as mortality and clinical observations. The present study shows that when serious cytotoxicity is suggested by increased % hedgehogs in the comet assay, histopathological examination should be included for the evaluation of a positive response. Copyright © 2015 Elsevier B.V. All rights reserved.

The impact of assumptions regarding vaccine-induced immunity on the public health and cost-effectiveness of hepatitis A vaccination: Is one dose sufficient?

PubMed

Curran, Desmond; de Ridder, Marc; Van Effelterre, Thierry

2016-11-01

Hepatitis A vaccination stimulates memory cells to produce an anamnestic response. In this study, we used a mathematical model to examine how long-term immune memory might convey additional protection against clinical/icteric infections. Dynamic and decision models were used to estimate the expected number of cases, and the costs and quality-adjusted life-years (QALYs), respectively. Several scenarios were explored by assuming: (1) varying duration of vaccine-induced immune memory, (2) and/or varying levels of vaccine-induced immune memory protection (IMP), (3) and/or varying levels of infectiousness in vaccinated individuals with IMP. The base case analysis assumed a time horizon of 25 y (2012 - 2036), with additional analyses over 50 and 75 y. The analyses were conducted in the Mexican public health system perspective. In the base case that assumed no vaccine-induced IMP, the 2-dose hepatitis A vaccination strategy was cost-effective compared with the 1-dose strategy over the 3 time horizons. However, it was not cost-effective if we assumed additional IMP durations of at least 10 y in the 25-y horizon. In the 50- and 75-y horizons, the 2-dose strategy was always cost-effective, except when 100% reduction in the probability of icteric Infections, 75% reduction in infectiousness, and mean durations of IMP of at least 50 y were assumed. This analysis indicates that routine vaccination of toddlers against hepatitis A virus would be cost-effective in Mexico using a single-dose vaccination strategy. However, the cost-effectiveness of a second dose depends on the assumptions of additional protection by IMP and the time horizon over which the analysis is performed.

The impact of assumptions regarding vaccine-induced immunity on the public health and cost-effectiveness of hepatitis A vaccination: Is one dose sufficient?

PubMed Central

Curran, Desmond; de Ridder, Marc; Van Effelterre, Thierry

2016-01-01

ABSTRACT Hepatitis A vaccination stimulates memory cells to produce an anamnestic response. In this study, we used a mathematical model to examine how long-term immune memory might convey additional protection against clinical/icteric infections. Dynamic and decision models were used to estimate the expected number of cases, and the costs and quality-adjusted life-years (QALYs), respectively. Several scenarios were explored by assuming: (1) varying duration of vaccine-induced immune memory, (2) and/or varying levels of vaccine-induced immune memory protection (IMP), (3) and/or varying levels of infectiousness in vaccinated individuals with IMP. The base case analysis assumed a time horizon of 25 y (2012 – 2036), with additional analyses over 50 and 75 y. The analyses were conducted in the Mexican public health system perspective. In the base case that assumed no vaccine-induced IMP, the 2-dose hepatitis A vaccination strategy was cost-effective compared with the 1-dose strategy over the 3 time horizons. However, it was not cost-effective if we assumed additional IMP durations of at least 10 y in the 25-y horizon. In the 50- and 75-y horizons, the 2-dose strategy was always cost-effective, except when 100% reduction in the probability of icteric Infections, 75% reduction in infectiousness, and mean durations of IMP of at least 50 y were assumed. This analysis indicates that routine vaccination of toddlers against hepatitis A virus would be cost-effective in Mexico using a single-dose vaccination strategy. However, the cost-effectiveness of a second dose depends on the assumptions of additional protection by IMP and the time horizon over which the analysis is performed. PMID:27428611

Locomotor activity and tissue levels following acute administration of lambda- and gamma-cyhalothrin in rats

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

Moser, Virginia C., E-mail: Moser.ginger@epa.gov

Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., λ-cyhalothrin) as well as enriched active isomers (e.g., γ-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of λ- and γ-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5 h after oral gavagemore » dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for γ-cyhalothrin was lower than for λ-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the γ-isomer (1.29 mg/kg) compared to λ-cyhalothrin (2.65 mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of γ-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While γ-cyhalothrin was 2-fold more potent based on administered dose, the differences based on internal concentrations were less, with γ-cyhalothrin being 1.3- to 1.6-fold more potent than λ-cyhalothrin. These potency differences are consistent with the purity of the λ-isomer (approximately 43%) compared to the enriched isomer γ-cyhalothrin (approximately 98%). Thus, administered dose as well as differences in cyhalothrin isomers is a good predictor of behavioral effects. - Highlights: • Acute changes in locomotor activity were produced by λ- and γ-cyhalothrin. • γ-Cyhalothrin was about 2-fold more potent than λ-cyhalothrin. • Brain and plasma levels were tightly correlated across doses. • Activity changes correlated well with brain and plasma concentrations.« less

Radiation assessment to paediatric with F-18-FDG undergo whole-body PET/CT examination

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

Dhalisa, H., E-mail: dhalisa82@gmail.com; Rafidah, Z.; Mohamad, A. S.

2016-01-22

This study was carried out on wholebody radiation dose assessment to paediatrics patient who undergo PET/CT scanner at Institut Kanser Negara. Consist of 68 patients with varies of malignancies and epilepsy disease case covering age between 2 years to 12 years old. This is a retrospective study from 2010-2014. The use of PET/CT scanner as an advanced tool has been proven to give an extra radiation dose to the patient. It is because of the radiation exposure from the combination of both CT and PET scans rather than a single CT or PET scan. Furthermore, a study on radiation dosemore » to paediatric patient undergoing PET/CT is rare in Malaysia. So, the aim of this study is to estimate the wholebody effective dose to paediatric patient in Malaysia. Effective dose from PET scan was calculated based on the activity of F18 FDG and dose coefficient reported in International Commission on Radiological Protection (ICRP) Publication 106. Effective dose from CT was determined using k coefficient as reported in ICRP publication 102 and Dose Length Product (DLP) value. The average effective dose from PET and CT were found to be 7.05mSv and 5.77mSv respectively. The mean wholebody effective dose received by a patient with combined PETCT examination was 12.78mSv. These results could be used as reference for dosimetry of a patient undergoing PETCT examination in Malaysia.« less

Research on Ratio of Dosage of Drugs in Traditional Chinese Prescriptions by Data Mining.

PubMed

Yu, Xing-Wen; Gong, Qing-Yue; Hu, Kong-Fa; Mao, Wen-Jing; Zhang, Wei-Ming

2017-01-01

Maximizing the effectiveness of prescriptions and minimizing adverse effects of drugs is a key component of the health care of patients. In the practice of traditional Chinese medicine (TCM), it is important to provide clinicians a reference for dosing of prescribed drugs. The traditional Cheng-Church biclustering algorithm (CC) is optimized and the data of TCM prescription dose is analyzed by using the optimization algorithm. Based on an analysis of 212 prescriptions related to TCM treatment of kidney diseases, the study generated 87 prescription dose quantum matrices and each sub-matrix represents the referential value of the doses of drugs in different recipes. The optimized CC algorithm can effectively eliminate the interference of zero in the original dose matrix of TCM prescriptions and avoid zero appearing in output sub-matrix. This results in the ability to effectively analyze the reference value of drugs in different prescriptions related to kidney diseases, so as to provide valuable reference for clinicians to use drugs rationally.

Gender-Specific Differences in Low-Dose Haloperidol Response for Prevention of Postoperative Nausea and Vomiting: A Register-Based Cohort Study.

PubMed

Brettner, Florian; Janitza, Silke; Prüll, Kathrin; Weninger, Ernst; Mansmann, Ulrich; Küchenhoff, Helmut; Jovanovic, Alexander; Pollwein, Bernhard; Chappell, Daniel; Zwissler, Bernhard; von Dossow, Vera

2016-01-01

Postoperative nausea and vomiting (PONV) is one of the most common and distressing complications after general anesthesia and surgery, with young non-smoking females receiving postoperative opioids being high-risk patients. This register-based study aims to evaluate the effect of low-dose haloperidol (0.5 mg intravenously) directly after induction of general anesthesia to reduce the incidence of PONV in the postoperative anesthesiological care unit (PACU). Multivariable regression models were used to investigate the association between low-dose haloperidol and the occurrence of PONV using a patient registry containing 2,617 surgical procedures carried out at an university hospital. Haloperidol 0.5 mg is associated with a reduced risk of PONV in the total collective (adjusted odds ratio = 0.75, 95% confidence interval: [0.56, 0.99], p = 0.05). The results indicate that there is a reduced risk in male patients (adjusted odds ratio = 0.45, 95% confidence interval: [0.28, 0.73], p = 0.001) if a dose of 0.5 mg haloperidol was administered while there seems to be no effect in females (adjusted odds ratio = 1.02, 95% confidence interval: [0.71, 1.46], p = 0.93). Currently known risk factors for PONV such as female gender, duration of anesthesia and the use of opioids were confirmed in our analysis. This study suggests that low-dose haloperidol has an antiemetic effect in male patients but has no effect in female patients. A confirmation of the gender-specific effects we have observed in this register-based cohort study might have major implications on clinical daily routine.

Gender-Specific Differences in Low-Dose Haloperidol Response for Prevention of Postoperative Nausea and Vomiting: A Register-Based Cohort Study

PubMed Central

Prüll, Kathrin; Weninger, Ernst; Mansmann, Ulrich; Küchenhoff, Helmut; Jovanovic, Alexander; Pollwein, Bernhard; Chappell, Daniel; Zwissler, Bernhard; von Dossow, Vera

2016-01-01

Background Postoperative nausea and vomiting (PONV) is one of the most common and distressing complications after general anesthesia and surgery, with young non-smoking females receiving postoperative opioids being high-risk patients. This register-based study aims to evaluate the effect of low-dose haloperidol (0.5 mg intravenously) directly after induction of general anesthesia to reduce the incidence of PONV in the postoperative anesthesiological care unit (PACU). Methods Multivariable regression models were used to investigate the association between low-dose haloperidol and the occurrence of PONV using a patient registry containing 2,617 surgical procedures carried out at an university hospital. Results Haloperidol 0.5 mg is associated with a reduced risk of PONV in the total collective (adjusted odds ratio = 0.75, 95% confidence interval: [0.56, 0.99], p = 0.05). The results indicate that there is a reduced risk in male patients (adjusted odds ratio = 0.45, 95% confidence interval: [0.28, 0.73], p = 0.001) if a dose of 0.5 mg haloperidol was administered while there seems to be no effect in females (adjusted odds ratio = 1.02, 95% confidence interval: [0.71, 1.46], p = 0.93). Currently known risk factors for PONV such as female gender, duration of anesthesia and the use of opioids were confirmed in our analysis. Conclusion This study suggests that low-dose haloperidol has an antiemetic effect in male patients but has no effect in female patients. A confirmation of the gender-specific effects we have observed in this register-based cohort study might have major implications on clinical daily routine. PMID:26751066

Population pharmacokinetics of busulfan in pediatric and young adult patients undergoing hematopoietic cell transplant: a model-based dosing algorithm for personalized therapy and implementation into routine clinical use.

PubMed

Long-Boyle, Janel R; Savic, Rada; Yan, Shirley; Bartelink, Imke; Musick, Lisa; French, Deborah; Law, Jason; Horn, Biljana; Cowan, Morton J; Dvorak, Christopher C

2015-04-01

Population pharmacokinetic (PK) studies of busulfan in children have shown that individualized model-based algorithms provide improved targeted busulfan therapy when compared with conventional dose guidelines. The adoption of population PK models into routine clinical practice has been hampered by the tendency of pharmacologists to develop complex models too impractical for clinicians to use. The authors aimed to develop a population PK model for busulfan in children that can reliably achieve therapeutic exposure (concentration at steady state) and implement a simple model-based tool for the initial dosing of busulfan in children undergoing hematopoietic cell transplantation. Model development was conducted using retrospective data available in 90 pediatric and young adult patients who had undergone hematopoietic cell transplantation with busulfan conditioning. Busulfan drug levels and potential covariates influencing drug exposure were analyzed using the nonlinear mixed effects modeling software, NONMEM. The final population PK model was implemented into a clinician-friendly Microsoft Excel-based tool and used to recommend initial doses of busulfan in a group of 21 pediatric patients prospectively dosed based on the population PK model. Modeling of busulfan time-concentration data indicates that busulfan clearance displays nonlinearity in children, decreasing up to approximately 20% between the concentrations of 250-2000 ng/mL. Important patient-specific covariates found to significantly impact busulfan clearance were actual body weight and age. The percentage of individuals achieving a therapeutic concentration at steady state was significantly higher in subjects receiving initial doses based on the population PK model (81%) than in historical controls dosed on conventional guidelines (52%) (P = 0.02). When compared with the conventional dosing guidelines, the model-based algorithm demonstrates significant improvement for providing targeted busulfan therapy in children and young adults.

Model-based evaluation of cost-effectiveness of nerve growth factor inhibitors in knee osteoarthritis: impact of drug cost, toxicity, and means of administration.

PubMed

Losina, E; Michl, G; Collins, J E; Hunter, D J; Jordan, J M; Yelin, E; Paltiel, A D; Katz, J N

2016-05-01

Studies suggest nerve growth factor inhibitors (NGFi) relieve pain but may accelerate disease progression in some patients with osteoarthritis (OA). We sought cost and toxicity thresholds that would make NGFi a cost-effective treatment for moderate-to-severe knee OA. We used the Osteoarthritis Policy (OAPol) model to estimate the cost-effectiveness of NGFi compared to standard of care (SOC) in OA, using Tanezumab as an example. Efficacy and rates of accelerated OA progression were based on published studies. We varied the price/dose from $200 to $1000. We considered self-administered subcutaneous (SC) injections (no administration cost) vs provider-administered intravenous (IV) infusion ($69-$433/dose). Strategies were defined as cost-effective if their incremental cost-effectiveness ratio (ICER) was less than $100,000/quality-adjusted life year (QALY). In sensitivity analyses we varied efficacy, toxicity, and costs. SOC in patients with high levels of pain led to an average discounted quality-adjusted life expectancy of 11.15 QALYs, a lifetime risk of total knee replacement surgery (TKR) of 74%, and cumulative discounted direct medical costs of $148,700. Adding Tanezumab increased QALYs to 11.42, reduced primary TKR utilization to 63%, and increased costs to between $155,400 and $199,500. In the base-case analysis, Tanezumab at $600/dose was cost-effective when delivered outside of a hospital. At $1000/dose, Tanezumab was not cost-effective in all but the most optimistic scenario. Only at rates of accelerated OA progression of 10% or more (10-fold higher than reported values) did Tanezumab decrease QALYs and fail to represent a viable option. At $100,000/QALY, Tanezumab would be cost effective if priced ≤$400/dose in all settings except IV hospital delivery. Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Multiple nicotine training doses in mice as a basis for differentiating the effects of smoking cessation aids.

PubMed

Cunningham, Colin S; McMahon, Lance R

2013-07-01

Receptor mechanisms underlying the behavioral effects of clinically used nicotinic acetylcholine receptor agonists have not been fully established. Drug discrimination was used to compare receptor mechanisms underlying the effects of smoking cessation aids. Separate groups of male C57BL/6J mice discriminated 0.56, 1, or 1.78 mg/kg of nicotine base. Nicotine, varenicline, and cytisine were administered alone, in combination with each other, and in combination with mecamylamine and dihydro-β-erythroidine (DHβE). Midazolam and morphine were tested to examine sensitivity to non-nicotinics. The ED50 value of nicotine to produce discriminative stimulus effects systematically increased as training dose increased. Varenicline and cytisine did not fully substitute for nicotine and, as compared with nicotine, their ED50 values varied less systematically as a function of nicotine training dose. Morphine did not substitute for nicotine, whereas midazolam substituted for the low and not the higher training doses of nicotine. As training dose increased, the dose of mecamylamine needed to produce a significant rightward shift in the nicotine dose-effect function also increased. DHβE antagonized nicotine in animals discriminating the smallest dose of nicotine. Varenicline did not antagonize the effects of nicotine, whereas cytisine produced a modest though significant antagonism of nicotine. These results suggest that differences in pharmacologic mechanism between nicotine, varenicline, and cytisine include not only differences in efficacy at a common subtype of nicotinic acetylcholine receptor, but also differential affinity and/or efficacy at multiple receptor subtypes.

Management of cosmic radiation exposure for aircraft crew in Japan.

PubMed

Yasuda, Hiroshi; Sato, Tatsuhiko; Yonehara, Hidenori; Kosako, Toshiso; Fujitaka, Kazunobu; Sasaki, Yasuhito

2011-07-01

The International Commission on Radiological Protection has recommended that cosmic radiation exposure of crew in commercial jet aircraft be considered as occupational exposure. In Japan, the Radiation Council of the government has established a guideline that requests domestic airlines to voluntarily keep the effective dose of cosmic radiation for aircraft crew below 5 mSv y(-1). The guideline also gives some advice and policies regarding the method of cosmic radiation dosimetry, the necessity of explanation and education about this issue, a way to view and record dose data, and the necessity of medical examination for crew. The National Institute of Radiological Sciences helps the airlines to follow the guideline, particularly for the determination of aviation route doses by numerical simulation. The calculation is performed using an original, easy-to-use program package called 'JISCARD EX' coupled with a PHITS-based analytical model and a GEANT4-based particle tracing code. The new radiation weighting factors recommended in 2007 are employed for effective dose determination. The annual individual doses of aircraft crew were estimated using this program.

Dose reduction in 64-row whole-body CT in multiple trauma: an optimized CT protocol with iterative image reconstruction on a gemstone-based scintillator.

PubMed

Geyer, Lucas L; Körner, Markus; Harrieder, Andreas; Mueck, Fabian G; Deak, Zsuzsanna; Wirth, Stefan; Linsenmaier, Ulrich

2016-01-01

Evaluation of potential dose savings by implementing adaptive statistical iterative reconstruction (ASiR) on a gemstone-based scintillator in a clinical 64-row whole-body CT (WBCT) protocol after multiple trauma. Dose reports of 152 WBCT scans were analysed for two 64-row multidetector CT scanners (Scanners A and B); the main scanning parameters were kept constant. ASiR and a gemstone-based scintillator were used in Scanner B, and the noise index was adjusted (head: 5.2 vs 6.0; thorax/abdomen: 29.0 vs 46.0). The scan length, CT dose index (CTDI) and dose-length product (DLP) were analysed. The estimated mean effective dose was calculated using normalized conversion factors. Student's t-test was used for statistics. Both the mean CTDI (mGy) (Scanner A: 53.8 ± 2.0, 10.3 ± 2.5, 14.4 ± 3.7; Scanner B: 48.7 ± 2.2, 7.1 ± 2.3, 9.1 ± 3.6; p < 0.001, respectively) and the mean DLP (mGy cm) (Scanner A: 1318.9 ± 167.8, 509.3 ± 134.7, 848.8 ± 254.0; Scanner B: 1190.6 ± 172.6, 354.6 ± 128.3, 561.0 ± 246.7; p < 0.001, respectively) for the head, thorax and abdomen were significantly reduced with Scanner B. There was no relevant difference in scan length. The total mean effective dose (mSv) was significantly decreased with Scanner B (24.4 ± 6.0, 17.2 ± 5.8; p < 0.001). The implementation of ASiR and a gemstone-based scintillator allows for significant dose savings in a clinical WBCT protocol. Recent technical developments can significantly reduce radiation dose of WBCT in multiple trauma. Dose reductions of 10-34% can be achieved.

How Does Patient Radiation Exposure Compare With Low-dose O-arm Versus Fluoroscopy for Pedicle Screw Placement in Idiopathic Scoliosis?

PubMed

Su, Alvin W; McIntosh, Amy L; Schueler, Beth A; Milbrandt, Todd A; Winkler, Jennifer A; Stans, Anthony A; Larson, A Noelle

Intraoperative C-arm fluoroscopy and low-dose O-arm are both reasonable means to assist in screw placement for idiopathic scoliosis surgery. Both using pediatric low-dose O-arm settings and minimizing the number of radiographs during C-arm fluoroscopy guidance decrease patient radiation exposure and its deleterious biological effect that may be associated with cancer risk. We hypothesized that the radiation dose for C-arm-guided fluoroscopy is no less than low-dose O-arm scanning for placement of pedicle screws. A multicenter matched-control cohort study of 28 patients in total was conducted. Fourteen patients who underwent O-arm-guided pedicle screw insertion for spinal fusion surgery in 1 institution were matched to another 14 patients who underwent C-arm fluoroscopy guidance in the other institution in terms of the age of surgery, body weight, and number of imaged spine levels. The total effective dose was compared. A low-dose pediatric protocol was used for all O-arm scans with an effective dose of 0.65 mSv per scan. The effective dose of C-arm fluoroscopy was determined using anthropomorphic phantoms that represented the thoracic and lumbar spine in anteroposterior and lateral views, respectively. The clinical outcome and complications of all patients were documented. The mean total effective dose for the O-arm group was approximately 4 times higher than that of the C-arm group (P<0.0001). The effective dose for the C-arm patients had high variability based on fluoroscopy time and did not correlate with the number of imaged spine levels or body weight. The effective dose of 1 low-dose pediatric O-arm scan approximated 85 seconds of the C-arm fluoroscopy time. All patients had satisfactory clinical outcomes without major complications that required returning to the operating room. Radiation exposure required for O-arm scans can be higher than that required for C-arm fluoroscopy, but it depends on fluoroscopy time. Inclusion of more medical centers and surgeons will better account for the variability of C-arm dose due to distinct patient characteristics, surgeon's preference, and individual institution's protocol. Level III-case-control study.

Cost-effectiveness of high-dose atorvastatin compared with regular dose simvastatin.

PubMed

Lindgren, Peter; Graff, Jennifer; Olsson, Anders G; Pedersen, Terje J; Jönsson, Bengt

2007-06-01

The aim of the study was to evaluate the long-term cost-effectiveness of high-dose atorvastatin when compared with generic simvastatin for secondary prevention in Denmark, Finland, Norway, and Sweden based on the recently completed IDEAL trial. The IDEAL trial showed that high-dose treatment with atorvastatin was associated with fewer non-fatal myocardial infarctions (MI) or coronary heart disease death (RR 0.89; 95% CI 0.78-1.01) and major cardiovascular events by (RR 0.87; 95% CI 0.77-0.98) or any coronary event (RR 0.84; 95% CI 0.76-0.91) than simvastatin with no significant difference in the number of serious adverse events. Costs during the trial period was estimated based on the trial data and a Markov model was constructed where the risk of MIs and revascularization procedures and the long-term costs, quality of life, and mortality associated with these events was simulated. Costs were based on resource consumptions recorded in the trial multiplied with recent unit costs from each country. Both direct health care costs and indirect costs (costs from lost production due to work absence) were included. Intervention lasted for the duration of the trial (4.8 years) while health-effects and costs are predicted for the lifespan of the patient. The main outcome was quality adjusted life-years (QALY) gained. High-dose treatment was predicted to lead to a mean increase in survival of 0.049 years per patient and 0.033 QALYs gained. The cost to gain one QALY was predicted to 47,197euro (Denmark), 62,639euro (Finland), 35,210euro (Norway), and 43,667euro (Sweden), with cost-effectiveness ratio decreasing with higher risk. In the prevention of cardiovascular events among patients with a previous MI, high-dose atorvastatin appears to be a cost-effective strategy when compared with generic simvastatin 20-40 mg in Denmark, Norway, and Sweden. In Finland, it is cost-effective in high-risk patients. The key driver of the cost-effectiveness is the price-difference between 80 mg atorvastatin and generic simvastatin.

Comparing risk estimates following diagnostic CT radiation exposures employing different methodological approaches.

PubMed

Kashcheev, Valery V; Pryakhin, Evgeny A; Menyaylo, Alexander N; Chekin, Sergey Yu; Ivanov, Viktor K

2014-06-01

The current study has two aims: the first is to quantify the difference between radiation risks estimated with the use of organ or effective doses, particularly when planning pediatric and adult computed tomography (CT) examinations. The second aim is to determine the method of calculating organ doses and cancer risk using dose-length product (DLP) for typical routine CT examinations. In both cases, the radiation-induced cancer risks from medical CT examinations were evaluated as a function of gender and age. Lifetime attributable risk values from CT scanning were estimated with the use of ICRP (Publication 103) risk models and Russian national medical statistics data. For populations under the age of 50 y, the risk estimates based on organ doses usually are 30% higher than estimates based on effective doses. In older populations, the difference can be up to a factor of 2.5. The typical distributions of organ doses were defined for Chest Routine, Abdominal Routine, and Head Routine examinations. The distributions of organ doses were dependent on the anatomical region of scanning. The most exposed organs/tissues were thyroid, breast, esophagus, and lungs in cases of Chest Routine examination; liver, stomach, colon, ovaries, and bladder in cases of Abdominal Routine examination; and brain for Head Routine examinations. The conversion factors for calculation of typical organ doses or tissues at risk using DLP were determined. Lifetime attributable risk of cancer estimated with organ doses calculated from DLP was compared with the risk estimated on the basis of organ doses measured with the use of silicon photodiode dosimeters. The estimated difference in LAR is less than 29%.

Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

PubMed

Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

2016-05-01

In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of pill burden on dosing preferences, willingness to pay, and likely adherence among patients with type 2 diabetes

PubMed Central

Hauber, A Brett; Han, Steven; Yang, Jui-Chen; Gantz, Ira; Tunceli, Kaan; Gonzalez, Juan Marcos; Brodovicz, Kimberly; Alexander, Charles M; Davies, Michael; Iglay, Kristy; Zhang, Qiaoyi; Radican, Larry

2013-01-01

Purpose To quantify willingness-to-pay (WTP) for reducing pill burden and dosing frequency among patients with type 2 diabetes mellitus (T2DM), and to examine the effect of dosing frequency and pill burden on likely medication adherence. Patients and methods Participants were US adults with T2DM on oral antihyperglycemic therapy. Each patient completed an online discrete-choice experiment (DCE) with eight choice questions, each including a pair of hypothetical medication profiles. Each profile was defined by reduction in average glucose (AG), daily dosing, chance of mild-to-moderate stomach problems, frequency of hypoglycemia, weight change, incremental risk of congestive heart failure (CHF), and cost. Patients were asked to rate their likely adherence to the profiles presented in each question. Choice questions were based on a predetermined experimental design. Choice data were analyzed using random-parameters logit. Likely treatment adherence was analyzed using a Heckman two-stage model. Results Of the 1,114 patients who completed the survey, 90 had lower dosing burden (<5 pills/day taken once/day or as needed) for all medications, and 1,024 had higher dosing burden (≥5 pills/day or more than once/day). Reduction in AG was valued most highly by patients. Hypoglycemia, chance of mild-to-moderate stomach problems, weight change, incremental risk of CHF, and daily dosing were less valued. Patients with higher current dosing burden had lower WTP for more convenient dosing schedules than patients with lower current dosing burden. Changes in dosing and cost impacted likely adherence. The magnitude of the impact of dosing on likely adherence was higher for patients with lower current dosing burden than for patients with higher current dosing burden. Conclusion Patients with T2DM were willing to pay for improvements in efficacy, side effects, and dosing. Patients’ WTP for more convenient dosing depended on current dosing burden, as did the effect of these attributes on likely adherence. PMID:24086104

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.

Rare-Earth Ions in Niobium-Based Devices as a Quantum Memory: Magneto-Optical Effects on Room Temperature Electrical Transport

DTIC Science & Technology

2016-09-01

rare-earth neodymium by ion implantation in thin films of niobium and niobium-based heterostructure devices. We model the ion implantation process...the films and devices so they can properly designed and optimized for utility as quantum memory. We find that the magnetic field has a strong effect...thin films of niobium. Simulations are made at low 1013 cm-2 and high 1014 cm-2 dose at 60 keV. At high dose, disorder induced is significantly

The contribution of interventional cardiology procedures to the population radiation dose in a ‘health-care level I’ representative region

PubMed Central

Peruzzo Cornetto, Andrea; Aimonetto, Stefania; Pisano, Francesco; Giudice, Marcello; Sicuro, Marco; Meloni, Teodoro; Tofani, Santi

2016-01-01

This study evaluates per-procedure, collective and per capita effective dose to the population by interventional cardiology (IC) procedures performed during 2002–11 at the main hospital of Aosta Valley Region that can be considered as representative of the health-care level I countries, as defined by the UNSCEAR, based on its socio-demographic characteristics. IC procedures investigated were often multiple procedures in patients older than 60 y. The median extreme dose-area product values of 300 and 22 908 cGycm2 were found for standard pacemaker implantation and coronary angioplasty, respectively, while the relative mean per-procedure effective dose ranged from 0.7 to 47 mSv. A 3-fold increase in frequency has been observed together with a correlated increase in the delivered per capita dose (0.05–0.27 mSv y−1) and the collective dose (5.8–35 man Sv y−1). Doses increased particularly from 2008 onwards mainly because of the introduction of coronary angioplasty procedures in the authors’ institution. IC practice contributed remarkably in terms of effective dose to the population, delivering ∼10 % of the total dose by medical ionising radiation examination categories. PMID:26012484

Non-vascular interventional procedures: effective dose to patient and equivalent dose to abdominal organs by means of DICOM images and Monte Carlo simulation.

PubMed

Longo, Mariaconcetta; Marchioni, Chiara; Insero, Teresa; Donnarumma, Raffaella; D'Adamo, Alessandro; Lucatelli, Pierleone; Fanelli, Fabrizio; Salvatori, Filippo Maria; Cannavale, Alessandro; Di Castro, Elisabetta

2016-03-01

This study evaluates X-ray exposure in patient undergoing abdominal extra-vascular interventional procedures by means of Digital Imaging and COmmunications in Medicine (DICOM) image headers and Monte Carlo simulation. The main aim was to assess the effective and equivalent doses, under the hypothesis of their correlation with the dose area product (DAP) measured during each examination. This allows to collect dosimetric information about each patient and to evaluate associated risks without resorting to in vivo dosimetry. The dose calculation was performed in 79 procedures through the Monte Carlo simulator PCXMC (A PC-based Monte Carlo program for calculating patient doses in medical X-ray examinations), by using the real geometrical and dosimetric irradiation conditions, automatically extracted from DICOM headers. The DAP measurements were also validated by using thermoluminescent dosemeters on an anthropomorphic phantom. The expected linear correlation between effective doses and DAP was confirmed with an R(2) of 0.974. Moreover, in order to easily calculate patient doses, conversion coefficients that relate equivalent doses to measurable quantities, such as DAP, were obtained. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Surface effects on the radiation response of nanoporous Au foams

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

Fu, E. G.; Caro, M.; Wang, Y. Q.

2012-11-05

We report on an experimental and simulation campaign aimed at exploring the radiation response of nanoporous Au (np-Au) foams. We find different defect accumulation behavior by varying radiation dose-rate in ion-irradiated np-Au foams. Stacking fault tetrahedra are formed when np-Au foams are irradiated at high dose-rate, but they do not seem to be formed in np-Au at low dose-rate irradiation. A model is proposed to explain the dose-rate dependent defect accumulation based on these results.

4D dose simulation in volumetric arc therapy: Accuracy and affecting parameters

PubMed Central

Werner, René

2017-01-01

Radiotherapy of lung and liver lesions has changed from normofractioned 3D-CRT to stereotactic treatment in a single or few fractions, often employing volumetric arc therapy (VMAT)-based techniques. Potential unintended interference of respiratory target motion and dynamically changing beam parameters during VMAT dose delivery motivates establishing 4D quality assurance (4D QA) procedures to assess appropriateness of generated VMAT treatment plans when taking into account patient-specific motion characteristics. Current approaches are motion phantom-based 4D QA and image-based 4D VMAT dose simulation. Whereas phantom-based 4D QA is usually restricted to a small number of measurements, the computational approaches allow simulating many motion scenarios. However, 4D VMAT dose simulation depends on various input parameters, influencing estimated doses along with mitigating simulation reliability. Thus, aiming at routine use of simulation-based 4D VMAT QA, the impact of such parameters as well as the overall accuracy of the 4D VMAT dose simulation has to be studied in detail–which is the topic of the present work. In detail, we introduce the principles of 4D VMAT dose simulation, identify influencing parameters and assess their impact on 4D dose simulation accuracy by comparison of simulated motion-affected dose distributions to corresponding dosimetric motion phantom measurements. Exploiting an ITV-based treatment planning approach, VMAT treatment plans were generated for a motion phantom and different motion scenarios (sinusoidal motion of different period/direction; regular/irregular motion). 4D VMAT dose simulation results and dose measurements were compared by local 3% / 3 mm γ-evaluation, with the measured dose distributions serving as ground truth. Overall γ-passing rates of simulations and dynamic measurements ranged from 97% to 100% (mean across all motion scenarios: 98% ± 1%); corresponding values for comparison of different day repeat measurements were between 98% and 100%. Parameters of major influence on 4D VMAT dose simulation accuracy were the degree of temporal discretization of the dose delivery process (the higher, the better) and correct alignment of the assumed breathing phases at the beginning of the dose measurements and simulations. Given the high γ-passing rates between simulated motion-affected doses and dynamic measurements, we consider the simulations to provide a reliable basis for assessment of VMAT motion effects that–in the sense of 4D QA of VMAT treatment plans–allows to verify target coverage in hypofractioned VMAT-based radiotherapy of moving targets. Remaining differences between measurements and simulations motivate, however, further detailed studies. PMID:28231337

4D dose simulation in volumetric arc therapy: Accuracy and affecting parameters.

PubMed

Sothmann, Thilo; Gauer, Tobias; Werner, René

2017-01-01

Radiotherapy of lung and liver lesions has changed from normofractioned 3D-CRT to stereotactic treatment in a single or few fractions, often employing volumetric arc therapy (VMAT)-based techniques. Potential unintended interference of respiratory target motion and dynamically changing beam parameters during VMAT dose delivery motivates establishing 4D quality assurance (4D QA) procedures to assess appropriateness of generated VMAT treatment plans when taking into account patient-specific motion characteristics. Current approaches are motion phantom-based 4D QA and image-based 4D VMAT dose simulation. Whereas phantom-based 4D QA is usually restricted to a small number of measurements, the computational approaches allow simulating many motion scenarios. However, 4D VMAT dose simulation depends on various input parameters, influencing estimated doses along with mitigating simulation reliability. Thus, aiming at routine use of simulation-based 4D VMAT QA, the impact of such parameters as well as the overall accuracy of the 4D VMAT dose simulation has to be studied in detail-which is the topic of the present work. In detail, we introduce the principles of 4D VMAT dose simulation, identify influencing parameters and assess their impact on 4D dose simulation accuracy by comparison of simulated motion-affected dose distributions to corresponding dosimetric motion phantom measurements. Exploiting an ITV-based treatment planning approach, VMAT treatment plans were generated for a motion phantom and different motion scenarios (sinusoidal motion of different period/direction; regular/irregular motion). 4D VMAT dose simulation results and dose measurements were compared by local 3% / 3 mm γ-evaluation, with the measured dose distributions serving as ground truth. Overall γ-passing rates of simulations and dynamic measurements ranged from 97% to 100% (mean across all motion scenarios: 98% ± 1%); corresponding values for comparison of different day repeat measurements were between 98% and 100%. Parameters of major influence on 4D VMAT dose simulation accuracy were the degree of temporal discretization of the dose delivery process (the higher, the better) and correct alignment of the assumed breathing phases at the beginning of the dose measurements and simulations. Given the high γ-passing rates between simulated motion-affected doses and dynamic measurements, we consider the simulations to provide a reliable basis for assessment of VMAT motion effects that-in the sense of 4D QA of VMAT treatment plans-allows to verify target coverage in hypofractioned VMAT-based radiotherapy of moving targets. Remaining differences between measurements and simulations motivate, however, further detailed studies.

Toward computer-aided emphysema quantification on ultralow-dose CT: reproducibility of ventrodorsal gravity effect measurement and correction

NASA Astrophysics Data System (ADS)

Wiemker, Rafael; Opfer, Roland; Bülow, Thomas; Rogalla, Patrik; Steinberg, Amnon; Dharaiya, Ekta; Subramanyan, Krishna

2007-03-01

Computer aided quantification of emphysema in high resolution CT data is based on identifying low attenuation areas below clinically determined Hounsfield thresholds. However, the emphysema quantification is prone to error since a gravity effect can influence the mean attenuation of healthy lung parenchyma up to +/- 50 HU between ventral and dorsal lung areas. Comparing ultra-low-dose (7 mAs) and standard-dose (70 mAs) CT scans of each patient we show that measurement of the ventrodorsal gravity effect is patient specific but reproducible. It can be measured and corrected in an unsupervised way using robust fitting of a linear function.

MAX meets ADAM: a dosimetric comparison between a voxel-based and a mathematical model for external exposure to photons

NASA Astrophysics Data System (ADS)

Kramer, R.; Vieira, J. W.; Khoury, H. J.; Lima, F. de Andrade

2004-03-01

The International Commission on Radiological Protection intends to revise the organ and tissue equivalent dose conversion coefficients published in various reports. For this purpose the mathematical human medical internal radiation dose (MIRD) phantoms, actually in use, have to be replaced by recently developed voxel-based phantoms. This study investigates the dosimetric consequences, especially with respect to the effective male dose, if not only a MIRD phantom is replaced by a voxel phantom, but also if the tissue compositions and the radiation transport codes are changed. This task will be resolved by systematically replacing in the mathematical ADAM/GSF exposure model, first the radiation transport code, then the tissue composition and finally the phantom anatomy, in order to arrive at the voxel-based MAX/EGS4 exposure model. The results show that the combined effect of these replacements can decrease the effective male dose by up to 25% for external exposures to photons for incident energies above 30 keV for different field geometries, mainly because of increased shielding by a heterogeneous skeleton and by the overlying adipose and muscle tissue, and also because of the positions internal organs have in a realistically designed human body compared to their positions in the mathematically constructed phantom.

Impact of heterogeneity-corrected dose calculation using a grid-based Boltzmann solver on breast and cervix cancer brachytherapy.

PubMed

Hofbauer, Julia; Kirisits, Christian; Resch, Alexandra; Xu, Yingjie; Sturdza, Alina; Pötter, Richard; Nesvacil, Nicole

2016-04-01

To analyze the impact of heterogeneity-corrected dose calculation on dosimetric quality parameters in gynecological and breast brachytherapy using Acuros, a grid-based Boltzmann equation solver (GBBS), and to evaluate the shielding effects of different cervix brachytherapy applicators. Calculations with TG-43 and Acuros were based on computed tomography (CT) retrospectively, for 10 cases of accelerated partial breast irradiation and 9 cervix cancer cases treated with tandem-ring applicators. Phantom CT-scans of different applicators (plastic and titanium) were acquired. For breast cases the V20Gyαβ3 to lung, the D0.1cm(3) , D1cm(3) , D2cm(3) to rib, the D0.1cm(3) , D1cm(3) , D10cm(3) to skin, and Dmax for all structures were reported. For cervix cases, the D0.1cm(3) , D2cm(3) to bladder, rectum and sigmoid, and the D50, D90, D98, V100 for the CTVHR were reported. For the phantom study, surrogates for target and organ at risk were created for a similar dose volume histogram (DVH) analysis. Absorbed dose and equivalent dose to 2 Gy fractionation (EQD2) were used for comparison. Calculations with TG-43 overestimated the dose for all dosimetric indices investigated. For breast, a decrease of ~8% was found for D10cm(3) to the skin and 5% for D2cm(3) to rib, resulting in a difference ~ -1.5 Gy EQD2 for overall treatment. Smaller effects were found for cervix cases with the plastic applicator, with up to -2% (-0.2 Gy EQD2) per fraction for organs at risk and -0.5% (-0.3 Gy EQD2) per fraction for CTVHR. The shielding effect of the titanium applicator resulted in a decrease of 2% for D2cm(3) to the organ at risk versus 0.7% for plastic. Lower doses were reported when calculating with Acuros compared to TG-43. Differences in dose parameters were larger in breast cases. A lower impact on clinical dose parameters was found for the cervix cases. Applicator material causes systematic shielding effects that can be taken into account.

Temporal Lobe Reactions After Radiotherapy With Carbon Ions: Incidence and Estimation of the Relative Biological Effectiveness by the Local Effect Model

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

Schlampp, Ingmar; Karger, Christian P.; Jaekel, Oliver

2011-07-01

Purpose: To identify predictors for the development of temporal lobe reactions (TLR) after carbon ion radiation therapy (RT) for radiation-resistant tumors in the central nervous system and to evaluate the predictions of the local effect model (LEM) used for calculation of the biologically effective dose. Methods and Materials: This retrospective study reports the TLR rates in patients with skull base chordomas and chondrosarcomas irradiated with carbon ions at GSI, Darmstadt, Germany, in the years 2002 and 2003. Calculation of the relative biological effectiveness and dose optimization of treatment plans were performed on the basis of the LEM. Clinical examinations andmore » magnetic resonance imaging (MRI) were performed at 3, 6, and 12 months after RT and annually thereafter. Local contrast medium enhancement in temporal lobes, as detected on MRI, was regarded as radiation-induced TLR. Dose-volume histograms of 118 temporal lobes in 59 patients were analyzed, and 16 therapy-associated and 2 patient-associated factors were statistically evaluated for their predictive value for the occurrence of TLR. Results: Median follow-up was 2.5 years (range, 0.3--6.6 years). Age and maximum dose applied to at least 1 cm{sup 3} of the temporal lobe (D{sub max,V-1cm}3, maximum dose in the remaining temporal lobe volume, excluding the volume 1 cm{sup 3} with the highest dose) were found to be the most important predictors for TLR. Dose response curves of D{sub max,V-1cm}3 were calculated. The biologically equivalent tolerance doses for the 5% and 50% probabilities to develop TLR were 68.8 {+-} 3.3 Gy equivalents (GyE) and 87.3 {+-} 2.8 GyE, respectively. Conclusions: D{sub max,V-1cm}3 is predictive for radiation-induced TLR. The tolerance doses obtained seem to be consistent with published data for highly conformal photon and proton irradiations. We could not detect any clinically relevant deviations between clinical findings and expectations based on predictions of the LEM.« less

The Influence of Nicotine Dose and Nicotine Dose Expectancy on the Cognitive and Subjective Effects of Cigarette Smoking

PubMed Central

Juliano, Laura M.; Fucito, Lisa M.; Harrell, Paul T.

2013-01-01

This study investigated the independent and interactive effects of nicotine dose and nicotine dose expectancy on smoking outcomes using a 2 (given nicotine vs. placebo) × 2 (told nicotine vs. placebo) Balanced Placebo Design (BPD). Smokers (N = 148) completed the Rapid Visual Information Processing Task (RVIP) and measures of smoking urge, mood, and cigarette ratings (e.g., satisfying) after smoking a nicotine or placebo cigarette crossed with instructions that the cigarette contained either nicotine or no nicotine. Nicotine cigarettes (0.6 mg nicotine) produced better sustained attention performance than placebos as indicated by RVIP reaction time, hits, and sensitivity (A′). Nicotine cigarettes also produced better mood and greater rewarding subjective effects of the cigarettes on 11 of 11 dimensions compared to placebos. Nicotine instructions resulted in fewer RVIP false alarms, better mood, and greater rewarding subjective effects of the cigarettes on 9 of 11 dimensions compared to placebo instructions. Nicotine dose by nicotine dose expectancy interactions were also observed for urge and tension-anxiety, such that the dose expectancy manipulation produced differential effects only among those who smoked placebo cigarettes. In contrast a significant interaction for self-reported vigor-activity demonstrated that the dose expectancy manipulation produced effects only among those who smoked nicotine cigarettes. This study provides additional evidence that nicotine improves cognitive performance, and provides initial evidence that denicotinized cigarettes smoked under the guise that they contain nicotine influence cognitive performance, albeit with less robust effects than nicotine. These data may inform the development of expectancy-based interventions for tobacco dependence. PMID:21463067

SU-C-210-05: Evaluation of Robustness: Dosimetric Effects of Anatomical Changes During Fractionated Radiation Treatment of Pancreatic Cancer Patients

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

Horst, A van der; Houweling, A C; Bijveld, M M C

2015-06-15

Purpose: Pancreatic tumors show large interfractional position variations. In addition, changes in gastrointestinal air volume and body contour take place during treatment. We aim to investigate the robustness of the clinical treatment plans by quantifying the dosimetric effects of these anatomical changes. Methods: Calculations were performed for up to now 3 pancreatic cancer patients who had intratumoral fiducials for daily CBCT-based positioning during their 3-week treatment. For each patient, deformable image registration of the planning CT was used to assign Hounsfield Units to each of the 13—15 CBCTs; air volumes and body contour were copied from CBCT. The clinical treatmentmore » plan was used (CTV-PTV margin = 10 mm; 36Gy; 10MV; 1 arc VMAT). Fraction dose distributions were calculated and accumulated. The V95% of the clinical target volume (CTV) and planning target volume (PTV) were analyzed, as well as the dose to stomach, duodenum and liver. Dose accumulation was done for patient positioning based on the fiducials (as clinically used) as well as for positioning based on bony anatomy. Results: For all three patients, the V95% of the CTV remained 100%, for both fiducial- and bony anatomy-based positioning. For fiducial-based positioning, dose to duodenum en stomach showed no discernable differences with planned dose. For bony anatomy-based positioning, the PTV V95% of the patient with the largest systematic difference in tumor position (patient 1) decreased to 85%; the liver Dmax increased from 33.5Gy (planned) to 35.5Gy. Conclusion: When using intratumoral fiducials, CTV dose coverage was only mildly affected by the daily anatomical changes. When using bony anatomy for patient positioning, we found a decline in PTV dose coverage due to the interfractional tumor position variations. Photon irradiation treatment plans for pancreatic tumors are robust to variations in body contour and gastrointestinal gas, but the use of fiducial-based daily position verification is imperative. This work was supported by the foundation Bergh in het Zadel through the Dutch Cancer Society (KWF Kankerbestrijding) project No. UVA 2011-5271.« less

Simulation of computed tomography dose based on voxel phantom

NASA Astrophysics Data System (ADS)

Liu, Chunyu; Lv, Xiangbo; Li, Zhaojun

2017-01-01

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

Optimization of Catheter Based rtPA Thrombolysis in a Novel In Vitro Clot Model for Intracerebral Hemorrhage

PubMed Central

Masomi-Bornwasser, Julia; Müller-Werkmeister, Hendrik; Kantelhardt, Sven Rainer; König, Jochem; Kempski, Oliver; Giese, Alf

2017-01-01

Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral hemorrhage (ICH). Optimal dose and schedule are still unclear. The aim of this study was to create a reliable in vitro blood clot model for investigation of optimal drug dose and timing. An in vitro clot model was established, using 25 mL and 50 mL of human blood. Catheters were placed into the clots and three groups, using intraclot application of rtPA, placebo, and catheter alone, were analyzed. Dose-response relationship, repetition, and duration of rtPA treatment and its effectiveness in aged clots were investigated. A significant relative end weight difference was found in rtPA treated clots compared to catheter alone (p = 0.002) and placebo treated clots (p < 0.001). Dose-response analysis revealed 95% effective dose around 1 mg rtPA in 25 and 50 mL clots. Approximately 80% of relative clot lysis could be achieved after 15 min incubation. Lysis of aged clots was less effective. A new clot model for in vitro investigation was established. Our data suggest that current protocols for rtPA based ICH therapy may be optimized by using less rtPA at shorter incubation times. PMID:28459065

Cumulative effects of anti-androgenic chemical mixtures and ...

EPA Pesticide Factsheets

Kembra L. Howdeshell and L. Earl Gray, Jr.Toxicological studies of defined chemical mixtures assist human health risk assessment by characterizing the joint action of chemicals. This presentation will review the effects of anti-androgenic chemical mixtures on reproductive tract development in rats with a special focus on the reproductive toxicant phthalates. Observed mixture data are compared to mathematical mixture model predictions to determine how the individual chemicals in a mixture interact (e.g., response addition – probabilities of response for each individual chemical are added; dose-addition – the doses of each individual chemical at a given mixture dose are combined together based on the relative potency of the individual chemicals). Phthalate mixtures are observed to act in a dose-additive manner based on the relative potency of the individual phthalates to suppress fetal testosterone production. Similar dose-additive effects have been reported for mixtures of phthalates with anti-androgenic pesticides of differing mechanisms. Data from these phthalate experiments in rats can be used in conjunction with human biomonitoring data to determine individual hazard ratios. Furthermore, data from the toxicological studies can inform the analysis of human biomonitoring data on the association of detected chemicals and their metabolites with measured health outcomes. Data from phthalate experiments in rats can be used in conjunction with human biomonit

Optimization of Catheter Based rtPA Thrombolysis in a Novel In Vitro Clot Model for Intracerebral Hemorrhage.

PubMed

Keric, Naureen; Masomi-Bornwasser, Julia; Müller-Werkmeister, Hendrik; Kantelhardt, Sven Rainer; König, Jochem; Kempski, Oliver; Giese, Alf

2017-01-01

Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an alternative therapy for spontaneous intracerebral hemorrhage (ICH). Optimal dose and schedule are still unclear. The aim of this study was to create a reliable in vitro blood clot model for investigation of optimal drug dose and timing. An in vitro clot model was established, using 25 mL and 50 mL of human blood. Catheters were placed into the clots and three groups, using intraclot application of rtPA, placebo, and catheter alone, were analyzed. Dose-response relationship, repetition, and duration of rtPA treatment and its effectiveness in aged clots were investigated. A significant relative end weight difference was found in rtPA treated clots compared to catheter alone ( p = 0.002) and placebo treated clots ( p < 0.001). Dose-response analysis revealed 95% effective dose around 1 mg rtPA in 25 and 50 mL clots. Approximately 80% of relative clot lysis could be achieved after 15 min incubation. Lysis of aged clots was less effective. A new clot model for in vitro investigation was established. Our data suggest that current protocols for rtPA based ICH therapy may be optimized by using less rtPA at shorter incubation times.

Improved dosimetry techniques for intravascular brachytherapy

NASA Astrophysics Data System (ADS)

Sehgal, Varun

Coronary artery disease leads to the accumulation of atheromatous plaque leading to coronary stenosis. Coronary intervention techniques such as balloon angioplasty and atherectomy are used to address coronary stenosis and establish a stable lumen thus enhancing blood flow to the myocardium. Restenosis or re-blockage of the arteries is a major limitation of the above mentioned interventional techniques. Neointimal hyperplasia or proliferation of cells in response to the vascular injury as a result of coronary intervention is considered to be one of the major causes of restenosis. Recent studies indicated that irradiation of the coronary lesion site, with radiation doses ranging from 15 to 30 Gy, leads to diminishing neointimal hyperplasia with subsequent reduction in restenosis. The radiation dose is given by catheter-based radiation delivery systems using beta-emitters 90Sr/90Y, 32P and gamma-emitting 192Ir among others. However the dose schema used for dose prescription for these sources are relatively simplistic, and are based on calculations using uniform homogenous water or tissue media and simple cylinder geometry. Stenotic coronary vessels are invariably lined with atheromatous plaque of heterogeneous composition, the radiation dose distribution obtained from such dosimetry data can cause significant variations in the actual dose received by a given patient. Such discrepancies in dose calculation can introduce relatively large uncertainties in the limits of dose window for effective and safe application of intravascular brachytherapy, and consequently in the clinical evaluation of the efficacy of this modality. In this research study we investigated the effect of different geometrical and material heterogeneities, including residual plaque, catheter non-centering, lesion eccentricity and cardiac motion on the radiation dose delivered at the lesion site. Correction factors including dose perturbation factors and dose variation factors have been calculated using Monte Carlo-based radiation transport code MCNP and tabulated for a range of different coronary geometries and different radionuclides. A new technique using imaging techniques such as intravascular ultrasound and angiography to assess dosimetry for realistic coronary arteries is also introduced. The results indicate the need for accurate assessment of post-intervention clinical measurements such as minimal lumen diameter and residual plaque burden and incorporating them into dose calculations.

A retrospective analysis of outcomes of dalteparin use in pediatric patients: a single institution experience.

PubMed

Warad, Deepti; Rao, Amulya Nageswara; Mullikin, Trey; Graner, Kevin; Shaughnessy, William J; Pruthi, Rajiv K; Rodriguez, Vilmarie

2015-08-01

Dalteparin is a commonly used low molecular weight heparin (LMWH) with extensive safety data in adults. With distinct advantages of once daily dosing and relative safety in renal impairment, it has been used off-label in pediatric practice; however, age-based dosing guidelines, safety and efficacy data in children are evolving. To report our institutional experience with the use of dalteparin in the treatment and prophylaxis of venous thromboembolism (VTE) in pediatric patients. Retrospective chart review of all children (0-18years) that received dalteparin from December 1, 2000 through December 31, 2011. Doses per unit body weight per day (units/kg/day) were calculated for age-based group comparisons. Of 166 patients identified, 116 (70%) received prophylactic doses while 50 (30%) received therapeutic doses of dalteparin. Infants (<1year) required significantly higher weight-based dosing to achieve therapeutic anti-Xa levels compared to children (1-10years) or adolescents (>10-18years) (mean dose units/kg/day; 396.6 versus 236.7 and 178.8 respectively, p<0.0001). Overall response rate, including complete and partial thrombus resolution, was 83%. Bleeding complications were minor and the rates were similar in therapeutic and prophylaxis patients. No significant differences in dosing or bleeding events were noted based on obesity or malignancy. In our experience, dalteparin is effective for prophylaxis and therapy of VTE in pediatric patients. Dosing should be customized in an age-based manner with close monitoring of anti-Xa activity in order to achieve optimal levels, prevent bleeding complications, and to allow full benefit of prevention or therapy of thrombotic complications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prospective Intervention of a Novel Levothyroxine Dosing Protocol Based on Body Mass Index after Thyroidectomy.

PubMed

Elfenbein, Dawn M; Schaefer, Sarah; Shumway, Cynthia; Chen, Herbert; Sippel, Rebecca S; Schneider, David F

2016-01-01

Weight-based postoperative levothyroxine (LT4) dosing often fails to appropriately dose overweight and underweight patients. Previously, we created an LT4-dosing algorithm based on BMI. We hypothesize that more patients will achieve euthyroidism at their postoperative visit with the use of the protocol. A prospective evaluation was performed of our previously published BMI-based LT4 dosing. All adults who underwent thyroidectomy for benign disease between January 1, 2011 and December 31, 2013 were included; the new protocol was implemented in October 2012. Serum TSH was measured for all patients 6 to 8 weeks postoperatively, and adjustments were based on TSH. Three hundred and thirty patients were included, with 54% undergoing thyroidectomy after institution of the protocol. The groups were well matched. Before protocol implementation, LT4 was dosed solely by weight and 25% of patients were euthyroid at initial follow-up. After the protocol, 39% of patients were euthyroid (p = 0.01). The percentage of patients who were given too high a dose of LT4 remained the same (46% vs 42%), and there was a significant reduction in the number of patients who were given too little (29% vs 19%; p = 0.05). The effect was most profound in patients with low and normal BMI, and there were slight differences between sexes. Although correct initial dosing of LT4 remains challenging, this dosing protocol that we developed and implemented has improved patient care by increasing the number of patients who achieve euthyroidism at the first postoperative visit. We have made a change to our original protocol to incorporate sex differences into the calculation. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

SU-E-T-503: IMRT Optimization Using Monte Carlo Dose Engine: The Effect of Statistical Uncertainty.

PubMed

Tian, Z; Jia, X; Graves, Y; Uribe-Sanchez, A; Jiang, S

2012-06-01

With the development of ultra-fast GPU-based Monte Carlo (MC) dose engine, it becomes clinically realistic to compute the dose-deposition coefficients (DDC) for IMRT optimization using MC simulation. However, it is still time-consuming if we want to compute DDC with small statistical uncertainty. This work studies the effects of the statistical error in DDC matrix on IMRT optimization. The MC-computed DDC matrices are simulated here by adding statistical uncertainties at a desired level to the ones generated with a finite-size pencil beam algorithm. A statistical uncertainty model for MC dose calculation is employed. We adopt a penalty-based quadratic optimization model and gradient descent method to optimize fluence map and then recalculate the corresponding actual dose distribution using the noise-free DDC matrix. The impacts of DDC noise are assessed in terms of the deviation of the resulted dose distributions. We have also used a stochastic perturbation theory to theoretically estimate the statistical errors of dose distributions on a simplified optimization model. A head-and-neck case is used to investigate the perturbation to IMRT plan due to MC's statistical uncertainty. The relative errors of the final dose distributions of the optimized IMRT are found to be much smaller than those in the DDC matrix, which is consistent with our theoretical estimation. When history number is decreased from 108 to 106, the dose-volume-histograms are still very similar to the error-free DVHs while the error in DDC is about 3.8%. The results illustrate that the statistical errors in the DDC matrix have a relatively small effect on IMRT optimization in dose domain. This indicates we can use relatively small number of histories to obtain the DDC matrix with MC simulation within a reasonable amount of time, without considerably compromising the accuracy of the optimized treatment plan. This work is supported by Varian Medical Systems through a Master Research Agreement. © 2012 American Association of Physicists in Medicine.

The effects of Taraxacum officinale extracts (TOE) supplementation on physical fatigue in mice.

PubMed

Jinchun, Zhang; Jie, Chen

2011-01-01

The study is to investigate the effect of Taraxacum officinale extracts (TOE) supplementation on physical fatigue based on the forced swimming capacity in mice. Forty Kunming male mice were randomly divided into 4 groups, i.e., normal control (NC) and three doses of TOE treated group (High-dose, Middle-dose and Low-dose). Three TOE treated groups were treated by oral TOE with 10, 30 and 100mg/kg b.w respectively for a period of 42 days. The normal control group was given a corresponding volume of sterile distilled water. After 6 weeks, the forced swimming capacity and blood biochemical parameters in mice were measured, and the result showed that TOE had an anti- physical fatigue effect. It enhanced the maximum swimming capacity of mice, effectively delayed the lowering of glucose in the blood, and prevented the increase in lactate and triglyceride concentrations.

Costs of delivering human papillomavirus vaccination to schoolgirls in Mwanza Region, Tanzania

PubMed Central

2012-01-01

Background Cervical cancer is the leading cause of female cancer-related deaths in Tanzania. Vaccination against human papillomavirus (HPV) offers a new opportunity to control this disease. This study aimed to estimate the costs of a school-based HPV vaccination project in three districts in Mwanza Region (NCT ID: NCT01173900), Tanzania and to model incremental scaled-up costs of a regional vaccination program. Methods We first conducted a top-down cost analysis of the vaccination project, comparing observed costs of age-based (girls born in 1998) and class-based (class 6) vaccine delivery in a total of 134 primary schools. Based on the observed project costs, we then modeled incremental costs of a scaled-up vaccination program for Mwanza Region from the perspective of the Tanzanian government, assuming that HPV vaccines would be delivered through the Expanded Programme on Immunization (EPI). Results Total economic project costs for delivering 3 doses of HPV vaccine to 4,211 girls were estimated at about US$349,400 (including a vaccine price of US$5 per dose). Costs per fully-immunized girl were lower for class-based delivery than for age-based delivery. Incremental economic scaled-up costs for class-based vaccination of 50,290 girls in Mwanza Region were estimated at US$1.3 million. Economic scaled-up costs per fully-immunized girl were US$26.41, including HPV vaccine at US$5 per dose. Excluding vaccine costs, vaccine could be delivered at an incremental economic cost of US$3.09 per dose and US$9.76 per fully-immunized girl. Financial scaled-up costs, excluding costs of the vaccine and salaries of existing staff were estimated at US$1.73 per dose. Conclusions Project costs of class-based vaccination were found to be below those of age-based vaccination because of more eligible girls being identified and higher vaccine uptake. We estimate that vaccine can be delivered at costs that would make HPV vaccination a very cost-effective intervention. Potentially, integrating HPV vaccine delivery with cost-effective school-based health interventions and a reduction of vaccine price below US$5 per dose would further reduce the costs per fully HPV-immunized girl. PMID:23148516

Submillisievert Radiation Dose Coronary CT Angiography: Clinical Impact of the Knowledge-Based Iterative Model Reconstruction.

PubMed

Iyama, Yuji; Nakaura, Takeshi; Kidoh, Masafumi; Oda, Seitaro; Utsunomiya, Daisuke; Sakaino, Naritsugu; Tokuyasu, Shinichi; Osakabe, Hirokazu; Harada, Kazunori; Yamashita, Yasuyuki

2016-11-01

The purpose of this study was to evaluate the noise and image quality of images reconstructed with a knowledge-based iterative model reconstruction (knowledge-based IMR) in ultra-low dose cardiac computed tomography (CT). We performed submillisievert radiation dose coronary CT angiography on 43 patients. We also performed a phantom study to evaluate the influence of object size with the automatic exposure control phantom. We reconstructed clinical and phantom studies with filtered back projection (FBP), hybrid iterative reconstruction (hybrid IR), and knowledge-based IMR. We measured effective dose of patients and compared CT number, image noise, and contrast noise ratio in ascending aorta of each reconstruction technique. We compared the relationship between image noise and body mass index for the clinical study, and object size for phantom study. The mean effective dose was 0.98 ± 0.25 mSv. The image noise of knowledge-based IMR images was significantly lower than those of FBP and hybrid IR images (knowledge-based IMR: 19.4 ± 2.8; FBP: 126.7 ± 35.0; hybrid IR: 48.8 ± 12.8, respectively) (P < .01). The contrast noise ratio of knowledge-based IMR images was significantly higher than those of FBP and hybrid IR images (knowledge-based IMR: 29.1 ± 5.4; FBP: 4.6 ± 1.3; hybrid IR: 13.1 ± 3.5, respectively) (P < .01). There were moderate correlations between image noise and body mass index in FBP (r = 0.57, P < .01) and hybrid IR techniques (r = 0.42, P < .01); however, these correlations were weak in knowledge-based IMR (r = 0.27, P < .01). Compared to FBP and hybrid IR, the knowledge-based IMR offers significant noise reduction and improvement in image quality in submillisievert radiation dose cardiac CT. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

Costs of delivering human papillomavirus vaccination to schoolgirls in Mwanza Region, Tanzania.

PubMed

Quentin, Wilm; Terris-Prestholt, Fern; Changalucha, John; Soteli, Selephina; Edmunds, W John; Hutubessy, Raymond; Ross, David A; Kapiga, Saidi; Hayes, Richard; Watson-Jones, Deborah

2012-11-13

Cervical cancer is the leading cause of female cancer-related deaths in Tanzania. Vaccination against human papillomavirus (HPV) offers a new opportunity to control this disease. This study aimed to estimate the costs of a school-based HPV vaccination project in three districts in Mwanza Region (NCT ID: NCT01173900), Tanzania and to model incremental scaled-up costs of a regional vaccination program. We first conducted a top-down cost analysis of the vaccination project, comparing observed costs of age-based (girls born in 1998) and class-based (class 6) vaccine delivery in a total of 134 primary schools. Based on the observed project costs, we then modeled incremental costs of a scaled-up vaccination program for Mwanza Region from the perspective of the Tanzanian government, assuming that HPV vaccines would be delivered through the Expanded Programme on Immunization (EPI). Total economic project costs for delivering 3 doses of HPV vaccine to 4,211 girls were estimated at about US$349,400 (including a vaccine price of US$5 per dose). Costs per fully-immunized girl were lower for class-based delivery than for age-based delivery. Incremental economic scaled-up costs for class-based vaccination of 50,290 girls in Mwanza Region were estimated at US$1.3 million. Economic scaled-up costs per fully-immunized girl were US$26.41, including HPV vaccine at US$5 per dose. Excluding vaccine costs, vaccine could be delivered at an incremental economic cost of US$3.09 per dose and US$9.76 per fully-immunized girl. Financial scaled-up costs, excluding costs of the vaccine and salaries of existing staff were estimated at US$1.73 per dose. Project costs of class-based vaccination were found to be below those of age-based vaccination because of more eligible girls being identified and higher vaccine uptake. We estimate that vaccine can be delivered at costs that would make HPV vaccination a very cost-effective intervention. Potentially, integrating HPV vaccine delivery with cost-effective school-based health interventions and a reduction of vaccine price below US$5 per dose would further reduce the costs per fully HPV-immunized girl.

Applying Emax model and bivariate thin plate splines to assess drug interactions

PubMed Central

Kong, Maiying; Lee, J. Jack

2014-01-01

We review the semiparametric approach previously proposed by Kong and Lee and extend it to a case in which the dose-effect curves follow the Emax model instead of the median effect equation. When the maximum effects for the investigated drugs are different, we provide a procedure to obtain the additive effect based on the Loewe additivity model. Then, we apply a bivariate thin plate spline approach to estimate the effect beyond additivity along with its 95% point-wise confidence interval as well as its 95% simultaneous confidence interval for any combination dose. Thus, synergy, additivity, and antagonism can be identified. The advantages of the method are that it provides an overall assessment of the combination effect on the entire two-dimensional dose space spanned by the experimental doses, and it enables us to identify complex patterns of drug interaction in combination studies. In addition, this approach is robust to outliers. To illustrate this procedure, we analyzed data from two case studies. PMID:20036878

Applying Emax model and bivariate thin plate splines to assess drug interactions.

PubMed

Kong, Maiying; Lee, J Jack

2010-01-01

We review the semiparametric approach previously proposed by Kong and Lee and extend it to a case in which the dose-effect curves follow the Emax model instead of the median effect equation. When the maximum effects for the investigated drugs are different, we provide a procedure to obtain the additive effect based on the Loewe additivity model. Then, we apply a bivariate thin plate spline approach to estimate the effect beyond additivity along with its 95 per cent point-wise confidence interval as well as its 95 per cent simultaneous confidence interval for any combination dose. Thus, synergy, additivity, and antagonism can be identified. The advantages of the method are that it provides an overall assessment of the combination effect on the entire two-dimensional dose space spanned by the experimental doses, and it enables us to identify complex patterns of drug interaction in combination studies. In addition, this approach is robust to outliers. To illustrate this procedure, we analyzed data from two case studies.

SU-E-T-280: Reconstructed Rectal Wall Dose Map-Based Verification of Rectal Dose Sparing Effect According to Rectum Definition Methods and Dose Perturbation by Air Cavity in Endo-Rectal Balloon

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

Park, J; Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul; Park, H

Purpose: Dosimetric effect and discrepancy according to the rectum definition methods and dose perturbation by air cavity in an endo-rectal balloon (ERB) were verified using rectal-wall (Rwall) dose maps considering systematic errors in dose optimization and calculation accuracy in intensity-modulated radiation treatment (IMRT) for prostate cancer patients. Methods: When the inflated ERB having average diameter of 4.5 cm and air volume of 100 cc is used for patient, Rwall doses were predicted by pencil-beam convolution (PBC), anisotropic analytic algorithm (AAA), and AcurosXB (AXB) with material assignment function. The errors of dose optimization and calculation by separating air cavity from themore » whole rectum (Rwhole) were verified with measured rectal doses. The Rwall doses affected by the dose perturbation of air cavity were evaluated using a featured rectal phantom allowing insert of rolled-up gafchromic films and glass rod detectors placed along the rectum perimeter. Inner and outer Rwall doses were verified with reconstructed predicted rectal wall dose maps. Dose errors and extent at dose levels were evaluated with estimated rectal toxicity. Results: While AXB showed insignificant difference of target dose coverage, Rwall doses underestimated by up to 20% in dose optimization for the Rwhole than Rwall at all dose range except for the maximum dose. As dose optimization for Rwall was applied, the Rwall doses presented dose error less than 3% between dose calculation algorithm except for overestimation of maximum rectal dose up to 5% in PBC. Dose optimization for Rwhole caused dose difference of Rwall especially at intermediate doses. Conclusion: Dose optimization for Rwall could be suggested for more accurate prediction of rectal wall dose prediction and dose perturbation effect by air cavity in IMRT for prostate cancer. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (MSIP) (Grant No. 200900420)« less

Parotid Glands Dose–Effect Relationships Based on Their Actually Delivered Doses: Implications for Adaptive Replanning in Radiation Therapy of Head-and-Neck Cancer

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

Hunter, Klaudia U.; Fernandes, Laura L.; Vineberg, Karen A.

2013-11-15

Purpose: Doses actually delivered to the parotid glands during radiation therapy often exceed planned doses. We hypothesized that the delivered doses correlate better with parotid salivary output than the planned doses, used in all previous studies, and that determining these correlations will help make decisions regarding adaptive radiation therapy (ART) aimed at reducing the delivered doses. Methods and Materials: In this prospective study, oropharyngeal cancer patients treated definitively with chemoirradiation underwent daily cone-beam computed tomography (CBCT) with clinical setup alignment based on the C2 posterior edge. Parotid glands in the CBCTs were aligned by deformable registration to calculate cumulative deliveredmore » doses. Stimulated salivary flow rates were measured separately from each parotid gland pretherapy and periodically posttherapy. Results: Thirty-six parotid glands of 18 patients were analyzed. Average mean planned doses was 32 Gy, and differences from planned to delivered mean gland doses were −4.9 to +8.4 Gy, median difference +2.2 Gy in glands in which delivered doses increased relative to planned. Both planned and delivered mean doses were significantly correlated with posttreatment salivary outputs at almost all posttherapy time points, without statistically significant differences in the correlations. Large dispersions (on average, SD 3.6 Gy) characterized the dose–effect relationships for both. The differences between the cumulative delivered doses and planned doses were evident at first fraction (r=.92, P<.0001) because of complex setup deviations (eg, rotations and neck articulations), uncorrected by the translational clinical alignments. Conclusions: After daily translational setup corrections, differences between planned and delivered doses in most glands were small relative to the SDs of the dose–saliva data, suggesting that ART is not likely to gain measurable salivary output improvement in most cases. These differences were observed at first treatment, indicating potential benefit for more complex setup corrections or adaptive interventions in the minority of patients with large deviations detected early by CBCT.« less

SU-F-BRD-07: Fast Monte Carlo-Based Biological Optimization of Proton Therapy Treatment Plans for Thyroid Tumors

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

Wan Chan Tseung, H; Ma, J; Ma, D

2015-06-15

Purpose: To demonstrate the feasibility of fast Monte Carlo (MC) based biological planning for the treatment of thyroid tumors in spot-scanning proton therapy. Methods: Recently, we developed a fast and accurate GPU-based MC simulation of proton transport that was benchmarked against Geant4.9.6 and used as the dose calculation engine in a clinically-applicable GPU-accelerated IMPT optimizer. Besides dose, it can simultaneously score the dose-averaged LET (LETd), which makes fast biological dose (BD) estimates possible. To convert from LETd to BD, we used a linear relation based on cellular irradiation data. Given a thyroid patient with a 93cc tumor volume, we createdmore » a 2-field IMPT plan in Eclipse (Varian Medical Systems). This plan was re-calculated with our MC to obtain the BD distribution. A second 5-field plan was made with our in-house optimizer, using pre-generated MC dose and LETd maps. Constraints were placed to maintain the target dose to within 25% of the prescription, while maximizing the BD. The plan optimization and calculation of dose and LETd maps were performed on a GPU cluster. The conventional IMPT and biologically-optimized plans were compared. Results: The mean target physical and biological doses from our biologically-optimized plan were, respectively, 5% and 14% higher than those from the MC re-calculation of the IMPT plan. Dose sparing to critical structures in our plan was also improved. The biological optimization, including the initial dose and LETd map calculations, can be completed in a clinically viable time (∼30 minutes) on a cluster of 25 GPUs. Conclusion: Taking advantage of GPU acceleration, we created a MC-based, biologically optimized treatment plan for a thyroid patient. Compared to a standard IMPT plan, a 5% increase in the target’s physical dose resulted in ∼3 times as much increase in the BD. Biological planning was thus effective in escalating the target BD.« less

SU-F-T-222: Dose of Fetus and Infant Following Accidental Intakes of I-131 by the Mother

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

Wang, Y; Hu, P

Purpose: To estimate the calculation of absorbed dose to the fetus and infants from intakes of I-131 by the mother. Thus provide some advice to the radioprotection of radioactive accident. Methods: In this clinical case, a staff of nuclear medicine accidently intake I-131 during (10–12 weeks) and after pregnancy. The infant was born at full term, but both lobes of the thyroid gland were found to be absent (bilobar thyroid agenesis). It was suspected that the fetal thyroid agenesis may be related with mother’s contamination of I-131 during pregnancy. Urine samples for 24h were collected at different times after administeredmore » and radioactivity were measured to calculate the dose of intake I-131. Calculate the intake I-131 by the results of personal TLD dosimeter. We adopted the mean of two calculated results as the I-131 intake. According to the dose of intake I-131 by the mother, effective dose and absorbed dose of thyroid for mother, fetus and infant were calculated. Results: The intake of I-131 was estimated for 8.18 mCi. I-131 intake was calculated for 7.9 mCi based on data of TLD dosimeter. We adopted the mean of two results as the I-131 intake. The final result was 8.0 mCi. Effective dose and absorbed dose of thyroid for mother were 7.3Sv and 164 Gy, effective dose and absorbed dose of thyroid for fetus were 2.035 Sv and 40.7 Gy, effective dose and absorbed dose of thyroid for infant were 16.25 Sv and 355Gy. Conclusion: The intake during pregnancy was about 1mCi. The absorbed dose of thyroid of the mother was 19.5Gy, whereas the effective of infant was estimated for 40.7Gy. The function of the mother’s thyroid was normal after diagnosis. But the infant was diagnosed as bilobar thyroid agenesis.« less

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

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

Park, J; Molecular Imaging Program at Stanford, Stanford, CA; Bio-X Program, Stanford, CA

2015-06-15

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

Antitumor Activities of Rauwolfia vomitoria Extract and Potentiation of Carboplatin Effects Against Ovarian Cancer.

PubMed

Yu, Jun; Ma, Yan; Drisko, Jeanne; Chen, Qi

2013-12-01

Tumor resistance to platinum-based drugs has been an obstacle to the treatment of ovarian cancer. Extract of the plant Rauwolfia vomitoria has long been used by cancer patients. However, there have not been systematic studies of its anticancer activity. In an effort to enhance the effectiveness of platinum-based drugs, we investigated the anticancer effect of a Rauwolfia vomitoria extract (Rau), both alone and in combination with carboplatin (Cp). In vitro cytotoxicity and colony formation were evaluated in several ovarian cancer cell lines. In vivo effects were evaluated in an intraperitoneal ovarian cancer mouse model. The combination of Rau and Cp was assessed using Chou-Talalay's constant ratio design and median effect analysis based on the isobologram principle to determine the combination index values. Rau decreased cell growth in all 3 tested ovarian cancer cell lines dose dependently and completely inhibited formation of colonies in soft agar. Apoptosis was induced in a time- and dose-dependent manner and was the predominant form of Rau-induced cell death. Synergy of Rau with Cp was detected, with combination index values <1 and dose reduction index values for Cp ranging from 1.7- to 7-fold. Tumor growth in mice was significantly suppressed by 36% or 66% with Rau treatment alone at a low (20 mg/kg) or a high dose (50 mg/kg), respectively, an effect comparable to that of Cp alone. The volume of ascitic fluid and the number of nonblood cells in ascites were also significantly decreased. Combining Rau with Cp remarkably enhanced the effect of Cp and reduced tumor burden by 87% to 90% and ascites volume by 89% to 97%. Rau has potent antitumor activity and in combination significantly enhances the effect of Cp against ovarian cancer.

Treatment plan comparison between helical tomotherapy and MLC-based IMRT using radiobiological measures

NASA Astrophysics Data System (ADS)

Mavroidis, Panayiotis; Costa Ferreira, Brigida; Shi, Chengyu; Lind, Bengt K.; Papanikolaou, Nikos

2007-07-01

The rapid implementation of advanced treatment planning and delivery technologies for radiation therapy has brought new challenges in evaluating the most effective treatment modality. Intensity-modulated radiotherapy (IMRT) using multi-leaf collimators (MLC) and helical tomotherapy (HT) are becoming popular modes of treatment delivery and their application and effectiveness continues to be investigated. Presently, there are several treatment planning systems (TPS) that can generate and optimize IMRT plans based on user-defined objective functions for the internal target volume (ITV) and organs at risk (OAR). However, the radiobiological parameters of the different tumours and normal tissues are typically not taken into account during dose prescription and optimization of a treatment plan or during plan evaluation. The suitability of a treatment plan is typically decided based on dosimetric criteria such as dose-volume histograms (DVH), maximum, minimum, mean and standard deviation of the dose distribution. For a more comprehensive treatment plan evaluation, the biologically effective uniform dose ({\\bar{\\bar{D}}}) is applied together with the complication-free tumour control probability (P+). Its utilization is demonstrated using three clinical cases that were planned with two different forms of IMRT. In this study, three different cancer types at different anatomical sites were investigated: head and neck, lung and prostate cancers. For each cancer type, a linac MLC-based step-and-shoot IMRT plan and a HT plan were developed. The MLC-based IMRT treatment plans were developed on the Philips treatment-planning platform, using the Pinnacle 7.6 software release. For the tomotherapy HiArt plans, the dedicated tomotherapy treatment planning station was used, running version 2.1.2. By using {\\bar{\\bar{D}}} as the common prescription point of the treatment plans and plotting the tissue response probabilities versus {\\bar{\\bar{D}}} for a range of prescription doses, a number of plan trials can be compared based on radiobiological measures. The applied plan evaluation method shows that in the head and neck cancer case the HT treatment gives better results than MLC-based IMRT in terms of expected clinical outcome (P+ of 62.2% and 46.0%, {\\bar{\\bar{D}}} to the ITV of 72.3 Gy and 70.7 Gy, respectively). In the lung cancer and prostate cancer cases, the MLC-based IMRT plans are better over the clinically useful dose prescription range. For the lung cancer case, the HT and MLC-based IMRT plans give a P+ of 66.9% and 72.9%, {\\bar{\\bar{D}}} to the ITV of 64.0 Gy and 66.9 Gy, respectively. Similarly, for the prostate cancer case, the two radiation modalities give a P+ of 68.7% and 72.2%, {\\bar{\\bar{D}}} to the ITV of 86.0 Gy and 85.9 Gy, respectively. If a higher risk of complications (higher than 5%) could be allowed, the complication-free tumour control could increase by over 40%, 2% and 30% compared to the initial dose prescription for the three cancer cases, respectively. Both MLC-based IMRT and HT can encompass the often-large ITV required while they minimize the volume of the organs at risk receiving high doses. Radiobiological evaluation of treatment plans may provide an improved correlation of the delivered treatment with the clinical outcome by taking into account the dose-response characteristics of the irradiated targets and normal tissues. There may exist clinical cases, which may look dosimetrically similar but in radiobiological terms may be quite different. In such situations, traditional dose-based evaluation tools can be complemented by the use of P_ +{-}{\\bar{\\bar{D}}} diagrams to effectively evaluate and compare treatment plans.

Renal uptake of radiolabeled octreotide in human subjects is efficiently inhibited by succinylated gelatin.

PubMed

Vegt, Erik; Wetzels, Jack F M; Russel, Frans G M; Masereeuw, Rosalinde; Boerman, Otto C; van Eerd, Juliette E; Corstens, Frans H M; Oyen, Wim J G

2006-03-01

Peptide receptor-mediated radiotherapy of neuroendocrine and other somatostatin receptor-positive tumors with radiolabeled somatostatin analogs has been applied in several experimental settings. The kidneys are the organs responsible for dose-limiting toxicity attributable to the retention of radiolabeled octreotide in the renal cortex, leading to a relatively high radiation dose that may result in irreversible loss of kidney function. The administration of basic amino acids reduces renal uptake but does have significant side effects. We observed that gelatin-based plasma expanders induced tubular low-molecular-weight proteinuria in healthy volunteers, suggesting that components in these solutions can interfere with the tubular reabsorption of proteins and peptides. Here, we studied the effects of infusion of low doses of the plasma expander succinylated gelatin (GELO) on the renal uptake of 111In-labeled octreotide (111In-OCT). Five healthy volunteers were given 111In-OCT, first in combination with normal saline and 2 wk later in combination with GELO. Scintigraphic images of the kidneys as well as blood and urine samples were analyzed. To exclude a nonspecific hemodynamic effect of the plasma expander, the procedure was repeated with 5 other volunteers who received the carbohydrate-based plasma expander hydroxyethyl starch (HES). Low doses of GELO were able to effectively reduce the kidney retention of 111In-OCT. The renal radiation dose was significantly reduced by 45% +/- 10% (mean +/- SD) (P = 0.006), whereas HES showed no significant effect (0% +/- 12%). The infusion of GELO did not cause any side effects. GELO effectively reduces the renal uptake of 111In-OCT. In contrast to currently used mixtures of amino acids, GELO does not cause any side effects.

Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs

PubMed Central

Hwang, Jae-Sik; Kim, Myoung-Jun; Choi, Young Whan; Han, Kyoung-Goo; Kang, Jong-Koo

2015-01-01

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day. PMID:25874036

Single- and Repeat-dose Oral Toxicity Studies of Lithospermum erythrorhizon Extract in Dogs.

PubMed

Nam, Chunja; Hwang, Jae-Sik; Kim, Myoung-Jun; Choi, Young Whan; Han, Kyoung-Goo; Kang, Jong-Koo

2015-03-01

Lithospermum erythrorhizon has long been used in traditional Asian medicine for the treatment of diseases, including skin cancer. The oral toxicity of a hexane extract of Lithospermum erythrorhizon root (LEH) was investigated in Beagle dogs by using single escalating doses, two-week dose range-finding, and 4-week oral repeat dosing. In the single dose-escalating oral toxicity study, no animal died, showed adverse clinical signs, or changes in body weight gain at LEH doses of up to 2,000 mg/kg. In a 2 week dose range-finding study, no treatment-related adverse effects were detected by urinalysis, hematology, blood biochemistry, organ weights, or gross and histopathological examinations at doses of up to 500 mg LEH/kg/day. In the 4 week repeat-dose toxicity study, a weight loss or decreased weight gain was observed at 300 mg/kg/day. Although levels of serum triglyceride and total bilirubin were increased in a dose dependent manner, there were no related morphological changes. Based on these findings, the sub-acute no observable adverse effect level for 4-week oral administration of LEH in Beagles was 100 mg/kg/day.

New Fetal Dose Estimates from 18F-FDG Administered During Pregnancy: Standardization of Dose Calculations and Estimations with Voxel-Based Anthropomorphic Phantoms.

PubMed

Zanotti-Fregonara, Paolo; Chastan, Mathieu; Edet-Sanson, Agathe; Ekmekcioglu, Ozgul; Erdogan, Ezgi Basak; Hapdey, Sebastien; Hindie, Elif; Stabin, Michael G

2016-11-01

Data from the literature show that the fetal absorbed dose from 18 F-FDG administration to the pregnant mother ranges from 0.5E-2 to 4E-2 mGy/MBq. These figures were, however, obtained using different quantification techniques and with basic geometric anthropomorphic phantoms. The aim of this study was to refine the fetal dose estimates of published as well as new cases using realistic voxel-based phantoms. The 18 F-FDG doses to the fetus (n = 19; 5-34 wk of pregnancy) were calculated with new voxel-based anthropomorphic phantoms of the pregnant woman. The image-derived fetal time-integrated activity values were combined with those of the mothers' organs from the International Commission on Radiological Protection publication 106 and the dynamic bladder model with a 1-h bladder-voiding interval. The dose to the uterus was used as a proxy for early pregnancy (up to 10 wk). The time-integrated activities were entered into OLINDA/EXM 1.1 to derive the dose with the classic anthropomorphic phantoms of pregnant women, then into OLINDA/EXM 2.0 to assess the dose using new voxel-based phantoms. The average fetal doses (mGy/MBq) with OLINDA/EXM 2.0 were 2.5E-02 in early pregnancy, 1.3E-02 in the late part of the first trimester, 8.5E-03 in the second trimester, and 5.1E-03 in the third trimester. The differences compared with the doses calculated with OLINDA/EXM 1.1 were +7%, +70%, +35%, and -8%, respectively. Except in late pregnancy, the doses estimated with realistic voxelwise anthropomorphic phantoms are higher than the doses derived from old geometric phantoms. The doses remain, however, well below the threshold for any deterministic effects. Thus, pregnancy is not an absolute contraindication of a clinically justified 18 F-FDG PET scan. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

SU-E-I-37: Eye Lens Dose Reduction From CT Scan Using Organ Based Tube Current Modulation

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

Liu, H; Rensselaer Polytechnic Inst., Troy, NY; Liu, T

Purpose: To investigate the eye lens dose reduction by CT scan with organ based tube current modulation (OBTCM) using GPU Monte Carlo code ARCHER-CT. Methods: 36 X-ray sources and bowtie filters were placed around the patient head with the projection angle interval of 10° for one rotation of CT scan, each projection was simulated respectively. The voxel eye models with high resolution(0.1mm*0.1mm*0.1mm) were used in the simulation and different tube voltage including 80kVp, 100kVp, 120kVp and 140kVp were taken into consideration. Results: The radiation doses to the eye lens increased with the tube voltage raised from 80kVp to 140kVp, andmore » the dose results from 0° (AP) direction are much higher than those from 180° (PA) direction for all the 4 different tube voltage investigated. This 360° projection dose characteristic enables organ based TCM, which can reduce the eye lens dose by more than 55%. Conclusion: As the eye lens belongs to superficial tissues, its radiation dose to external exposure like CT is direction sensitive, and this characteristic feature makes organ based TCM to be an effective way to reduce the eye lens dose, so more clinical use of this technique were recommended. National Nature Science Foundation of China(No.11475047)« less

Lateral topography for reducing effective dose in low-dose chest CT.

PubMed

Bang, Dong-Ho; Lim, Daekeon; Hwang, Wi-Sub; Park, Seong-Hoon; Jeong, Ok-man; Kang, Kyung Wook; Kang, Hohyung

2013-06-01

The purposes of this study were to assess radiation exposure during low-dose chest CT by using lateral topography and to compare the lateral topographic findings with findings obtained with anteroposterior topography alone and anteroposterior and lateral topography combined. From November 2011 to February 2012, 210 male subjects were enrolled in the study. Age, weight, and height of the men were recorded. All subjects were placed into one of three subgroups based on the type of topographic image obtained: anteroposterior topography, lateral topography, and both anteroposterior and lateral topography. Imaging was performed with a 128-MDCT scanner. CT, except for topography, was the same for all subjects. A radiologist analyzed each image, recorded scan length, checked for any insufficiencies in the FOV, and calculated the effective radiation dose. One-way analysis of variance and multiple comparisons were used to compare the effective radiation exposure and scan length between groups. The mean scan length in the anteroposterior topography group was significantly greater than that of the lateral topography group and the combined anteroposterior and lateral topography group (p < 0.001). The mean effective radiation dose for the lateral topography group (0.735 ± 0.033 mSv) was significantly lower than that for the anteroposterior topography group (0.763 ± 0.038 mSv) and the combined anteroposterior and lateral topography group (0.773 ± 0.038) (p < 0.001). Lateral topographic low-dose CT was associated with a lower effective radiation dose and scan length than either anteroposterior topographic low-dose chest CT or low-dose chest CT with both anteroposterior and lateral topograms.

The effect of radiation dose reduction on computer-aided detection (CAD) performance in a low-dose lung cancer screening population.

PubMed

Young, Stefano; Lo, Pechin; Kim, Grace; Brown, Matthew; Hoffman, John; Hsu, William; Wahi-Anwar, Wasil; Flores, Carlos; Lee, Grace; Noo, Frederic; Goldin, Jonathan; McNitt-Gray, Michael

2017-04-01

Lung cancer screening with low-dose CT has recently been approved for reimbursement, heralding the arrival of such screening services worldwide. Computer-aided detection (CAD) tools offer the potential to assist radiologists in detecting nodules in these screening exams. In lung screening, as in all CT exams, there is interest in further reducing radiation dose. However, the effects of continued dose reduction on CAD performance are not fully understood. In this work, we investigated the effect of reducing radiation dose on CAD lung nodule detection performance in a screening population. The raw projection data files were collected from 481 patients who underwent low-dose screening CT exams at our institution as part of the National Lung Screening Trial (NLST). All scans were performed on a multidetector scanner (Sensation 64, Siemens Healthcare, Forchheim Germany) according to the NLST protocol, which called for a fixed tube current scan of 25 effective mAs for standard-sized patients and 40 effective mAs for larger patients. The raw projection data were input to a reduced-dose simulation software to create simulated reduced-dose scans corresponding to 50% and 25% of the original protocols. All raw data files were reconstructed at the scanner with 1 mm slice thickness and B50 kernel. The lungs were segmented semi-automatically, and all images and segmentations were input to an in-house CAD algorithm trained on higher dose scans (75-300 mAs). CAD findings were compared to a reference standard generated by an experienced reader. Nodule- and patient-level sensitivities were calculated along with false positives per scan, all of which were evaluated in terms of the relative change with respect to dose. Nodules were subdivided based on size and solidity into categories analogous to the LungRADS assessment categories, and sub-analyses were performed. From the 481 patients in this study, 82 had at least one nodule (prevalence of 17%) and 399 did not (83%). A total of 118 nodules were identified. Twenty-seven nodules (23%) corresponded to LungRADS category 4 based on size and composition, while 18 (15%) corresponded to LungRADS category 3 and 73 (61%) corresponded to LungRADS category 2. For solid nodules ≥8 mm, patient-level median sensitivities were 100% at all three dose levels, and mean sensitivities were 72%, 63%, and 63% at original, 50%, and 25% dose, respectively. Overall mean patient-level sensitivities for nodules ranging from 3 to 45 mm were 38%, 37%, and 38% at original, 50%, and 25% dose due to the prevalence of smaller nodules and nonsolid nodules in our reference standard. The mean false-positive rates were 3, 5, and 13 per case. CAD sensitivity decreased very slightly for larger nodules as dose was reduced, indicating that reducing the dose to 50% of original levels may be investigated further for use in CT screening. However, the effect of dose was small relative to the effect of the nodule size and solidity characteristics. The number of false positives per scan increased substantially at 25% dose, illustrating the importance of tuning CAD algorithms to very challenging, high-noise screening exams. © 2017 American Association of Physicists in Medicine.

Effect of iron salt type and dosing mode on Fenton-based pretreatment of rice straw for enzymatic hydrolysis.

PubMed

Gan, Yu-Yan; Zhou, Si-Li; Dai, Xiao; Wu, Han; Xiong, Zi-Yao; Qin, Yuan-Hang; Ma, Jiayu; Yang, Li; Wu, Zai-Kun; Wang, Tie-Lin; Wang, Wei-Guo; Wang, Cun-Wen

2018-06-15

Fenton-based processes with four different iron salts in two different dosing modes were used to pretreat rice straw (RS) samples to increase their enzymatic digestibility. The composition analysis shows that the RS sample pretreated by the dosing mode of iron salt adding into H 2 O 2 has a much lower hemicellulose content than that pretreated by the dosing mode of H 2 O 2 adding into iron salt, and the RS sample pretreated by the chloride salt-based Fenton process has a much lower lignin content and a slightly lower hemicellulose content than that pretreated by the sulphate salt-based Fenton process. The higher concentration of reducing sugar observed on the RS sample with lower lignin and hemicellulose contents justifies that the Fenton-based process could enhance the enzymic hydrolysis of RS by removing hemicellulose and lignin and increasing its accessibility to cellulase. FeCl 3 ·6H 2 O adding into H 2 O 2 is the most efficient Fenton-based process for RS pretreatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Uptake and toxicity of glyphosate in the lichen Xanthoria parietina (L.) Th. Fr.

PubMed

Vannini, Andrea; Guarnieri, Massimo; Bačkor, Martin; Bilová, Ivana; Loppi, Stefano

2015-12-01

This study investigated if treatment of the lichen Xanthoria parietina (L.) Th. Fr. with glyphosate caused uptake of this herbicide as well as physiological alterations. Samples were treated with Glifene SL®, a common commercial glyphosate-based herbicide, at the lowest recommended doses (3.6g/L) as well as with doses slightly higher than the highest suggested (36 g/L). The results clearly showed glyphosate uptake in X. parietina proportionally to the dose provided. Adverse physiological effects were evident on the photosynthetic apparatus (photosynthetic efficiency, chlorophyll a content, chlorophyll degradation) as well as on the fungal respiration rates and cell membrane integrity (ergosterol content, dehydrogenase activity) already after 24h from treatment, also at the low application dose. It is concluded that lichens are suitable organisms for monitoring unwanted biological effects from the application of glyphosate-based herbicides, as well as for detecting the accumulation of this compound in the biota, thus screening for its environmental fate. Copyright © 2015 Elsevier Inc. All rights reserved.

Spatial Prediction of Coxiella burnetii Outbreak Exposure via Notified Case Counts in a Dose-Response Model.

PubMed

Brooke, Russell J; Kretzschmar, Mirjam E E; Hackert, Volker; Hoebe, Christian J P A; Teunis, Peter F M; Waller, Lance A

2017-01-01

We develop a novel approach to study an outbreak of Q fever in 2009 in the Netherlands by combining a human dose-response model with geostatistics prediction to relate probability of infection and associated probability of illness to an effective dose of Coxiella burnetii. The spatial distribution of the 220 notified cases in the at-risk population are translated into a smooth spatial field of dose. Based on these symptomatic cases, the dose-response model predicts a median of 611 asymptomatic infections (95% range: 410, 1,084) for the 220 reported symptomatic cases in the at-risk population; 2.78 (95% range: 1.86, 4.93) asymptomatic infections for each reported case. The low attack rates observed during the outbreak range from (Equation is included in full-text article.)to (Equation is included in full-text article.). The estimated peak levels of exposure extend to the north-east from the point source with an increasing proportion of asymptomatic infections further from the source. Our work combines established methodology from model-based geostatistics and dose-response modeling allowing for a novel approach to study outbreaks. Unobserved infections and the spatially varying effective dose can be predicted using the flexible framework without assuming any underlying spatial structure of the outbreak process. Such predictions are important for targeting interventions during an outbreak, estimating future disease burden, and determining acceptable risk levels.

TH-A-BRD-01: Radiation Biology for Radiation Therapy Physicists

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

Orton, C; Borras, C; Carlson, D

Mechanisms by which radiation kills cells and ways cell damage can be repaired will be reviewed. The radiobiological parameters of dose, fractionation, delivery time, dose rate, and LET will be discussed. The linear-quadratic model for cell survival for high and low dose rate treatments and the effect of repopulation will be presented and discussed. The rationale for various radiotherapy techniques such as conventional fractionation, hyperfractionation, hypofractionation, and low and high dose rate brachytherapy, including permanent implants, will be presented. The radiobiological principles underlying radiation protection guidelines and the different radiation dosimetry terms used in radiation biology and in radiation protectionmore » will be reviewed. Human data on radiation induced cancer, including increases in the risk of second cancers following radiation therapy, as well as data on radiation induced tissue reactions, such as cardiovascular effects, for follow up times up to 20–40 years, published by ICRP, NCRP and BEIR Committees, will be examined. The latest risk estimates per unit dose will be presented. Their adoption in recent radiation protection standards and guidelines and their impact on patient and workers safety in radiotherapy will be discussed. Biologically-guided radiotherapy (BGRT) provides a systematic method to derive prescription doses that integrate patient-specific information about tumor and normal tissue biology. Treatment individualization based on patient-specific biology requires the identification of biological objective functions to facilitate the design and comparison of competing treatment modalities. Biological objectives provide a more direct approach to plan optimization instead of relying solely on dose-based surrogates and can incorporate factors that alter radiation response, such as DNA repair, tumor hypoxia, and relative biological effectiveness. We review concepts motivating biological objectives and provide examples of how they might be used to address clinically relevant problems. Underlying assumptions and limitations of existing models and their proper application will be discussed. This multidisciplinary educational session combines the fundamentals of radiobiology for radiation therapy and radiation protection with the practical application of biophysical models for treatment planning and evaluation. Learning Objectives: To understand fractionation in teletherapy and dose rate techniques in brachytherapy. To understand how the linear-quadratic models the effect of radiobiological parameters for radiotherapy. To understand the radiobiological basis of radiation protection standards applied to radiotherapy. To distinguish between stochastic effects and tissue reactions. To learn how to apply concepts of biological effective dose and RBE-weighted dose and to incorporate biological factors that alter radiation response. To discuss clinical strategies to increase therapeutic ratio, i.e., maximize local control while minimizing the risk of acute and late normal tissue effects.« less

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short‐Acting β‐Agonist Formulations

PubMed Central

Zeng, Yaohui; Singh, Sachinkumar; Wang, Kai

2017-01-01

Abstract Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3‐by‐1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration–recommended 3‐by‐1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3‐by‐1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90‐μg test dose and a 720‐μg reference dose (42% cost reduction). Combining a 180‐μg test dose and a 720‐μg reference dose produced an estimated 36% cost reduction. PMID:29281130

A group sequential adaptive treatment assignment design for proof of concept and dose selection in headache trials.

PubMed

Hall, David B; Meier, Ulrich; Diener, Hans-Cristoph

2005-06-01

The trial objective was to test whether a new mechanism of action would effectively treat migraine headaches and to select a dose range for further investigation. The motivation for a group sequential, adaptive, placebo-controlled trial design was (1) limited information about where across the range of seven doses to focus attention, (2) a need to limit sample size for a complicated inpatient treatment and (3) a desire to reduce exposure of patients to ineffective treatment. A design based on group sequential and up and down designs was developed and operational characteristics were explored by trial simulation. The primary outcome was headache response at 2 h after treatment. Groups of four treated and two placebo patients were assigned to one dose. Adaptive dose selection was based on response rates of 60% seen with other migraine treatments. If more than 60% of treated patients responded, then the next dose was the next lower dose; otherwise, the dose was increased. A stopping rule of at least five groups at the target dose and at least four groups at that dose with more than 60% response was developed to ensure that a selected dose would be statistically significantly (p=0.05) superior to placebo. Simulations indicated good characteristics in terms of control of type 1 error, sufficient power, modest expected sample size and modest bias in estimation. The trial design is attractive for phase 2 clinical trials when response is acute and simple, ideally binary, placebo comparator is required, and patient accrual is relatively slow allowing for the collection and processing of results as a basis for the adaptive assignment of patients to dose groups. The acute migraine trial based on this design was successful in both proof of concept and dose range selection.

SU-F-T-266: Dynalogs Based Evaluation of Different Dose Rate IMRT Using DVH and Gamma Index

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

Ahmed, S; Ahmed, S; Ahmed, F

2016-06-15

Purpose: This work investigates the impact of low and high dose rate on IMRT through Dynalogs by evaluating Gamma Index and Dose Volume Histogram. Methods: The Eclipse™ treatment planning software was used to generate plans on prostate and head and neck sites. A range of dose rates 300 MU/min and 600 MU/min were applied to each plan in order to investigate their effect on the beam ON time, efficiency and accuracy. Each plan had distinct monitor units per fraction, delivery time, mean dose rate and leaf speed. The DVH data was used in the assessment of the conformity and planmore » quality.The treatments were delivered on Varian™ Clinac 2100C accelerator equipped with 120 leaf millennium MLC. Dynalogs of each plan were analyzed by MATLAB™ program. Fluence measurements were performed using the Sun Nuclear™ 2D diode array and results were assessed, based on Gamma analysis of dose fluence maps, beam delivery statistics and Dynalogs data. Results: Minor differences found by adjusted R-squared analysis of DVH’s for all the plans with different dose rates. It has been also found that more and larger fields have greater time reduction at high dose rate and there was a sharp decrease in number of control points observed in dynalog files by switching dose rate from 300 MU/min to 600 MU/min. Gamma Analysis of all plans passes the confidence limit of ≥95% with greater number of passing points in 300 MU/min dose rate plans. Conclusion: The dynalog files are compatible tool for software based IMRT QA. It can work perfectly parallel to measurement based QA setup and stand-by procedure for pre and post delivery of treatment plan.« less

Automated estimation of abdominal effective diameter for body size normalization of CT dose.

PubMed

Cheng, Phillip M

2013-06-01

Most CT dose data aggregation methods do not currently adjust dose values for patient size. This work proposes a simple heuristic for reliably computing an effective diameter of a patient from an abdominal CT image. Evaluation of this method on 106 patients scanned on Philips Brilliance 64 and Brilliance Big Bore scanners demonstrates close correspondence between computed and manually measured patient effective diameters, with a mean absolute error of 1.0 cm (error range +2.2 to -0.4 cm). This level of correspondence was also demonstrated for 60 patients on Siemens, General Electric, and Toshiba scanners. A calculated effective diameter in the middle slice of an abdominal CT study was found to be a close approximation of the mean calculated effective diameter for the study, with a mean absolute error of approximately 1.0 cm (error range +3.5 to -2.2 cm). Furthermore, the mean absolute error for an adjusted mean volume computed tomography dose index (CTDIvol) using a mid-study calculated effective diameter, versus a mean per-slice adjusted CTDIvol based on the calculated effective diameter of each slice, was 0.59 mGy (error range 1.64 to -3.12 mGy). These results are used to calculate approximate normalized dose length product values in an abdominal CT dose database of 12,506 studies.

In vitro dermal disposition of abamectin (avermectin B(1)) in livestock.

PubMed

Baynes, Ronald E

2004-06-01

Many avermectins are approved for topical application in domestic animals. However, extralabel use may result in significant dermal absorption and consequently the potential for adverse effects or violative residues. The primary aim of this study was to assess dermal disposition of abamectin in vitro in bovine, caprine, ovine, and porcine skin dosed in 100% isopropanol, commercial alcohol-based (Ivomec), or oil-based (Eprinex) formulations. Skin sections were perfused in a flow-through diffusion cell system for 8 h, and the disposition of radiolabel abamectin was determined from perfusate and skin samples. Abamectin absorption ranged from 0.09% to 0.20% dose and there were no significant differences between formulations in each species. Isopropanol significantly increased skin deposition in all species when compared to the oil formulation. Absorption was significantly greater in bovine skin than in porcine skin for the isopropanol-containing formulations, but there were no significant species differences for the oil formulation. While significant levels (11.69-50.23% dose) remained on the skin surface, the highest levels deposited in viable skin were observed in caprine skin (28.09% dose) and the lowest levels were in porcine skin (1.50% dose) which could lead to systemic absorption. In summary, these 8-h experiments demonstrated that the alcohol-based formulations compared to oil-based formulations enhanced abamectin absorption and skin deposition in several animal species, and this effect is more likely to be observed in ruminant species than in porcine species.

Is Weight-Based Adjustment of Automatic Exposure Control Necessary for the Reduction of Chest CT Radiation Dose?

PubMed Central

Prakash, Priyanka; Gilman, Matthew D.; Shepard, Jo-Anne O.; Digumarthy, Subba R.

2010-01-01

Objective To assess the effects of radiation dose reduction in the chest CT using a weight-based adjustment of the automatic exposure control (AEC) technique. Materials and Methods With Institutional Review Board Approval, 60 patients (mean age, 59.1 years; M:F = 35:25) and 57 weight-matched patients (mean age, 52.3 years, M:F = 25:32) were scanned using a weight-adjusted AEC and non-weight-adjusted AEC, respectively on a 64-slice multidetector CT with a 0.984:1 pitch, 0.5 second rotation time, 40 mm table feed/rotation, and 2.5 mm section thickness. Patients were categorized into 3 weight categories; < 60 kg (n = 17), 60-90 kg (n = 52), and > 90 kg (n = 48). Patient weights, scanning parameters, CT dose index volumes (CTDIvol) and dose length product (DLP) were recorded, while effective dose (ED) was estimated. Image noise was measured in the descending thoracic aorta. Data were analyzed using a standard statistical package (SAS/STAT) (Version 9.1, SAS institute Inc, Cary, NC). Results Compared to the non-weight-adjusted AEC, the weight-adjusted AEC technique resulted in an average decrease of 29% in CTDIvol and a 27% effective dose reduction (p < 0.0001). With weight-adjusted AEC, the CTDIvol decreased to 15.8, 15.9, and 27.3 mGy for the < 60, 60-90 and > 91 kg weight groups, respectively, compared to 20.3, 27.9 and 32.8 mGy, with non-weight-adjusted AEC. No significant difference was observed for objective image noise between the chest CT acquired with the non-weight-adjusted (15.0 ± 3.1) and weight-adjusted (16.1 ± 5.6) AEC techniques (p > 0.05). Conclusion The results of this study suggest that AEC should be tailored according to patient weight. Without weight-based adjustment of AEC, patients are exposed to a 17 - 43% higher radiation-dose from a chest CT. PMID:20046494

Is weight-based adjustment of automatic exposure control necessary for the reduction of chest CT radiation dose?

PubMed

Prakash, Priyanka; Kalra, Mannudeep K; Gilman, Matthew D; Shepard, Jo-Anne O; Digumarthy, Subba R

2010-01-01

To assess the effects of radiation dose reduction in the chest CT using a weight-based adjustment of the automatic exposure control (AEC) technique. With Institutional Review Board Approval, 60 patients (mean age, 59.1 years; M:F = 35:25) and 57 weight-matched patients (mean age, 52.3 years, M:F = 25:32) were scanned using a weight-adjusted AEC and non-weight-adjusted AEC, respectively on a 64-slice multidetector CT with a 0.984:1 pitch, 0.5 second rotation time, 40 mm table feed/rotation, and 2.5 mm section thickness. Patients were categorized into 3 weight categories; < 60 kg (n = 17), 60-90 kg (n = 52), and > 90 kg (n = 48). Patient weights, scanning parameters, CT dose index volumes (CTDIvol) and dose length product (DLP) were recorded, while effective dose (ED) was estimated. Image noise was measured in the descending thoracic aorta. Data were analyzed using a standard statistical package (SAS/STAT) (Version 9.1, SAS institute Inc, Cary, NC). Compared to the non-weight-adjusted AEC, the weight-adjusted AEC technique resulted in an average decrease of 29% in CTDIvol and a 27% effective dose reduction (p < 0.0001). With weight-adjusted AEC, the CTDIvol decreased to 15.8, 15.9, and 27.3 mGy for the < 60, 60-90 and > 91 kg weight groups, respectively, compared to 20.3, 27.9 and 32.8 mGy, with non-weight-adjusted AEC. No significant difference was observed for objective image noise between the chest CT acquired with the non-weight-adjusted (15.0 +/- 3.1) and weight-adjusted (16.1 +/- 5.6) AEC techniques (p > 0.05). The results of this study suggest that AEC should be tailored according to patient weight. Without weight-based adjustment of AEC, patients are exposed to a 17 - 43% higher radiation-dose from a chest CT.

The effect of obesity on pathological complete response and survival in breast cancer patients receiving uncapped doses of neoadjuvant anthracycline-taxane-based chemotherapy.

PubMed

Farr, Alex; Stolz, Myriam; Baumann, Lukas; Bago-Horvath, Zsuzsanna; Oppolzer, Elisabeth; Pfeiler, Georg; Seifert, Michael; Singer, Christian F

2017-06-01

The effect of obesity in breast cancer patients undergoing neoadjuvant chemotherapy (NAC) remains controversial. The aim of this study was to determine the obesity-related effect on pathological complete response (pCR) and survival in women receiving full uncapped doses of NAC. We retrospectively analyzed the data of all consecutive women who underwent anthracycline-taxane-based NAC for primary breast cancer between 2005 and 2015 at the Department of Obstetrics and Gynecology, Medical University of Vienna. Following the WHO criteria, women with a body mass index (BMI) ≥30 kg/m 2 at baseline were considered obese, whereas those with a BMI <30 kg/m 2 were considered non-obese. Those with dose reductions or dose capping were not eligible for study inclusion. Cox regression and logistic regression were performed. The Kaplan-Meier method was used to analyze disease-free, progression-free, and overall survival. The pCR served as the main outcome measure. Among 120 women who received neoadjuvant epirubicin plus cyclophosphamide and docetaxel, 28 (23.3%) were obese and 92 (76.7%) were non-obese. In the multivariate logistic regression model that adjusted for potentially confounding variables, obesity had an independent positive predictive effect on pCR (OR 4.29, 95% CI, 1.42-13.91; p = 0.011), which was significant in the postmenopausal subgroup (OR 4.72, 95% CI, 1.47-15.84; p = 0.01). When comparing non-obese with obese women, we found that obese women experienced longer progression-free survival (HR 0.10, 95% CI, 8.448 × 10 -4 -0.81; p = 0.025). Obese women receiving full uncapped doses of anthracycline-taxane-based NAC have increased pCR and favorable progression-free survival. This could result from increased dose intensity with increased efficacy and toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Mesalamine, but Not Sulfasalazine, Reduces the Risk of Colorectal Neoplasia in Patients with Inflammatory Bowel Disease: An Agent-specific Systematic Review and Meta-analysis.

PubMed

OʼConnor, Anthony; Packey, Christopher D; Akbari, Mona; Moss, Alan C

2015-11-01

In some studies, 5-aminosalicylates as a class have been associated with protective effects against colorectal cancer in inflammatory bowel disease. In practice, only mesalamine at doses greater than 1.2 g per day is currently widely in this setting. The specific impact of mesalamine at these doses has not has not previously been determined. We performed a systematic review and meta-analysis of the effect of mesalamine on risk of colorectal neoplasia (CRN) from prior cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. A quality assessment was made of all included studies. Mesalamine was associated with a modest reduction in the odds ratio (OR) of CRN (OR = 0.6, 95% confidence interval, 0.4-0.9, P = 0.04). This effect was only noted in hospital-based studies and only in the reduction of all CRN (not cancers alone). Patients prescribed doses >1.2 g per day had a lower risk of CRN (OR = 0.5, 95% confidence interval, 0.3-0.9, P = 0.02) than lower doses. This effect was also only present in the hospital-based studies. In contrast, there was no reduction in the risk of CRN in patients prescribed sulfasalazine (OR = 0.8, 95% confidence interval, 0.5-1.2, P = 0.3), regardless of study setting. Mesalamine, particularly at doses >1.2 g per day, produces a modest reduction in the risk of CRN in inflammatory bowel disease patient populations from referral centers. Sulfasalazine does not seem to reduce the risk. No benefit was noted in population-based studies.

Fluence-to-dose conversion coefficients for neutrons and protons calculated using the PHITS code and ICRP/ICRU adult reference computational phantoms.

PubMed

Sato, Tatsuhiko; Endo, Akira; Zankl, Maria; Petoussi-Henss, Nina; Niita, Koji

2009-04-07

The fluence to organ-dose and effective-dose conversion coefficients for neutrons and protons with energies up to 100 GeV was calculated using the PHITS code coupled to male and female adult reference computational phantoms, which are to be released as a common ICRP/ICRU publication. For the calculation, the radiation and tissue weighting factors, w(R) and w(T), respectively, as revised in ICRP Publication 103 were employed. The conversion coefficients for effective dose equivalents derived using the radiation quality factors of both Q(L) and Q(y) relationships were also estimated, utilizing the functions for calculating the probability densities of the absorbed dose in terms of LET (L) and lineal energy (y), respectively, implemented in PHITS. By comparing these data with the corresponding data for the effective dose, we found that the numerical compatibilities of the revised w(R) with the Q(L) and Q(y) relationships are fairly established. The calculated data of these dose conversion coefficients are indispensable for constructing the radiation protection systems based on the new recommendations given in ICRP103 for aircrews and astronauts, as well as for workers in accelerators and nuclear facilities.

Patient- and cohort-specific dose and risk estimation for abdominopelvic CT: a study based on 100 patients

NASA Astrophysics Data System (ADS)

Tian, Xiaoyu; Li, Xiang; Segars, W. Paul; Frush, Donald P.; Samei, Ehsan

2012-03-01

The purpose of this work was twofold: (a) to estimate patient- and cohort-specific radiation dose and cancer risk index for abdominopelvic computer tomography (CT) scans; (b) to evaluate the effects of patient anatomical characteristics (size, age, and gender) and CT scanner model on dose and risk conversion coefficients. The study included 100 patient models (42 pediatric models, 58 adult models) and multi-detector array CT scanners from two commercial manufacturers (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare). A previously-validated Monte Carlo program was used to simulate organ dose for each patient model and each scanner, from which DLP-normalized-effective dose (k factor) and DLP-normalized-risk index values (q factor) were derived. The k factor showed exponential decrease with increasing patient size. For a given gender, q factor showed exponential decrease with both increasing patient size and patient age. The discrepancies in k and q factors across scanners were on average 8% and 15%, respectively. This study demonstrates the feasibility of estimating patient-specific organ dose and cohort-specific effective dose and risk index in abdominopelvic CT requiring only the knowledge of patient size, gender, and age.

SU-E-I-57: Evaluation and Optimization of Effective-Dose Using Different Beam-Hardening Filters in Clinical Pediatric Shunt CT Protocol

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

Gill, K; Aldoohan, S; Collier, J

Purpose: Study image optimization and radiation dose reduction in pediatric shunt CT scanning protocol through the use of different beam-hardening filters Methods: A 64-slice CT scanner at OU Childrens Hospital has been used to evaluate CT image contrast-to-noise ratio (CNR) and measure effective-doses based on the concept of CT dose index (CTDIvol) using the pediatric head shunt scanning protocol. The routine axial pediatric head shunt scanning protocol that has been optimized for the intrinsic x-ray tube filter has been used to evaluate CNR by acquiring images using the ACR approved CT-phantom and radiation dose CTphantom, which was used to measuremore » CTDIvol. These results were set as reference points to study and evaluate the effects of adding different filtering materials (i.e. Tungsten, Tantalum, Titanium, Nickel and Copper filters) to the existing filter on image quality and radiation dose. To ensure optimal image quality, the scanner routine air calibration was run for each added filter. The image CNR was evaluated for different kVps and wide range of mAs values using above mentioned beam-hardening filters. These scanning protocols were run under axial as well as under helical techniques. The CTDIvol and the effective-dose were measured and calculated for all scanning protocols and added filtration, including the intrinsic x-ray tube filter. Results: Beam-hardening filter shapes energy spectrum, which reduces the dose by 27%. No noticeable changes in image low contrast detectability Conclusion: Effective-dose is very much dependent on the CTDIVol, which is further very much dependent on beam-hardening filters. Substantial reduction in effective-dose is realized using beam-hardening filters as compare to the intrinsic filter. This phantom study showed that significant radiation dose reduction could be achieved in CT pediatric shunt scanning protocols without compromising in diagnostic value of image quality.« less

Dose-response studies and 'no-effect-levels' of N-nitroso compounds: some general aspects.

PubMed

Preussmann, R

1980-01-01

One major problem in the evaluation of potential carcinogenic food additives and contaminants is that of thresholds or, better, of 'no-adverse-effect-levels'. Arguments in favor of the postulated 'irreversibility' of carcinogenic effects are based on dose-response studies, single dose and multigeneration experiments as well as on the concept of somatic mutation as the first step in carcinogenesis with subsequent transmittance of induced defects during cell replication. The problem of extrapolation of results of animal experiments using high doses to low exposure and low incidences in man is not yet solved satisfactorily. Possible practical consequences include zero tolerance, acceptable thresholds at low risk and safety factors. Acceptable intakes should never be considered constants but should be changeable as soon as new facts in regard to the safety evaluation are available.

Diagnostic x-ray dosimetry using Monte Carlo simulation.

PubMed

Ioppolo, J L; Price, R I; Tuchyna, T; Buckley, C E

2002-05-21

An Electron Gamma Shower version 4 (EGS4) based user code was developed to simulate the absorbed dose in humans during routine diagnostic radiological procedures. Measurements of absorbed dose using thermoluminescent dosimeters (TLDs) were compared directly with EGS4 simulations of absorbed dose in homogeneous, heterogeneous and anthropomorphic phantoms. Realistic voxel-based models characterizing the geometry of the phantoms were used as input to the EGS4 code. The voxel geometry of the anthropomorphic Rando phantom was derived from a CT scan of Rando. The 100 kVp diagnostic energy x-ray spectra of the apparatus used to irradiate the phantoms were measured, and provided as input to the EGS4 code. The TLDs were placed at evenly spaced points symmetrically about the central beam axis, which was perpendicular to the cathode-anode x-ray axis at a number of depths. The TLD measurements in the homogeneous and heterogenous phantoms were on average within 7% of the values calculated by EGS4. Estimates of effective dose with errors less than 10% required fewer numbers of photon histories (1 x 10(7)) than required for the calculation of dose profiles (1 x 10(9)). The EGS4 code was able to satisfactorily predict and thereby provide an instrument for reducing patient and staff effective dose imparted during radiological investigations.

Diagnostic x-ray dosimetry using Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Ioppolo, J. L.; Price, R. I.; Tuchyna, T.; Buckley, C. E.

2002-05-01

An Electron Gamma Shower version 4 (EGS4) based user code was developed to simulate the absorbed dose in humans during routine diagnostic radiological procedures. Measurements of absorbed dose using thermoluminescent dosimeters (TLDs) were compared directly with EGS4 simulations of absorbed dose in homogeneous, heterogeneous and anthropomorphic phantoms. Realistic voxel-based models characterizing the geometry of the phantoms were used as input to the EGS4 code. The voxel geometry of the anthropomorphic Rando phantom was derived from a CT scan of Rando. The 100 kVp diagnostic energy x-ray spectra of the apparatus used to irradiate the phantoms were measured, and provided as input to the EGS4 code. The TLDs were placed at evenly spaced points symmetrically about the central beam axis, which was perpendicular to the cathode-anode x-ray axis at a number of depths. The TLD measurements in the homogeneous and heterogenous phantoms were on average within 7% of the values calculated by EGS4. Estimates of effective dose with errors less than 10% required fewer numbers of photon histories (1 × 107) than required for the calculation of dose profiles (1 × 109). The EGS4 code was able to satisfactorily predict and thereby provide an instrument for reducing patient and staff effective dose imparted during radiological investigations.

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

¹H NMR-based metabolic profiling of naproxen-induced toxicity in rats.

PubMed

Jung, Jeeyoun; Park, Minhwa; Park, Hye Jin; Shim, Sun Bo; Cho, Yang Ha; Kim, Jinho; Lee, Ho-Sub; Ryu, Do Hyun; Choi, Donwoong; Hwang, Geum-Sook

2011-01-15

The dose-dependent perturbations in urinary metabolite concentrations caused by naproxen toxicity were investigated using ¹H NMR spectroscopy coupled with multivariate statistical analysis. Histopathologic evaluation of naproxen-induced acute gastrointestinal damage in rats demonstrated a significant dose-dependent effect. Furthermore, principal component analysis (PCA) of ¹H NMR from rat urine revealed a dose-dependent metabolic shift between the vehicle-treated control rats and rats treated with low-dose (10 mg/kg body weight), moderate-dose (50 mg/kg), and high-dose (100 mg/kg) naproxen, coinciding with their gastric damage scores after naproxen administration. The resultant metabolic profiles demonstrate that the naproxen-induced gastric damage exhibited energy metabolism perturbations that elevated their urinary levels of citrate, cis-aconitate, creatine, and creatine phosphate. In addition, naproxen administration decreased choline level and increased betaine level, indicating that it depleted the main protective constituent of the gastric mucosa. Moreover, naproxen stimulated the decomposition of tryptophan into kynurenate, which inhibits fibroblast growth factor-1 and delays ulcer healing. These findings demonstrate that ¹H NMR-based urinary metabolic profiling can facilitate noninvasive and rapid diagnosis of drug side effects and is suitable for elucidating possible biological pathways perturbed by drug toxicity. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

TU-A-12A-07: CT-Based Biomarkers to Characterize Lung Lesion: Effects of CT Dose, Slice Thickness and Reconstruction Algorithm Based Upon a Phantom Study

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

Zhao, B; Tan, Y; Tsai, W

2014-06-15

Purpose: Radiogenomics promises the ability to study cancer tumor genotype from the phenotype obtained through radiographic imaging. However, little attention has been paid to the sensitivity of image features, the image-based biomarkers, to imaging acquisition techniques. This study explores the impact of CT dose, slice thickness and reconstruction algorithm on measuring image features using a thorax phantom. Methods: Twentyfour phantom lesions of known volume (1 and 2mm), shape (spherical, elliptical, lobular and spicular) and density (-630, -10 and +100 HU) were scanned on a GE VCT at four doses (25, 50, 100, and 200 mAs). For each scan, six imagemore » series were reconstructed at three slice thicknesses of 5, 2.5 and 1.25mm with continuous intervals, using the lung and standard reconstruction algorithms. The lesions were segmented with an in-house 3D algorithm. Fifty (50) image features representing lesion size, shape, edge, and density distribution/texture were computed. Regression method was employed to analyze the effect of CT dose, slice of thickness and reconstruction algorithm on these features adjusting 3 confounding factors (size, density and shape of phantom lesions). Results: The coefficients of CT dose, slice thickness and reconstruction algorithm are presented in Table 1 in the supplementary material. No significant difference was found between the image features calculated on low dose CT scans (25mAs and 50mAs). About 50% texture features were found statistically different between low doses and high doses (100 and 200mAs). Significant differences were found for almost all features when calculated on 1.25mm, 2.5mm, and 5mm slice thickness images. Reconstruction algorithms significantly affected all density-based image features, but not morphological features. Conclusions: There is a great need to standardize the CT imaging protocols for radiogenomics study because CT dose, slice thickness and reconstruction algorithm impact quantitative image features to various degrees as our study has shown.« less

Estimating human-equivalent no observed adverse-effect levels for VOCs (volatile organic compounds) based on minimal knowledge of physiological parameters. Technical paper

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

Overton, J.H.; Jarabek, A.M.

1989-01-01

The U.S. EPA advocates the assessment of health-effects data and calculation of inhaled reference doses as benchmark values for gauging systemic toxicity to inhaled gases. The assessment often requires an inter- or intra-species dose extrapolation from no observed adverse effect level (NOAEL) exposure concentrations in animals to human equivalent NOAEL exposure concentrations. To achieve this, a dosimetric extrapolation procedure was developed based on the form or type of equations that describe the uptake and disposition of inhaled volatile organic compounds (VOCs) in physiologically-based pharmacokinetic (PB-PK) models. The procedure assumes allometric scaling of most physiological parameters and that the value ofmore » the time-integrated human arterial-blood concentration must be limited to no more than to that of experimental animals. The scaling assumption replaces the need for most parameter values and allows the derivation of a simple formula for dose extrapolation of VOCs that gives equivalent or more-conservative exposure concentrations values than those that would be obtained using a PB-PK model in which scaling was assumed.« less

In vivo dose perturbation effects of metallic dental alloys during head and neck irradiation with intensity modulated radiation therapy.

PubMed

Fuller, Clifton D; Diaz, Irma; Cavanaugh, Sean X; Eng, Tony Y

2004-07-01

A patient with base of tongue squamous sell carcinoma, with significant CT artifact-inducing metallic alloy, non-removable dental restorations in both the mandible and maxilla was identified. Simultaneous with IMRT treatment, thermoluminescent dosimeters (TLDs) were placed in the oral cavity. After a series of three treatments, the data from the TLDs and software calculations were analyzed. Analysis of mean in vivo TLD dosimetry reveals differentials from software predicted dose calculation that fall within acceptable dose variation limits. IMRT dose calculation software is a relatively accurate predictor of dose attenuation and augmentation due to dental alloys within the treatment volume, as measured by intra-oral thermoluminescent dosimetry. IMRT represents a safe and effective methodology to treat patients with non-removable metallic dental work who have head and neck cancer.

Patient specific computerized phantoms to estimate dose in pediatric CT

NASA Astrophysics Data System (ADS)

Segars, W. P.; Sturgeon, G.; Li, X.; Cheng, L.; Ceritoglu, C.; Ratnanather, J. T.; Miller, M. I.; Tsui, B. M. W.; Frush, D.; Samei, E.

2009-02-01

We create a series of detailed computerized phantoms to estimate patient organ and effective dose in pediatric CT and investigate techniques for efficiently creating patient-specific phantoms based on imaging data. The initial anatomy of each phantom was previously developed based on manual segmentation of pediatric CT data. Each phantom was extended to include a more detailed anatomy based on morphing an existing adult phantom in our laboratory to match the framework (based on segmentation) defined for the target pediatric model. By morphing a template anatomy to match the patient data in the LDDMM framework, it was possible to create a patient specific phantom with many anatomical structures, some not visible in the CT data. The adult models contain thousands of defined structures that were transformed to define them in each pediatric anatomy. The accuracy of this method, under different conditions, was tested using a known voxelized phantom as the target. Errors were measured in terms of a distance map between the predicted organ surfaces and the known ones. We also compared calculated dose measurements to see the effect of different magnitudes of errors in morphing. Despite some variations in organ geometry, dose measurements from morphing predictions were found to agree with those calculated from the voxelized phantom thus demonstrating the feasibility of our methods.

Relative radiological risks derived from different TENORM wastes in Malaysia.

PubMed

Ismail, B; Teng, I L; Muhammad Samudi, Y

2011-11-01

In Malaysia technologically enhanced naturally occurring radioactive materials (TENORM) wastes are mainly the product of the oil and gas industry and mineral processing. Among these TENORM wastes are tin tailing, tin slag, gypsum and oil sludge. Mineral processing and oil and gas industries produce large volume of TENORM wastes that has become a radiological concern to the authorities. A study was carried out to assess the radiological risk related to workers working at these disposal sites and landfills as well as to the members of the public should these areas be developed for future land use. Radiological risk was assessed based on the magnitude of radiation hazard, effective dose rates and excess cancer risks. Effective dose rates and excess cancer risks were estimated using RESRAD 6.4 computer code. All data on the activity concentrations of NORM in wastes and sludges used in this study were obtained from the Atomic Energy Licensing Board, Malaysia, and they were collected over a period of between 5 and 10 y. Results obtained showed that there was a wide range in the total activity concentrations (TAC) of nuclides in the TENORM wastes. With the exception of tin slag and tin tailing-based TENORM wastes, all other TENORM wastes have TAC values comparable to that of Malaysia's soil. Occupational Effective Dose Rates estimated in all landfill areas were lower than the 20 mSv y(-1) permissible dose limit. The average Excess Cancer Risk Coefficient was estimated to be 2.77×10(-3) risk per mSv. The effective dose rates for residents living on gypsum and oil sludge-based TENORM wastes landfills were estimated to be lower than the permissible dose limit for members of the public, and was also comparable to that of the average Malaysia's ordinary soils. The average excess cancer risk coefficient was estimated to be 3.19×10(-3) risk per mSv. Results obtained suggest that gypsum and oil sludge-based TENORM wastes should be exempted from any radiological regulatory control and should be considered radiologically safe for future land use.

EFFECTS OF REACTOR RADIATION ON THE ELECTRICAL PROPERTIES OF ELECTRONIC COMPONENTS. PART II. VACUUM TUBES, TRANSISTORS AND TRANSFORMERS

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

Miglicco, P.S.; Spears, A.B.; Howell, D.B.

1957-11-22

Several types of vacuum tubes, transistors and transformers were irradiated with the Convair-Fort Worth Ground Test Reactor. The components were subjected to five different fluxes ranging from 10/sup 6/ to 10/sup 10/n/sub F// cm/sup 2/-sec and 10/sup 8/ to 10/sup 12/ gamma /cm/sup 2/-sec. The total integrated flux received was 10/sup 14/n/sub F//cm/sup 2/ and 10/sup 16/ gamma / cm/sup 2/. An attempt was made to separate radiation damage as a function of dose rate from radiation damage as a function of dose. The components were irradiated first at several low dose rates so that dose rate effects could bemore » studied while the accumulated dose was small, and then at a high dose rate to obtain the desired dose. However, because of the long time required to complete a data gathering cycle, the accumulated dose hindered the separation of dose rate and dose effects. Thus, in the report, the damage to the components is reported as a function of integrated flux. For reference, the integrated flux accumulated at each power level is given. The transformers exhibited the greatest resistance to irradiation. Every important parameter of the transistors deteriorated in the radiation field. Postirradiation tests at room temperature showed no significant recovery in the transistor's characteristics. The plate current of 65% of the tubes tested increased during irradiation. This effect, based on postirradiation tests, is considered permanent. (auth)« less

Effects of Age, Sex, and Race on the Safety and Pharmacokinetics of Single and Multiple Doses of Azilsartan Medoxomil in Healthy Subjects.

PubMed

Harrell, Robert E; Karim, Aziz; Zhang, Wencan; Dudkowski, Caroline

2016-05-01

Azilsartan medoxomil (AZL-M) is an angiotensin II receptor blocker approved to treat hypertension. After oral dosing, AZL-M is quickly hydrolyzed to azilsartan (AZL). The aims of this study were to assess the effects of age, sex, and race on the pharmacokinetics of AZL-M in healthy subjects, as well as safety and tolerability. Sixty-one healthy adults were enrolled in this phase I, single-blind, randomized placebo-controlled study (placebo control was for assessment of safety/tolerability only). Subjects were stratified by age (18-45 vs. 65-85 years), sex, and race (black vs. white) and given oral AZL-M 60 mg (3 × 20 mg capsules) or placebo as a single dose (Day 1) and consecutive daily doses (Days 4-8) (6:2 ratio for AZL-M:placebo per group). Pharmacokinetics were evaluated (AZL-M patients only) on Days 1-3 and 8-9 and safety/tolerability was monitored. Age, sex, and race had no clinically meaningful effect on AZL exposures after single or multiple dosing. Pharmacokinetic parameters remained similar between Days 1 and 8 for each age, sex, and race subgroup. The frequency of adverse events was similar for AZL-M (32%) and placebo (29%). No discontinuations or serious adverse events occurred. Based on these pharmacokinetic and safety/tolerability findings, no AZL-M dose adjustments are required based on age, sex, or race (black/white).

Monte Carlo based estimation of organ and effective doses to patients undergoing hysterosalpingography and retrograde urethrography fluoroscopy procedures

NASA Astrophysics Data System (ADS)

Ngaile, J. E.; Msaki, P. K.; Kazema, R. R.

2018-04-01

Contrast investigations of hysterosalpingography (HSG) and retrograde urethrography (RUG) fluoroscopy procedures remain the dominant diagnostic tools for the investigation of infertility in females and urethral strictures in males, respectively, owing to the scarcity and high cost of services of alternative diagnostic technologies. In light of the radiological risks associated with contrast based investigations of the genitourinary tract systems, there is a need to assess the magnitude of radiation burden imparted to patients undergoing HSG and RUG fluoroscopy procedures in Tanzania. The air kerma area product (KAP), fluoroscopy time, number of images, organ dose and effective dose to patients undergoing HSG and RUG procedures were obtained from four hospitals. The KAP was measured using a flat transmission ionization chamber, while the organ and effective doses were estimated using the knowledge of the patient characteristics, patient related exposure parameters, geometry of examination, KAP and Monte Carlo calculations (PCXMC). The median values of KAP for the HSG and RUG were 2.2 Gy cm2 and 3.3 Gy cm2, respectively. The median organ doses in the present study for the ovaries, urinary bladder and uterus for the HSG procedures, were 1.0 mGy, 4.0 mGy and 1.6 mGy, respectively, while for urinary bladder and testes of the RUG were 3.4 mGy and 5.9 mGy, respectively. The median values of effective doses for the HSG and RUG procedures were 0.65 mSv and 0.59 mSv, respectively. The median values of effective dose per hospital for the HSG and RUG procedures had a range of 1.6-2.8 mSv and 1.9-5.6 mSv, respectively, while the overall differences between individual effective doses across the four hospitals varied by factors of up to 22.0 and 46.7, respectively for the HSG and RUG procedures. The proposed diagnostic reference levels (DRLs) for the HSG and RUG were for KAP 2.8 Gy cm2 and 3.9 Gy cm2, for fluoroscopy time 0.8 min and 0.9 min, and for number of images 5 and 4, respectively. The suggested DRLs for the HSG and RUG procedures may be used by the radiology departments in Tanzania for management of attained dose levels until the national DRLs are established.

Shading correction for cone-beam CT in radiotherapy: validation of dose calculation accuracy using clinical images

NASA Astrophysics Data System (ADS)

Marchant, T. E.; Joshi, K. D.; Moore, C. J.

2017-03-01

Cone-beam CT (CBCT) images are routinely acquired to verify patient position in radiotherapy (RT), but are typically not calibrated in Hounsfield Units (HU) and feature non-uniformity due to X-ray scatter and detector persistence effects. This prevents direct use of CBCT for re-calculation of RT delivered dose. We previously developed a prior-image based correction method to restore HU values and improve uniformity of CBCT images. Here we validate the accuracy with which corrected CBCT can be used for dosimetric assessment of RT delivery, using CBCT images and RT plans for 45 patients including pelvis, lung and head sites. Dose distributions were calculated based on each patient's original RT plan and using CBCT image values for tissue heterogeneity correction. Clinically relevant dose metrics were calculated (e.g. median and minimum target dose, maximum organ at risk dose). Accuracy of CBCT based dose metrics was determined using an "override ratio" method where the ratio of the dose metric to that calculated on a bulk-density assigned version of the image is assumed to be constant for each patient, allowing comparison to "gold standard" CT. For pelvis and head images the proportion of dose errors >2% was reduced from 40% to 1.3% after applying shading correction. For lung images the proportion of dose errors >3% was reduced from 66% to 2.2%. Application of shading correction to CBCT images greatly improves their utility for dosimetric assessment of RT delivery, allowing high confidence that CBCT dose calculations are accurate within 2-3%.

Adding Dopamine to Proxymetacaine or Oxybuprocaine Solutions Potentiates and Prolongs the Cutaneous Antinociception in Rats.

PubMed

Chen, Yu-Wen; Chiu, Chong-Chi; Lin, Heng-Teng; Wang, Jhi-Joung; Hung, Ching-Hsia

2018-05-01

We evaluated the interaction of dopamine-proxymetacaine and dopamine- oxybuprocaine antinociception using isobolograms. This experiment uses subcutaneous drug (proxymetacaine, oxybuprocaine, and dopamine) injections under the skin of the rat's back, thus simulating infiltration blocks. The dose-related antinociceptive curves of proxymetacaine and oxybuprocaine alone and in combination with dopamine were constructed, and then the antinociceptive interactions between the local anesthetic and dopamine were analyzed using isobolograms. Subcutaneous proxymetacaine, oxybuprocaine, and dopamine produced a sensory block to local skin pinpricks in a dose-dependent fashion. The rank order of potency was proxymetacaine (0.57 [0.52-0.63] μmol/kg) > oxybuprocaine (1.05 [0.96-1.15] μmol/kg) > dopamine (165 [154-177] μmol/kg; P < .01 for each comparison) based on the 50% effective dose values. On the equianesthetic basis (25% effective dose, 50% effective dose, and 75% effective dose), the nociceptive block duration of proxymetacaine or oxybuprocaine was shorter than that of dopamine (P < .01). Oxybuprocaine or proxymetacaine coinjected with dopamine elicited a synergistic antinociceptive effect and extended the duration of action. Oxybuprocaine and proxymetacaine had a higher potency and provoked a shorter duration of sensory block compared with dopamine. The use of dopamine increased the quality and duration of skin antinociception caused by oxybuprocaine and proxymetacaine.

Modeling the Prodromal Effects and Performance Reduction of Astronauts from Exposure to Large Solar Particle Events

NASA Technical Reports Server (NTRS)

Hu, S.; Kim, M. Y.; McClellan, G. E.; Nikjoo, H.; Cucinotta, F. A.

2007-01-01

In space exploration outside the Earth's geomagnetic field, radiation exposure from solar particle events (SPE) presents a health concern for astronauts, that could impair their performance and result in possibility of failure of the mission. Acute risks are especially of concern during spacewalks on the lunar surface because of the rapid onset of SPE's and science goals that involve long distances to crew habitats. Thus assessing the potential of early radiation effect under such adverse conditions is of prime importance. Here we present a biologic based mathematical model which describes the dose and time-dependent early human responses to ionizing radiation. We examine the possible early effects on crew behind various shielding materials from exposure to some historical large SPEs on the lunar and Mars surfaces. The doses and dose rates were calculated using the BRYNTRN code (Kim, M.Y, Hu, X, and Cucinotta, F.A, Effect of Shielding Materials from SPEs on the Lunar and Mars Surface, AIAA Space 2005, paper number AIAA-2005-6653, Long Beach, CA, August 30-September 1, 2005) and the hazard of the early radiation effects and performance reduction were calculated using the RIPD code (Anno, G.H, McClellan, G.E., Dore, M.A, Protracted Radiation-Induced Performance Decrement, Volume 1 Model Development,1996, Defense Nuclear Agency: Alexandria VA). Based on model assumptions we show that exposure to these historical SPEs do cause early effects to crew members and impair their performance if effective shielding and medical countermeasure tactics are not provided. The calculations show multiple occurrence of large SPEs in a short period of time significantly increase the severity of early illness, however early death from failure of the hematopoietic system is very unlikely because of the dose-rate and dose heterogeneity of SPEs. Results from these types of calculations will be a guide in design of protection systems and medical response strategy for astronauts in case of exposure to high dose irradiation during future space missions.

SU-F-18C-14: Hessian-Based Norm Penalty for Weighted Least-Square CBCT Reconstruction

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

Sun, T; Sun, N; Tan, S

Purpose: To develop a Hessian-based norm penalty for cone-beam CT (CBCT) reconstruction that has a similar ability in suppressing noise as the total variation (TV) penalty while avoiding the staircase effect and better preserving low-contrast objects. Methods: We extended the TV penalty to a Hessian-based norm penalty based on the Frobenius norm of the Hessian matrix of an image for CBCT reconstruction. The objective function was constructed using the penalized weighted least-square (PWLS) principle. An effective algorithm was developed to minimize the objective function using a majorization-minimization (MM) approach. We evaluated and compared the proposed penalty with the TV penaltymore » on a CatPhan 600 phantom and an anthropomorphic head phantom, each acquired at a low-dose protocol (10mA/10ms) and a high-dose protocol (80mA/12ms). For both penalties, contrast-to-noise (CNR) in four low-contrast regions-of-interest (ROIs) and the full-width-at-half-maximum (FWHM) of two point-like objects in constructed images were calculated and compared. Results: In the experiment of CatPhan 600 phantom, the Hessian-based norm penalty has slightly higher CNRs and approximately equivalent FWHM values compared with the TV penalty. In the experiment of the anthropomorphic head phantom at the low-dose protocol, the TV penalty result has several artificial piece-wise constant areas known as the staircase effect while in the Hessian-based norm penalty the image appears smoother and more similar to that of the FDK result using the high-dose protocol. Conclusion: The proposed Hessian-based norm penalty has a similar performance in suppressing noise to the TV penalty, but has a potential advantage in suppressing the staircase effect and preserving low-contrast objects. This work was supported in part by National Natural Science Foundation of China (NNSFC), under Grant Nos. 60971112 and 61375018, and Fundamental Research Funds for the Central Universities, under Grant No. 2012QN086.« less

Characterization and implementation of OSL dosimeters for use in evaluating the efficacy of organ-based tube current modulation for CT scans of the face and orbits

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

Marsh, R. M.; Silosky, M., E-mail: michael.silosky@ucdenver.edu

Purpose: The purpose of this work was to characterize commercially available optically stimulated luminescent (OSL) dosimeters for general clinical applications and apply the results to the development of a method to evaluate the efficacy of a vendor-specific organ-based tube current modulation application for both phantom and clinical computed tomography (CT) scans of the face and orbits. Methods: This study consisted of three components: (1) thorough characterization of the dosimeters for CT scans in phantom, including evaluations of depletion, fading, angular dependence, and conversion from counts to absorbed dose; (2) evaluation of the efficacy of using plastic glasses to position themore » dosimeters over the eyes in both phantom and clinical studies; and (3) preliminary dosimetry measurements made using organ-based tube current modulation in computed tomography dose index (CTDI) and anthropomorphic phantom studies. Results: (1) Depletion effects were found to have a linear relationship with the output of the OSL dosimeters (R{sup 2} = 0.96). Fading was found to affect dosimeter readings during the first two hours following exposure but had no effect during the remaining 60-h period observed. No significant angular dependence was observed for the exposure conditions used in this study (with p-values ranging from 0.9 to 0.26 for all t-tests). Dosimeter counts varied linearly with absorbed dose when measured in the center and 12 o’clock positions of the CTDI phantoms. These linear models of counts versus absorbed dose had overlapping 95% confidence intervals for the intercepts but not for the slopes. (2) When dosimeters were positioned using safety glasses, there was no adverse effect on image quality, and there was no statistically significant difference between this placement and placement of the dosimeters directly on the eyes of the phantom (p = 0.24). (3) When using organ-based tube current modulation, the dose to the lens of the eye was reduced between 19% and 43%, depending on the scan protocol used and the positioning of the phantom. Furthermore, the amount of dose reduction was significantly affected by the vertical position of the phantom, with the largest reduction in dose seen when the phantom was centered in the gantry. Conclusions: (1) An appropriate correction factor, specific to CT scanning, was developed to account for depletion and fading characteristics of the dosimeters. Additionally, an equation to convert dosimeter counts to absorbed dose was established. (2) The use of plastic safety glasses was validated as an appropriate positioning device when measuring dose to the lens of the eye. (3) The use of organ-based tube current modulation can reduce dose to the lens of the eye during CT scanning. The amount of dose reduction, however, is largely influenced by the positioning of the anatomy in the gantry.« less

Characterization and implementation of OSL dosimeters for use in evaluating the efficacy of organ-based tube current modulation for CT scans of the face and orbits.

PubMed

Marsh, R M; Silosky, M

2015-04-01

The purpose of this work was to characterize commercially available optically stimulated luminescent (OSL) dosimeters for general clinical applications and apply the results to the development of a method to evaluate the efficacy of a vendor-specific organ-based tube current modulation application for both phantom and clinical computed tomography (CT) scans of the face and orbits. This study consisted of three components: (1) thorough characterization of the dosimeters for CT scans in phantom, including evaluations of depletion, fading, angular dependence, and conversion from counts to absorbed dose; (2) evaluation of the efficacy of using plastic glasses to position the dosimeters over the eyes in both phantom and clinical studies; and (3) preliminary dosimetry measurements made using organ-based tube current modulation in computed tomography dose index (CTDI) and anthropomorphic phantom studies. (1) Depletion effects were found to have a linear relationship with the output of the OSL dosimeters (R(2) = 0.96). Fading was found to affect dosimeter readings during the first two hours following exposure but had no effect during the remaining 60-h period observed. No significant angular dependence was observed for the exposure conditions used in this study (with p-values ranging from 0.9 to 0.26 for all t-tests). Dosimeter counts varied linearly with absorbed dose when measured in the center and 12 o'clock positions of the CTDI phantoms. These linear models of counts versus absorbed dose had overlapping 95% confidence intervals for the intercepts but not for the slopes. (2) When dosimeters were positioned using safety glasses, there was no adverse effect on image quality, and there was no statistically significant difference between this placement and placement of the dosimeters directly on the eyes of the phantom (p = 0.24). (3) When using organ-based tube current modulation, the dose to the lens of the eye was reduced between 19% and 43%, depending on the scan protocol used and the positioning of the phantom. Furthermore, the amount of dose reduction was significantly affected by the vertical position of the phantom, with the largest reduction in dose seen when the phantom was centered in the gantry. (1) An appropriate correction factor, specific to CT scanning, was developed to account for depletion and fading characteristics of the dosimeters. Additionally, an equation to convert dosimeter counts to absorbed dose was established. (2) The use of plastic safety glasses was validated as an appropriate positioning device when measuring dose to the lens of the eye. (3) The use of organ-based tube current modulation can reduce dose to the lens of the eye during CT scanning. The amount of dose reduction, however, is largely influenced by the positioning of the anatomy in the gantry.

Validation of OMI erythemal doses with multi-sensor ground-based measurements in Thessaloniki, Greece

NASA Astrophysics Data System (ADS)

Zempila, Melina Maria; Fountoulakis, Ilias; Taylor, Michael; Kazadzis, Stelios; Arola, Antti; Koukouli, Maria Elissavet; Bais, Alkiviadis; Meleti, Chariklia; Balis, Dimitrios

2018-06-01

The aim of this study is to validate the Ozone Monitoring Instrument (OMI) erythemal dose rates using ground-based measurements in Thessaloniki, Greece. In the Laboratory of Atmospheric Physics of the Aristotle University of Thessaloniki, a Yankee Environmental System UVB-1 radiometer measures the erythemal dose rates every minute, and a Norsk Institutt for Luftforskning (NILU) multi-filter radiometer provides multi-filter based irradiances that were used to derive erythemal dose rates for the period 2005-2014. Both these datasets were independently validated against collocated UV irradiance spectra from a Brewer MkIII spectrophotometer. Cloud detection was performed based on measurements of the global horizontal radiation from a Kipp & Zonen pyranometer and from NILU measurements in the visible range. The satellite versus ground observation validation was performed taking into account the effect of temporal averaging, limitations related to OMI quality control criteria, cloud conditions, the solar zenith angle and atmospheric aerosol loading. Aerosol optical depth was also retrieved using a collocated CIMEL sunphotometer in order to assess its impact on the comparisons. The effect of total ozone columns satellite versus ground-based differences on the erythemal dose comparisons was also investigated. Since most of the public awareness alerts are based on UV Index (UVI) classifications, an analysis and assessment of OMI capability for retrieving UVIs was also performed. An overestimation of the OMI erythemal product by 3-6% and 4-8% with respect to ground measurements is observed when examining overpass and noontime estimates respectively. The comparisons revealed a relatively small solar zenith angle dependence, with the OMI data showing a slight dependence on aerosol load, especially at high aerosol optical depth values. A mean underestimation of 2% in OMI total ozone columns under cloud-free conditions was found to lead to an overestimation in OMI erythemal doses of 1-5%.While OMI overestimated the erythemal dose rates over the range of cloudiness conditions examined, its UVIs were found to be reliable for the purpose of characterizing the ambient UV radiation impact.

TH-A-9A-01: Active Optical Flow Model: Predicting Voxel-Level Dose Prediction in Spine SBRT

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

Liu, J; Wu, Q.J.; Yin, F

2014-06-15

Purpose: To predict voxel-level dose distribution and enable effective evaluation of cord dose sparing in spine SBRT. Methods: We present an active optical flow model (AOFM) to statistically describe cord dose variations and train a predictive model to represent correlations between AOFM and PTV contours. Thirty clinically accepted spine SBRT plans are evenly divided into training and testing datasets. The development of predictive model consists of 1) collecting a sequence of dose maps including PTV and OAR (spinal cord) as well as a set of associated PTV contours adjacent to OAR from the training dataset, 2) classifying data into fivemore » groups based on PTV's locations relative to OAR, two “Top”s, “Left”, “Right”, and “Bottom”, 3) randomly selecting a dose map as the reference in each group and applying rigid registration and optical flow deformation to match all other maps to the reference, 4) building AOFM by importing optical flow vectors and dose values into the principal component analysis (PCA), 5) applying another PCA to features of PTV and OAR contours to generate an active shape model (ASM), and 6) computing a linear regression model of correlations between AOFM and ASM.When predicting dose distribution of a new case in the testing dataset, the PTV is first assigned to a group based on its contour characteristics. Contour features are then transformed into ASM's principal coordinates of the selected group. Finally, voxel-level dose distribution is determined by mapping from the ASM space to the AOFM space using the predictive model. Results: The DVHs predicted by the AOFM-based model and those in clinical plans are comparable in training and testing datasets. At 2% volume the dose difference between predicted and clinical plans is 4.2±4.4% and 3.3±3.5% in the training and testing datasets, respectively. Conclusion: The AOFM is effective in predicting voxel-level dose distribution for spine SBRT. Partially supported by NIH/NCI under grant #R21CA161389 and a master research grant by Varian Medical System.« less

Are Recommended Doses of Acetaminophen Effective for Children Aged 2 to 3 Years? A Pharmacokinetic Modeling Answer.

PubMed

Abourbih, Daniel Asher; Gosselin, Sophie; Villeneuve, Eric; Kazim, Sara

2016-01-01

Acetaminophen (APAP) elixir is a widely used pediatric antipyretic medication. It has been shown that up to 30% of febrile children presenting to a large urban pediatric emergency department received inadequate APAP dosages at home with errors primarily due to age-based dosing. Parental education material in the form of weight-based dosing guides has been proposed; however, validation of current recommended APAP dosages using pharmacokinetic models is needed. This study used a mathematical model of APAP absorption to predict plasma concentrations and to compare them with the range required to reach and achieve antipyresis (10-20 μg/mL). A common APAP preparation (Children's Tylenol Elixir) was tested (children aged 2-3 years, 10.9-15.9 kg). The manufacturer's suggested dose of 160 mg was compared with the standard 10 to 15 mg/kg dose range. The model predicts a peak plasma concentration between 6.38 and 8.55 μg/mL for 10 mg/kg dose and 9.57 and 12.8 μg/mL for 15 mg/kg dose. The manufacturer's suggested dose of 160 mg was tested across the limits of the weight range (10.9-15.9 kg). A peak plasma concentration between 9.36 and 12.6 μg/mL was found for the lower weight limit (10.9 kg child) and 6.42 to 8.61 μg/mL for the upper weight limit (15.9 kg child). With the use of this model, the 10 mg/kg dose does not reach the plasma concentration value for antipyresis (10-20 μg/mL), whereas 15 mg/kg is adequate only if assuming a greater absorption constant. The 160 mg dose is effective only for children weighing 10.9 kg. Individual differences in drug bioavailability, volume of distribution, and absorption/elimination constants undoubtedly exist, and future studies directly measuring plasma APAP concentration and pharmacokinetics are needed. However, these results indicate that dosages for APAP in children should be weight based and manufacturers should review their dosing recommendations.

The influence of non-DNA-targeted effects on carbon ion–induced low-dose hyper-radiosensitivity in MRC-5 cells

PubMed Central

Ye, Fei; Ning, Jing; Liu, Xinguo; Jin, Xiaodong; Wang, Tieshan; Li, Qiang

2016-01-01

Low-dose hyper-radiosensitivity (LDHRS) is a hot topic in normal tissue radiation protection. However, the primary causes for LDHRS still remain unclear. In this study, the impact of non-DNA-targeted effects (NTEs) on high-LET radiation–induced LDHRS was investigated. Human normal lung fibroblast MRC-5 cells were irradiated with high-LET carbon ions, and low-dose biological effects (in terms of various bio-endpoints, including colony formation, DNA damage and micronuclei formation) were detected under conditions with and without gap junctional intercellular communication (GJIC) inhibition. LDHRS was observed when the radiation dose was <0.2 Gy for all bio-endpoints under investigation, but vanished when the GJIC was suppressed. Based on the probability of cells being hit and micro-dose per cell calculation, we deduced that the LDHRS phenomenon came from the combined action of direct hits and NTEs. We concluded that GJIC definitely plays an important role in cytotoxic substance spreading in high-LET carbon ion–induced LDHRS. PMID:26559335

Acute Lethality after Fast-Neutron and X-Irradiation of Tribolium confusum

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

Glenn, Norman D.; Ducoff, Howard S.

1976-01-01

The acute lethal effects of fast neutrons and of X-rays on adults and larvae of T. confusum are compared. The time course of mortality of adults of the Oklahoma strain was the same after midlethal doses of neutrons and X-rays, although the neutrons were about twice as effective as X-rays in producing lethality, based on LD 50(35). The neutron RBE for adults of the Ebony mutant strain was also about 2, but that for Oklahoma larvae was about 3.85. Larvae surviving midlethal doses of neutrons showed a tendency toward wing abnormalities and delayed pupation. Dose-fractionation recovery with neutron doses inmore » the midlethal range was not detectable in the adults or in the larvae. A considerable sparing effect of dose fractionation was found in X-irradiated adults. Finally, also presented are techniques for using a beam port of a Triga research reactor for fast-neutron irradiation and a method of neutron and gamma dosimetry.« less

Toxicity of o,p′-DDE to medaka d-rR strain after a one-time embryonic exposure by in ovo nanoinjection: An early through juvenile life cycle assessment

USGS Publications Warehouse

Villalobos, Sergio A.; Papoulias, Diana M.; Pastva, Stephanie D.; Blankenship, Alan L.; Meadows, John C.; Tillitt, Donald E.; Giesy, John P.

2003-01-01

The toxicity of o,p′-DDE (1,1-dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethylene) was evaluated in embryos of medaka (Oryzias latipes) following a one time exposure via nanoinjection. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of 4 graded doses (0.0005-0.5 ng/egg) of o,p′-DDE in triolein. Embryos were allowed to develop, and fry were reared. Embryonic survival was monitored daily during the first 10 d until hatching and thereafter, on a weekly basis until day 59, at which time the fish were monitored for sexual maturity until day 107. In general, o,p′-DDE caused a dose- and time-dependent mortality. No changes in mortality were observed between the last two time points (day 38 and 59, respectively), and hence a 59 day-LD50 of 346 ng o,p′-DDE/egg was derived from the linear dose-response relationship. Prior to late stage death, only isolated cases of cardiovascular lesions and spinal deformities were observed, but were not dose-dependent. The lowest observable adverse effect level (LOAEL), based on upper 95% CI for regression line=0.0018 mg/kg, and the LOAEL based on exposure doses=0.5 mg/kg. Likewise, the no observable adverse effect level (NOAEL) based on linear extrapolation to 100% survival=0.0000388 mg/kg, while the NOAEL based on exposure doses=0.05 mg/kg. The nanoinjection medaka model has potential in the study of hormonally active compounds in the environment.

Reversal of neuromuscular blockade by sugammadex in laparoscopic bariatric surgery: In support of dose reduction.

PubMed

Badaoui, Rachid; Cabaret, Aurélie; Alami, Youssef; Zogheib, Elie; Popov, Ivan; Lorne, Emmanuel; Dupont, Hervé

2016-02-01

Sugammadex is the first molecule able to antagonize steroidal muscle relaxants with few adverse effects. Doses are adjusted to body weight and the level of neuromuscular blockade. Sleeve gastrectomy is becoming a very popular form of bariatric surgery. It requires deep muscle relaxation followed by complete and rapid reversal to decrease postoperative and especially post-anaesthetic morbidity. Sugammadex is therefore particularly indicated in this setting. The objective of this study was to evaluate the deep neuromuscular blockade reversal time after administration of various doses of sugammadex (based on real weight or at lower doses). Secondary endpoints were the interval between the sugammadex injection and extubation and transfer from the operating room to the recovery room. We then investigated any complications observed in the recovery room. This pilot, prospective, observational, clinical practice evaluation study was conducted in the Amiens University Hospital. Neuromuscular blockade was induced by rocuronium. At the end of the operation, deep neuromuscular blockade was reversed by sugammadex at the dose of 4mg/kg. Sixty-four patients were included: 31 patients received sugammadex at a dosage based on their real weight (RW) and 33 patients received a lower dose (based on ideal weight [IW]). For identical rocuronium doses calculated based on IBW, sugammadex doses were significantly lower in the IW group: 349 (± 65) mg versus 508 (± 75) mg (P<0.0001). Despite this dose reduction, neuromuscular blockade reversal took 115 (± 69) s in the IW group versus 87 (± 40) s in the RW group, but with no significant difference between the two groups (P=0.08). The intervals between injection of sugammadex and extubation (P=0.07) and transfer from the operating room to the recovery room (P=0.68) were also non-significantly longer in the IW group. The mean dose of sugammadex used by anaesthetists in the IW group was 4mg/kg of ideal weight increased by 35% to 50% (n=20; 351±34mg). No sugammadex adverse effects and no residual neuromuscular blockades were observed. Postoperative nausea and vomiting (PONV) was observed in 19.4% of patients in the real weight group versus 27.3% in the ideal weight group (P=NS). Reversal of deep neuromuscular blockades by sugammadex in obese subjects can be performed at doses of 4mg/kg of ideal weight plus 35-50% with no clinical consequences and no accentuation of adverse effects. Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Radon 222 in drinking water resources of Iran: A systematic review, meta-analysis and probabilistic risk assessment (Monte Carlo simulation).

PubMed

Keramati, Hassan; Ghorbani, Raheb; Fakhri, Yadolah; Mousavi Khaneghah, Amin; Conti, Gea Oliveri; Ferrante, Margherita; Ghaderpoori, Mansour; Taghavi, Mahmoud; Baninameh, Zahra; Bay, Abotaleb; Golaki, Mohammad; Moradi, Bigard

2018-05-01

The current study was performed to review the conducted studies regarding the concentration of radon 222 in the tap drinking water; furthermore, by estimation of ingestion and inhalation effective dose, the health risk assessment in the adults and children using MCS technique was assessed. All related studies published among January 1990 to October 2016; were screened in the available databases such as Web of Science, PubMed, Science Direct, Scopus, SID, and Irandoc. The total effective dose was estimated by calculating E ing (Effective dose of ingestion) and E inh (Effective dose of inhalation) by Monte Carlo simulation (MCS) method. The range of ND ─ 40.9 Bq/L for radon 222 in water resources was proposed after evaluation of data collected from 13 studies with 1079 samples. The overall concentration of radon 222 in drinking water in Iran was 3.98: 95%CI (3.79 ─ 4.17 Bq/L). Also, the effective ingestion dose of radon 222 in adults age groups was 1.35 times higher than children. The rank order of drinking water resources based on the concentration of radon 222 was Spring > Spring and Well > Well > Spring and Qanat > Tap water. The overall concentration of radon 222 in drinking water in Iran was lower than WHO and EPA standard limits. Also, the rank order regarding area studied based on the concentration of radon 222 was Gillan > Mashhad > Mazandaran > Kerman > Yazd > Tehran > Kermanshah > Golestan > Hormozgan. The effective ingestion dose of radon 222 to consumers in the Gillan, Mashhad, Mazandaran, and Kerman were higher than WHO guidance (0.1 mSv/y). Also except consumers in the Hormozgan, inhalation effective dose radon 222, in the other investigated areas were higher than WHO guidance (0.1 mSv/y). Therefore, it is recommended to conduct the required programs regarding control and elimination of radon 222 concentration in Iranian drinking water supply. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-09-01

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

An improved MCNP version of the NORMAN voxel phantom for dosimetry studies.

PubMed

Ferrari, P; Gualdrini, G

2005-09-21

In recent years voxel phantoms have been developed on the basis of tomographic data of real individuals allowing new sets of conversion coefficients to be calculated for effective dose. Progress in radiation studies brought ICRP to revise its recommendations and a new report, already circulated in draft form, is expected to change the actual effective dose evaluation method. In the present paper the voxel phantom NORMAN developed at HPA, formerly NRPB, was employed with MCNP Monte Carlo code. A modified version of the phantom, NORMAN-05, was developed to take into account the new set of tissues and weighting factors proposed in the cited ICRP draft. Air kerma to organ equivalent dose and effective dose conversion coefficients for antero-posterior and postero-anterior parallel photon beam irradiations, from 20 keV to 10 MeV, have been calculated and compared with data obtained in other laboratories using different numerical phantoms. Obtained results are in good agreement with published data with some differences for the effective dose calculated employing the proposed new tissue weighting factors set in comparison with previous evaluations based on the ICRP 60 report.

Patient-specific dose estimation for pediatric abdomen-pelvis CT

NASA Astrophysics Data System (ADS)

Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

2009-02-01

The purpose of this study is to develop a method for estimating patient-specific dose from abdomen-pelvis CT examinations and to investigate dose variation across patients in the same weight group. Our study consisted of seven pediatric patients in the same weight/protocol group, for whom full-body computer models were previously created based on the patients' CT data obtained for clinical indications. Organ and effective dose of these patients from an abdomen-pelvis scan protocol (LightSpeed VCT scanner, 120-kVp, 85-90 mA, 0.4-s gantry rotation period, 1.375-pitch, 40-mm beam collimation, and small body scan field-of-view) was calculated using a Monte Carlo program previously developed and validated for the same CT system. The seven patients had effective dose of 2.4-2.8 mSv, corresponding to normalized effective dose of 6.6-8.3 mSv/100mAs (coefficient of variation: 7.6%). Dose variations across the patients were small for large organs in the scan coverage (mean: 6.6%; range: 4.9%-9.2%), larger for small organs in the scan coverage (mean: 10.3%; range: 1.4%-15.6%), and the largest for organs partially or completely outside the scan coverage (mean: 14.8%; range: 5.7%-27.7%). Normalized effective dose correlated strongly with body weight (correlation coefficient: r = -0.94). Normalized dose to the kidney and the adrenal gland correlated strongly with mid-liver equivalent diameter (kidney: r = -0.97; adrenal glands: r = -0.98). Normalized dose to the small intestine correlated strongly with mid-intestine equivalent diameter (r = -0.97). These strong correlations suggest that patient-specific dose may be estimated for any other child in the same size group who undergoes the abdomen-pelvis scan.

Plasma induced DNA damage: Comparison with the effects of ionizing radiation

NASA Astrophysics Data System (ADS)

Lazović, S.; Maletić, D.; Leskovac, A.; Filipović, J.; Puač, N.; Malović, G.; Joksić, G.; Petrović, Z. Lj.

2014-09-01

We use human primary fibroblasts for comparing plasma and gamma rays induced DNA damage. In both cases, DNA strand breaks occur, but of fundamentally different nature. Unlike gamma exposure, contact with plasma predominantly leads to single strand breaks and base-damages, while double strand breaks are mainly consequence of the cell repair mechanisms. Different cell signaling mechanisms are detected confirming this (ataxia telangiectasia mutated - ATM and ataxia telangiectasia and Rad3 related - ATR, respectively). The effective plasma doses can be tuned to match the typical therapeutic doses of 2 Gy. Tailoring the effective dose through plasma power and duration of the treatment enables safety precautions mainly by inducing apoptosis and consequently reduced frequency of micronuclei.

A step-up test procedure to find the minimum effective dose.

PubMed

Wang, Weizhen; Peng, Jianan

2015-01-01

It is of great interest to find the minimum effective dose (MED) in dose-response studies. A sequence of decreasing null hypotheses to find the MED is formulated under the assumption of nondecreasing dose response means. A step-up multiple test procedure that controls the familywise error rate (FWER) is constructed based on the maximum likelihood estimators for the monotone normal means. When the MED is equal to one, the proposed test is uniformly more powerful than Hsu and Berger's test (1999). Also, a simulation study shows a substantial power improvement for the proposed test over four competitors. Three R-codes are provided in Supplemental Materials for this article. Go to the publishers online edition of Journal of Biopharmaceutical Statistics to view the files.

Comparative transcriptome analysis of rice seedlings induced by different doses of heavy ion radiation

NASA Astrophysics Data System (ADS)

Zhao, Qian; Sun, Yeqing; Wang, Wei

2016-07-01

Highly ionizing radiation (HZE) in space is considered as a main factor causing biological effects on plant seeds. To investigate the different effects on genome-wide gene expression of low-dose and high-dose ion radiation, we carried out ground-base carbon particle HZE experiments with different cumulative doses (0Gy, 0.2Gy, 2Gy) to rice seeds and then performed comparative transcriptome analysis of the rice seedlings. We identified a total of 2551 and 1464 differentially expressed genes (DEGs) in low-dose and high-dose radiation groups, respectively. Gene ontology analyses indicated that low-dose and high-dose ion radiation both led to multiple physiological and biochemical activities changes in rice. By Gene Ontology analyses, the results showed that only one process-oxidation reduction process was enriched in the biological process category after high-dose ion radiation, while more processes such as response to biotic stimulus, heme binding, tetrapyrrole binding, oxidoreductase activity, catalytic activity and oxidoreductase activity were significantly enriched after low-dose ion radiation. The results indicated that the rice plants only focused on the process of oxidation reduction to response to high-dose ion radiation, whereas it was a coordination of multiple biological processes to response to low-dose ion radiation. To elucidate the transcriptional regulation of radiation stress-responsive genes, we identified several DEGs-encoding TFs. AP2/EREBP, bHLH, C2H2, MYB and WRKY TF families were altered significantly in response to ion radiation. Mapman analysis speculated that the biological effects on rice seedlings caused by the radiation stress might share similar mechanisms with the biotic stress. Our findings highlight important alterations in the expression of radiation response genes, metabolic pathways, and TF-encoding genes in rice seedlings exposed to low-dose and high-dose ion radiation.

Definition of medical event is to be based on the total source strength for evaluation of permanent prostate brachytherapy: A report from the American Society for Radiation Oncology.

PubMed

Nag, Subir; Demanes, D Jeffrey; Hagan, Michael; Rivard, Mark J; Thomadsen, Bruce R; Welsh, James S; Williamson, Jeffrey F

2011-10-01

The Nuclear Regulatory Commission deems it to be a medical event (ME) if the total dose delivered differs from the prescribed dose by 20% or more. A dose-based definition of ME is not appropriate for permanent prostate brachytherapy as it generates too many spurious MEs and thereby creates unnecessary apprehension in patients, and ties up regulatory bodies and the licensees in unnecessary and burdensome investigations. A more suitable definition of ME is required for permanent prostate brachytherapy. The American Society for Radiation Oncology (ASTRO) formed a working group of experienced clinicians to review the literature, assess the validity of current regulations, and make specific recommendations about the definition of an ME in permanent prostate brachytherapy. The working group found that the current definition of ME in §35.3045 as "the total dose delivered differs from the prescribed dose by 20 percent or more" was not suitable for permanent prostate brachytherapy since the prostate volume (and hence the resultant calculated prostate dose) is dependent on the timing of the imaging, the imaging modality used, the observer variability in prostate contouring, the planning margins used, inadequacies of brachytherapy treatment planning systems to calculate tissue doses, and seed migration within and outside the prostate. If a dose-based definition for permanent implants is applied strictly, many properly executed implants would be improperly classified as an ME leading to a detrimental effect on brachytherapy. The working group found that a source strength-based criterion, of >20% of source strength prescribed in the post-procedure written directive being implanted outside the planning target volume is more appropriate for defining ME in permanent prostate brachytherapy. ASTRO recommends that the definition of ME for permanent prostate brachytherapy should not be dose based but should be based upon the source strength (air-kerma strength) administered.

Estimating radiation dose to organs of patients undergoing conventional and novel multidetector CT exams using Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Angel, Erin

Advances in Computed Tomography (CT) technology have led to an increase in the modality's diagnostic capabilities and therefore its utilization, which has in turn led to an increase in radiation exposure to the patient population. As a result, CT imaging currently constitutes approximately half of the collective exposure to ionizing radiation from medical procedures. In order to understand the radiation risk, it is necessary to estimate the radiation doses absorbed by patients undergoing CT imaging. The most widely accepted risk models are based on radiosensitive organ dose as opposed to whole body dose. In this research, radiosensitive organ dose was estimated using Monte Carlo based simulations incorporating detailed multidetector CT (MDCT) scanner models, specific scan protocols, and using patient models based on accurate patient anatomy and representing a range of patient sizes. Organ dose estimates were estimated for clinical MDCT exam protocols which pose a specific concern for radiosensitive organs or regions. These dose estimates include estimation of fetal dose for pregnant patients undergoing abdomen pelvis CT exams or undergoing exams to diagnose pulmonary embolism and venous thromboembolism. Breast and lung dose were estimated for patients undergoing coronary CTA imaging, conventional fixed tube current chest CT, and conventional tube current modulated (TCM) chest CT exams. The correlation of organ dose with patient size was quantified for pregnant patients undergoing abdomen/pelvis exams and for all breast and lung dose estimates presented. Novel dose reduction techniques were developed that incorporate organ location and are specifically designed to reduce close to radiosensitive organs during CT acquisition. A generalizable model was created for simulating conventional and novel attenuation-based TCM algorithms which can be used in simulations estimating organ dose for any patient model. The generalizable model is a significant contribution of this work as it lays the foundation for the future of simulating TCM using Monte Carlo methods. As a result of this research organ dose can be estimated for individual patients undergoing specific conventional MDCT exams. This research also brings understanding to conventional and novel close reduction techniques in CT and their effect on organ dose.

Monte Carlo calculated doses to treatment volumes and organs at risk for permanent implant lung brachytherapy

NASA Astrophysics Data System (ADS)

Sutherland, J. G. H.; Furutani, K. M.; Thomson, R. M.

2013-10-01

Iodine-125 (125I) and Caesium-131 (131Cs) brachytherapy have been used with sublobar resection to treat stage I non-small cell lung cancer and other radionuclides, 169Yb and 103Pd, are considered for these treatments. This work investigates the dosimetry of permanent implant lung brachytherapy for a range of source energies and various implant sites in the lung. Monte Carlo calculated doses are calculated in a patient CT-derived computational phantom using the EGsnrc user-code BrachyDose. Calculations are performed for 103Pd, 125I, 131Cs seeds and 50 and 100 keV point sources for 17 implant positions. Doses to treatment volumes, ipsilateral lung, aorta, and heart are determined and compared to those determined using the TG-43 approach. Considerable variation with source energy and differences between model-based and TG-43 doses are found for both treatment volumes and organs. Doses to the heart and aorta generally increase with increasing source energy. TG-43 underestimates the dose to the heart and aorta for all implants except those nearest to these organs where the dose is overestimated. Results suggest that model-based dose calculations are crucial for selecting prescription doses, comparing clinical endpoints, and studying radiobiological effects for permanent implant lung brachytherapy.

Abdominal CT with model-based iterative reconstruction (MBIR): initial results of a prospective trial comparing ultralow-dose with standard-dose imaging.

PubMed

Pickhardt, Perry J; Lubner, Meghan G; Kim, David H; Tang, Jie; Ruma, Julie A; del Rio, Alejandro Muñoz; Chen, Guang-Hong

2012-12-01

The purpose of this study was to report preliminary results of an ongoing prospective trial of ultralow-dose abdominal MDCT. Imaging with standard-dose contrast-enhanced (n = 21) and unenhanced (n = 24) clinical abdominal MDCT protocols was immediately followed by ultralow-dose imaging of a matched series of 45 consecutively registered adults (mean age, 57.9 years; mean body mass index, 28.5). The ultralow-dose images were reconstructed with filtered back projection (FBP), adaptive statistical iterative reconstruction (ASIR), and model-based iterative reconstruction (MBIR). Standard-dose series were reconstructed with FBP (reference standard). Image noise was measured at multiple predefined sites. Two blinded abdominal radiologists interpreted randomly presented ultralow-dose images for multilevel subjective image quality (5-point scale) and depiction of organ-based focal lesions. Mean dose reduction relative to the standard series was 74% (median, 78%; range, 57-88%; mean effective dose, 1.90 mSv). Mean multiorgan image noise for low-dose MBIR was 14.7 ± 2.6 HU, significantly lower than standard-dose FBP (28.9 ± 9.9 HU), low-dose FBP (59.2 ± 23.3 HU), and ASIR (45.6 ± 14.1 HU) (p < 0.001). The mean subjective image quality score for low-dose MBIR (3.0 ± 0.5) was significantly higher than for low-dose FBP (1.6 ± 0.7) and ASIR (1.8 ± 0.7) (p < 0.001). Readers identified 213 focal noncalcific lesions with standard-dose FBP. Pooled lesion detection was higher for low-dose MBIR (79.3% [169/213]) compared with low-dose FBP (66.2% [141/213]) and ASIR (62.0% [132/213]) (p < 0.05). MBIR shows great potential for substantially reducing radiation doses at routine abdominal CT. Both FBP and ASIR are limited in this regard owing to reduced image quality and diagnostic capability. Further investigation is needed to determine the optimal dose level for MBIR that maintains adequate diagnostic performance. In general, objective and subjective image quality measurements do not necessarily correlate with diagnostic performance at ultralow-dose CT.

Pharmacokinetic study of single- and multiple-dosing with metolazone tablets in healthy Chinese population.

PubMed

Li, Xueqing; Wang, Rutao; Liu, Yang; Liu, Yun; Zheng, Heng; Feng, Yabo; Zhao, Na; Geng, Hongbin; Zhang, Wanzhi; Wen, Aidong

2017-11-16

Metolazone is a diuretic, saluretic and antihypertensive chemical compound from the quinazoline category that possesses medicinal features similar to those of other thiazide diuretic drugs. However, the pharmacokinetics of metolazone in the Chinese population has rarely been studied. This study aimed to examine the pharmacokinetic characteristics, safety characteristic, and tolerability of metolazone in healthy Chinese subjects after single and multiple doses taken orally as well as the effects that food and gender have on oral metolazone pharmacokinetic parameters. An open-label, randomized, and single- and multiple-dosing investigation was performed in healthy Chinese subjects. The investigation included 3 study groups: the 0.5 mg, 1 mg and 2 mg dose groups were the single-dose study groups in the first stage. Eligible volunteers were randomly and orally administered a single 0.5 mg, 1 mg, or 2 mg metolazone tablet. The 0.5 mg dose group was also part of the multiple-dose study group, and the 1 mg dose group was the food-effect study group in the second stage. Human plasma samples were gathered pre-dosing and up to 48 h after dosing. The human plasma sample concentration of metolazone was quantified using a validated liquid chromatography tandem mass spectrometry method. Pharmacokinetic data were calculated by a noncompartmental analysis method using WinNonlin version 6.4. Tolerability was evaluated based on adverse events, medical examination, 12-lead ECG, and other clinical laboratory exams. Thirty eligible subjects (15 men and 15 women) were registered in our investigation and completed all of the study stages. The AUC and C max showed dose proportionality after a single dose based on the linear-regression analysis. A comparison of the pharmacokinetic data revealed that the differences between the male and female groups were not statistically significant. The t max of metolazone was increased by approximately 100% in the fed condition. Metolazone was well tolerated at the tested dose, and no adverse effects were observed. Single dosing with 0.5 mg, 1 mg, or 2 mg metolazone yielded linear plasma pharmacokinetic properties in healthy Chinese subjects. Multiple oral doses of metolazone did not display significantly different distributions or elimination characteristics from those observed for a single dose. Gender factors did not appear to influence the pharmacokinetic parameter variation of metolazone. The t max of metolazone increased in the fed condition. Metolazone was well tolerated at the tested dose in this study. This investigation is retrospectively registered at chictr.org.cn (ChiCTR-IIR-17012929, October 09 2017).

Ultralow-dose computed tomography imaging for surgery of midfacial and orbital fractures using ASIR and MBIR.

PubMed

Widmann, G; Dalla Torre, D; Hoermann, R; Schullian, P; Gassner, E M; Bale, R; Puelacher, W

2015-04-01

The influence of dose reductions on diagnostic quality using a series of high-resolution ultralow-dose computed tomography (CT) scans for computer-assisted planning and surgery including the most recent iterative reconstruction algorithms was evaluated and compared with the fracture detectability of a standard cranial emergency protocol. A human cadaver head including the mandible was artificially prepared with midfacial and orbital fractures and scanned using a 64-multislice CT scanner. The CT dose index volume (CTDIvol) and effective doses were calculated using application software. Noise was evaluated as the standard deviation in Hounsfield units within an identical region of interest in the posterior fossa. Diagnostic quality was assessed by consensus reading of a craniomaxillofacial surgeon and radiologist. Compared with the emergency protocol at CTDIvol 35.3 mGy and effective dose 3.6 mSv, low-dose protocols down to CTDIvol 1.0 mGy and 0.1 mSv (97% dose reduction) may be sufficient for the diagnosis of dislocated craniofacial fractures. Non-dislocated fractures may be detected at CTDIvol 2.6 mGy and 0.3 mSv (93% dose reduction). Adaptive statistical iterative reconstruction (ASIR) 50 and 100 reduced average noise by 30% and 56%, and model-based iterative reconstruction (MBIR) by 93%. However, the detection rate of fractures could not be improved due to smoothing effects. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Evaluation of organ doses and specific k effective dose of 64-slice CT thorax examination using an adult anthropomorphic phantom

NASA Astrophysics Data System (ADS)

Hashim, S.; Karim, M. K. A.; Bakar, K. A.; Sabarudin, A.; Chin, A. W.; Saripan, M. I.; Bradley, D. A.

2016-09-01

The magnitude of radiation dose in computed tomography (CT) depends on the scan acquisition parameters, investigated herein using an anthropomorphic phantom (RANDO®) and thermoluminescence dosimeters (TLD). Specific interest was in the organ doses resulting from CT thorax examination, the specific k coefficient for effective dose estimation for particular protocols also being determined. For measurement of doses representing five main organs (thyroid, lung, liver, esophagus and skin), TLD-100 (LiF:Mg, Ti) were inserted into selected holes in a phantom slab. Five CT thorax protocols were investigated, one routine (R1) and four that were modified protocols (R2 to R5). Organ doses were ranked from greatest to least, found to lie in the order: thyroid>skin>lung>liver>breast. The greatest dose, for thyroid at 25 mGy, was that in use of R1 while the lowest, at 8.8 mGy, was in breast tissue using R3. Effective dose (E) was estimated using three standard methods: the International Commission on Radiological Protection (ICRP)-103 recommendation (E103), the computational phantom CT-EXPO (E(CTEXPO)) method, and the dose-length product (DLP) based approach. E103 k factors were constant for all protocols, 8% less than that of the universal k factor. Due to inconsistency in tube potential and pitch factor the k factors from CTEXPO were found to vary between 0.015 and 0.010 for protocols R3 and R5. With considerable variation between scan acquisition parameters and organ doses, optimization of practice is necessary in order to reduce patient organ dose.

The effect of statistical noise on IMRT plan quality and convergence for MC-based and MC-correction-based optimized treatment plans.

PubMed

Siebers, Jeffrey V

2008-04-04

Monte Carlo (MC) is rarely used for IMRT plan optimization outside of research centres due to the extensive computational resources or long computation times required to complete the process. Time can be reduced by degrading the statistical precision of the MC dose calculation used within the optimization loop. However, this eventually introduces optimization convergence errors (OCEs). This study determines the statistical noise levels tolerated during MC-IMRT optimization under the condition that the optimized plan has OCEs <100 cGy (1.5% of the prescription dose) for MC-optimized IMRT treatment plans.Seven-field prostate IMRT treatment plans for 10 prostate patients are used in this study. Pre-optimization is performed for deliverable beams with a pencil-beam (PB) dose algorithm. Further deliverable-based optimization proceeds using: (1) MC-based optimization, where dose is recomputed with MC after each intensity update or (2) a once-corrected (OC) MC-hybrid optimization, where a MC dose computation defines beam-by-beam dose correction matrices that are used during a PB-based optimization. Optimizations are performed with nominal per beam MC statistical precisions of 2, 5, 8, 10, 15, and 20%. Following optimizer convergence, beams are re-computed with MC using 2% per beam nominal statistical precision and the 2 PTV and 10 OAR dose indices used in the optimization objective function are tallied. For both the MC-optimization and OC-optimization methods, statistical equivalence tests found that OCEs are less than 1.5% of the prescription dose for plans optimized with nominal statistical uncertainties of up to 10% per beam. The achieved statistical uncertainty in the patient for the 10% per beam simulations from the combination of the 7 beams is ~3% with respect to maximum dose for voxels with D>0.5D(max). The MC dose computation time for the OC-optimization is only 6.2 minutes on a single 3 Ghz processor with results clinically equivalent to high precision MC computations.

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

PubMed

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

2011-12-01

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

Influence of high dose of phytase and an emulsifier on performance, apparent metabolisable energy and nitrogen retention in broilers fed on diets containing soy oil or tallow.

PubMed

Zaefarian, F; Romero, L F; Ravindran, V

2015-01-01

The effects of high dose of microbial phytase and an emulsifier on the performance, apparent metabolisable energy (AME) and nitrogen (N) retention in broilers fed on diets containing different fat sources were examined in a 5-week trial. Two fat sources (soy oil and tallow), two inclusion levels of E. coli phytase (500 or 1000 phytase units (FTU)/kg diet) and two inclusion levels of lysolecithin emulsifier (0 or 3.5 g/kg of diet) were evaluated in a 2 × 2 × 2 factorial arrangement of treatments. Throughout the 5-week trial, soy oil supplementation improved weight gain and feed per gain compared with tallow, but had no effect on feed intake. The high dose of phytase increased the weight gain and feed intake and lowered the feed per gain during d 1-21, but had no effect on performance parameters over the whole trial period. An effect of emulsifier was observed for feed intake during d 1-21 and over the whole trial period. Addition of emulsifier increased feed intake compared with diets without emulsifier. During weeks 1, 2, 3 and 5, birds fed on soy oil-based diets had higher nitrogen-corrected AME (AMEN) compared with those fed on tallow-based diets. During weeks 2, 3 and 5, the effect of phytase was significant for AMEN, with the high dose increasing the AMEN. During week 2, AMEN was increased with emulsifier addition. During weeks 1, 2, 3 and 5, birds fed on soy oil-based diets had higher fat retention compared with those fed on tallow-based diets. The high dose of phytase improved the retention of fat during week 5 and the addition of emulsifier resulted in higher fat retention during week 1. During weeks 2, 3 and 5, an interaction between fat source × phytase × emulsifier was observed for N retention. In soy oil-based diets, emulsifier plus 1000 FTU/kg phytase increased N retention compared with other groups, while in tallow-based diets, emulsifier addition increased N retention in diets with 500 FTU/kg, but not in 1000 FTU/kg diet. Overall, the present data suggest that the dietary fat source influenced performance, AMEN and fat retention in broiler chickens. There is opportunity to improve bird performance during d 1-21, AMEN and fat retention with higher doses of microbial phytase. Addition of the emulsifier increased the AMEN during week 2 and tract retention of fat during week 1, but this effect was not translated into improvements in performance.

Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies.

PubMed

Chou, Ting-Chao

2006-09-01

The median-effect equation derived from the mass-action law principle at equilibrium-steady state via mathematical induction and deduction for different reaction sequences and mechanisms and different types of inhibition has been shown to be the unified theory for the Michaelis-Menten equation, Hill equation, Henderson-Hasselbalch equation, and Scatchard equation. It is shown that dose and effect are interchangeable via defined parameters. This general equation for the single drug effect has been extended to the multiple drug effect equation for n drugs. These equations provide the theoretical basis for the combination index (CI)-isobologram equation that allows quantitative determination of drug interactions, where CI < 1, = 1, and > 1 indicate synergism, additive effect, and antagonism, respectively. Based on these algorithms, computer software has been developed to allow automated simulation of synergism and antagonism at all dose or effect levels. It displays the dose-effect curve, median-effect plot, combination index plot, isobologram, dose-reduction index plot, and polygonogram for in vitro or in vivo studies. This theoretical development, experimental design, and computerized data analysis have facilitated dose-effect analysis for single drug evaluation or carcinogen and radiation risk assessment, as well as for drug or other entity combinations in a vast field of disciplines of biomedical sciences. In this review, selected examples of applications are given, and step-by-step examples of experimental designs and real data analysis are also illustrated. The merging of the mass-action law principle with mathematical induction-deduction has been proven to be a unique and effective scientific method for general theory development. The median-effect principle and its mass-action law based computer software are gaining increased applications in biomedical sciences, from how to effectively evaluate a single compound or entity to how to beneficially use multiple drugs or modalities in combination therapies.

Genetic susceptibility: radiation effects relevant to space travel.

PubMed

Peng, Yuanlin; Nagasawa, Hatsumi; Warner, Christy; Bedford, Joel S

2012-11-01

Genetic variation in the capacity to repair radiation damage is an important factor influencing both cellular and tissue radiosensitivity variation among individuals as well as dose rate effects associated with such damage. This paper consists of two parts. The first part reviews some of the available data relating to genetic components governing such variability among individuals in susceptibility to radiation damage relevant for radiation protection and discusses the possibility and extent to which these may also apply for space radiations. The second part focuses on the importance of dose rate effects and genetic-based variations that influence them. Very few dose rate effect studies have been carried out for the kinds of radiations encountered in space. The authors present here new data on the production of chromosomal aberrations in noncycling low passage human ATM+/+ or ATM+/- cells following irradiations with protons (50 MeV or 1 GeV), 1 GeV(-1) n iron ions and gamma rays, where doses were delivered at a high dose rate of 700 mGy(-1) min, or a lower dose rate of 5 mGy min(-1). Dose responses were essentially linear over the dose ranges tested and not significantly different for the two cell strains. Values of the dose rate effectiveness factor (DREF) were expressed as the ratio of the slopes of the dose-response curves for the high versus the lower (5 mGy min(-1)) dose rate exposures. The authors refer to this as the DREF5. For the gamma ray standard, DREF5 values of approximately two were observed. Similar dose rate effects were seen for both energies of protons (DREF5 ≈ 2.2 in both cases). For 1 GeV(-1) n iron ions [linear energy transfer (LET) ≈ 150 keV μ(-1)], the DREF5 was not 1 as might have been expected on the basis of LET alone but was approximately 1.3. From these results and conditions, the authors estimate that the relative biological effectiveness for 1 GeV(-1) n iron ions for high and low dose rates, respectively, were about 10 and 15 rather than around 20 for low dose rates, as has been assumed by most recommendations from radiation protection organizations for charged particles of this LET. The authors suggest that similar studies using appropriate animal models of carcinogenesis would be valuable.

SU-F-BRB-14: Dosimetric Effects at Air- Tissue Boundary Due to Magnetic Field in MR-Guided IMRT/VMAT Delivery for Head and Neck Cancer

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

Prior, P; Chen, X; Schultz, C

Purpose: The advent of the MR-Linac enables real-time and high soft tissue contrast image guidance in radiation therapy (RT) delivery. Potential hot-spots at air-tissue interfaces, such as the sphenoid sinus, in RT for head and neck cancer (HNC), could potentially occur due to the electron return effect (ERE). In this study, we investigate the dosimetric effects of ERE on the dose distribution at air-tissues interfaces in HNC IMRT treatment planning. Methods: IMRT plans were generated based on planning CT’s acquired for HNC cases (nasopharynx, base of skull and paranasal sinus) using a research planning system (Monaco, v5.09.06, Elekta) employing Montemore » Carlo dose calculations with or without the presence of a transverse magnetic field (TMF). The dose in the air cavity was calculated in a 1 & 2 mm thick tissue layer, while the dose to the skin was calculated in a 1, 3 and 5 mm thick tissue layer. The maximum dose received in 1 cc volume, D1cc, were collected at different TMF strengths. Plan qualities generated with or without TMF or with increasing TMF were compared in terms of commonly-used dose-volume parameters (DVPs). Results: Variations in DVPs between plans with and without a TMF present were found to be within 5% of the planning CT. The presence of a TMF results in <5% changes in sinus air tissue interface. The largest skin dose differences with and without TMF were found within 1 mm of the skin surface Conclusion: The presence of a TMF results in practically insignificant changes in HNC IMRT plan quality, except for skin dose. Planning optimization with skin DV constraints could reduce the skin doses. This research was partially supported by Elekta Inc. (Crowley, U.K.)« less

Radiation doses for pediatric nuclear medicine studies: comparing the North American consensus guidelines and the pediatric dosage card of the European Association of Nuclear Medicine.

PubMed

Grant, Frederick D; Gelfand, Michael J; Drubach, Laura A; Treves, S Ted; Fahey, Frederic H

2015-04-01

Estimated radiation dose is important for assessing and communicating the risks and benefits of pediatric nuclear medicine studies. Radiation dose depends on the radiopharmaceutical, the administered activity, and patient factors such as age and size. Most radiation dose estimates for pediatric nuclear medicine have not been based on administered activities of radiopharmaceuticals recommended by established practice guidelines. The dosage card of the European Association of Nuclear Medicine (EANM) and the North American consensus guidelines each provide recommendations of administered activities of radiopharmaceuticals in children, but there are substantial differences between these two guidelines. For 12 commonly performed pediatric nuclear medicine studies, two established pediatric radiopharmaceutical administration guidelines were used to calculate updated radiation dose estimates and to compare the radiation exposure resulting from the recommendations of each of the guidelines. Estimated radiation doses were calculated for 12 common procedures in pediatric nuclear medicine using administered activities recommended by the dosage card of the EANM (version 1.5.2008) and the 2010 North American consensus guidelines for radiopharmaceutical administered activities in pediatrics. Based on standard models and nominal age-based weights, radiation dose was estimated for typical patients at ages 1, 5, 10 and 15 years and adult. The resulting effective doses were compared, with differences greater than 20% considered significant. Following either the EANM dosage card or the 2010 North American guidelines, the highest effective doses occur with radiopharmaceuticals labeled with fluorine-18 and iodine-123. In 24% of cases, following the North American consensus guidelines would result in a substantially higher radiation dose. The guidelines of the EANM dosage card would lead to a substantially higher radiation dose in 39% of all cases, and in 62% of cases in which patients were age 5 years or younger. For 12 commonly performed pediatric nuclear medicine studies, updated radiation dose estimates can guide efforts to reduce radiation exposure and provide current information for discussing radiation exposure and risk with referring physicians, patients and families. There can be substantial differences in radiation exposure for the same procedure, depending upon which of these two guidelines is followed. This discordance identifies opportunities for harmonization of the guidelines, which may lead to further reduction in nuclear medicine radiation doses in children.

Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice

NASA Astrophysics Data System (ADS)

Yu, Kanglun; Doherty, Alison H.; Genik, Paula C.; Gookin, Sara E.; Roteliuk, Danielle M.; Wojda, Samantha J.; Jiang, Zhi-Sheng; McGee-Lawrence, Meghan E.; Weil, Michael M.; Donahue, Seth W.

2017-11-01

During spaceflight, crewmembers are subjected to biomechanical and biological challenges including microgravity and radiation. In the skeleton, spaceflight leads to bone loss, increasing the risk of fracture. Studies utilizing hindlimb suspension (HLS) as a ground-based model of spaceflight often neglect the concomitant effects of radiation exposure, and even when radiation is accounted for, it is often delivered at a high-dose rate over a very short period of time, which does not faithfully mimic spaceflight conditions. This study was designed to investigate the skeletal effects of low-dose rate gamma irradiation (8.5 cGy gamma radiation per day for 20 days, amounting to a total dose of 1.7 Gy) when administered simultaneously to disuse from HLS. The goal was to determine whether continuous, low-dose rate radiation administered during disuse would exacerbate bone loss in a murine HLS model. Four groups of 16 week old female C57BL/6 mice were studied: weight bearing + no radiation (WB+NR), HLS + NR, WB + radiation exposure (WB+RAD), and HLS+RAD. Surprisingly, although HLS led to cortical and trabecular bone loss, concurrent radiation exposure did not exacerbate these effects. Our results raise the possibility that mechanical unloading has larger effects on the bone loss that occurs during spaceflight than low-dose rate radiation.

Some considerations concerning the theory of combined toxicity: a case study of subchronic experimental intoxication with cadmium and lead.

PubMed

Varaksin, Anatoly N; Katsnelson, Boris A; Panov, Vladimir G; Privalova, Larisa I; Kireyeva, Ekaterina P; Valamina, Irene E; Beresneva, Olga Yu

2014-02-01

Rats were exposed intraperitoneally (3 times a week up to 20 injections) to either Cadmium and Lead salts in doses equivalent to their 0.05 LD50 separately or combined in the same or halved doses. Toxic effects were assessed by more than 40 functional, biochemical and morphometric indices. We analysed the results obtained aiming at determination of the type of combined toxicity using either common sense considerations based on descriptive statistics or two mathematical models based (a) on ANOVA and (b) on Mathematical Theory of Experimental Design, which correspond, respectively, to the widely recognised paradigms of effect additivity and dose additivity. Nevertheless, these approaches have led us unanimously to the following conclusions: (1) The above paradigms are virtually interchangeable and should be regarded as different methods of modelling the combined toxicity rather than as reflecting fundamentally differing processes. (2) Within both models there exist not merely three traditionally used types of combined toxicity (additivity, subadditivity and superadditivity) but at least 10 variants of it depending on exactly which effect is considered and on its level, as well as on the dose levels and their ratio. Copyright © 2013 Elsevier Ltd. All rights reserved.

Comparison of two methods for minimizing the effect of delayed charge on the dose delivered with a synchrotron based discrete spot scanning proton beam.

PubMed

Whitaker, Thomas J; Beltran, Chris; Tryggestad, Erik; Bues, Martin; Kruse, Jon J; Remmes, Nicholas B; Tasson, Alexandria; Herman, Michael G

2014-08-01

Delayed charge is a small amount of charge that is delivered to the patient after the planned irradiation is halted, which may degrade the quality of the treatment by delivering unwarranted dose to the patient. This study compares two methods for minimizing the effect of delayed charge on the dose delivered with a synchrotron based discrete spot scanning proton beam. The delivery of several treatment plans was simulated by applying a normally distributed value of delayed charge, with a mean of 0.001(SD 0.00025) MU, to each spot. Two correction methods were used to account for the delayed charge. Method one (CM1), which is in active clinical use, accounts for the delayed charge by adjusting the MU of the current spot based on the cumulative MU. Method two (CM2) in addition reduces the planned MU by a predicted value. Every fraction of a treatment was simulated using each method and then recomputed in the treatment planning system. The dose difference between the original plan and the sum of the simulated fractions was evaluated. Both methods were tested in a water phantom with a single beam and simple target geometry. Two separate phantom tests were performed. In one test the dose per fraction was varied from 0.5 to 2 Gy using 25 fractions per plan. In the other test the number fractions were varied from 1 to 25, using 2 Gy per fraction. Three patient plans were used to determine the effect of delayed charge on the delivered dose under realistic clinical conditions. The order of spot delivery using CM1 was investigated by randomly selecting the starting spot for each layer, and by alternating per layer the starting spot from first to last. Only discrete spot scanning was considered in this study. Using the phantom setup and varying the dose per fraction, the maximum dose difference for each plan of 25 fractions was 0.37-0.39 Gy and 0.03-0.05 Gy for CM1 and CM2, respectively. While varying the total number of fractions, the maximum dose difference increased at a rate of 0.015 Gy and 0.0018 Gy per fraction for CM1 and CM2, respectively. For CM1, the largest dose difference was found at the location of the first spot in each energy layer, whereas for CM2 the difference in dose was small and showed no dependence on location. For CM1, all of the fields in the patient plans had an area where their excess dose overlapped. No such correlation was found when using CM2. Randomly selecting the starting spot reduces the maximum dose difference from 0.708 to 0.15 Gy. Alternating between first and last spot reduces the maximum dose difference from 0.708 to 0.37 Gy. In the patient plans the excess dose scaled linearly at 0.014 Gy per field per fraction for CM1 and standard delivery order. The predictive model CM2 is superior to a cumulative irradiation model CM1 for minimizing the effects of delayed charge, particularly when considering maximal dose discrepancies and the potential for unplanned hot-spots. This study shows that the dose discrepancy potentially scales at 0.014 Gy per field per fraction for CM1.

Ibrutinib Dosing Strategies Based on Interaction Potential of CYP3A4 Perpetrators Using Physiologically Based Pharmacokinetic Modeling.

PubMed

de Zwart, L; Snoeys, J; De Jong, J; Sukbuntherng, J; Mannaert, E; Monshouwer, M

2016-11-01

Based on ibrutinib pharmacokinetics and potential sensitivity towards CYP3A4-mediated drug-drug interactions (DDIs), a physiologically based pharmacokinetic approach was developed to mechanistically describe DDI with various CYP3A4 perpetrators in healthy men under fasting conditions. These models were verified using clinical data for ketoconazole (strong CYP3A4 inhibitor) and used to prospectively predict and confirm the inducing effect of rifampin (strong CYP3A4 inducer); DDIs with mild (fluvoxamine, azithromycin) and moderate inhibitors (diltiazem, voriconazole, clarithromycin, itraconazole, erythromycin), and moderate (efavirenz) and strong CYP3A4 inducers (carbamazepine), were also predicted. Ketoconazole increased ibrutinib area under the curve (AUC) by 24-fold, while rifampin decreased ibrutinib AUC by 10-fold; coadministration of ibrutinib with strong inhibitors or inducers should be avoided. The ibrutinib dose should be reduced to 140 mg (quarter of maximal prescribed dose) when coadministered with moderate CYP3A4 inhibitors so that exposures remain within observed ranges at therapeutic doses. Thus, dose recommendations for CYP3A4 perpetrator use during ibrutinib treatment were developed and approved for labeling. © 2016 American Society for Clinical Pharmacology and Therapeutics.

Gender Differences in Radiation Dose from Nuclear Cardiology Studies Across the World: Findings from the International Atomic Energy Agency Nuclear Cardiology Protocols Study (INCAPS) Registry

PubMed Central

Shi, Lynn; Dorbala, Sharmila; Paez, Diana; Shaw, Leslee J.; Zukotynski, Katherine A.; Pascual, Thomas N. B.; Karthikeyan, Ganesan; Vitola, João V.; Better, Nathan; Bokhari, Nadia; Rehani, Madan M.; Kashyap, Ravi; Dondi, Maurizio; Mercuri, Mathew; Einstein, Andrew J.

2016-01-01

OBJECTIVES The aim of this study was to investigate gender-based differences in nuclear cardiology practice, globally, with particular focus on laboratory volume, radiation dose, protocols, and best practices. BACKGROUND It is unclear if gender-based differences exist in radiation exposure for nuclear cardiology procedures. METHODS In a large multicenter observational cross-sectional study encompassing 7911 patients in 65 countries, radiation effective dose was estimated for each examination. Patient-level best practices relating to radiation exposure were compared between genders. Analysis of covariance was utilized to determine any difference in radiation exposure according to gender, region, and the interaction between gender and region. Linear, logistic, and hierarchical regression models were developed to evaluate gender-based differences in radiation exposure and laboratory adherence to best practices. We also included the United Nations’ gender inequality and human development indices as covariates in multivariable models. RESULTS The proportion of MPI studies performed in women varied between countries, however there was no significant correlation with gender inequality index. Globally, mean effective dose for nuclear cardiology procedures was only slightly lower in women (9.6±4.5 mSv) than in men (10.3±4.5 mSv men, p<0.001), with a difference of only 0.3 mSv in a multivariable model adjusting for patient age and weight. Stress-only imaging was performed more frequently in women (12.5% vs. 8.4%, p<0.001), however camera-based dose-reduction strategies were used less frequently in women (58.6% vs. 65.5%, p<0.001). CONCLUSIONS Despite significant worldwide variation in best practice use and radiation doses from nuclear cardiology procedures, only small differences were observed between genders worldwide. Regional variations noted in MPI use and radiation dose offer potential opportunities to address gender-related differences in delivery of nuclear cardiology care. PMID:27056156

Population Pharmacokinetics of Busulfan in Pediatric and Young Adult Patients Undergoing Hematopoietic Cell Transplant: A Model-Based Dosing Algorithm for Personalized Therapy and Implementation into Routine Clinical Use

PubMed Central

Long-Boyle, Janel; Savic, Rada; Yan, Shirley; Bartelink, Imke; Musick, Lisa; French, Deborah; Law, Jason; Horn, Biljana; Cowan, Morton J.; Dvorak, Christopher C.

2014-01-01

Background Population pharmacokinetic (PK) studies of busulfan in children have shown that individualized model-based algorithms provide improved targeted busulfan therapy when compared to conventional dosing. The adoption of population PK models into routine clinical practice has been hampered by the tendency of pharmacologists to develop complex models too impractical for clinicians to use. The authors aimed to develop a population PK model for busulfan in children that can reliably achieve therapeutic exposure (concentration-at-steady-state, Css) and implement a simple, model-based tool for the initial dosing of busulfan in children undergoing HCT. Patients and Methods Model development was conducted using retrospective data available in 90 pediatric and young adult patients who had undergone HCT with busulfan conditioning. Busulfan drug levels and potential covariates influencing drug exposure were analyzed using the non-linear mixed effects modeling software, NONMEM. The final population PK model was implemented into a clinician-friendly, Microsoft Excel-based tool and used to recommend initial doses of busulfan in a group of 21 pediatric patients prospectively dosed based on the population PK model. Results Modeling of busulfan time-concentration data indicates busulfan CL displays non-linearity in children, decreasing up to approximately 20% between the concentrations of 250–2000 ng/mL. Important patient-specific covariates found to significantly impact busulfan CL were actual body weight and age. The percentage of individuals achieving a therapeutic Css was significantly higher in subjects receiving initial doses based on the population PK model (81%) versus historical controls dosed on conventional guidelines (52%) (p = 0.02). Conclusion When compared to the conventional dosing guidelines, the model-based algorithm demonstrates significant improvement for providing targeted busulfan therapy in children and young adults. PMID:25162216

DETERMINATION OF NATIONAL DIAGNOSTIC REFERENCE LEVELS IN COMPUTED TOMOGRAPHY EXAMINATIONS OF IRAN BY A NEW QUALITY CONTROL-BASED DOSE SURVEY METHOD.

PubMed

Sohrabi, Mehdi; Parsi, Masoumeh; Mianji, Fereidoun

2018-05-01

National diagnostic reference levels (NDRLs) of Iran were determined for the four most common CT examinations including head, sinus, chest and abdomen/pelvis. A new 'quality control (QC)-based dose survey method', as developed by us, was applied to 157 CT scanners in Iran (2014-15) with different slice classes, models and geographic spread across the country. The NDRLs for head, sinus, chest and abdomen/pelvis examinations are 58, 29, 12 and 14 mGy for CTDIVol and 750, 300, 300 and 650 mGy.cm for DLP, respectively. The 'QC-based dose survey method' was further proven that it is a simple, accurate and practical method for a time and cost-effective NDRLs determination. One effective approach for optimization of the CT examination protocols at the national level is the provision of an adequate standardized training of the radiologists, technicians and medical physicists on the patient radiation protection principles and implementation of the DRL concept in clinical practices.

The economics of a pharmacy-based central intravenous additive service for paediatric patients.

PubMed

Armour, D J; Cairns, C J; Costello, I; Riley, S J; Davies, E G

1996-10-01

This study was designed to compare the costs of a pharmacy-based Central Intravenous Additive Service (CIVAS) with those of traditional ward-based preparation of intravenous doses for a paediatric population. Labour costs were derived from timings of preparation of individual doses in both the pharmacy and ward by an independent observer. The use of disposables and diluents was recorded and their acquisition costs apportioned to the cost of each dose prepared. Data were collected from 20 CIVAS sessions (501 doses) and 26 ward-based sessions (30 doses). In addition, the costs avoided by the use of part vials in CIVAS was calculated. This was derived from a total of 50 CIVAS sessions. Labour, disposable and diluent costs were significantly lower for CIVAS compared with ward-based preparation (p < 0.001). The ratio of costs per dose [in 1994 pounds sterling] between ward and pharmacy was 2.35:1 (2.51 pounds:1.07 pounds). Sensitivity analysis of the best and worst staff mixes in both locations ranged from 2.3:1 to 4.0:1, always in favour of CIVAS. There were considerable costs avoided in CIVAS from the multiple use of vials; the estimated annual sum derived from the study was 44,000 pounds. In addition, CIVAS was less vulnerable to unanticipated interruptions in work flow than ward-based preparation. CIVAS for children was more economical than traditional ward-based preparation, because of a cost-minimisation effect. Sensitivity analysis showed that these advantages were maintained over a full range of skill mixes. Additionally, significant savings accrued from the multiple use of vials in CIVAS.

Patient-specific radiation dose and cancer risk estimation in pediatric chest CT: a study in 30 patients

NASA Astrophysics Data System (ADS)

Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Frush, Donald P.

2010-04-01

Radiation-dose awareness and optimization in CT can greatly benefit from a dosereporting system that provides radiation dose and cancer risk estimates specific to each patient and each CT examination. Recently, we reported a method for estimating patientspecific dose from pediatric chest CT. The purpose of this study is to extend that effort to patient-specific risk estimation and to a population of pediatric CT patients. Our study included thirty pediatric CT patients (16 males and 14 females; 0-16 years old), for whom full-body computer models were recently created based on the patients' clinical CT data. Using a validated Monte Carlo program, organ dose received by the thirty patients from a chest scan protocol (LightSpeed VCT, 120 kVp, 1.375 pitch, 40-mm collimation, pediatric body scan field-of-view) was simulated and used to estimate patient-specific effective dose. Risks of cancer incidence were calculated for radiosensitive organs using gender-, age-, and tissue-specific risk coefficients and were used to derive patientspecific effective risk. The thirty patients had normalized effective dose of 3.7-10.4 mSv/100 mAs and normalized effective risk of 0.5-5.8 cases/1000 exposed persons/100 mAs. Normalized lung dose and risk of lung cancer correlated strongly with average chest diameter (correlation coefficient: r = -0.98 to -0.99). Normalized effective risk also correlated strongly with average chest diameter (r = -0.97 to -0.98). These strong correlations can be used to estimate patient-specific dose and risk prior to or after an imaging study to potentially guide healthcare providers in justifying CT examinations and to guide individualized protocol design and optimization.

Every-other-day Dosing of Oral Viscous Budesonide Is not Effective in the Management of Eosinophlic Esophagitis.

PubMed

Rubinstein, Eitan; Hait, Elizabeth E; Mitchell, Paul D; Lee, John J

2018-03-01

Eosinophilic esophagitis (EoE) is a clinicopathologic disorder characterized histologically by esophageal eosinophilia. Oral viscous budesonide (OVB) is an effective treatment with remission rates reported between 55% and 87%; however, topical corticosteroids are associated with increased risk of candidal esophagitis and adrenal suppression. Attempts to decrease the daily dose of topical steroids have resulted in disease relapse. The objective of this study was to determine whether or not reducing the frequency of OVB administration would be effective in controlling esophageal eosinophilia in children and adolescents. Data were obtained by retrospective chart review of patients at Boston Children's Hospital diagnosed with EoE, based on endoscopic findings of >15 eosinophils per high power field (eos/HPF) on esophageal biopsies while on acid blockade. Patients with histologic evidence of response (<15 eos/HPF) while on daily OVB had been offered the option of maintenance therapy based on a Monday-Wednesday-Friday (MWF) dosing regimen. Changes in peak esophageal eosinophil counts over time were examined. Eight male patients ages 5 to 18 years attained clinical response while receiving daily OVB and were subsequently maintained on a MWF OVB dosing regimen for 3 to 7 months. All 8 patients showed an increase in peak esophageal eosinophils, with 7 of 8 (88%) experiencing disease relapse. In fact, the distribution of peak esophageal eosinophils after MWF dosing was not statistically different from peak levels at diagnosis (P = 0.95). An MWF dosing regimen of OVB was not effective at maintaining histologic response in children and adolescents with EoE. Larger prospective studies are warranted to confirm these results.

A multicenter dose-escalation study of the analgesic and adverse effects of an oral cannabis extract (Cannador) for postoperative pain management.

PubMed

Holdcroft, Anita; Maze, Mervyn; Doré, Caroline; Tebbs, Susan; Thompson, Simon

2006-05-01

Cannabinoids have dose-related antinociceptive effects in animals. This clinical study aimed to investigate whether a single oral dose of cannabis plant extract (Cannador; Institute for Clinical Research, IKF, Berlin, Germany) could provide pain relief with minimal side effects for postoperative pain. Patients (aged 18-75 yr) were recruited and consented before surgery if patient-controlled analgesia was planned for provision of postoperative pain relief. Each patient received a single dose of 5, 10, or 15 mg Cannador if he or she had at least moderate pain after stopping patient-controlled analgesia. Starting with 5 mg, dose escalation was based on the number of patients requesting rescue analgesia and adverse effects. Pain relief, pain intensity, and side effects were recorded over 6 h and analyzed using tests for trend with dose. Rescue analgesia was requested by all 11 patients (100%) receiving 5 mg, 15 of 30 patient (50%) receiving 10 mg, and 6 of 24 patients (25%) receiving 15 mg Cannador (log rank test for trend in time to rescue analgesia with dose P < 0.001). There were also significant trends across the escalating dose groups for decreasing pain intensity at rest (P = 0.01), increasing sedation (P = 0.03), and more adverse events (P = 0.002). The number needed to treat to prevent one rescue analgesia request for the 10-mg and 15-mg doses, relative to 5 mg, were 2.0 (95% confidence interval, 1.5-3.1) and 1.3 (95% confidence interval, 1.1-1.7), respectively. The study was terminated because of a serious vasovagal adverse event in a patient receiving 15 mg. These significant dose-related improvements in rescue analgesia requirements in the 10 mg and 15 mg groups provide a number needed to treat that is equivalent to many routinely used analgesics without frequent adverse effects.

Fibrinolytic activity and dose-dependent effect of incubating human blood clots in caffeic acid phenethyl ester: in vitro assays.

PubMed

Elnager, Abuzar; Hassan, Rosline; Idris, Zamzuri; Mustafa, Zulkifli; Wan-Arfah, Nadiah; Sulaiman, S A; Gan, Siew Hua; Abdullah, Wan Zaidah

2015-01-01

Background. Caffeic acid phenethyl ester (CAPE) has been reported to possess time-dependent fibrinolytic activity by in vitro assay. This study is aimed at investigating fibrinolytic dose-dependent activity of CAPE using in vitro assays. Methods. Standardized human whole blood (WB) clots were incubated in either blank controls or different concentrations of CAPE (3.75, 7.50, 15.00, 22.50, and 30.00 mM). After 3 hours, D-dimer (DD) levels and WB clot weights were measured for each concentration. Thromboelastography (TEG) parameters were recorded following CAPE incubation, and fibrin morphology was examined under a confocal microscope. Results. Overall, mean DD (μg/mL) levels were significantly different across samples incubated with different CAPE concentrations, and the median pre- and postincubation WB clot weights (grams) were significantly decreased for each CAPE concentration. Fibrin removal was observed microscopically and indicated dose-dependent effects. Based on the TEG test, the Ly30 fibrinolytic parameter was significantly different between samples incubated with two different CAPE concentrations (15.0 and 22.50 mM). The 50% effective dose (ED50) of CAPE (based on DD) was 1.99 mg/mL. Conclusions. This study suggests that CAPE possesses fibrinolytic activity following in vitro incubation and that it has dose-dependent activities. Therefore, further investigation into CAPE as a potential alternative thrombolytic agent should be conducted.

Impact of x-ray dose on track formation and data analysis for CR-39-based proton diagnostics

NASA Astrophysics Data System (ADS)

Rinderknecht, H. G.; Rojas-Herrera, J.; Zylstra, A. B.; Frenje, J. A.; Gatu Johnson, M.; Sio, H.; Sinenian, N.; Rosenberg, M. J.; Li, C. K.; Séguin, F. H.; Petrasso, R. D.; Filkins, T.; Steidle, Jeffrey A.; Steidle, Jessica A.; Traynor, N.; Freeman, C.

2015-12-01

The nuclear track detector CR-39 is used extensively for charged particle diagnosis, in particular proton spectroscopy, at inertial confinement fusion facilities. These detectors can absorb x-ray doses from the experiments in the order of 1-100 Gy, the effects of which are not accounted for in the previous detector calibrations. X-ray dose absorbed in the CR-39 has previously been shown to affect the track size of alpha particles in the detector, primarily due to a measured reduction in the material bulk etch rate [Rojas-Herrera et al., Rev. Sci. Instrum. 86, 033501 (2015)]. Similar to the previous findings for alpha particles, protons with energies in the range 0.5-9.1 MeV are shown to produce tracks that are systematically smaller as a function of the absorbed x-ray dose in the CR-39. The reduction of track size due to x-ray dose is found to diminish with time between exposure and etching if the CR-39 is stored at ambient temperature, and complete recovery is observed after two weeks. The impact of this effect on the analysis of data from existing CR-39-based proton diagnostics on OMEGA and the National Ignition Facility is evaluated and best practices are proposed for cases in which the effect of x rays is significant.

Impact of x-ray dose on track formation and data analysis for CR-39-based proton diagnostics

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

Rinderknecht, H. G.; Rojas-Herrera, J.; Zylstra, A. B.

The nuclear track detector CR-39 is used extensively for charged particle diagnosis, in particular proton spectroscopy, at inertial confinement fusion facilities. These detectors can absorb x-ray doses from the experiments in the order of 1–100 Gy, the effects of which are not accounted for in the previous detector calibrations. X-ray dose absorbed in the CR-39 has previously been shown to affect the track size of alpha particles in the detector, primarily due to a measured reduction in the material bulk etch rate [Rojas-Herrera et al., Rev. Sci. Instrum. 86, 033501 (2015)]. Similar to the previous findings for alpha particles, protonsmore » with energies in the range 0.5–9.1 MeV are shown to produce tracks that are systematically smaller as a function of the absorbed x-ray dose in the CR-39. The reduction of track size due to x-ray dose is found to diminish with time between exposure and etching if the CR-39 is stored at ambient temperature, and complete recovery is observed after two weeks. Furthermore, the impact of this effect on the analysis of data from existing CR-39-based proton diagnostics on OMEGA and the National Ignition Facility is evaluated and best practices are proposed for cases in which the effect of x rays is significant.« less

Impact of x-ray dose on track formation and data analysis for CR-39-based proton diagnostics

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

Rinderknecht, H. G., E-mail: rinderknecht1@llnl.gov; Rojas-Herrera, J.; Zylstra, A. B.

The nuclear track detector CR-39 is used extensively for charged particle diagnosis, in particular proton spectroscopy, at inertial confinement fusion facilities. These detectors can absorb x-ray doses from the experiments in the order of 1–100 Gy, the effects of which are not accounted for in the previous detector calibrations. X-ray dose absorbed in the CR-39 has previously been shown to affect the track size of alpha particles in the detector, primarily due to a measured reduction in the material bulk etch rate [Rojas-Herrera et al., Rev. Sci. Instrum. 86, 033501 (2015)]. Similar to the previous findings for alpha particles, protonsmore » with energies in the range 0.5–9.1 MeV are shown to produce tracks that are systematically smaller as a function of the absorbed x-ray dose in the CR-39. The reduction of track size due to x-ray dose is found to diminish with time between exposure and etching if the CR-39 is stored at ambient temperature, and complete recovery is observed after two weeks. The impact of this effect on the analysis of data from existing CR-39-based proton diagnostics on OMEGA and the National Ignition Facility is evaluated and best practices are proposed for cases in which the effect of x rays is significant.« less

Impact of x-ray dose on track formation and data analysis for CR-39-based proton diagnostics

DOE PAGES

Rinderknecht, H. G.; Rojas-Herrera, J.; Zylstra, A. B.; ...

2015-12-23

The nuclear track detector CR-39 is used extensively for charged particle diagnosis, in particular proton spectroscopy, at inertial confinement fusion facilities. These detectors can absorb x-ray doses from the experiments in the order of 1–100 Gy, the effects of which are not accounted for in the previous detector calibrations. X-ray dose absorbed in the CR-39 has previously been shown to affect the track size of alpha particles in the detector, primarily due to a measured reduction in the material bulk etch rate [Rojas-Herrera et al., Rev. Sci. Instrum. 86, 033501 (2015)]. Similar to the previous findings for alpha particles, protonsmore » with energies in the range 0.5–9.1 MeV are shown to produce tracks that are systematically smaller as a function of the absorbed x-ray dose in the CR-39. The reduction of track size due to x-ray dose is found to diminish with time between exposure and etching if the CR-39 is stored at ambient temperature, and complete recovery is observed after two weeks. Furthermore, the impact of this effect on the analysis of data from existing CR-39-based proton diagnostics on OMEGA and the National Ignition Facility is evaluated and best practices are proposed for cases in which the effect of x rays is significant.« less

A multi-GPU real-time dose simulation software framework for lung radiotherapy.

PubMed

Santhanam, A P; Min, Y; Neelakkantan, H; Papp, N; Meeks, S L; Kupelian, P A

2012-09-01

Medical simulation frameworks facilitate both the preoperative and postoperative analysis of the patient's pathophysical condition. Of particular importance is the simulation of radiation dose delivery for real-time radiotherapy monitoring and retrospective analyses of the patient's treatment. In this paper, a software framework tailored for the development of simulation-based real-time radiation dose monitoring medical applications is discussed. A multi-GPU-based computational framework coupled with inter-process communication methods is introduced for simulating the radiation dose delivery on a deformable 3D volumetric lung model and its real-time visualization. The model deformation and the corresponding dose calculation are allocated among the GPUs in a task-specific manner and is performed in a pipelined manner. Radiation dose calculations are computed on two different GPU hardware architectures. The integration of this computational framework with a front-end software layer and back-end patient database repository is also discussed. Real-time simulation of the dose delivered is achieved at once every 120 ms using the proposed framework. With a linear increase in the number of GPU cores, the computational time of the simulation was linearly decreased. The inter-process communication time also improved with an increase in the hardware memory. Variations in the delivered dose and computational speedup for variations in the data dimensions are investigated using D70 and D90 as well as gEUD as metrics for a set of 14 patients. Computational speed-up increased with an increase in the beam dimensions when compared with a CPU-based commercial software while the error in the dose calculation was <1%. Our analyses show that the framework applied to deformable lung model-based radiotherapy is an effective tool for performing both real-time and retrospective analyses.

A Pilot Study: Cardiac Parameters in Children Receiving New-Generation Antidepressants.

PubMed

Uchida, Mai; Spencer, Andrea E; Kenworthy, Tara; Chan, James; Fitzgerald, Maura; Rosales, Ana Maria; Kagan, Elana; Saunders, Alexandra; Biederman, Joseph

2017-06-01

Because of concerns about potential associations between high doses of citalopram and QTc prolongation in adults, this study examined whether such associations are operant in children. We hypothesized that therapeutic doses of nontricyclic antidepressant medications (non-TCAs) prescribed to children would be cardiovascularly safe. The sample consisted of 49 psychiatrically referred children and adolescents 6 to 17 years old of both sexes treated with a non-TCA (citalopram, escitalopram, fluoxetine, paroxetine, sertraline, bupropion, duloxetine, venlafaxine, mirtazapine). To standardize the doses of different antidepressants, we converted doses of individual medicines into "citalopram equivalent doses" (CEDs) based on dosing recommendation for individual antidepressants. Correlation analysis was carried out to compare the continuous and weight-based CED to variables of interest. A QTc grouping was defined as normal, borderline, or abnormal, and CED was compared across QTc groupings using linear regression. An antidepressant dosage group was defined as low or high dose, and a t test compared variables of interest across dosage groups. No significant associations were found between total or weight-corrected CEDs of any antidepressant examined and QTc or any other electrocardiogram or blood pressure parameters. In patients taking citalopram or escitalopram, a significant correlation was found between PR interval and total daily dose, which disappeared when weight-based doses were used or when corrected by age. Although limited by a relatively small sample size, these results suggest that therapeutic doses of non-TCA antidepressants when used in children do not seem to be associated with prolonged QTc interval or other adverse cardiovascular effects.

Monte Carlo dosimetry for {sup 103}Pd, {sup 125}I, and {sup 131}Cs ocular brachytherapy with various plaque models using an eye phantom

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

Lesperance, Marielle; Martinov, M.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca

Purpose: To investigate dosimetry for ocular brachytherapy for a range of eye plaque models containing{sup 103}Pd, {sup 125}I, or {sup 131}Cs seeds with model-based dose calculations. Methods: Five representative plaque models are developed based on a literature review and are compared to the standardized COMS plaque, including plaques consisting of a stainless steel backing and acrylic insert, and gold alloy backings with: short collimating lips and acrylic insert, no lips and silicone polymer insert, no lips and a thin acrylic layer, and individual collimating slots for each seed within the backing and no insert. Monte Carlo simulations are performed usingmore » the EGSnrc user-code BrachyDose for single and multiple seed configurations for the plaques in water and within an eye model (including nonwater media). Simulations under TG-43 assumptions are also performed, i.e., with the same seed configurations in water, neglecting interseed and plaque effects. Maximum and average doses to ocular structures as well as isodose contours are compared for simulations of each radionuclide within the plaque models. Results: The presence of the plaque affects the dose distribution substantially along the plaque axis for both single seed and multiseed simulations of each plaque design in water. Of all the plaque models, the COMS plaque generally has the largest effect on the dose distribution in water along the plaque axis. Differences between doses for single and multiple seed configurations vary between plaque models and radionuclides. Collimation is most substantial for the plaque with individual collimating slots. For plaques in the full eye model, average dose in the tumor region differs from those for the TG-43 simulations by up to 10% for{sup 125}I and {sup 131}Cs, and up to 17% for {sup 103}Pd, and in the lens region by up to 29% for {sup 125}I, 34% for {sup 103}Pd, and 28% for {sup 131}Cs. For the same prescription dose to the tumor apex, the lowest doses to critical ocular structures are generally delivered with plaques containing {sup 103}Pd seeds. Conclusions: The combined effects of ocular and plaque media on dose are significant and vary with plaque model and radionuclide, suggesting the importance of model-based dose calculations employing accurate ocular and plaque media and geometries for eye plaque brachytherapy.« less

Process evaluation of the Enabling Mothers toPrevent Pediatric Obesity Through Web-Based Learning and Reciprocal Determinism (EMPOWER) randomized control trial.

PubMed

Knowlden, Adam P; Sharma, Manoj

2014-09-01

Family-and-home-based interventions are an important vehicle for preventing childhood obesity. Systematic process evaluations have not been routinely conducted in assessment of these interventions. The purpose of this study was to plan and conduct a process evaluation of the Enabling Mothers to Prevent Pediatric Obesity Through Web-Based Learning and Reciprocal Determinism (EMPOWER) randomized control trial. The trial was composed of two web-based, mother-centered interventions for prevention of obesity in children between 4 and 6 years of age. Process evaluation used the components of program fidelity, dose delivered, dose received, context, reach, and recruitment. Categorical process evaluation data (program fidelity, dose delivered, dose exposure, and context) were assessed using Program Implementation Index (PII) values. Continuous process evaluation variables (dose satisfaction and recruitment) were assessed using ANOVA tests to evaluate mean differences between groups (experimental and control) and sessions (sessions 1 through 5). Process evaluation results found that both groups (experimental and control) were equivalent, and interventions were administered as planned. Analysis of web-based intervention process objectives requires tailoring of process evaluation models for online delivery. Dissemination of process evaluation results can advance best practices for implementing effective online health promotion programs. © 2014 Society for Public Health Education.

Aripiprazole Lauroxil

PubMed Central

Hard, Marjie L.; Mills, Richard J.; Sadler, Brian M.; Turncliff, Ryan Z.; Citrome, Leslie

2017-01-01

Abstract Background Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice. Methods Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model. The model was subsequently used to evaluate various dose levels and frequency and the impact of dosing delay on aripiprazole concentrations. Findings The results of the model indicate that aripiprazole is released into the systemic circulation after 5 to 6 days, and release continues for an additional 36 days. The slow increase in aripiprazole concentration after injection necessitates the coadministration of oral aripiprazole for 21 days with the first injection. Based on the PopPK model simulations, a dosing interval of 882 mg every 6 weeks results in aripiprazole concentrations that fall within the concentration range associated with the efficacious aripiprazole lauroxil dose range (441–882 mg dosed monthly). A 662-mg monthly dose also resulted in aripiprazole concentrations within the efficacious dose range. Aripiprazole lauroxil administration results in prolonged exposure, such that dose delays of 2 to 4 weeks, depending on the dose regimen, do not require oral aripiprazole supplementation upon resumption of dosing. Conclusions This PopPK model and model-based simulations were effective means for evaluating aripiprazole lauroxil dosing regimens and management of missed doses. Such analyses play an important role in determining the use of this long-acting antipsychotic in clinical practice. PMID:28350572

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

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

Deasy, J.

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

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

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

Mayo, C.

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

Is There a Role for Intravenous Subdissociative-Dose Ketamine Administered as an Adjunct to Opioids or as a Single Agent for Acute Pain Management in the Emergency Department?

PubMed

Motov, Sergey; Rosenbaum, Steven; Vilke, Gary M; Nakajima, Yuko

2016-12-01

Whether acute or chronic, emergency physicians frequently encounter patients reporting pain. It is the responsibility of the emergency physician to assess and evaluate, and if appropriate, safely and effectively reduce pain. Recently, analgesics other than opioids are being considered in an effort to provide safe alternatives for pain management in the emergency department (ED). Opioids have significant adverse effects such as respiratory depression, hypotension, and sedation, to say nothing of their potential for abuse. Although ketamine has long been used in the ED for procedural sedation and rapid sequence intubation, it is used infrequently for analgesia. Recent evidence suggests that ketamine use in subdissociative doses proves to be effective for pain control and serves as a feasible alternative to traditional opioids. This paper evaluates ketamine's analgesic effectiveness and safety in the ED. This is a literature review of randomized controlled trials, systematic reviews, meta-analyses, and observational studies evaluating ketamine for pain control in the ED setting. Based on these search parameters, eight studies were included in the final analysis and graded based on the American Academy of Emergency Medicine Clinical Practice Committee manuscript review process. A total of eight papers were reviewed in detail and graded. Recommendations were given based upon this review process. Subdissociative-dose ketamine (low-dose ketamine) is effective and safe to use alone or in combination with opioid analgesics for the treatment of acute pain in the ED. Its use is associated with higher rates of minor, but well-tolerated adverse side effects. Copyright © 2016 Elsevier Inc. All rights reserved.

IDACstar: A MCNP Application to Perform Realistic Dose Estimations from Internal or External Contamination of Radiopharmaceuticals.

PubMed

Ören, Ünal; Hiller, Mauritius; Andersson, M

2017-04-28

A Monte Carlo-based stand-alone program, IDACstar (Internal Dose Assessment by Computer), was developed, dedicated to perform radiation dose calculations using complex voxel simulations. To test the program, two irradiation situations were simulated, one hypothetical contamination case with 600 MBq of 99mTc and one extravasation case involving 370 MBq of 18F-FDG. The effective dose was estimated to be 0.042 mSv for the contamination case and 4.5 mSv for the extravasation case. IDACstar has demonstrated that dosimetry results from contamination or extravasation cases can be acquired with great ease. An effective tool for radiation protection applications is provided with IDACstar allowing physicists at nuclear medicine departments to easily quantify the radiation risk of stochastic effects when a radiation accident has occurred. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico

PubMed Central

Luevano-Gurrola, Sergio; Perez-Tapia, Angelica; Pinedo-Alvarez, Carmelo; Carrillo-Flores, Jorge; Montero-Cabrera, Maria Elena; Renteria-Villalobos, Marusia

2015-01-01

Determining ionizing radiation in a geographic area serves to assess its effects on a population’s health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h−1. At the same sites, 48 soil samples were taken to obtain the activity concentrations of 226Ra, 232Th and 40K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h−1. Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg−1, for 226Ra, 232Th and 40K, respectively. From the analysis, the spatial distribution of 232Th, 226Ra and 40K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize. PMID:26437425

Lifetime Effective Dose Assessment Based on Background Outdoor Gamma Exposure in Chihuahua City, Mexico.

PubMed

Luevano-Gurrola, Sergio; Perez-Tapia, Angelica; Pinedo-Alvarez, Carmelo; Carrillo-Flores, Jorge; Montero-Cabrera, Maria Elena; Renteria-Villalobos, Marusia

2015-09-30

Determining ionizing radiation in a geographic area serves to assess its effects on a population's health. The aim of this study was to evaluate the spatial distribution of the background environmental outdoor gamma dose rates in Chihuahua City. This study also estimated the annual effective dose and the lifetime cancer risks of the population of this city. To determine the outdoor gamma dose rate in air, the annual effective dose and the lifetime cancer risk, 48 sampling points were randomly selected in Chihuahua City. Outdoor gamma dose rate measurements were carried out by using a Geiger-Müller counter. Outdoor gamma dose rates ranged from 113 to 310 nGy·h(-1). At the same sites, 48 soil samples were taken to obtain the activity concentrations of (226)Ra, (232)Th and (40)K and to calculate their terrestrial gamma dose rates. Radioisotope activity concentrations were determined by gamma spectrometry. Calculated gamma dose rates ranged from 56 to 193 nGy·h(-1). Results indicated that the lifetime effective dose of the inhabitants of Chihuahua City is on average 19.8 mSv, resulting in a lifetime cancer risk of 0.001. In addition, the mean of the activity concentrations in soil were 52, 73 and 1097 Bq·kg(-1), for (226)Ra, (232)Th and (40)K, respectively. From the analysis, the spatial distribution of (232)Th, (226)Ra and (40)K is to the north, to the north-center and to the south of city, respectively. In conclusion, the natural background gamma dose received by the inhabitants of Chihuahua City is high and mainly due to the geological characteristics of the zone. From the radiological point of view, this kind of study allows us to identify the importance of manmade environments, which are often highly variable and difficult to characterize.

Celecoxib interferes to a limited extent with aspirin‐mediated inhibition of platelets aggregation

PubMed Central

Ruzov, Mark; Rimon, Gilad; Pikovsky, Oleg

2015-01-01

Aims The aim of the study was to analyze the interaction between celecoxib and low dose aspirin for COX‐1 binding and its consequences on the aspirin‐mediated antiplatelet effects. Methods We investigated ex vivo the interaction between celecoxib and aspirin for COX‐1 binding and measured the resulting antiplatelet effects. We applied mechanism‐based pharmacokinetic−pharmacodynamic (PKPD) modelling to analyze these data and to predict in vivo platelet aggregation for different doses and administration schedules of aspirin and celecoxib. Results The predictions of the PK‐PD model were consistent with results from previous studies that investigated interaction between aspirin and celecoxib. The modelling results indicate that celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. The extent of this interaction can be substantial (up to 15% increase in platelet aggregation by 200 mg day−1 celecoxib when combined with low dose aspirin) during the first days of aspirin administration in patients who are already treated with celecoxib, and it cannot be prevented by separate administration of the interacting drugs. Conclusions At the recommended therapeutic doses, celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. Patients receiving a combination of low dose aspirin and the recommended doses of celecoxib were not identified to have increased risk of cardiovascular and cerebrovascular events due to competition between these drugs for COX‐1 binding. Interaction between low dose aspirin and other COX‐2 inhibitors and its clinical consequences requires further investigation. PMID:26456703

Dosimetric impacts of microgravity: an analysis of 5th, 50th and 95th percentile male and female astronauts

NASA Astrophysics Data System (ADS)

Bahadori, Amir A.; Van Baalen, Mary; Shavers, Mark R.; Semones, Edward J.; Bolch, Wesley E.

2012-02-01

Computational phantoms serve an important role in organ dosimetry and risk assessment performed at the National Aeronautics and Space Administration (NASA). A previous study investigated the impact on organ dose equivalents and effective doses from the use of the University of Florida hybrid adult male (UFHADM) and adult female (UFHADF) phantoms at differing height and weight percentiles versus those given by the two existing NASA phantoms, the computerized anatomical man (CAM) and female (CAF) (Bahadori et al 2011 Phys. Med. Biol. 56 1671-94). In the present study, the UFHADM and UFHADF phantoms of different body sizes were further altered to incorporate the effects of microgravity. Body self-shielding distributions are generated using the voxel-based ray tracer (VoBRaT), and the results are combined with depth dose data from the NASA codes BRYNTRN and HZETRN to yield organ dose equivalents and their rates for a variety of space radiation environments. It is found that while organ dose equivalents are indeed altered by the physiological effects of microgravity, the magnitude of the change in overall risk (indicated by the effective dose) is minimal for the spectra and simplified shielding configurations considered. The results also indicate, however, that UFHADM and UFHADF could be useful in designing dose reduction strategies through optimized positioning of an astronaut during encounters with solar particle events.

A Biomechanical Model for Lung Fibrosis in Proton Beam Therapy

NASA Astrophysics Data System (ADS)

King, David J. S.

The physics of protons makes them well-suited to conformal radiotherapy due to the well-known Bragg peak effect. From a proton's inherent stopping power, uncertainty effects can cause a small amount of dose to overflow to an organ at risk (OAR). Previous models for calculating normal tissue complication probabilities (NTCPs) relied on the equivalent uniform dose model (EUD), in which the organ was split into 1/3, 2/3 or whole organ irradiation. However, the problem of dealing with volumes <1/3 of the total volume renders this EUD based approach no longer applicable. In this work the case for an experimental data-based replacement at low volumes is investigated. Lung fibrosis is investigated as an NTCP effect typically arising from dose overflow from tumour irradiation at the spinal base. Considering a 3D geometrical model of the lungs, irradiations are modelled with variable parameters of dose overflow. To calculate NTCPs without the EUD model, experimental data is used from the quantitative analysis of normal tissue effects in the clinic (QUANTEC) data. Additional side projects are also investigated, introduced and explained at various points. A typical radiotherapy course for the patient of 30x2Gy per fraction is simulated. A range of geometry of the target volume and irradiation types is investigated. Investigations with X-rays found the majority of the data point ratios (ratio of EUD values found from calculation based and data based methods) at 20% within unity showing a relatively close agreement. The ratios have not systematically preferred one particular type of predictive method. No Vx metric was found to consistently outperform another. In certain cases there is a good agreement and not in other cases which can be found predicted in the literature. The overall results leads to conclusion that there is no reason to discount the use of the data based predictive method particularly, as a low volume replacement predictive method.

A Model of Regularization Parameter Determination in Low-Dose X-Ray CT Reconstruction Based on Dictionary Learning.

PubMed

Zhang, Cheng; Zhang, Tao; Zheng, Jian; Li, Ming; Lu, Yanfei; You, Jiali; Guan, Yihui

2015-01-01

In recent years, X-ray computed tomography (CT) is becoming widely used to reveal patient's anatomical information. However, the side effect of radiation, relating to genetic or cancerous diseases, has caused great public concern. The problem is how to minimize radiation dose significantly while maintaining image quality. As a practical application of compressed sensing theory, one category of methods takes total variation (TV) minimization as the sparse constraint, which makes it possible and effective to get a reconstruction image of high quality in the undersampling situation. On the other hand, a preliminary attempt of low-dose CT reconstruction based on dictionary learning seems to be another effective choice. But some critical parameters, such as the regularization parameter, cannot be determined by detecting datasets. In this paper, we propose a reweighted objective function that contributes to a numerical calculation model of the regularization parameter. A number of experiments demonstrate that this strategy performs well with better reconstruction images and saving of a large amount of time.

Interpretation of Biochemical Tests Using the Reference Change Value in Monitoring Adverse Effects of Oral Isotretinoin in 102 Ethnic Turkish Patients.

PubMed

Bugdayci, Guler; Polat, Mualla; Oguzman, Hamdi; Cinpolat, Havva Yasemin

2016-08-01

The aim of this study was to model the use of reference change values (RCVs) for the follow-up of 4 parameters of patients using oral isotretinoin which is gaining widespread popularity for monitoring the side effects of the treatment. 102 patients received 30 mg/day oral isotretinoin for 24 weeks for the diagnosis of acne vulgaris. Repetitive measurements of the patients were interpreted with RCVs, after comparing the first and second doses based on RCVs: TC, TG, AST and ALT results increased in 12%, 20%, 14% and 12% of the patients respectively. When the first dose was compared with the last dose, the increases were 20%, 29%, 22% and 18% respectively interpreted as significant changes based on laboratory medicine. A more sensitive follow-up is possible in the monitorization of adverse effects by using RCVs method. © American Society for Clinical Pathology, 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Cost effectiveness analysis of elementary school-located vaccination against influenza--results from a randomized controlled trial.

PubMed

Yoo, Byung-Kwang; Humiston, Sharon G; Szilagyi, Peter G; Schaffer, Stanley J; Long, Christine; Kolasa, Maureen

2013-04-19

School-located vaccination against influenza (SLV-I) has been suggested to help meet the need for annual vaccination of large numbers of school-aged children with seasonal influenza vaccine. However, little is known about the cost and cost-effectiveness of SLV-I. We conducted a cost-analysis and a cost-effectiveness analysis based on a randomized controlled trial (RCT) of an SLV-I program implemented in Monroe County, New York during the 2009-2010 vaccination season. We hypothesized that SLV-I is more cost effective, or less-costly, compared to a conventional, office-located influenza vaccination delivery. First and second SLV-I clinics were offered in 21 intervention elementary schools (n=9027 children) with standard of care (no SLV-I) in 11 control schools (n=4534 children). The direct costs, to purchase and administer vaccines, were estimated from our RCT. The effectiveness measure, receipt of ≥1 dose of influenza vaccine, was 13.2 percentage points higher in SLV-I schools than control schools. The school costs ($9.16/dose in 2009 dollars) plus project costs ($23.00/dose) plus vendor costs excluding vaccine purchase ($19.89/dose) was higher in direct costs ($52.05/dose) than the previously reported mean/median cost [$38.23/$21.44 per dose] for providing influenza vaccination in pediatric practices. However SLV-I averted parent costs to visit medical practices ($35.08 per vaccine). Combining direct and averted costs through Monte Carlo Simulation, SLV-I costs were $19.26/dose in net costs, which is below practice-based influenza vaccination costs. The incremental cost-effectiveness ratio (ICER) was estimated to be $92.50 or $38.59 (also including averted parent costs). When additionally accounting for the costs averted by disease prevention (i.e., both reduced disease transmission to household members and reduced loss of productivity from caring for a sick child), the SLV-I model appears to be cost-saving to society, compared to "no vaccination". Our findings support the expanded implementation of SLV-I, but also the need to focus on efficient delivery to reduce direct costs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Development of a dual phantom technique for measuring the fast neutron component of dose in boron neutron capture therapy.

PubMed

Sakurai, Yoshinori; Tanaka, Hiroki; Kondo, Natsuko; Kinashi, Yuko; Suzuki, Minoru; Masunaga, Shinichiro; Ono, Koji; Maruhashi, Akira

2015-11-01

Research and development of various accelerator-based irradiation systems for boron neutron capture therapy (BNCT) is underway throughout the world. Many of these systems are nearing or have started clinical trials. Before the start of treatment with BNCT, the relative biological effectiveness (RBE) for the fast neutrons (over 10 keV) incident to the irradiation field must be estimated. Measurements of RBE are typically performed by biological experiments with a phantom. Although the dose deposition due to secondary gamma rays is dominant, the relative contributions of thermal neutrons (below 0.5 eV) and fast neutrons are virtually equivalent under typical irradiation conditions in a water and/or acrylic phantom. Uniform contributions to the dose deposited from thermal and fast neutrons are based in part on relatively inaccurate dose information for fast neutrons. This study sought to improve the accuracy in the dose estimation for fast neutrons by using two phantoms made of different materials in which the dose components can be separated according to differences in the interaction cross sections. The development of a "dual phantom technique" for measuring the fast neutron component of dose is reported. One phantom was filled with pure water. The other phantom was filled with a water solution of lithium hydroxide (LiOH) capitalizing on the absorbing characteristics of lithium-6 (Li-6) for thermal neutrons. Monte Carlo simulations were used to determine the ideal mixing ratio of Li-6 in LiOH solution. Changes in the depth dose distributions for each respective dose component along the central beam axis were used to assess the LiOH concentration at the 0, 0.001, 0.01, 0.1, 1, and 10 wt. % levels. Simulations were also performed with the phantom filled with 10 wt. % 6LiOH solution for 95%-enriched Li-6. A phantom was constructed containing 10 wt. % 6LiOH solution based on the simulation results. Experimental characterization of the depth dose distributions of the neutron and gamma-ray components along the central axis was performed at Heavy Water Neutron Irradiation Facility installed at Kyoto University Reactor using activation foils and thermoluminescent dosimeters, respectively. Simulation results demonstrated that the absorbing effect for thermal neutrons occurred when the LiOH concentration was over 1%. The most effective Li-6 concentration was determined to be enriched 6LiOH with a solubility approaching its upper limit. Experiments confirmed that the thermal neutron flux and secondary gamma-ray dose rate decreased substantially; however, the fast neutron flux and primary gamma-ray dose rate were hardly affected in the 10%-6LiOH phantom. It was confirmed that the dose contribution of fast neutrons is improved from approximately 10% in the pure water phantom to approximately 50% in the 10%-6LiOH phantom. The dual phantom technique using the combination of a pure water phantom and a 10%-6LiOH phantom developed in this work provides an effective method for dose estimation of the fast neutron component in BNCT. Improvement in the accuracy achieved with the proposed technique results in improved RBE estimation for biological experiments and clinical practice.

Simulation-Based Sodium Thiosulfate Dosing Strategies for the Treatment of Calciphylaxis

PubMed Central

Singh, Rajendra Pratap; Derendorf, Hartmut

2011-01-01

Summary Background and objectives Calciphylaxis remains a poorly understood life-threatening disorder with limited therapeutic options. Sodium thiosulfate (STS) has reported efficacy, thought to be because solubilizing calcium deposits promote clearance by hemodialysis (HD). Lack of rigorous pharmacokinetic studies makes it problematic for determining proper STS dosing given the expanding range of dialysis prescriptions and intensities. Design, setting, participants, & measurements The purpose of this study was to determine the dosing strategies for STS during different dialysis regimens. Given reported successes using an empiric 25 g, intravenous, 3 times per week after HD, simulations were performed to predict dosing guidelines for alternative, more or less intense dialysis to produce equivalent area under the curve drug exposure. The modeled prescriptions varied HD time from 12 to 40 h/wk over three to six sessions (Qb 200 to 400 ml/min, Qd 500 to 800 ml/min), and continuous venovenous hemodialysis at low flow rates (Qb 100 to 200 ml/min, Qd 35 to 50 ml/min), using high-flux polysulfone hemofilters. Results Simulations showed a marked variation in STS doses depending on HD frequency and duration. Blood and dialysate flows have a less prominent effect. Assuming no residual renal function, HD prescription permutations caused the dose to vary from 72 to 245 g/wk (70-kg adult), and the simulations provide specific guidelines for clinicians. Conclusions Based on the success reported for one STS dosing regimen and assuming area under the curve exposure of STS is proportional to its effect, pharmacokinetic simulations can be used to calculate the dose for alternative, higher or lower intensity dialysis regimens. These strategies are imperative to assure adequate treatment for this mortal disease, as well as to avoid toxicity from excess dosing. PMID:21441129

Effective Dose Equivalent due to Cosmic Ray Particles and Their Secondary Particles on the Moon

NASA Astrophysics Data System (ADS)

Hayatsu, Kanako; Hareyama, Makoto; Kobayashi, Shingo; Karouji, Yuzuru; Sakurai, K.; Sihver, Lembit; Hasebe, N.

Estimation of radiation dose on and under the lunar surface is quite important for human activity on the Moon and for the future lunar bases construction. Radiation environment on the Moon is much different from that on the Earth. Galactic cosmic rays (GCRs) and solar energetic particles (SEPs) directly penetrate the lunar surface because of no atmosphere and no magnetic field around the Moon. Then, they generate many secondary particles such as neutrons, gamma rays and other charged particles by nuclear interactions with soils and regolith breccias under the lunar surface. Therefore, the estimation of radiation dose from them on the surface and the underground of the Moon are essential for safety human activities. In this study, the effective dose equivalents at the surface and various depths of the Moon were estimated using by the latest cosmic rays observation and developed calculation code. The largest contribution to the dose on the surface is primary charged particles in GCRs and SEPs, while in the ground, secondary neutrons are the most dominant. In particular, the dose from neutrons becomes maximal at 70-80 g/cm2 in depth of lunar soil, because fast neutrons with about 1.0 MeV are mostly produced at this depth and give the largest dose. On the lunar surface, the doses originated from large SEPs are very hazardous. We estimated the effective dose equivalents due to such large SEPs and the effects of aluminum shield for the large flare on the human body. In the presentation, we summarize and discuss the improved calculation results of radiation doses due to GCR particles and their secondary particles in the lunar subsurface. These results will provide useful data for the future exploration of the Moon.

Effect of Low (5 mg) vs. High (20-40 mg) Rosuvastatin Dose on 24h Arterial Stiffness, Central Haemodynamics, and Non-Alcoholic Fatty Liver Disease in Patients with Optimally Controlled Arterial Hypertension.

PubMed

Mitsiou, Eudoxia; Boutari, Chrysoula; Kotsis, Vasilios; Georgianou, Eleni; Doumas, Michael; Karagiannis, Asterios; Athyros, Vasilios G

2018-01-01

Arterial Stiffness (AS) and Non-Alcoholic Fatty Liver Diseases (NAFLD) are 2 related, prevalent, risk predictors of Cardiovascular Disease (CVD). We assessed the effect of low dose (5 mg/day) vs. high dose (20-40 mg/day) rosuvastatin on aortic elasticity and central haemodynamics as well as on NAFLD in patients with Arterial Hypertension (AH). Forty patients with optimally controlled AH were randomised to 2 rosuvastatin doses and followed for 6 months. 24h AS was assessed by Mobil-O-Graph, which calculates (adjusted for age and gender) Pulse Wave Velocity (PWV), adjusted for Heart Rate (HR) augmentation index (AIx75%) and central haemodynamics. The diagnosis of NAFLD was based on >5% liver steatosis on ultrasound and moderately elevated serum levels of liver enzymes. Both doses of rosuvastatin reduced Central Pulse Pressure (cPP), PWV and AIx75% (adjusted for HR) to normal values (p = NS adjusted for age, gender and HR). Liver enzymes were reduced in those with NAFLD to normal, but steatosis was reduced more by the 20-40 mg/day rosuvastatin dose (p=0.01) compared with the 5 mg/day dose. Both doses of rosuvastatin had a beneficial effect on AS; the high dose was more efficient in reducing PWVs and central haemodynamics, and also the high dose was more effective in ameliorating NAFLD. Given that AH control was optimal and lipid values attained targets, 4 other CVD predictors were also addressed. Larger and longer term studies are needed to demonstrate the clinical benefit of such treatment preference. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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.

Effects of gamma irradiation dose-rate on sterile male Aedesaegypti

NASA Astrophysics Data System (ADS)

Ernawan, Beni; Tambunan, Usman Sumo Friend; Sugoro, Irawan; Sasmita, Hadian Iman

2017-06-01

Aedesaegypti is the most important vector for dengue, yellow fever and Zika viruses. Considering its medical importance, vector population control program utilizing radiation-based sterile insect technique (SIT) is one of the potential methods for preventing and limiting the dispersal of these viruses. The present study was undertaken to evaluate the dose-rates effects of γ-sterilization on quality parameters of sterile males. Males Ae.aegypti at the pupal stage were sterilized by applying 70 Gyγ-rays in varies dose-rates, i.e. 0 (control), 300, 600, 900, 1200 and 1500Gy/h utilizing panoramic irradiator. Adult males that emerged from the pupal stage were assessed for their quality parameters, which are the percentage of emergence, longevity, sterility and mating competitiveness. The results herein indicate that there was no major effect of dose-rate on the percentage of emergence, the data showedthat there were no differences between irradiated males compared with control. Generally, the longevity of irradiated males was lower compared to control. The data also demonstrated that longevity was significantly increased at the dose-rate from 300 to 900Gy/h, then decreased at the dose-rate 900 to 1500 Gy/h. Sterility of irradiated maleswas significantly different compared to control, while there was no significantly different at dose rate 300 to 1500 Gy/h. Mating competitiveness of irradiated males was increased at the dose rate from 300 to 1200 Gy/h, then the value was decreased significantly at the dose rate 1500 Gy/h. The dose-rate effects of γ-sterilization were discussed in the context genetic vector control, in particular, the SIT. The results give information and contribute to better understanding towards γ-sterilization optimization and quality parameters of sterile male Ae. aegypti on SIT methods.

Pharmacokinetics and Pharmacokinetic/Pharmacodynamic Modeling of Filgotinib (GLPG0634), a Selective JAK1 Inhibitor, in Support of Phase IIB Dose Selection.

PubMed

Namour, Florence; Diderichsen, Paul Matthias; Cox, Eugène; Vayssière, Béatrice; Van der Aa, Annegret; Tasset, Chantal; Van't Klooster, Gerben

2015-08-01

Filgotinib (GLPG0634) is a selective inhibitor of Janus kinase 1 (JAK1) currently in development for the treatment of rheumatoid arthritis and Crohn's disease. While less selective JAK inhibitors have shown long-term efficacy in treating inflammatory conditions, this was accompanied by dose-limiting side effects. Here, we describe the pharmacokinetics of filgotinib and its active metabolite in healthy volunteers and the use of pharmacokinetic-pharmacodynamic modeling and simulation to support dose selection for phase IIB in patients with rheumatoid arthritis. Two trials were conducted in healthy male volunteers. In the first trial, filgotinib was administered as single doses from 10 mg up to multiple daily doses of 200 mg. In the second trial, daily doses of 300 and 450 mg for 10 days were evaluated. Non-compartmental analysis was used to determine individual pharmacokinetic parameters for filgotinib and its metabolite. The overall pharmacodynamic activity for the two moieties was assessed in whole blood using interleukin-6-induced phosphorylation of signal-transducer and activator of transcription 1 as a biomarker for JAK1 activity. These data were used to conduct non-linear mixed-effects modeling to investigate a pharmacokinetic/pharmacodynamic relationship. Modeling and simulation on the basis of early clinical data suggest that the pharmacokinetics of filgotinib are dose proportional up to 200 mg, in agreement with observed data, and support that both filgotinib and its metabolite contribute to its pharmacodynamic effects. Simulation of biomarker response supports that the maximum pharmacodynamic effect is reached at a daily dose of 200 mg filgotinib. Based on these results, a daily dose range up to 200 mg has been selected for phase IIB dose-finding studies in patients with rheumatoid arthritis.

Effects of Different Types of Statins on Lipid Profile: A Perspective on Asians.

PubMed

Meor Anuar Shuhaili, Meor Fairuz Rizal; Samsudin, Intan Nureslyna; Stanslas, Johnson; Hasan, Shariful; Thambiah, Subashini C

2017-04-01

The present review aimed at reviewing the effects of different statins on lipid profile, particularly in Asians. PubMed searches were conducted using the keywords 'statin, effect, and lipid profile' from database inception through March 2016. In this review, 718 articles were retrieved from the primary search. After reviewing the titles, abstracts, and full texts, we found that 59 studies met our inclusion criteria. These also included subsequent reference searches of retrieved articles. CURVES study compared the effect on lipid profile between atorvastatin and other statins. This study demonstrated that low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) were reduced more with atorvastatin compared to simvastatin, pravastatin, lovastatin, and fluvastatin. However, simvastatin provided a greater elevation of high-density lipoprotein cholesterol (HDL-C) compared to atorvastatin. The STELLAR trial was based on dose-to-dose comparisons between atorvastatin and rosuvastatin efficacy in reducing LDL-C. Te present study also revealed that as the doses of rosuvastatin, simvastatin, and pravastatin increased, HDL-C also increased, with rosuvastatin having the greatest effect. However, HDL-C levels decreased as the dose of atorvastatin increased. The DISCOVERY study involving the Asian population revealed that the percentage of patients achieving the European goals for LDL-C and TC at 12 weeks was higher in rosuvastatin group compared to atorvastatin group. The effects of statins on lipid profile are dose dependent. Most studies showed that rosuvastatin has the best effect on lipid profile. Prescribing lower doses of statins in Asians seems necessary.

Effects of Surgery and Proton Therapy on Cerebral White Matter of Craniopharyngioma Patients

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

Uh, Jinsoo, E-mail: jinsoo.uh@stjude.org; Merchant, Thomas E.; Li, Yimei

Purpose: The purpose of this study was to determine radiation dose effect on the structural integrity of cerebral white matter in craniopharyngioma patients receiving surgery and proton therapy. Methods and Materials: Fifty-one patients (2.1-19.3 years of age) with craniopharyngioma underwent surgery and proton therapy in a prospective therapeutic trial. Anatomical magnetic resonance images acquired after surgery but before proton therapy were inspected to identify white matter structures intersected by surgical corridors and catheter tracks. Longitudinal diffusion tensor imaging (DTI) was performed to measure microstructural integrity changes in cerebral white matter. Fractional anisotropy (FA) derived from DTI was statistically analyzed for 51more » atlas-based white matter structures of the brain to determine radiation dose effect. FA in surgery-affected regions in the corpus callosum was compared to that in its intact counterpart to determine whether surgical defects affect radiation dose effect. Results: Surgical defects were seen most frequently in the corpus callosum because of transcallosal resection of tumors and insertion of ventricular or cyst catheters. Longitudinal DTI data indicated reductions in FA 3 months after therapy, which was followed by a recovery in most white matter structures. A greater FA reduction was correlated with a higher radiation dose in 20 white matter structures, indicating a radiation dose effect. The average FA in the surgery-affected regions before proton therapy was smaller (P=.0001) than that in their non–surgery-affected counterparts with more intensified subsequent reduction of FA (P=.0083) after therapy, suggesting that surgery accentuated the radiation dose effect. Conclusions: DTI data suggest that mild radiation dose effects occur in patients with craniopharyngioma receiving surgery and proton therapy. Surgical defects present at the time of proton therapy appear to accentuate the radiation dose effect longitudinally. This study supports consideration of pre-existing surgical defects and their locations in proton therapy planning and studies of treatment effect.« less

Developmental toxicity study of D-tagatose in rats.

PubMed

Kruger, C L; Whittaker, M H; Frankos, V H; Schroeder, R E

1999-04-01

D-tagatose is a low-calorie sweetener that tastes like sucrose. The developmental toxicity of D-tagatose was investigated in Crl:CD(SD)BR rats administered D-tagatose at three dose levels (4000, 12,000, and 20,000 mg/kg body wt/day) via gastric intubation on days 6-15 of gestation. No compound-related toxicity was seen among any of the maternal groups. No treatment-related clinical effects were seen in the maternal animals at the 4000 mg/kg/day dose level. At the mid- and high-dose levels, most maternal animals had unformed or watery stools; this effect was most prominent early in the treatment period (Gestation Days 6-8). This effect was attributed to the osmotic effect of the large amount of D-tagatose given to the animals at these doses. Since D-tagatose is not digested or absorbed to a large extent, most of the sugar passes into the colon where it absorbs water and is fermented by colonic bacteria. Mean weight gain for the low- and mid-dose animals was comparable to the control; however, the high-dose group experienced a mean weight loss over the Gestation Day 6-9 interval. Over the entire treatment interval, however, mean weight gain for the high-dose animals was comparable to control. The decreased weight gain in the high-dose animals during the Gestation Day 6-9 interval was considered to be a direct result of laxation. In addition to the effect of laxation on body weight, reduced food consumption also contributed to the decreased weight gain. In the low-dose animals, no effect on food consumption was seen; however, both mid- and high-dose animals had food consumption values that were statistically significantly lower than the control. Food consumption was lowest during the Gestation Day 6-9 interval, the period when laxation was most prominent. Food consumption rebounded and was statistically significantly higher than the control for the mid- and high-dose animals during the posttreatment interval. Maternal liver weight for the low-dose animals was comparable to the control. However, a statistically significant increase in mean maternal liver weight was noted for the mid-and high-dose animals. Based on a lack of any corresponding histopathology, the increased liver weights were not considered toxicologically significant. There were no adverse effects on reproductive performance noted in any treatment group. No adverse treatment-related fetal effects on fetal weight, sex distribution, liver weight, or external, skeletal, or visceral malformations were noted at any dose level. Copyright 1999 Academic Press.

Ultrasound-guided corticosteroid injection therapy for juvenile idiopathic arthritis: 12-year care experience.

PubMed

Young, Cody M; Shiels, William E; Coley, Brian D; Hogan, Mark J; Murakami, James W; Jones, Karla; Higgins, Gloria C; Rennebohm, Robert M

2012-12-01

Intra-articular corticosteroid injections are a safe and effective treatment for patients with juvenile idiopathic arthritis. The potential scope of care in ultrasound-guided corticosteroid therapy in children and a joint-based corticosteroid dose protocol designed to optimize interdisciplinary care are not found in the current literature. The purpose of this study was to report the spectrum of care, technique and safety of ultrasound-guided corticosteroid injection therapy in patients with juvenile idiopathic arthritis and to propose an age-weight-joint-based corticosteroid dose protocol. A retrospective analysis was performed of 198 patients (ages 21 months to 28 years) referred for treatment of juvenile idiopathic arthritis with corticosteroid therapy. Symptomatic joints and tendon sheaths were treated as prescribed by the referring rheumatologist. An age-weight-joint-based dose protocol was developed and utilized for corticosteroid dose prescription. A total of 1,444 corticosteroid injections (1,340 joints, 104 tendon sheaths) were performed under US guidance. Injection sites included small, medium and large appendicular skeletal joints (upper extremity 497, lower extremity 837) and six temporomandibular joints. For patients with recurrent symptoms, 414 repeat injections were performed, with an average time interval of 17.7 months (range, 0.5-101.5 months) between injections. Complications occurred in 2.6% of injections and included subcutaneous tissue atrophy, skin hypopigmentation, erythema and pruritis. US-guided corticosteroid injection therapy provides dynamic, precise and safe treatment of a broad spectrum of joints and tendon sheaths throughout the entire pediatric musculoskeletal system. An age-weight-joint-based corticosteroid dose protocol is effective and integral to interdisciplinary care of patients with juvenile idiopathic arthritis.

Radiobiology of hypofractionated stereotactic radiotherapy: what are the optimal fractionation schedules?

PubMed Central

Shibamoto, Yuta; Miyakawa, Akifumi; Otsuka, Shinya; Iwata, Hiromitsu

2016-01-01

In hypofractionated stereotactic radiotherapy (SRT), high doses per fraction are usually used and the dose delivery pattern is different from that of conventional radiation. The daily dose is usually given intermittently over a longer time compared with conventional radiotherapy. During prolonged radiation delivery, sublethal damage repair takes place, leading to the decreased effect of radiation. In in vivo tumors, however, this decrease in effect may be counterbalanced by rapid reoxygenation. Another issue related to hypofractionated SRT is the mathematical model for dose evaluation and conversion. The linear–quadratic (LQ) model and biologically effective dose (BED) have been suggested to be incorrect when used for hypofractionation. The LQ model overestimates the effect of high fractional doses of radiation. BED is particularly incorrect when used for tumor responses in vivo, since it does not take reoxygenation into account. Correction of the errors, estimated at 5–20%, associated with the use of BED is necessary when it is used for SRT. High fractional doses have been reported to exhibit effects against tumor vasculature and enhance host immunity, leading to increased antitumor effects. This may be an interesting topic that should be further investigated. Radioresistance of hypoxic tumor cells is more problematic in hypofractionated SRT, so trials of hypoxia-targeted agents are encouraged in the future. In this review, the radiobiological characteristics of hypofractionated SRT are summarized, and based on the considerations, we would like to recommend 60 Gy in eight fractions delivered three times a week for lung tumors larger than 2 cm in diameter. PMID:27006380

SU-E-T-488: An Iso-Dose Curve Based Interactive IMRT Optimization System for Physician-Driven Plan Tuning

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

Shi, F; Tian, Z; Jia, X

Purpose: In treatment plan optimization for Intensity Modulated Radiation Therapy (IMRT), after a plan is initially developed by a dosimetrist, the attending physician evaluates its quality and often would like to improve it. As opposed to having the dosimetrist implement the improvements, it is desirable to have the physician directly and efficiently modify the plan for a more streamlined and effective workflow. In this project, we developed an interactive optimization system for physicians to conveniently and efficiently fine-tune iso-dose curves. Methods: An interactive interface is developed under C++/Qt. The physician first examines iso-dose lines. S/he then picks an iso-dose curvemore » to be improved and drags it to a more desired configuration using a computer mouse or touchpad. Once the mouse is released, a voxel-based optimization engine is launched. The weighting factors corresponding to voxels between the iso-dose lines before and after the dragging are modified. The underlying algorithm then takes these factors as input to re-optimize the plan in near real-time on a GPU platform, yielding a new plan best matching the physician's desire. The re-optimized DVHs and iso-dose curves are then updated for the next iteration of modifications. This process is repeated until a physician satisfactory plan is achieved. Results: We have tested this system for a series of IMRT plans. Results indicate that our system provides the physicians an intuitive and efficient tool to edit the iso-dose curves according to their preference. The input information is used to guide plan re-optimization, which is achieved in near real-time using our GPU-based optimization engine. Typically, a satisfactory plan can be developed by a physician in a few minutes using this tool. Conclusion: With our system, physicians are able to manipulate iso-dose curves according to their preferences. Preliminary results demonstrate the feasibility and effectiveness of this tool.« less

The effect of dose heterogeneity on radiation risk in medical imaging.

PubMed

Samei, Ehsan; Li, Xiang; Chen, Baiyu; Reiman, Robert

2013-06-01

The current estimations of risk associated with medical imaging procedures rely on assessing the organ dose via direct measurements or simulation. The dose to each organ is assumed to be homogeneous. To take into account the differences in radiation sensitivities, the mean organ doses are weighted by a corresponding tissue-weighting coefficients provided by ICRP to calculate the effective dose, which has been used as a surrogate of radiation risk. However, those coefficients were derived under the assumption of a homogeneous dose distribution within each organ. That assumption is significantly violated in most medical-imaging procedures. In helical chest CT, for example, superficial organs (e.g. breasts) demonstrate a heterogeneous dose distribution, whereas organs on the peripheries of the irradiation field (e.g. liver) might possess a discontinuous dose profile. Projection radiography and mammography involve an even higher level of organ dose heterogeneity spanning up to two orders of magnitude. As such, mean dose or point measured dose values do not reflect the maximum energy deposited per unit volume of the organ. In this paper, the magnitude of the dose heterogeneity in both CT and projection X-ray imaging was reported, using Monte Carlo methods. The lung dose demonstrated factors of 1.7 and 2.2 difference between the mean and maximum dose for chest CT and radiography, respectively. The corresponding values for the liver were 1.9 and 3.5. For mammography and breast tomosynthesis, the difference between mean glandular dose and maximum glandular dose was 3.1. Risk models based on the mean dose were found to provide a reasonable reflection of cancer risk. However, for leukaemia, they were found to significantly under-represent the risk when the organ dose distribution is heterogeneous. A systematic study is needed to develop a risk model for heterogeneous dose distributions.

The effect of hypofractionated radiation and magnetic nanoparticle hyperthermia on tumor immunogenicity and overall treatment response

NASA Astrophysics Data System (ADS)

Hoopes, P. Jack; Wagner, Robert J.; Song, Ailin; Osterberg, Bjorn; Gladstone, David J.; Bursey, Alicea A.; Fiering, Steven N.; Giustini, Andrew J.

2017-02-01

It is now known that many tumors develop molecular signals (immune checkpoint modulators) that inhibit an effective tumor immune response. New information also suggest that even well-known cancer treatment modalities such as radiation and hyperthermia generate potentially beneficial immune responses that have been blocked or mitigated by such immune checkpoints, or similar molecules. The cancer therapy challenge is to; a) identify these treatment-based immune signals (proteins, antigens, etc.); b) the treatment doses or regimens that produce them; and c) the mechanisms that block or have the potential to promote them. The goal of this preliminary study, using the B6 mouse - B16 tumor model, clinically relevant radiation doses and fractionation schemes (including those used clinically in hypofractionated radiation therapy), magnetic nanoparticle hyperthermia (mNPH) and sophisticated protein, immune and tumor growth analysis techniques and modulators, is to determine the effect of specific radiation or hyperthermia alone and combined on overall treatment efficacy and immunologic response mechanisms. Preliminary analysis suggests that radiation dose (10 Gy vs. 2 Gy) significantly alters the mechanism of cell death (apoptosis vs. mitosis vs. necrosis) and the resulting immunogenicity. Our hypothesis and data suggest this difference is protein/antigen and immune recognition-based. Similarly, our evidence suggest that radiation doses larger than the conventional 2 Gy dose and specific hyperthermia doses and techniques (including mNP hyperthermia treatment) can be immunologically different, and potentially superior to, the radiation and heat therapy regimens that are typically used in research and clinical practice.

Methadone dosage and its relationship to quality of life, satisfaction, psychopathology, cognitive performance and additional consumption of non-prescribed drugs.

PubMed

Pedrero-Pérez, Eduardo J; MethaQoL, Grupo

2016-06-14

The effectiveness of methadone maintenance treatment is beyond any doubt, but there remains some incertitude about the appropriate and effective dosage and the objectives that should be achieved by this therapy. Some authors maintain that only doses higher than 50-60 mg/day ought to be considered effective, since only these block all the opioid receptors. But others propose the use of doses adjusted to the needs of the patient, based on their recovery process. Quality of life, satisfaction with treatment, psychopathological symptoms, cognitive performance and additional intake of illegal and unprescribed drugs were evaluated in a representative sample of all patients treated with opioid agonists in the Addiction Institute of Madrid (N = 1898, n = 450) and the Junta de Extremadura (N = 100, n = 65). The results revealed a negative relationship between dose and quality of life, psychopathological symptoms and cognitive performance. Satisfaction with treatment, based on doses negotiated together by doctor and patient, was very high, regardless of the dose. To establish hypothetical causal dependencies among the studied variables structural equation modelling was performed. The results reject the need for high dosage if not required by the patient, and highlight the benefits of other psychosocial interventions that lead to recovery, despite the chronification that could imply the use of high doses. Whereas high dosage programmes provide better indicators of social control, the patient's quality of life must be one of the main indicators of a successful treatment, as in any other health problem.

Skeletal dosimetry for external exposure to photons based on µCT images of spongiosa from different bone sites

NASA Astrophysics Data System (ADS)

Kramer, R.; Khoury, H. J.; Vieira, J. W.; Kawrakow, I.

2007-11-01

Micro computed tomography (µCT) images of human spongiosa have recently been used for skeletal dosimetry with respect to external exposure to photon radiation. In this previous investigation, the calculation of equivalent dose to the red bone marrow (RBM) and to the bone surface cells (BSC) was based on five different clusters of micro matrices derived from µCT images of vertebrae, and the BSC equivalent dose for 10 µm thickness of the BSC layer was determined using an extrapolation method. The purpose of this study is to extend the earlier investigation by using µCT images from eight different bone sites and by introducing an algorithm for the direct calculation of the BSC equivalent dose with sub-micro voxel resolution. The results show that for given trabecular bone volume fractions (TBVFs) the whole-body RBM equivalent dose does not depend on bone site-specific properties or imaging parameters. However, this study demonstrates that apart from the TBVF and the BSC layer thickness, the BSC equivalent dose additionally depends on a so-called trabecular bone structure (TBS) effect, i.e. that the contribution of photo-electrons released in trabecular bone to the BSC equivalent dose also depends on the bone site-specific structure of the trabeculae. For a given bone site, the TBS effect is also a function of the thickness of the BSC layer, and it could be shown that this effect would disappear almost completely, should the BSC layer thickness be raised from 10 to 50 µm, according to new radiobiological findings.

Acute toxicity of subcutaneously administered vitamin E isomers delta- and gamma-tocotrienol in mice.

PubMed

Swift, Sibyl N; Pessu, Roli L; Chakraborty, Kushal; Villa, Vilmar; Lombardini, Eric; Ghosh, Sanchita P

2014-01-01

The toxicity of parenterally administered vitamin E isomers, delta-tocotrienol (DT3) and gamma-tocotrienol (GT3), was evaluated in male and female CD2F1 mice. In an acute toxicity study, a single dose of DT3 or GT3 was administered subcutaneously in a dose range of 200 to 800 mg/kg. A mild to moderately severe dermatitis was observed clinically and microscopically in animals at the injection site at doses above 200 mg/kg. The severity of the reaction was reduced when the drug concentration was lowered. Neither drug produced detectable toxic effects in any other tissue at the doses tested. Based on histopathological analysis for both DT3 and GT3, and macroscopic observations of inflammation at the injection site, a dose of 300 mg/kg was selected as the lowest toxic dose in a 30-day toxicity study performed in male mice. At this dose, a mild skin irritation occurred at the injection site that recovered completely by the end of the experimental period. At a dose of 300 mg/kg of DT3 or GT3, no adverse effects were observed in any tissues or organs. © The Author(s) 2014.

Dosimetric Evaluation of Metal Artefact Reduction using Metal Artefact Reduction (MAR) Algorithm and Dual-energy Computed Tomography (CT) Method

NASA Astrophysics Data System (ADS)

Laguda, Edcer Jerecho

Purpose: Computed Tomography (CT) is one of the standard diagnostic imaging modalities for the evaluation of a patient's medical condition. In comparison to other imaging modalities such as Magnetic Resonance Imaging (MRI), CT is a fast acquisition imaging device with higher spatial resolution and higher contrast-to-noise ratio (CNR) for bony structures. CT images are presented through a gray scale of independent values in Hounsfield units (HU). High HU-valued materials represent higher density. High density materials, such as metal, tend to erroneously increase the HU values around it due to reconstruction software limitations. This problem of increased HU values due to metal presence is referred to as metal artefacts. Hip prostheses, dental fillings, aneurysm clips, and spinal clips are a few examples of metal objects that are of clinical relevance. These implants create artefacts such as beam hardening and photon starvation that distort CT images and degrade image quality. This is of great significance because the distortions may cause improper evaluation of images and inaccurate dose calculation in the treatment planning system. Different algorithms are being developed to reduce these artefacts for better image quality for both diagnostic and therapeutic purposes. However, very limited information is available about the effect of artefact correction on dose calculation accuracy. This research study evaluates the dosimetric effect of metal artefact reduction algorithms on severe artefacts on CT images. This study uses Gemstone Spectral Imaging (GSI)-based MAR algorithm, projection-based Metal Artefact Reduction (MAR) algorithm, and the Dual-Energy method. Materials and Methods: The Gemstone Spectral Imaging (GSI)-based and SMART Metal Artefact Reduction (MAR) algorithms are metal artefact reduction protocols embedded in two different CT scanner models by General Electric (GE), and the Dual-Energy Imaging Method was developed at Duke University. All three approaches were applied in this research for dosimetric evaluation on CT images with severe metal artefacts. The first part of the research used a water phantom with four iodine syringes. Two sets of plans, multi-arc plans and single-arc plans, using the Volumetric Modulated Arc therapy (VMAT) technique were designed to avoid or minimize influences from high-density objects. The second part of the research used projection-based MAR Algorithm and the Dual-Energy Method. Calculated Doses (Mean, Minimum, and Maximum Doses) to the planning treatment volume (PTV) were compared and homogeneity index (HI) calculated. Results: (1) Without the GSI-based MAR application, a percent error between mean dose and the absolute dose ranging from 3.4-5.7% per fraction was observed. In contrast, the error was decreased to a range of 0.09-2.3% per fraction with the GSI-based MAR algorithm. There was a percent difference ranging from 1.7-4.2% per fraction between with and without using the GSI-based MAR algorithm. (2) A range of 0.1-3.2% difference was observed for the maximum dose values, 1.5-10.4% for minimum dose difference, and 1.4-1.7% difference on the mean doses. Homogeneity indexes (HI) ranging from 0.068-0.065 for dual-energy method and 0.063-0.141 with projection-based MAR algorithm were also calculated. Conclusion: (1) Percent error without using the GSI-based MAR algorithm may deviate as high as 5.7%. This error invalidates the goal of Radiation Therapy to provide a more precise treatment. Thus, GSI-based MAR algorithm was desirable due to its better dose calculation accuracy. (2) Based on direct numerical observation, there was no apparent deviation between the mean doses of different techniques but deviation was evident on the maximum and minimum doses. The HI for the dual-energy method almost achieved the desirable null values. In conclusion, the Dual-Energy method gave better dose calculation accuracy to the planning treatment volume (PTV) for images with metal artefacts than with or without GE MAR Algorithm.

Locomotor activity and tissue levels following acute ...

EPA Pesticide Factsheets

Pyrethroids produce neurotoxicity that depends, in part, on the chemical structure. Common behavioral effects include locomotor activity changes and specific toxic syndromes (types I and II). In general these neurobehavioral effects correlate well with peak internal dose metrics. Products of cyhalothrin, a type II pyrethroid, include mixtures of isomers (e.g., λ-cyhalothrin) as well as enriched active isomers (e.g., γ-cyhalothrin). We measured acute changes in locomotor activity in adult male rats and directly correlated these changes to peak brain and plasma concentrations of λ- and γ-cyhalothrin using a within-subject design. One-hour locomotor activity studies were conducted 1.5 h after oral gavage dosing, and immediately thereafter plasma and brains were collected for analyzing tissue levels using LC/MS/MS methods. Both isomers produced dose-related decreases in activity counts, and the effective dose range for γ-cyhalothrin was lower than for λ-cyhalothrin. Doses calculated to decrease activity by 50% were 2-fold lower for the γ-isomer (1.29 mg/kg) compared to λ-cyhalothrin (2.65 mg/kg). Salivation, typical of type II pyrethroids, was also observed at lower doses of γ-cyhalothrin. Administered dose correlated well with brain and plasma concentrations, which furthermore showed good correlations with activity changes. Brain and plasma levels were tightly correlated across doses. While γ-cyhalothrin was 2-fold more potent based on administ

Low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors: a phase I/II report.

PubMed

Fan, Hui; Lu, Xuechun; Wang, Xiaohui; Liu, Yang; Guo, Bo; Zhang, Yan; Zhang, Wenying; Nie, Jing; Feng, Kaichao; Chen, Meixia; Zhang, Yajing; Wang, Yao; Shi, Fengxia; Fu, Xiaobing; Zhu, Hongli; Han, Weidong

2014-01-01

Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation modulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose decitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however, they are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of DNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a new treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our trial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort was optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous treatment. We also identified a significant correlation between the PFS to previous treatment and clinical response. The low-dose DAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients with refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifier NCT01799083).

Plasma induced DNA damage: Comparison with the effects of ionizing radiation

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

Lazović, S.; Maletić, D.; Puač, N.

2014-09-22

We use human primary fibroblasts for comparing plasma and gamma rays induced DNA damage. In both cases, DNA strand breaks occur, but of fundamentally different nature. Unlike gamma exposure, contact with plasma predominantly leads to single strand breaks and base-damages, while double strand breaks are mainly consequence of the cell repair mechanisms. Different cell signaling mechanisms are detected confirming this (ataxia telangiectasia mutated - ATM and ataxia telangiectasia and Rad3 related - ATR, respectively). The effective plasma doses can be tuned to match the typical therapeutic doses of 2 Gy. Tailoring the effective dose through plasma power and duration of themore » treatment enables safety precautions mainly by inducing apoptosis and consequently reduced frequency of micronuclei.« less

Convolution-based estimation of organ dose in tube current modulated CT

NASA Astrophysics Data System (ADS)

Tian, Xiaoyu; Segars, W. Paul; Dixon, Robert L.; Samei, Ehsan

2016-05-01

Estimating organ dose for clinical patients requires accurate modeling of the patient anatomy and the dose field of the CT exam. The modeling of patient anatomy can be achieved using a library of representative computational phantoms (Samei et al 2014 Pediatr. Radiol. 44 460-7). The modeling of the dose field can be challenging for CT exams performed with a tube current modulation (TCM) technique. The purpose of this work was to effectively model the dose field for TCM exams using a convolution-based method. A framework was further proposed for prospective and retrospective organ dose estimation in clinical practice. The study included 60 adult patients (age range: 18-70 years, weight range: 60-180 kg). Patient-specific computational phantoms were generated based on patient CT image datasets. A previously validated Monte Carlo simulation program was used to model a clinical CT scanner (SOMATOM Definition Flash, Siemens Healthcare, Forchheim, Germany). A practical strategy was developed to achieve real-time organ dose estimation for a given clinical patient. CTDIvol-normalized organ dose coefficients ({{h}\\text{Organ}} ) under constant tube current were estimated and modeled as a function of patient size. Each clinical patient in the library was optimally matched to another computational phantom to obtain a representation of organ location/distribution. The patient organ distribution was convolved with a dose distribution profile to generate {{≤ft(\\text{CTD}{{\\text{I}}\\text{vol}}\\right)}\\text{organ, \\text{convolution}}} values that quantified the regional dose field for each organ. The organ dose was estimated by multiplying {{≤ft(\\text{CTD}{{\\text{I}}\\text{vol}}\\right)}\\text{organ, \\text{convolution}}} with the organ dose coefficients ({{h}\\text{Organ}} ). To validate the accuracy of this dose estimation technique, the organ dose of the original clinical patient was estimated using Monte Carlo program with TCM profiles explicitly modeled. The discrepancy between the estimated organ dose and dose simulated using TCM Monte Carlo program was quantified. We further compared the convolution-based organ dose estimation method with two other strategies with different approaches of quantifying the irradiation field. The proposed convolution-based estimation method showed good accuracy with the organ dose simulated using the TCM Monte Carlo simulation. The average percentage error (normalized by CTDIvol) was generally within 10% across all organs and modulation profiles, except for organs located in the pelvic and shoulder regions. This study developed an improved method that accurately quantifies the irradiation field under TCM scans. The results suggested that organ dose could be estimated in real-time both prospectively (with the localizer information only) and retrospectively (with acquired CT data).

External dose-rate conversion factors of radionuclides for air submersion, ground surface contamination and water immersion based on the new ICRP dosimetric setting.

PubMed

Yoo, Song Jae; Jang, Han-Ki; Lee, Jai-Ki; Noh, Siwan; Cho, Gyuseong

2013-01-01

For the assessment of external doses due to contaminated environment, the dose-rate conversion factors (DCFs) prescribed in Federal Guidance Report 12 (FGR 12) and FGR 13 have been widely used. Recently, there were significant changes in dosimetric models and parameters, which include the use of the Reference Male and Female Phantoms and the revised tissue weighting factors, as well as the updated decay data of radionuclides. In this study, the DCFs for effective and equivalent doses were calculated for three exposure settings: skyshine, groundshine and water immersion. Doses to the Reference Phantoms were calculated by Monte Carlo simulations with the MCNPX 2.7.0 radiation transport code for 26 mono-energy photons between 0.01 and 10 MeV. The transport calculations were performed for the source volume within the cut-off distances practically contributing to the dose rates, which were determined by a simplified calculation model. For small tissues for which the reduction of variances are difficult, the equivalent dose ratios to a larger tissue (with lower statistical errors) nearby were employed to make the calculation efficient. Empirical response functions relating photon energies, and the organ equivalent doses or the effective doses were then derived by the use of cubic-spline fitting of the resulting doses for 26 energy points. The DCFs for all radionuclides considered important were evaluated by combining the photon emission data of the radionuclide and the empirical response functions. Finally, contributions of accompanied beta particles to the skin equivalent doses and the effective doses were calculated separately and added to the DCFs. For radionuclides considered in this study, the new DCFs for the three exposure settings were within ±10 % when compared with DCFs in FGR 13.

External dose-rate conversion factors of radionuclides for air submersion, ground surface contamination and water immersion based on the new ICRP dosimetric setting

PubMed Central

Yoo, Song Jae; Jang, Han-Ki; Lee, Jai-Ki; Noh, Siwan; Cho, Gyuseong

2013-01-01

For the assessment of external doses due to contaminated environment, the dose-rate conversion factors (DCFs) prescribed in Federal Guidance Report 12 (FGR 12) and FGR 13 have been widely used. Recently, there were significant changes in dosimetric models and parameters, which include the use of the Reference Male and Female Phantoms and the revised tissue weighting factors, as well as the updated decay data of radionuclides. In this study, the DCFs for effective and equivalent doses were calculated for three exposure settings: skyshine, groundshine and water immersion. Doses to the Reference Phantoms were calculated by Monte Carlo simulations with the MCNPX 2.7.0 radiation transport code for 26 mono-energy photons between 0.01 and 10 MeV. The transport calculations were performed for the source volume within the cut-off distances practically contributing to the dose rates, which were determined by a simplified calculation model. For small tissues for which the reduction of variances are difficult, the equivalent dose ratios to a larger tissue (with lower statistical errors) nearby were employed to make the calculation efficient. Empirical response functions relating photon energies, and the organ equivalent doses or the effective doses were then derived by the use of cubic-spline fitting of the resulting doses for 26 energy points. The DCFs for all radionuclides considered important were evaluated by combining the photon emission data of the radionuclide and the empirical response functions. Finally, contributions of accompanied beta particles to the skin equivalent doses and the effective doses were calculated separately and added to the DCFs. For radionuclides considered in this study, the new DCFs for the three exposure settings were within ±10 % when compared with DCFs in FGR 13. PMID:23542764

Dose coefficients in pediatric and adult abdominopelvic CT based on 100 patient models.

PubMed

Tian, Xiaoyu; Li, Xiang; Segars, W Paul; Frush, Donald P; Paulson, Erik K; Samei, Ehsan

2013-12-21

Recent studies have shown the feasibility of estimating patient dose from a CT exam using CTDI(vol)-normalized-organ dose (denoted as h), DLP-normalized-effective dose (denoted as k), and DLP-normalized-risk index (denoted as q). However, previous studies were limited to a small number of phantom models. The purpose of this work was to provide dose coefficients (h, k, and q) across a large number of computational models covering a broad range of patient anatomy, age, size percentile, and gender. The study consisted of 100 patient computer models (age range, 0 to 78 y.o.; weight range, 2-180 kg) including 42 pediatric models (age range, 0 to 16 y.o.; weight range, 2-80 kg) and 58 adult models (age range, 18 to 78 y.o.; weight range, 57-180 kg). Multi-detector array CT scanners from two commercial manufacturers (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare) were included. A previously-validated Monte Carlo program was used to simulate organ dose for each patient model and each scanner, from which h, k, and q were derived. The relationships between h, k, and q and patient characteristics (size, age, and gender) were ascertained. The differences in conversion coefficients across the scanners were further characterized. CTDI(vol)-normalized-organ dose (h) showed an exponential decrease with increasing patient size. For organs within the image coverage, the average differences of h across scanners were less than 15%. That value increased to 29% for organs on the periphery or outside the image coverage, and to 8% for distributed organs, respectively. The DLP-normalized-effective dose (k) decreased exponentially with increasing patient size. For a given gender, the DLP-normalized-risk index (q) showed an exponential decrease with both increasing patient size and patient age. The average differences in k and q across scanners were 8% and 10%, respectively. This study demonstrated that the knowledge of patient information and CTDIvol/DLP values may be used to estimate organ dose, effective dose, and risk index in abdominopelvic CT based on the coefficients derived from a large population of pediatric and adult patients.

Dose coefficients in pediatric and adult abdominopelvic CT based on 100 patient models

NASA Astrophysics Data System (ADS)

Tian, Xiaoyu; Li, Xiang; Segars, W. Paul; Frush, Donald P.; Paulson, Erik K.; Samei, Ehsan

2013-12-01

Recent studies have shown the feasibility of estimating patient dose from a CT exam using CTDIvol-normalized-organ dose (denoted as h), DLP-normalized-effective dose (denoted as k), and DLP-normalized-risk index (denoted as q). However, previous studies were limited to a small number of phantom models. The purpose of this work was to provide dose coefficients (h, k, and q) across a large number of computational models covering a broad range of patient anatomy, age, size percentile, and gender. The study consisted of 100 patient computer models (age range, 0 to 78 y.o.; weight range, 2-180 kg) including 42 pediatric models (age range, 0 to 16 y.o.; weight range, 2-80 kg) and 58 adult models (age range, 18 to 78 y.o.; weight range, 57-180 kg). Multi-detector array CT scanners from two commercial manufacturers (LightSpeed VCT, GE Healthcare; SOMATOM Definition Flash, Siemens Healthcare) were included. A previously-validated Monte Carlo program was used to simulate organ dose for each patient model and each scanner, from which h, k, and q were derived. The relationships between h, k, and q and patient characteristics (size, age, and gender) were ascertained. The differences in conversion coefficients across the scanners were further characterized. CTDIvol-normalized-organ dose (h) showed an exponential decrease with increasing patient size. For organs within the image coverage, the average differences of h across scanners were less than 15%. That value increased to 29% for organs on the periphery or outside the image coverage, and to 8% for distributed organs, respectively. The DLP-normalized-effective dose (k) decreased exponentially with increasing patient size. For a given gender, the DLP-normalized-risk index (q) showed an exponential decrease with both increasing patient size and patient age. The average differences in k and q across scanners were 8% and 10%, respectively. This study demonstrated that the knowledge of patient information and CTDIvol/DLP values may be used to estimate organ dose, effective dose, and risk index in abdominopelvic CT based on the coefficients derived from a large population of pediatric and adult patients.

Out-of-field doses from pediatric craniospinal irradiations using 3D-CRT, IMRT, helical tomotherapy and electron-based therapy

NASA Astrophysics Data System (ADS)

De Saint-Hubert, Marijke; Verellen, Dirk; Poels, Kenneth; Crijns, Wouter; Magliona, Federica; Depuydt, Tom; Vanhavere, Filip; Struelens, Lara

2017-07-01

Medulloblastoma treatment involves irradiation of the entire central nervous system, i.e. craniospinal irradiation (CSI). This is associated with the significant exposure of large volumes of healthy tissue and there is growing concern regarding treatment-associated side effects. The current study compares out-of-field organ doses in children receiving CSI through 3D-conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT), helical tomotherapy (HT) and an electron-based technique, and includes radiation doses resulting from imaging performed during treatment. An extensive phantom study is performed, using an anthropomorphic phantom corresponding to a five year old child, in which organ absorbed doses are measured using thermoluminescent detectors. Additionally, the study evaluates and explores tools for calculating out-of-field patient doses using the treatment planning system (TPS) and analytical models. In our study, 3D-CRT resulted in very high doses to a limited number of organs, while it was able to spare organs such as the lungs and breast when compared to IMRT and HT. Both IMRT and HT spread the dose over more organs and were able to spare the heart, thyroid, bladder, uterus and testes when compared to 3D-CRT. The electron-based technique considerably decreased the out-of-field doses in deep-seated organs but could not avoid nearby out-of-field organs such as the lungs, ribs, adrenals, kidneys and uterus. The daily imaging dose is small compared to the treatment dose burden. The TPS error for out-of-field doses was most pronounced for organs further away from the target; nevertheless, no systematic underestimation was observed for any of the studied TPS systems. Finally, analytical modeling was most optimal for 3D-CRT although the number of organs that could be modeled was limited. To conclude, none of the techniques studied was capable of sparing all organs from out-of-field doses. Nevertheless, the electron-based technique showed the most promise for out-of-field organ dose reduction during CSI when compared to photon techniques.

Radon survey and soil gamma doses in primary schools of Batman, Turkey.

PubMed

Damla, Nevzat; Aldemir, Kamuran

2014-06-01

A survey was conducted to evaluate levels of indoor radon and gamma doses in 42 primary schools located in Batman, southeastern Anatolia, Turkey. Indoor radon measurements were carried out using CR-39 solid-state nuclear track detector-based radon dosimeters. The overall mean annual (222)Rn activity in the surveyed area was found to be 49 Bq m(-3) (equivalent to an annual effective dose of 0.25 mSv). However, in one of the districts (Besiri) the maximum radon value turned out to be 307 Bq m(-3). The estimated annual effective doses are less than the recommended action level (3-10 mSv). It is found that the radon concentration decreases with increasing floor number. The concentrations of natural and artificial radioisotopes were determined using gamma-ray spectroscopy for soil samples collected in close vicinity of the studied schools. The mean gamma activity concentrations in the soil samples were 31, 25, 329 and 12 Bq kg(-1) for (226)Ra, (232)Th, (40)K and (137)Cs, respectively. The radiological parameters such as the absorbed dose rate in air and the annual effective dose equivalent were calculated. These radiological parameters were evaluated and compared with the internationally recommended values.

SU-F-I-38: Patient Organ Specific Dose Assessment in Coronary CT Angiograph Using Voxellaized Volume Dose Index in Monte Carlo Simulation

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

Fallal, Mohammadi Gh.; Riyahi, Alam N.; Graily, Gh.

Purpose: Clinical use of multi detector computed tomography(MDCT) in diagnosis of diseases due to high speed in data acquisition and high spatial resolution is significantly increased. Regarding to the high radiation dose in CT and necessity of patient specific radiation risk assessment, the adoption of new method in the calculation of organ dose is completely required and necessary. In this study by introducing a conversion factor, patient organ dose in thorax region based on CT image data using MC system was calculated. Methods: The geometry of x-ray tube, inherent filter, bow tie filter and collimator were designed using EGSnrc/BEAMnrc MC-systemmore » component modules according to GE-Light-speed 64-slices CT-scanner geometry. CT-scan image of patient thorax as a specific phantom was voxellised with 6.25mm3 in voxel and 64×64×20 matrix size. Dose to thorax organ include esophagus, lung, heart, breast, ribs, muscle, spine, spinal cord with imaging technical condition of prospectively-gated-coronary CT-Angiography(PGT) as a step and shoot method, were calculated. Irradiation of patient specific phantom was performed using a dedicated MC-code as DOSXYZnrc with PGT-irradiation model. The ratio of organ dose value calculated in MC-method to the volume CT dose index(CTDIvol) reported by CT-scanner machine according to PGT radiation technique has been introduced as conversion factor. Results: In PGT method, CTDIvol was 10.6mGy and Organ Dose/CTDIvol conversion factor for esophagus, lung, heart, breast, ribs, muscle, spine and spinal cord were obtained as; 0.96, 1.46, 1.2, 3.28. 6.68. 1.35, 3.41 and 0.93 respectively. Conclusion: The results showed while, underestimation of patient dose was found in dose calculation based on CTDIvol, also dose to breast is higher than the other studies. Therefore, the method in this study can be used to provide the actual patient organ dose in CT imaging based on CTDIvol in order to calculation of real effective dose(ED) based on organ dose. This work has been supported by the research chancellor of tehran university of medical sciences(tums), school of medicine, Tehran, Iran.« less

Systemic effects of low-dose dopamine during administration of cytarabine.

PubMed

Connelly, James; Benani, Dina J; Newman, Matthew; Burton, Bradley; Crow, Jessica; Levis, Mark

2017-09-01

Purpose Low-dose dopamine has been utilized to improve renal blood flow, urine output, and reduce drug-induced nephrotoxicity. The purpose of this study was to assess changes in renal function, cardiovascular adverse events, and neurologic toxicity in patients receiving cytarabine with or without low-dose dopamine. Methods A retrospective, single-center, cohort study of patients receiving cytarabine at 667 mg/m 2 /dose or greater, with or without dopamine at ≤5 mcg/kg/min. Cohorts were based upon initiation or absence of low-dose dopamine; cytarabine only, cytarabine + pre- and day of low-dose dopamine, and cytarabine + post-low-dose dopamine. Renal outcomes (urine output, serum creatinine, and creatinine clearance) were compared with baseline and between cohorts. Safety endpoints (arrhythmias, tachycardia, and neurotoxicity) were compared between cohorts based on low-dose dopamine exposure. Results There was no difference in urine output from baseline in all cohorts. Comparing cytarabine only and pre- and day of low-dose dopamine cohorts, there was no difference in urine output. In those receiving low-dose dopamine, there was no difference in serum creatinine and creatinine clearance from baseline. No arrhythmias were documented during the study period, and there was no difference in the incidence of tachycardia between groups (P = 0.66). Neurotoxicity was reported in three patients who were on low-dose dopamine. Conclusion Though variation existed in individual patients administered low-dose dopamine, the use of low-dose dopamine did not significantly impact renal function in this small sample at a single institution. In addition, low-dose dopamine did not negatively impact cardiovascular function.

Concordance of transcriptional and apical benchmark dose levels for conazole-ind uced liver effects in mice

EPA Science Inventory

The ability to anchor chemical class-based gene expression changes to phenotypic lesions and to describe these changes as a function of dose and time can inform mode of action and improve quantitative risk assessment. Previous research identified a 330-gene cluster commonly resp...

Peginterferon alfa-2b and weight-based or flat-dose ribavirin in chronic hepatitis C patients: a randomized trial.

PubMed

Jacobson, Ira M; Brown, Robert S; Freilich, Bradley; Afdhal, Nezam; Kwo, Paul Y; Santoro, John; Becker, Scott; Wakil, Adil E; Pound, David; Godofsky, Eliot; Strauss, Robert; Bernstein, David; Flamm, Steven; Pauly, Mary Pat; Mukhopadhyay, Pabak; Griffel, Louis H; Brass, Clifford A

2007-10-01

This prospective, multicenter, community-based and academic-based, open-label, investigator-initiated, U.S. study evaluated efficacy and safety of pegylated interferon (PEG-IFN) alfa-2b plus a flat or weight-based dose of ribavirin (RBV) in adults with chronic hepatitis C. Patients (n = 5027) were randomly assigned to receive PEG-IFN alfa-2b 1.5 microg/kg/week plus flat-dose (800 mg/day) or weight-based (800-1400 mg/day) RBV for 48 weeks (patients with genotype 1, 4, 5, or 6) and for 24 or 48 weeks (genotype 2/3 patients). Primary end point was sustained virologic response (undetectable [<125 IU/mL] serum hepatitis C virus RNA at 24-week follow-up). Sustained virologic response, but not end-of-treatment, rates were significantly higher with weight-based than with flat-dose RBV (44.2% versus 40.5%; P = 0.008). Sustained virologic response rates by intention-to-treat analysis were 34.0% and 28.9%, respectively, in genotype 1 patients (P = 0.005) and 31.2% and 26.7%, respectively, in genotype 1 patients with high baseline viral load (P = 0.056). In genotype 2/3 patients, rates were not significantly different (61.8% and 59.5%, respectively) regardless of treatment duration. Besides greater hemoglobin reductions with weight-based RBV, safety profiles were similar across RBV dosing groups, including the 1400-mg/day group. PEG-IFN alfa-2b plus weight-based RBV is more effective than flat-dose RBV, particularly in genotype 1 patients, providing equivalent efficacy across all weight groups. RBV 1400 mg/day is appropriate for patients 105 to 125 kg. For genotype 2/3 patients, 24 weeks of treatment with flat-dose RBV is adequate; no evidence of additional benefit of extending treatment to 48 weeks was demonstrated.

Gamma irradiation induced effects of butyl rubber based damping material

NASA Astrophysics Data System (ADS)

Chen, Hong-Bing; Wang, Pu-Cheng; Liu, Bo; Zhang, Feng-Shun; Ao, Yin-Yong

2018-04-01

The effects of gamma irradiation on the butyl rubber based damping material (BRP) at various doses in nitrogen were investigated in this study. The results show that irradiation leads to radiolysis of BRP, with extractives increasing from 14.9 ± 0.8% of control to 37.2 ± 1.2% of sample irradiated at 350 kGy, while the swelling ratio increasing from 294 ± 3% to 766 ± 4%. The further investigation of the extractives with FTIR shows that the newly generated extractives are organic compounds containing C-H and C˭C bonds, with molecular weight ranging from 26,500 to 46,300. SEM characterization shows smoother surface with holes disappearing with increasing absorbed doses, consistent with "softer" material because of radiolysis. Dynamic mechanical study of BRP show that tan δ first slightly then obviously increases with increasing absorbed dose, while storage modulus slightly decreases. The tensile testing shows that the tensile strength decreases while the elongation at break increases with increasing dose. The positron annihilation lifetime spectroscopy show no obvious relations between free volume parameters and the damping properties, indicating the complicated influencing factors of damping properties.

Effect of gamma radiation on the physico-chemical properties of alginate-based films and beads

NASA Astrophysics Data System (ADS)

Huq, Tanzina; Khan, Avik; Dussault, Dominic; Salmieri, Stephane; Khan, Ruhul A.; Lacroix, Monique

2012-08-01

Alginate solution (3%, w/v) was prepared using deionized water from its powder. Then the solution was exposed to gamma radiation (0.1-25 kGy). The alginate films were prepared by solution casting. It was found that gamma radiation has strong effect on alginate solution. At low doses, mechanical strength of the alginate films improved but after 5 kGy dose, the strength started to decrease. The mechanism of alginate radiolysis in aqueous solution is discussed. Film formation was not possible from alginate solution at doses >5 kGy. The mechanical properties such as puncture strength (PS), puncture deformation (PD), viscoelasticity (Y) coefficient of the un-irradiated films were investigated. The values of PS, PD and Y coefficient of the films were 333 N/mm, 3.20 mm and 27%, respectively. Alginate beads were prepared from 3% alginate solution (w/v) by ionotropic gelation method in 5% CaCl2 solution. The rate of gel swelling improved in irradiated alginate-based beads at low doses (up to 0.5 kGy).

Clinical application of a nomogram based on age, serum FSH and AMH to select the FSH starting dose in IVF/ICSI cycles: a retrospective two-centres study.

PubMed

Papaleo, Enrico; Zaffagnini, Stefano; Munaretto, Maria; Vanni, Valeria Stella; Rebonato, Giorgia; Grisendi, Valentina; Di Paola, Rossana; La Marca, Antonio

2016-12-01

To externally validate a nomogram based on ovarian reserve markers as a tool to optimize the FSH starting dose in IVF/ICSI cycles. A two-centres retrospective study including 398 infertile women undergoing their first IVF/ICSI cycle (June 2013-June 2014). IVF data were retrieved from two independent IVF centres in Italy (San Raffaele Hospital, Centre 1; Verona Hospital, Centre 2). A central lab for the routine measurement of AMH and FSH was used for both centres. All women were treated based on physical and hormonal characteristics according to locally adopted protocols. The nomogram was then retrospectively applied to the patients comparing the calculated starting dose to the one actually given. In Centre 1, 64/131 women (48.8%) had an ovarian response below the target. While 45 of these patients were treated with a maximal FSH starting dose (≥225 IU), n=19/131 (14.5%) were treated with a submaximal dose. The vast majority of them (n=17/19) would have received a higher FSH starting dose by using the nomogram. Seventeen patients (n=17/131) had hyper response and about half of them would have been treated with a reduced FSH starting dose according to the nomogram. In Centre 2, 142/267 patients (53.2%) had an ovarian response below the target. While 136 of these were treated with a maximal FSH starting dose (≥225 IU), n=6/267 were treated with a submaximal dose. The majority of them (n=5/6) would have received a higher FSH starting dose. Thirty-two (n=32/267) patients had hyper response and more than half of them would have been treated with a reduced FSH dose. In both Centres, applying the nomogram would have resulted in more appropriate FSH starting doses compared to the the ones actually given based on clinicians choices. The use of an objective algorithm based on patient's age, serum FSH and AMH levels may thus be an effective advice on the selection of the tailored FSH starting dose. Hence, the use of this easily available nomogram could increase the proportion of patients achieving the optimal ovarian response. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effectiveness of the training material in drug-dose calculation skills.

PubMed

Basak, Tulay; Aslan, Ozlem; Unver, Vesile; Yildiz, Dilek

2016-07-01

The aim of study was to evaluate the effectiveness of the training material based on low-level environmental fidelity simulation in drug-dose calculation skills in senior nursing students. A quasi-experimental design with one group. The sample included senior nursing students attending a nursing school in Turkey in the period December 2012-January 2013. Eighty-two senior nursing students were included in the sample. Data were obtained using a data collection form which was developed by the researchers. A paired-sample t-test was used to compare the pretest and post-test scores. The difference between the mean pretest score and the mean post-test score was statistically significant (P < 0.05). This study revealed that the training material based on low-level environmental fidelity simulation positively impacted accurate drug-dose calculation skills in senior nursing students. © 2016 Japan Academy of Nursing Science.

Single dose treatment of malaria - current status and perspectives.

PubMed

Mischlinger, Johannes; Agnandji, Selidji T; Ramharter, Michael

2016-07-01

Despite increased international efforts for control and ultimate elimination, malaria remains a major health problem. Currently, artemisinin-based combination therapies are the treatment of choice for uncomplicated malaria exhibiting high efficacy in clinical trial settings in sub-Saharan Africa. However, their administration over a three-day period is associated with important problems of treatment adherence resulting in markedly reduced effectiveness of currently recommended antimalarials under real world settings. Antimalarial drug candidates and antimalarial drug combinations currently under advanced clinical development for the indication as single dose antimalarial therapy. Expert commentary: Several new drug candidates and combinations are currently undergoing pivotal proof-of-concept studies or clinical development programmes. The development of a single dose combination therapy would constitute a breakthrough in the control of malaria. Such an innovative treatment approach would simultaneously close the effectiveness gap of current three-day therapies and revolutionize population based interventions in the context of malaria elimination campaigns.

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

PubMed

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

2010-07-01

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

Exposure to cosmic radiation of British Airways flying crew on ultralonghaul routes.

PubMed

Bagshaw, M; Irvine, D; Davies, D M

1996-07-01

British Airways has carried out radiation monitoring in Concorde for more than 20 years and has used a heuristic model based on data quoted by the National Aeronautics and Space Administration (NASA) to model radiation exposure in all longhaul fleets. From these data it has been calculated that no flight deck crew would exceed the control level of 6 mSv/y currently under consideration by regulatory authorities, which is three tenths of the occupational dose limit of 20 mSv/y recommended by the International Commission on Radiological Protection (ICRP). The model suggested that less than 4% of cabin crew based in Tokyo flying only between London and Japan could reach or exceed the 6 mSv/y level, based on a predicted effective dose rate of 7 microSv/h. To validate this calculation a sampling measurement programme was carried out on nine round trips flown by a Boeing 747-400 between London and Tokyo. The radiation field was measured with dosimeters used for routine personal monitoring (thermoluminescence dosimeters (TLDs) and polyallydiglycol carbonate neutron dosimeters). The limitations of the methodology are acknowledged, but the results indicate that the effective dose rate was 6 microSv/h which is consistent with the predicted effective dose rate of 7 microSv/h. This result, which is in accordance with other reported studies indicates that it is unlikely that any of the cabin crew based in Tokyo exceeded the 6 mSv/y level. In accordance with "as low as reasonably achievable" principles British Airways will continue to monitor flying crew routes and hours flown to ensure compliance.

SU-F-T-516: Effects of Inter-Fraction Organ Displacement/deformation On the Delivered Doses to the Heart, Esophagus, and Lungs in Patients Receiving Thoracic Radiotherapy

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

Hammers, J; Matney, J; Kaidar-Person, O

Purpose: To quantitatively assess the effects of inter-fraction changes in organ shape and location on the delivered dose distribution to the organs at risk (OAR) in lung cancer patients. Methods: This study analyzes treatment data of 10 patients, who were treated to 60Gy in 30 fractions. In each fraction a cone beam CT (CBCT) was acquired. Each CBCT was registered with the planning CT using deformable registration tools within MIM Software. The daily setup shifts were used to translate the planned dose distribution on the deformed planning CT. The structures of lungs, esophagus and heart were re-delineated by a physicianmore » on each CBCT. The doses delivered to each OAR, reflecting changes in the position and shape variations, were recomputed. Resultant daily dose volume histograms (DVHs) for OARs were computed and compared to those from the planning CT. Results: Based on the findings of two patients and 24 CBCTs analyzed so far, higher doses are delivered to the lungs and esophagus compared to the treatment plan. The dose differences per fraction between the delivered doses and those in the treatment plan are: for patient 1, lung mean dose = 5.3±1.3cGy and esophagus mean dose = 3.4±3.5cGy. For patient 2, lung mean dose = 12.0±3.9cGy and esophagus mean dose = 34.2±7.5cGy. Regarding the maximum dose to heart, the results varied (−18.9±22.0cGy for patient1 and 53.0±62.2cGy for patient2). Conclusion: The dosimetric effects of inter-fractional anatomical variations could be estimated using deformable image registration and manual organ segmentation for each CBCT. A considerable dose distribution variation between fractions was observed for the OARs. These changes are currently not taken into account while treating the patients and these may explain cases with severe side effects even when the treatment plan looks satisfactory. These results suggest the need for automated daily dose tracking and accumulation.« less

Error measure comparison of currently employed dose-modulation schemes for e-beam proximity effect control

NASA Astrophysics Data System (ADS)

Peckerar, Martin C.; Marrian, Christie R.

1995-05-01

Standard matrix inversion methods of e-beam proximity correction are compared with a variety of pseudoinverse approaches based on gradient descent. It is shown that the gradient descent methods can be modified using 'regularizers' (terms added to the cost function minimized during gradient descent). This modification solves the 'negative dose' problem in a mathematically sound way. Different techniques are contrasted using a weighted error measure approach. It is shown that the regularization approach leads to the highest quality images. In some cases, ignoring negative doses yields results which are worse than employing an uncorrected dose file.

SU-E-T-467: Implementation of Monte Carlo Dose Calculation for a Multileaf Collimator Equipped Robotic Radiotherapy System

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

Li, JS; Fan, J; Ma, C-M

Purpose: To improve the treatment efficiency and capabilities for full-body treatment, a robotic radiosurgery system has equipped with a multileaf collimator (MLC) to extend its accuracy and precision to radiation therapy. To model the MLC and include it in the Monte Carlo patient dose calculation is the goal of this work. Methods: The radiation source and the MLC were carefully modeled to consider the effects of the source size, collimator scattering, leaf transmission and leaf end shape. A source model was built based on the output factors, percentage depth dose curves and lateral dose profiles measured in a water phantom.more » MLC leaf shape, leaf end design and leaf tilt for minimizing the interleaf leakage and their effects on beam fluence and energy spectrum were all considered in the calculation. Transmission/leakage was added to the fluence based on the transmission factors of the leaf and the leaf end. The transmitted photon energy was tuned to consider the beam hardening effects. The calculated results with the Monte Carlo implementation was compared with measurements in homogeneous water phantom and inhomogeneous phantoms with slab lung or bone material for 4 square fields and 9 irregularly shaped fields. Results: The calculated output factors are compared with the measured ones and the difference is within 1% for different field sizes. The calculated dose distributions in the phantoms show good agreement with measurements using diode detector and films. The dose difference is within 2% inside the field and the distance to agreement is within 2mm in the penumbra region. The gamma passing rate is more than 95% with 2%/2mm criteria for all the test cases. Conclusion: Implementation of Monte Carlo dose calculation for a MLC equipped robotic radiosurgery system is completed successfully. The accuracy of Monte Carlo dose calculation with MLC is clinically acceptable. This work was supported by Accuray Inc.« less

SU-E-T-480: Radiobiological Dose Comparison of Single Fraction SRS, Multi-Fraction SRT and Multi-Stage SRS of Large Target Volumes Using the Linear-Quadratic Formula

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

Ding, C; Hrycushko, B; Jiang, S

2014-06-01

Purpose: To compare the radiobiological effect on large tumors and surrounding normal tissues from single fraction SRS, multi-fractionated SRT, and multi-staged SRS treatment. Methods: An anthropomorphic head phantom with a centrally located large volume target (18.2 cm{sup 3}) was scanned using a 16 slice large bore CT simulator. Scans were imported to the Multiplan treatment planning system where a total prescription dose of 20Gy was used for a single, three staged and three fractionated treatment. Cyber Knife treatment plans were inversely optimized for the target volume to achieve at least 95% coverage of the prescription dose. For the multistage plan,more » the target was segmented into three subtargets having similar volume and shape. Staged plans for individual subtargets were generated based on a planning technique where the beam MUs of the original plan on the total target volume are changed by weighting the MUs based on projected beam lengths within each subtarget. Dose matrices for each plan were export in DICOM format and used to calculate equivalent dose distributions in 2Gy fractions using an alpha beta ratio of 10 for the target and 3 for normal tissue. Results: Singe fraction SRS, multi-stage plan and multi-fractionated SRT plans had an average 2Gy dose equivalent to the target of 62.89Gy, 37.91Gy and 33.68Gy, respectively. The normal tissue within 12Gy physical dose region had an average 2Gy dose equivalent of 29.55Gy, 16.08Gy and 13.93Gy, respectively. Conclusion: The single fraction SRS plan had the largest predicted biological effect for the target and the surrounding normal tissue. The multi-stage treatment provided for a more potent biologically effect on target compared to the multi-fraction SRT treatments with less biological normal tissue than single-fraction SRS treatment.« less

Essential oils--their antimicrobial activity against Escherichia coli and effect on intestinal cell viability.

PubMed

Fabian, Dusan; Dusan, Fabian; Sabol, Marián; Marián, Sabol; Domaracká, Katarína; Katarína, Domaracká; Bujnáková, Dobroslava; Dobroslava, Bujnáková

2006-12-01

Essential oils are known to possess antimicrobial activity against a wide spectrum of bacteria. The main objective of this study was to evaluate possible harmful effects of four commonly used essential oils and their major components on intestinal cells. Antimicrobial activity of selected plant extracts against enteroinvasive Escherichia coli was dose dependent. However, doses of essential oils with the ability to completely inhibit bacterial growth (0.05%) showed also relatively high cytotoxicity to intestinal-like cells cultured in vitro. Lower doses of essential oils (0.01%) had only partial antimicrobial activity and their damaging effect on Caco-2 cells was only modest. Cell death assessment based on morphological and viability staining followed by fluorescence microscopy showed that essential oils of cinnamon and clove and their major component eugenol had almost no cytotoxic effect at lower doses. Although essential oil of oregano and its component carvacrol slightly increased the incidence of apoptotic cell death, they showed extensive antimicrobial activity even at lower concentrations. Relatively high cytotoxicity was demonstrated by thyme oil, which increased both apoptotic and necrotic cell death incidence. In contrast, its component thymol showed no cytotoxic effect as well as greatly-reduced ability to inhibit visible growth of the chosen pathogen in the doses used. On the other hand, the addition of all essential oils and their components at lower doses, with the exception of thyme oil, to bacterial suspension significantly reduced the cytotoxic effect of E. coli on Caco-2 cells after 1h culture. In conclusion, it is possible to find appropriate doses of essential oils showing both antimicrobial activity and very low detrimental effect on intestinal cells.

Genetic radiation risks: a neglected topic in the low dose debate

PubMed Central

2016-01-01

Objectives To investigate the accuracy and scientific validity of the current very low risk factor for hereditary diseases in humans following exposures to ionizing radiation adopted by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. The value is based on experiments on mice due to reportedly absent effects in the Japanese atomic bomb (Abomb) survivors. Methods To review the published evidence for heritable effects after ionising radiation exposures particularly, but not restricted to, populations exposed to contamination from the Chernobyl accident and from atmospheric nuclear test fallout. To make a compilation of findings about early deaths, congenital malformations, Down’s syndrome, cancer and other genetic effects observed in humans after the exposure of the parents. To also examine more closely the evidence from the Japanese A-bomb epidemiology and discuss its scientific validity. Results Nearly all types of hereditary defects were found at doses as low as one to 10 mSv. We discuss the clash between the current risk model and these observations on the basis of biological mechanism and assumptions about linear relationships between dose and effect in neonatal and foetal epidemiology. The evidence supports a dose response relationship which is non-linear and is either biphasic or supralinear (hogs-back) and largely either saturates or falls above 10 mSv. Conclusions We conclude that the current risk model for heritable effects of radiation is unsafe. The dose response relationship is non-linear with the greatest effects at the lowest doses. Using Chernobyl data we derive an excess relative risk for all malformations of 1.0 per 10 mSv cumulative dose. The safety of the Japanese A-bomb epidemiology is argued to be both scientifically and philosophically questionable owing to errors in the choice of control groups, omission of internal exposure effects and assumptions about linear dose response. PMID:26791091

Model-based dose calculations for COMS eye plaque brachytherapy using an anatomically realistic eye phantom

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

Lesperance, Marielle; Inglis-Whalen, M.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca

Purpose : To investigate the effects of the composition and geometry of ocular media and tissues surrounding the eye on dose distributions for COMS eye plaque brachytherapy with{sup 125}I, {sup 103}Pd, or {sup 131}Cs seeds, and to investigate doses to ocular structures. Methods : An anatomically and compositionally realistic voxelized eye model with a medial tumor is developed based on a literature review. Mass energy absorption and attenuation coefficients for ocular media are calculated. Radiation transport and dose deposition are simulated using the EGSnrc Monte Carlo user-code BrachyDose for a fully loaded COMS eye plaque within a water phantom andmore » our full eye model for the three radionuclides. A TG-43 simulation with the same seed configuration in a water phantom neglecting the plaque and interseed effects is also performed. The impact on dose distributions of varying tumor position, as well as tumor and surrounding tissue media is investigated. Each simulation and radionuclide is compared using isodose contours, dose volume histograms for the lens and tumor, maximum, minimum, and average doses to structures of interest, and doses to voxels of interest within the eye. Results : Mass energy absorption and attenuation coefficients of the ocular media differ from those of water by as much as 12% within the 20–30 keV photon energy range. For all radionuclides studied, average doses to the tumor and lens regions in the full eye model differ from those for the plaque in water by 8%–10% and 13%–14%, respectively; the average doses to the tumor and lens regions differ between the full eye model and the TG-43 simulation by 2%–17% and 29%–34%, respectively. Replacing the surrounding tissues in the eye model with water increases the maximum and average doses to the lens by 2% and 3%, respectively. Substituting the tumor medium in the eye model for water, soft tissue, or an alternate melanoma composition affects tumor dose compared to the default eye model simulation by up to 16%. In the full eye model simulations, the average dose to the lens is larger by 7%–9% than the dose to the center of the lens, and the maximum dose to the optic nerve is 17%–22% higher than the dose to the optic disk for all radionuclides. In general, when normalized to the same prescription dose at the tumor apex, doses delivered to all structures of interest in the full eye model are lowest for{sup 103}Pd and highest for {sup 131}Cs, except for the tumor where the average dose is highest for {sup 103}Pd and lowest for {sup 131}Cs. Conclusions : The eye is not radiologically water-equivalent, as doses from simulations of the plaque in the full eye model differ considerably from doses for the plaque in a water phantom and from simulated TG-43 calculated doses. This demonstrates the importance of model-based dose calculations for eye plaque brachytherapy, for which accurate elemental compositions of ocular media are necessary.« less

Low-dose CT reconstruction with patch based sparsity and similarity constraints

NASA Astrophysics Data System (ADS)

Xu, Qiong; Mou, Xuanqin

2014-03-01

As the rapid growth of CT based medical application, low-dose CT reconstruction becomes more and more important to human health. Compared with other methods, statistical iterative reconstruction (SIR) usually performs better in lowdose case. However, the reconstructed image quality of SIR highly depends on the prior based regularization due to the insufficient of low-dose data. The frequently-used regularization is developed from pixel based prior, such as the smoothness between adjacent pixels. This kind of pixel based constraint cannot distinguish noise and structures effectively. Recently, patch based methods, such as dictionary learning and non-local means filtering, have outperformed the conventional pixel based methods. Patch is a small area of image, which expresses structural information of image. In this paper, we propose to use patch based constraint to improve the image quality of low-dose CT reconstruction. In the SIR framework, both patch based sparsity and similarity are considered in the regularization term. On one hand, patch based sparsity is addressed by sparse representation and dictionary learning methods, on the other hand, patch based similarity is addressed by non-local means filtering method. We conducted a real data experiment to evaluate the proposed method. The experimental results validate this method can lead to better image with less noise and more detail than other methods in low-count and few-views cases.

Effect of leaded glasses and thyroid shielding on cone beam CT radiation dose in an adult female phantom

PubMed Central

Goren, AD; Prins, RD; Dauer, LT; Quinn, B; Al-Najjar, A; Faber, RD; Patchell, G; Branets, I; Colosi, DC

2013-01-01

Objectives: This study aims to demonstrate the effectiveness of leaded glasses in reducing the lens of eye dose and of lead thyroid collars in reducing the dose to the thyroid gland of an adult female from dental cone beam CT (CBCT). The effect of collimation on the radiation dose in head organs is also examined. Methods: Dose measurements were conducted by placing optically stimulated luminescent dosemeters in an anthropomorphic female phantom. Eye lens dose was measured by placing a dosemeter on the anterior surface of the phantom eye location. All exposures were performed on one commercially available dental CBCT machine, using selected collimation and exposure techniques. Each scan technique was performed without any lead shielding and then repeated with lead shielding in place. To calculate the percent reduction from lead shielding, the dose measured with lead shielding was divided by the dose measured without lead shielding. The percent reduction from collimation was calculated by comparing the dose measured with collimation to the dose measured without collimation. Results: The dose to the internal eye for one of the scans without leaded glasses or thyroid shield was 0.450 cGy and with glasses and thyroid shield was 0.116 cGy (a 74% reduction). The reduction to the lens of the eye was from 0.396 cGy to 0.153 cGy (a 61% reduction). Without glasses or thyroid shield, the thyroid dose was 0.158 cGy; and when both glasses and shield were used, the thyroid dose was reduced to 0.091 cGy (a 42% reduction). Conclusions: Collimation alone reduced the dose to the brain by up to 91%, with a similar reduction in other organs. Based on these data, leaded glasses, thyroid collars and collimation minimize the dose to organs outside the field of view. PMID:23412460

Nurse dose: what's in a concept?

PubMed

Manojlovich, Milisa; Sidani, Souraya

2008-08-01

Many researchers have sought to address the relationship between nursing care and patient outcomes, with inconsistent and contradictory findings. We conducted a concept analysis and concept derivation, basing our work on theoretical and empirical literature, to derive nurse dose as a concept that pulls into a coherent whole disparate variables used in staffing studies. We defined nurse dose as the level of nursing reflected in the purity, amount, frequency, and duration of nursing care needed to produce favorable outcomes. All four parameters of nurse dose used together can facilitate our understanding of how nursing contributes to patient outcomes. Ongoing investigation will help to identify the parameters of nurse dose that have the greatest effect on outcomes. 2008 Wiley Periodicals, Inc

Improved Tumor-Specific Drug Accumulation by Polymer Therapeutics with pH-Sensitive Drug Release Overcomes Chemotherapy Resistance.

PubMed

Heinrich, Anne-Kathrin; Lucas, Henrike; Schindler, Lucie; Chytil, Petr; Etrych, Tomáš; Mäder, Karsten; Mueller, Thomas

2016-05-01

The success of chemotherapy is limited by poor selectivity of active drugs combined with occurrence of tumor resistance. New star-like structured N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer-based drug delivery systems containing doxorubicin attached via a pH-sensitive hydrazone bond were designed and investigated for their ability to overcome chemotherapy resistance. These conjugates combine two strategies to achieve a high drug concentration selectively at the tumor site: (I) high accumulation by passive tumor targeting based on enhanced permeability and retention effect and (II) pH-sensitive site-specific drug release due to an acidic tumor microenvironment. Mice bearing doxorubicin-resistant xenograft tumors were treated with doxorubicin, PBS, poly HPMA (pHPMA) precursor or pHPMA-doxorubicin conjugate at different equivalent doses of 5 mg/kg bodyweight doxorubicin up to a 7-fold total dose using different treatment schedules. Intratumoral drug accumulation was analyzed by fluorescence imaging utilizing intrinsic fluorescence of doxorubicin. Free doxorubicin induced significant toxicity but hardly any tumor-inhibiting effects. Administering at least a 3-fold dose of pHPMA-doxorubicin conjugate was necessary to induce a transient response, whereas doses of about 5- to 6-fold induced strong regressions. Tumors completely disappeared in some cases. The onset of response was differential delayed depending on the tumor model, which could be ascribed to distinct characteristics of the microenvironment. Further fluorescence imaging-based analyses regarding underlying mechanisms of the delayed response revealed a related switch to a more supporting intratumoral microenvironment for effective drug release. In conclusion, the current study demonstrates that the concept of tumor site-restricted high-dose chemotherapy is able to overcome therapy resistance. Mol Cancer Ther; 15(5); 998-1007. ©2016 AACR. ©2016 American Association for Cancer Research.

Quantitative prediction of repaglinide-rifampicin complex drug interactions using dynamic and static mechanistic models: delineating differential CYP3A4 induction and OATP1B1 inhibition potential of rifampicin.

PubMed

Varma, Manthena V S; Lin, Jian; Bi, Yi-An; Rotter, Charles J; Fahmi, Odette A; Lam, Justine L; El-Kattan, Ayman F; Goosen, Theunis C; Lai, Yurong

2013-05-01

Repaglinide is mainly metabolized by cytochrome P450 enzymes CYP2C8 and CYP3A4, and it is also a substrate to a hepatic uptake transporter, organic anion transporting polypeptide (OATP)1B1. The purpose of this study is to predict the dosing time-dependent pharmacokinetic interactions of repaglinide with rifampicin, using mechanistic models. In vitro hepatic transport of repaglinide, characterized using sandwich-cultured human hepatocytes, and intrinsic metabolic parameters were used to build a dynamic whole-body physiologically-based pharmacokinetic (PBPK) model. The PBPK model adequately described repaglinide plasma concentration-time profiles and successfully predicted area under the plasma concentration-time curve ratios of repaglinide (within ± 25% error), dosed (staggered 0-24 hours) after rifampicin treatment when primarily considering induction of CYP3A4 and reversible inhibition of OATP1B1 by rifampicin. Further, a static mechanistic "extended net-effect" model incorporating transport and metabolic disposition parameters of repaglinide and interaction potency of rifampicin was devised. Predictions based on the static model are similar to those observed in the clinic (average error ∼19%) and to those based on the PBPK model. Both the models suggested that the combined effect of increased gut extraction and decreased hepatic uptake caused minimal repaglinide systemic exposure change when repaglinide is dosed simultaneously or 1 hour after the rifampicin dose. On the other hand, isolated induction effect as a result of temporal separation of the two drugs translated to an approximate 5-fold reduction in repaglinide systemic exposure. In conclusion, both dynamic and static mechanistic models are instrumental in delineating the quantitative contribution of transport and metabolism in the dosing time-dependent repaglinide-rifampicin interactions.

Evaluation of the stepwise collimation method for the reduction of the patient dose in full spine radiography

NASA Astrophysics Data System (ADS)

Lee, Boram; Lee, Sunyoung; Yang, Injeong; Yoon, Myeonggeun

2014-05-01

The purpose of this study is to evaluate the dose reduction when using the stepwise collimation method for scoliosis patients undergoing full spine radiography. A Monte Carlo simulation was carried out to acquire dose vs. volume data for organs at risk (OAR) in the human body. While the effective doses in full spine radiography were reduced by 8, 15, 27 and 44% by using four different sizes of the collimation, the doses to the skin were reduced by 31, 44, 55 and 66%, indicating that the reduction of the dose to the skin is higher than that to organs inside the body. Although the reduction rates were low for the gonad, being 9, 14, 18 and 23%, there was more than a 30% reduction in the dose to the heart, suggesting that the dose reduction depends significantly on the location of the OARs in the human body. The reduction rate of the secondary cancer risk based on the excess absolute risk (EAR) varied from 0.6 to 3.4 per 10,000 persons, depending on the size of the collimation. Our results suggest that the stepwise collimation method in full spine radiography can effectively reduce the patient dose and the radiation-induced secondary cancer risk.

Effect of Study Design on Sample Size in Studies Intended to Evaluate Bioequivalence of Inhaled Short-Acting β-Agonist Formulations.

PubMed

Zeng, Yaohui; Singh, Sachinkumar; Wang, Kai; Ahrens, Richard C

2018-04-01

Pharmacodynamic studies that use methacholine challenge to assess bioequivalence of generic and innovator albuterol formulations are generally designed per published Food and Drug Administration guidance, with 3 reference doses and 1 test dose (3-by-1 design). These studies are challenging and expensive to conduct, typically requiring large sample sizes. We proposed 14 modified study designs as alternatives to the Food and Drug Administration-recommended 3-by-1 design, hypothesizing that adding reference and/or test doses would reduce sample size and cost. We used Monte Carlo simulation to estimate sample size. Simulation inputs were selected based on published studies and our own experience with this type of trial. We also estimated effects of these modified study designs on study cost. Most of these altered designs reduced sample size and cost relative to the 3-by-1 design, some decreasing cost by more than 40%. The most effective single study dose to add was 180 μg of test formulation, which resulted in an estimated 30% relative cost reduction. Adding a single test dose of 90 μg was less effective, producing only a 13% cost reduction. Adding a lone reference dose of either 180, 270, or 360 μg yielded little benefit (less than 10% cost reduction), whereas adding 720 μg resulted in a 19% cost reduction. Of the 14 study design modifications we evaluated, the most effective was addition of both a 90-μg test dose and a 720-μg reference dose (42% cost reduction). Combining a 180-μg test dose and a 720-μg reference dose produced an estimated 36% cost reduction. © 2017, The Authors. The Journal of Clinical Pharmacology published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

A single-dose cytomegalovirus-based vaccine encoding tetanus toxin fragment C induces sustained levels of protective tetanus toxin antibodies in mice.

PubMed

Tierney, Rob; Nakai, Toru; Parkins, Christopher J; Caposio, Patrizia; Fairweather, Neil F; Sesardic, Dorothea; Jarvis, Michael A

2012-04-26

The current commercially available vaccine used to prevent tetanus disease following infection with the anaerobic bacterium Clostridium tetani is safe and effective. However, tetanus remains a major source of mortality in developing countries. In 2008, neonatal tetanus was estimated to have caused >59,000 deaths, accounting for 1% of worldwide infant mortality, primarily in poorer nations. The cost of multiple vaccine doses administered by injection necessary to achieve protective levels of anti-tetanus toxoid antibodies is the primary reason for low vaccine coverage. Herein, we show that a novel vaccine strategy using a cytomegalovirus (CMV)-based vaccine platform induces protective levels of anti-tetanus antibodies that are durable (lasting >13 months) in mice following only a single dose. This study demonstrates the ability of a 'single-dose' CMV-based vaccine strategy to induce durable protection, and supports the potential for a tetanus vaccine based on CMV to impact the incidence of tetanus in developing countries. Copyright © 2012 Elsevier Ltd. All rights reserved.

Strategies for Primary Prevention of Coronary Heart Disease Based on Risk Stratification by the ACC/AHA Lipid Guidelines, ATP III Guidelines, Coronary Calcium Scoring, and C-Reactive Protein, and a Global Treat-All Strategy: A Comparative--Effectiveness Modeling Study

PubMed Central

Galper, Benjamin Z.; Wang, Y. Claire; Einstein, Andrew J.

2015-01-01

Background Several approaches have been proposed for risk-stratification and primary prevention of coronary heart disease (CHD), but their comparative and cost-effectiveness is unknown. Methods We constructed a state-transition microsimulation model to compare multiple approaches to the primary prevention of CHD in a simulated cohort of men aged 45–75 and women 55–75. Risk-stratification strategies included the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on the treatment of blood cholesterol, the Adult Treatment Panel (ATP) III guidelines, and approaches based on coronary artery calcium (CAC) scoring and C-reactive protein (CRP). Additionally we assessed a treat-all strategy in which all individuals were prescribed either moderate-dose or high-dose statins and all males received low-dose aspirin. Outcome measures included CHD events, costs, medication-related side effects, radiation-attributable cancers, and quality-adjusted-life-years (QALYs) over a 30-year timeframe. Results Treat-all with high-dose statins dominated all other strategies for both men and women, gaining 15.7 million QALYs, preventing 7.3 million myocardial infarctions, and saving over $238 billion, compared to the status quo, far outweighing its associated adverse events including bleeding, hepatitis, myopathy, and new-onset diabetes. ACC/AHA guidelines were more cost-effective than ATP III guidelines for both men and women despite placing 8.7 million more people on statins. For women at low CHD risk, treat-all with high-dose statins was more likely to cause a statin-related adverse event than to prevent a CHD event. Conclusions Despite leading to a greater proportion of the population placed on statin therapy, the ACC/AHA guidelines are more cost-effective than ATP III. Even so, at generic prices, treating all men and women with statins and all men with low-dose aspirin appears to be more cost-effective than all risk-stratification approaches for the primary prevention of CHD. Especially for low-CHD risk women, decisions on the appropriate primary prevention strategy should be based on shared decision making between patients and healthcare providers. PMID:26422204

Moderators of Intervention Dose Effects on Diet Quality and Physical Activity Changes in a Church-Based, Multicomponent, Lifestyle Study: Delta Body and Soul III

ERIC Educational Resources Information Center

Thomson, J. L.; Zoellner, J. M.; Tussing-Humphreys, L. M.; Goodman, M. H.

2016-01-01

Many community-based lifestyle interventions targeting African Americans have reported positive effects on participants' dietary choices and physical activity habits. However, these effects vary and not all participants will have outcome changes. Moderation analysis can help explain differential effects observed, but are not often reported. Hence,…

SU-E-T-481: Dosimetric Effects of Tissue Heterogeneity in Proton Therapy: Monte Carlo Simulation and Experimental Study Using Animal Tissue Phantoms.

PubMed

Liu, Y; Zheng, Y

2012-06-01

Accurate determination of proton dosimetric effect for tissue heterogeneity is critical in proton therapy. Proton beams have finite range and consequently tissue heterogeneity plays a more critical role in proton therapy. The purpose of this study is to investigate the tissue heterogeneity effect in proton dosimetry based on anatomical-based Monte Carlo simulation using animal tissues. Animal tissues including a pig head and beef bulk were used in this study. Both pig head and beef were scanned using a GE CT scanner with 1.25 mm slice thickness. A treatment plan was created, using the CMS XiO treatment planning system (TPS) with a single proton spread-out-Bragg-peak beam (SOBP). Radiochromic films were placed at the distal falloff region. Image guidance was used to align the phantom before proton beams were delivered according to the treatment plan. The same two CT sets were converted to Monte Carlo simulation model. The Monte Carlo simulated dose calculations with/without tissue omposition were compared to TPS calculations and measurements. Based on the preliminary comparison, at the center of SOBP plane, the Monte Carlo simulation dose without tissue composition agreed generally well with TPS calculation. In the distal falloff region, the dose difference was large, and about 2 mm isodose line shift was observed with the consideration of tissue composition. The detailed comparison of dose distributions between Monte Carlo simulation, TPS calculations and measurements is underway. Accurate proton dose calculations are challenging in proton treatment planning for heterogeneous tissues. Tissue heterogeneity and tissue composition may lead to isodose line shifts up to a few millimeters in the distal falloff region. By simulating detailed particle transport and energy deposition, Monte Carlo simulations provide a verification method in proton dose calculation where inhomogeneous tissues are present. © 2012 American Association of Physicists in Medicine.

[The role of dosed walking in the combination with elements of cognitive training in the comprehensive treatment of the patients presenting with Alzheimer's disease].

PubMed

Zimushkina, N A; Kosareva, P V; Cherkasova, V G

The objective of the present study was to evaluate the effectiveness of dosed physical exercises for the combined treatment of the patients presenting with mild to moderate dementia associated with Alzheimer's disease (AD). The comprehensive examination involved 41 patients (32 women and 9 men) with the confirmed diagnosis of 'probable' AD with stages 1 and 2 of dementia and 17 healthy volunteers comprising the group of comparison. In all the patients, the neurological examination was supplemented by neuropsychological testing. Two treatment modalities were applied, one being conventional therapy with the use of memantine at the average effective dose, the other with the combination of memantine and dosed physical exercises including elements of cognitive training. In the group of patients treated with memantine alone, changes in cognitive performances among the men did not suggest any statistically significant positive trendency whereas the results of estimation in the women based on the clock drawing test (CDT) and the Mini-Mental State Examination (MMSE) scores revealed the significant improvement of cognitive performances. The most pronounced effects were documented in the women who had received combined therapy with the inclusion of dosed physical exercises in the form of walking. The comparison of the results of the treatment with observations of the patients included in the comparison group demonstrated the improvement of frontal cognitive functioning in the patients of both sexes under the influence of the combined treatment which manifested itself as the absence of the statistically significant differences between the results of the evaluation based on the Frontal Assessment Battery (FAB) scale. The prescription of dosed physical exercises with elements of cognitive training to be applied for the treatment of the patients presenting with dementia of different severity associated with Alzheimer's disease makes it possible to optimize the outcome of the conventional medical treatment and thereby to improve the results of scoring assessments of cognitive performances based on the MMSE, FAB, and CDT scales.

Mimicking the effects of spaceflight on bone: Combined effects of disuse and chronic low-dose rate radiation exposure on bone mass in mice.

PubMed

Yu, Kanglun; Doherty, Alison H; Genik, Paula C; Gookin, Sara E; Roteliuk, Danielle M; Wojda, Samantha J; Jiang, Zhi-Sheng; McGee-Lawrence, Meghan E; Weil, Michael M; Donahue, Seth W

2017-11-01

During spaceflight, crewmembers are subjected to biomechanical and biological challenges including microgravity and radiation. In the skeleton, spaceflight leads to bone loss, increasing the risk of fracture. Studies utilizing hindlimb suspension (HLS) as a ground-based model of spaceflight often neglect the concomitant effects of radiation exposure, and even when radiation is accounted for, it is often delivered at a high-dose rate over a very short period of time, which does not faithfully mimic spaceflight conditions. This study was designed to investigate the skeletal effects of low-dose rate gamma irradiation (8.5 cGy gamma radiation per day for 20 days, amounting to a total dose of 1.7 Gy) when administered simultaneously to disuse from HLS. The goal was to determine whether continuous, low-dose rate radiation administered during disuse would exacerbate bone loss in a murine HLS model. Four groups of 16 week old female C57BL/6 mice were studied: weight bearing + no radiation (WB+NR), HLS + NR, WB + radiation exposure (WB+RAD), and HLS+RAD. Surprisingly, although HLS led to cortical and trabecular bone loss, concurrent radiation exposure did not exacerbate these effects. Our results raise the possibility that mechanical unloading has larger effects on the bone loss that occurs during spaceflight than low-dose rate radiation. Copyright © 2017 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

Effect of treatment in fractionated schedules with the combination of x-irradiation and six cytotoxic drugs on the RIF-1 tumor and normal mouse skin

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

Lelieveld, P.; Scoles, M.A.; Brown, J.M.

1985-01-01

RIF-1 tumors, implanted syngeneically in the gastrocnemius muscles of the right hind legs of C3H/Km mice, were treated either with X ray alone, drug alone, or drug and X ray combined. The drugs tested were bleomycin, BCNU, cis-diamminedichloro platinum, adriamycin, cyclophosphamide, and actinomycin-D. All drugs were administered either in the maximum tolerated dose or a dose that causes minimal tumor growth delay. Both drugs and X rays were administered either as a single dose or in five daily fractions. In addition to the single modality controls, seven different schedules of combined modalities were tested. Tumors were measured periodically after treatmentmore » in order that the day at which each tumor reached 4 times its initial cross-sectional area, i.e., its size at the time of treatment, could be determined. The effect of treatment on tumors was based upon excess growth delay (GD), i.e., T400% (treated)-T400% (untreated control). Treatment effects for the same combined modality schedules were also determined for normal skin, using the early skin reaction as an endpoint. Dose effect factors (DEF) were computed for all combined modality schedules and were based upon calculated radiation dose equivalents. We also calculated supra-additivity ratios, SR/sub I/ and SR/sub II/, therapeutic gain factors and adjusted therapeutic gain factors. The only drugs to produce significant supra-additivity with X rays were cis-Pt and cyclo.« less

Low Dose of Doxorubicin Potentiates the Effect of Temozolomide in Glioblastoma Cells.

PubMed

Villodre, Emilly Schlee; Kipper, Franciele Cristina; Silva, Andrew Oliveira; Lenz, Guido; Lopez, Patrícia Luciana da Costa

2018-05-01

Glioblastoma (GBM) is an aggressive brain tumor with temozolomide (TMZ)-based chemotherapy as the main therapeutic strategy. Doxorubicin (DOX) is not used in gliomas due to its low bioavailability in the brain; however, new delivery strategies and low doses may be effective in the long term, especially as part of a drug cocktail. Our aim was to evaluate the chronic effects of low doses of DOX and TMZ in GBM. Human U87-ATCC cells and a primary GBM culture were chronically treated with TMZ (5 μM) and DOX (1 and 10 nM) alone or combined. DOX resulted in a reduction in the number of cells over a period of 35 days and delayed the cell regrowth. In addition, DOX induced cell senescence and reduced tumor sphere formation and the proportion of NANOG- and OCT4-positive cells after 7 days. Low doses of TMZ potentiated the effects of DOX on senescence and sphere formation. This combined response using low doses of DOX may pave the way for its use in glioma therapy, with new technologies to overcome its low blood-brain barrier permeability.

Measurements of long-term external and internal radiation exposure of inhabitants of some villages of the Bryansk region of Russia after the Chernobyl accident.

PubMed

Bernhardsson, C; Zvonova, I; Rääf, C; Mattsson, S

2011-10-15

A Nordic-Soviet programme was initiated in 1990 to evaluate the external and internal radiation exposure of the inhabitants of several villages in the Bryansk region of Russia. This area was one of the number of areas particularly affected by the nuclear accident at the Chernobyl Nuclear Power Plant in 1986. Measurements were carried out yearly until 1998 and after that more irregularly; in 2000, 2006 and 2008 respectively. The effective dose estimates were based on individual thermoluminescent dosemeters and on in vivo measurements of the whole body content of (137)Cs (and (134)Cs during the first years of the programme). The decrease in total effective dose during the almost 2 decade follow-up was due to a continuous decrease in the dominating external exposure and a less decreasing but highly variable exposure from internal irradiation. In 2008, the observed average effective dose (i.e. the sum of external and internal exposure) from Chernobyl (137)Cs to the residents was estimated to be 0.3mSv y(-1). This corresponds to 8% of the estimated annual dose in 1990 and to 1% of the estimated annual dose in 1986. As a mean for the population group and for the period of the present study (2006-2008), the average yearly effective dose from Chernobyl cesium was comparable to the absorbed dose obtained annually from external exposure to cosmic radiation plus internal exposure to naturally occurring radionuclides in the human body. Our data indicate that the effective dose from internal exposure is becoming increasingly important as the body burdens of Chernobyl (137)Cs are decreasing more slowly than the external exposure. However, over the years there have been large individual variations in both the external and internal effective doses, as well as differences between the villages investigated. These variations and differences are presented and discussed in this paper. Copyright © 2011 Elsevier B.V. All rights reserved.

An Adaptive Staggered Dose Design for a Normal Endpoint.

PubMed

Wu, Joseph; Menon, Sandeep; Chang, Mark

2015-01-01

In a clinical trial where several doses are compared to a control, a multi-stage design that combines both the selection of the best dose and the confirmation of this selected dose is desirable. An example is the two-stage drop-the-losers or pick-the-winner design, where inferior doses are dropped after interim analysis. Selection of target dose(s) can be based on ranking of observed effects, hypothesis testing with adjustment for multiplicity, or other criteria at interim stages. A number of methods have been proposed and have made significant gains in trial efficiency. However, many of these designs started off with all doses with equal allocation and did not consider prioritizing the doses using existing dose-response information. We propose an adaptive staggered dose procedure that allows explicit prioritization of doses and applies error spending scheme that favors doses with assumed better responses. This design starts off with only a subset of the doses and adaptively adds new doses depending on interim results. Using simulation, we have shown that this design performs better in terms of increased statistical power than the drop-the-losers design given strong prior information of dose response.

Cannabinoids induce apathetic and impulsive patterns of choice through CB1 receptors and TRPV1 channels.

PubMed

Fatahi, Zahra; Reisi, Zahra; Rainer, Gregor; Haghparast, Abbas; Khani, Abbas

2018-05-01

Despite evidence from psychiatry and psychology clinics pointing to altered cognition and decision making following the consumption of cannabis, the effects of cannabis derivatives are still under dispute and the mechanisms of cannabinoid effects on cognition are not known. In this study, we used effort-based and delay-based decision tasks and showed that ACEA, a potent cannabinoid agonist induced apathetic and impulsive patterns of choice in rats in a dose-dependent manner when locally injected into the anterior cingulate cortex (ACC) and orbitofrontal cortex (OFC), respectively. Pre-treatment with AM251, a selective cannabinoid type 1 (CB1) receptor antagonist, reversed ACEA-induced impulsive and apathetic patterns of choice in doses higher than a minimally effective dose. Unlike CB1 receptor antagonist, pretreatment with capsazepine, a transient receptor potential vanilloid type 1 (TRPV1) channel antagonist, was effective only at an intermediary dose. Furthermore, capsazepine per se induced impulsivity and apathy at a high dose suggesting a basal tonic activation of TRPV1 channels that exist in the ACC and OFC to support cost-benefit decision making and to help avoid apathetic and impulsive patterns of decision making. Taken together, unlike previous reports supporting opposing roles for the CB1 receptors and TRPV1 channels in anxiety and panic behavior, our findings demonstrate a different sort of interaction between endocannabinoid and endovanilloid systems and suggest that both systems contribute to the cognitive disrupting effects of cannabinoids. Given prevalent occurrence of apathy and particularly impulsivity in psychiatric disorders, these results have significant implications for pharmacotherapy research targeting these receptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

Promoting toddlers' positive social-emotional outcomes in low-income families: a play-based experimental study.

PubMed

Kochanska, Grazyna; Kim, Sanghag; Boldt, Lea J; Nordling, Jamie Koenig

2013-01-01

This multimethod study of mothers and toddlers (a) examined the effectiveness of a play-based intervention (child-oriented play vs. play-as-usual) on children's cooperation with their mothers and socioemotional competence; (b) introduced a robust new measure of maternal engagement in the intervention, reflected in the dose of child-oriented play the mother delivered to the child; and (c) examined ecological factors that predicted maternal engagement, and the effect of engagement on the outcomes. Low-income mothers (N = 186, 11% Latino, 27% minority) were randomized into child-oriented play group or play-as-usual group, participated in 8 play sessions, and played daily with their children for 10 weeks. Microscopic coding of mothers' behavior in play sessions assessed the dose of child-oriented play delivered to children; mothers' diaries assessed time in daily play. Children's cooperation with maternal control, observed in the laboratory, and mother-rated competence were measured before randomization (Pretest), after play sessions (Posttest 1), and 6 months later (Posttest 2). Children in both groups made significant gains in both outcomes. The gains in cooperation appeared longer lasting in child-oriented play group. Both groups made significantly greater gains than a "historical community control" group, an unrelated longitudinal study without any intervention. Structural equation analyses revealed that married mothers and those with fewer children delivered higher doses of child-oriented play, and those doses predicted children's higher cooperation and competence, with the effects of earlier scores covaried. The dose of time spent in daily play had no effect. Child-oriented play may be a promising, effective, and inexpensive means of promoting toddlers' positive development.

Promoting Toddlers’ Positive Social-Emotional Outcomes in Low-Income Families: A Play-Based Experimental Study

PubMed Central

Kochanska, Grazyna; Kim, Sanghag; Boldt, Lea J.; Nordling, Jamie Koenig

2013-01-01

Objectives This multi-method study of mothers and toddlers (a) examined the effectiveness of a play-based intervention (child-oriented play versus play-as-usual) on children’s cooperation with their mothers and socioemotional competence, (b) introduced a robust new measure of maternal engagement in the intervention, reflected in the dose of child-oriented play the mother delivered to the child, (c) examined ecological factors that predicted maternal engagement, and the effect of engagement on the outcomes. Methods Low-income mothers (N=186, 11% Latino, 27% minority) were randomized into Child-Oriented Play group or Play-as-Usual group, and participated in 8 play sessions and played daily with their children for 10 weeks. Microscopic coding of mothers’ behavior in play sessions assessed the dose of child-oriented play delivered to children; mothers’ diaries assessed time in daily play. Children’s cooperation with maternal control, observed in the laboratory, and mother-rated competence were measured before randomization (Pretest), after play sessions (Posttest 1), and 6 months later (Posttest 2). Results Children in both groups made significant gains in both outcomes. The gains in cooperation appeared longer lasting in Child-Oriented Play group. Both groups made significantly greater gains than a “historical community control” group, an unrelated longitudinal study without any intervention. Structural Equation Analyses revealed that married mothers, and those with fewer children delivered higher doses of child-oriented play, and those doses predicted children’s higher cooperation and competence, with the effects of earlier scores covaried. The dose of time spent in daily play had no effect. Conclusion Child-oriented play may be a promising, effective, and inexpensive means of promoting toddlers’ positive development. PMID:23557253

A generic biokinetic model for noble gases with application to radon

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

Leggett, Richard Wayne; Marsh, James; Gregoratto, Demetrio

The International Commission for Radiological Protection (ICRP) currently uses a dose conversion coefficient to calculate effective dose per unit exposure to radon and its progeny. The coefficient is derived by dividing the detriment associated with unit exposure to radon, as estimated from epidemiological studies, by the detriment per unit effective dose, as estimated mainly from atomic bomb survivor data and animal studies. In a recent statement the ICRP indicated that future guidance on exposure to radon and its progeny will be developed in the same way as guidance for any other radionuclide. That is, intake of radon and progeny willmore » be limited on the basis of effective dose coefficients derived from biokinetic and dosimetric models. This paper proposes a biokinetic model for systemic (absorbed) radon for use in the calculation of dose coefficients for inhaled or ingested radon. The model is based largely on physical laws governing transfer of a non-reactive and soluble gas between materials. Model predictions are shown to be consistent with results of controlled studies of the fate of internally deposited radon in human subjects.« less

Modeling physiological resistance in bacterial biofilms.

PubMed

Cogan, N G; Cortez, Ricardo; Fauci, Lisa

2005-07-01

A mathematical model of the action of antimicrobial agents on bacterial biofilms is presented. The model includes the fluid dynamics in and around the biofilm, advective and diffusive transport of two chemical constituents and the mechanism of physiological resistance. Although the mathematical model applies in three dimensions, we present two-dimensional simulations for arbitrary biofilm domains and various dosing strategies. The model allows the prediction of the spatial evolution of bacterial population and chemical constituents as well as different dosing strategies based on the fluid motion. We find that the interaction between the nutrient and the antimicrobial agent can reproduce survival curves which are comparable to other model predictions as well as experimental results. The model predicts that exposing the biofilm to low concentration doses of antimicrobial agent for longer time is more effective than short time dosing with high antimicrobial agent concentration. The effects of flow reversal and the roughness of the fluid/biofilm are also investigated. We find that reversing the flow increases the effectiveness of dosing. In addition, we show that overall survival decreases with increasing surface roughness.

Oral toxicity of 3-nitro-1,2,4-triazol-5-one in rats.

PubMed

Crouse, Lee C B; Lent, Emily May; Leach, Glenn J

2015-01-01

3-Nitro-1,2,4-triazol-5-one (NTO), an insensitive explosive, was evaluated to assess potential environmental and human health effects. A 14-day oral toxicity study in Sprague-Dawley rats was conducted with NTO in polyethylene glycol -200 by gavage at doses of 0, 250, 500, 1000, 1500, or 2000 mg/kg-d. Body mass and food consumption decreased in males (2000 mg/kg-d), and testes mass was reduced at doses of 500 mg/kg-d and greater. Based on the findings in the 14-day study, a 90-day study was conducted at doses of 0, 30, 100, 315, or 1000 mg/kg-d NTO. There was no effect on food consumption, body mass, or neurobehavioral parameters. Males in the 315 and 1000 mg/kg-d groups had reduced testes mass with associated tubular degeneration and atrophy. The testicular effects were the most sensitive adverse effect and were used to derive a benchmark dose (BMD) of 70 mg/kg-d with a 10% effect level (BMDL10) of 40 mg/kg-d. © The Author(s) 2015.

TU-G-BRA-04: Changes in Regional Lung Function Measured by 4D-CT Ventilation Imaging for Thoracic Radiotherapy

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

Nakajima, Y; Kadoya, N; Kabus, S

Purpose: To test the hypothesis: 4D-CT ventilation imaging can show the known effects of radiotherapy on lung function: (1) radiation-induced ventilation reductions, and (2) ventilation increases caused by tumor regression. Methods: Repeat 4D-CT scans (pre-, mid- and/or post-treatment) were acquired prospectively for 11 thoracic cancer patients in an IRB-approved clinical trial. A ventilation image for each time point was created using deformable image registration and the Hounsfield unit (HU)-based or Jacobian-based metric. The 11 patients were divided into two subgroups based on tumor volume reduction using a threshold of 5 cm{sup 3}. To quantify radiation-induced ventilation reduction, six patients whomore » showed a small tumor volume reduction (<5 cm{sup 3}) were analyzed for dose-response relationships. To investigate ventilation increase caused by tumor regression, two of the other five patients were analyzed to compare ventilation changes in the lung lobes affected and unaffected by the tumor. The remaining three patients were excluded because there were no unaffected lobes. Results: Dose-dependent reductions of HU-based ventilation were observed in a majority of the patient-specific dose-response curves and in the population-based dose-response curve, whereas no clear relationship was seen for Jacobian-based ventilation. The post-treatment population-based dose-response curve of HU-based ventilation demonstrated the average ventilation reductions of 20.9±7.0% at 35–40 Gy (equivalent dose in 2-Gy fractions, EQD2), and 40.6±22.9% at 75–80 Gy EQD2. Remarkable ventilation increases in the affected lobes were observed for the two patients who showed an average tumor volume reduction of 37.1 cm{sup 3} and re-opening airways. The mid-treatment increase in HU-based ventilation of patient 3 was 100.4% in the affected lobes, which was considerably greater than 7.8% in the unaffected lobes. Conclusion: This study has demonstrated that 4D-CT ventilation imaging shows the known effects of radiotherapy on lung function: radiation-induced ventilation reduction and ventilation increase caused by tumor regression, providing validation for 4D-CT ventilation imaging. This study was supported in part by a National Lung Cancer Partnership Young Investigator Research grant.« less

DEVELOPMENT OF A SET OF MESH-BASED AND AGE-DEPENDENT CHINESE PHANTOMS AND APPLICATION FOR CT DOSE CALCULATIONS.

PubMed

Pi, Yifei; Liu, Tianyu; Xu, X George

2018-06-01

Phantoms for organ dose calculations are essential in radiation protection dosimetry. This article describes the development of a set of mesh-based and age-dependent phantoms for Chinese populations using reference data recommended by the Chinese government and by the International Atomic Energy Agency (IAEA). Existing mesh-based RPI adult male (RPI-AM) and RPI adult female (RPI-AF) phantoms were deformed to form new phantoms according to anatomical data for the height and weight of Chinese individuals of 5 years old male, 5 years old female, 10 years old male, 10 years old female,15 years old male, 15 years old female, adult male and adult female-named USTC-5 M, USTC-5F, USTC-10M, USTC-10F, USTC-15M, USTC-15F, USTC-AM and USTC-AF, respectively. Following procedures to ensure the accuracy, more than 120 organs/tissues in each model were adjusted to match the Chinese reference parameters and the mass errors were within 0.5%. To demonstrate the usefulness, these new set of phantoms were combined with a fully validated model of the GE LightSpeed Pro 16 multi-detector computed tomography (MDCT) scanner and the GPU-based ARCHER Monte Carlo code to compute organ doses from CT examinations. Organ doses for adult models were then compared with the data of RPI-AM and RPI-AF under the same conditions. The absorbed doses and the effective doses of RPI phantoms are found to be lower than these of the USTC adult phantoms whose body sizes are smaller. Comparisons for the doses among different ages and genders were also made. It was found that teenagers receive more radiation doses than adults do. Such Chinese-specific phantoms are clearly better suited in organ dose studies for the Chinese individuals than phantoms designed for western populations. As already demonstrated, data derived from age-specific Chinese phantoms can help CT operators and designers to optimize image quality and doses.

Assessment of intake and internal dose from iodine-131 for exposed workers handling radiopharmaceutical products.

PubMed

Bitar, A; Maghrabi, M; Doubal, A W

2013-12-01

Two methods for determination of internal dose due to (131)I intake during the preparation and handling of iodine radiopharmaceutical products have been compared. The first method was based on the measurement of (131)I in 24-hour urine samples while the second method was based on the measurement in vivo of (131)I in thyroid. The results have shown that urine analysis method can be used as a screening test but not for internal dose assessment of exposed workers. Thyroid monitoring method was found to be more reliable and accurate method for assessing internal dose from (131)I intake. In addition, the assessed internal dose showed that the annual internal effective dose for some workers was below 1 mSv with no risk classification, whereas the results of other group of workers were between 1 and 6 mSv with low risk classification. Only one worker reached 7.66 mSv with high risk classification; and this worker must be monitored individually. © 2013 Elsevier Ltd. All rights reserved.

Comparison of Cognitive Performance Tests for Promethazine Pharmacodynamics in Human Subjects

NASA Technical Reports Server (NTRS)

Vaksman, Z.; Boyd, J. L.; Wang, Z.; Putcha, L.

2005-01-01

The objective of this study is to compare cognitive function tests, Automated Neurological Assessment Metrics (ANAM) based Readiness Evaluation System (ARES(Registered TradeMark)) on a Palm Pilot and Windows based Spaceflight Cognitive Assessment Tool (WinSCAT(Registered TradeMark)) on a personal computer (PC) to assess performance effects of promethazine (PMZ) after administration to human subjects. In a randomized placebo-controlled cross-over design, subjects received 12.5, 25, and 50 mg intramuscular (IM) PMZ or a placebo and completed 14 sessions with WinSCAT(Registered TradeMark) (v. 1.26) and ARES(Registered TradeMark) (v. 1.27) consecutively for 72 h post dose. Maximum plasma concentrations (4.25, 6.25 and 13.33 ng/ml) were linear with dose and were achieved by 0.75, 8, and 24 h after dosing for the three doses, respectively. No significant differences in cognitive function after PMZ dosing were detected using WinSCAT(Registered TradeMark), however, tests from ARES(Registered TradeMark) demonstrated concentration dependent decrements in reaction time associated with PMZ dose.

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

PubMed

Julien, Elizabeth; Boobis, Alan R; Olin, Stephen S

2009-09-01

The ILSI Research Foundation convened a cross-disciplinary working group to examine current approaches for assessing dose-response and identifying safe levels of intake or exposure for four categories of bioactive agents-food allergens, nutrients, pathogenic microorganisms, and environmental chemicals. This effort generated a common analytical framework-the Key Events Dose-Response Framework (KEDRF)-for systematically examining key events that occur between the initial dose of a bioactive agent and the effect of concern. Individual key events are considered with regard to factors that influence the dose-response relationship and factors that underlie variability in that relationship. This approach illuminates the connection between the processes occurring at the level of fundamental biology and the outcomes observed at the individual and population levels. Thus, it promotes an evidence-based approach for using mechanistic data to reduce reliance on default assumptions, to quantify variability, and to better characterize biological thresholds. This paper provides an overview of the KEDRF and introduces a series of four companion papers that illustrate initial application of the approach to a range of bioactive agents.

Adulticidal Susceptibility Evaluation of Aedes albopictus Using New Diagnostic Doses in Penang Island, Malaysia.

PubMed

Rahim, Junaid; Ahmad, Abu H; Ahmad, Hamdan; Ishak, Intan H; Rus, Adanan Che; Maimusa, Hamisu A

2017-09-01

Insecticide-based vector control approaches are facing challenges due to the development of resistance in vector mosquitoes. Therefore, a proper resistance surveillance program using baseline lethal concentrations is crucial for resistance management strategies. Currently, the World Health Organization's (WHO) diagnostic doses established for Aedes aegypti and Anopheles species are being used to study the resistance status of Aedes albopictus. In this study, we established the diagnostic doses for permethrin, deltamethrin, and malathion using a known susceptible reference strain. Five field-collected populations were screened against these doses, following the WHO protocol. This study established the diagnostic dose of malathion at 2.4%, permethrin at 0.95%, and deltamethrin at 0.28%, which differ from the WHO doses for Aedes aegypti and Anopheles spp. Among the insecticides tested on the 5 wild populations, only deltamethrin showed high effectiveness. Different susceptibility and resistance patterns were observed with permethrin, malathion, and dichloro-diphenyl-trichloroethane (DDT) at 4%. This study may assist the health authorities to improve future chemical-based vector control operations in dengue-endemic areas.

NOTE: Investigating the potential of polymer gel dosimetry for interventional radiology: first results

NASA Astrophysics Data System (ADS)

Antoniou, P. E.; Bousbouras, P.; Sandaltzopoulos, R.; Kaldoudi, E.

2008-04-01

Complex interventional radiology (IR) procedures contribute an increasing percentage of the overall medical radiation exposure of the population making accurate dosimetry a challenge. Magnetic resonance (MR) based polymer gel dosimetry has been widely employed in complex dosimetric problems in radiotherapy. The aim of this note is to investigate the feasibility of normoxic gel dosimetry in IR. Dose response, energy dependence and dose rate dependence were investigated in irradiation set-ups relevant to IR for a particular normoxic gel, based on methacrylic acid (MAA) as the monomer and including tetrakis-hydroxy-methyl-phosphonium chloride (THPC) as antioxidant. The gel presents a linear dose response beyond a 25 cGy threshold. No significant energy dependence was observed in the useful range of interventional radiology (80-110 kVp). A linear correlation between the gel response and dose rate was observed in the range of dose rates relevant to IR (5-8 cGy min-1). These results demonstrate a reduction of gel sensitivity at very low dose rate levels. A possible explanation of this effect is suggested.

Renal Drug Dosing

PubMed Central

Vogel, Erin A.; Billups, Sarah J.; Herner, Sheryl J.

2016-01-01

Summary Objective The purpose of this study was to compare the effectiveness of an outpatient renal dose adjustment alert via a computerized provider order entry (CPOE) clinical decision support system (CDSS) versus a CDSS with alerts made to dispensing pharmacists. Methods This was a retrospective analysis of patients with renal impairment and 30 medications that are contraindicated or require dose-adjustment in such patients. The primary outcome was the rate of renal dosing errors for study medications that were dispensed between August and December 2013, when a pharmacist-based CDSS was in place, versus August through December 2014, when a prescriber-based CDSS was in place. A dosing error was defined as a prescription for one of the study medications dispensed to a patient where the medication was contraindicated or improperly dosed based on the patient’s renal function. The denominator was all prescriptions for the study medications dispensed during each respective study period. Results During the pharmacist- and prescriber-based CDSS study periods, 49,054 and 50,678 prescriptions, respectively, were dispensed for one of the included medications. Of these, 878 (1.8%) and 758 (1.5%) prescriptions were dispensed to patients with renal impairment in the respective study periods. Patients in each group were similar with respect to age, sex, and renal function stage. Overall, the five-month error rate was 0.38%. Error rates were similar between the two groups: 0.36% and 0.40% in the pharmacist- and prescriber-based CDSS, respectively (p=0.523). The medication with the highest error rate was dofetilide (0.51% overall) while the medications with the lowest error rate were dabigatran, fondaparinux, and spironolactone (0.00% overall). Conclusions Prescriber- and pharmacist-based CDSS provided comparable, low rates of potential medication errors. Future studies should be undertaken to examine patient benefits of the prescriber-based CDSS. PMID:27466041

Threshold-driven optimization for reference-based auto-planning

NASA Astrophysics Data System (ADS)

Long, Troy; Chen, Mingli; Jiang, Steve; Lu, Weiguo

2018-02-01

We study threshold-driven optimization methodology for automatically generating a treatment plan that is motivated by a reference DVH for IMRT treatment planning. We present a framework for threshold-driven optimization for reference-based auto-planning (TORA). Commonly used voxel-based quadratic penalties have two components for penalizing under- and over-dosing of voxels: a reference dose threshold and associated penalty weight. Conventional manual- and auto-planning using such a function involves iteratively updating the preference weights while keeping the thresholds constant, an unintuitive and often inconsistent method for planning toward some reference DVH. However, driving a dose distribution by threshold values instead of preference weights can achieve similar plans with less computational effort. The proposed methodology spatially assigns reference DVH information to threshold values, and iteratively improves the quality of that assignment. The methodology effectively handles both sub-optimal and infeasible DVHs. TORA was applied to a prostate case and a liver case as a proof-of-concept. Reference DVHs were generated using a conventional voxel-based objective, then altered to be either infeasible or easy-to-achieve. TORA was able to closely recreate reference DVHs in 5-15 iterations of solving a simple convex sub-problem. TORA has the potential to be effective for auto-planning based on reference DVHs. As dose prediction and knowledge-based planning becomes more prevalent in the clinical setting, incorporating such data into the treatment planning model in a clear, efficient way will be crucial for automated planning. A threshold-focused objective tuning should be explored over conventional methods of updating preference weights for DVH-guided treatment planning.

Electron dose distributions caused by the contact-type metallic eye shield: Studies using Monte Carlo and pencil beam algorithms

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

Kang, Sei-Kwon; Yoon, Jai-Woong; Hwang, Taejin

A metallic contact eye shield has sometimes been used for eyelid treatment, but dose distribution has never been reported for a patient case. This study aimed to show the shield-incorporated CT-based dose distribution using the Pinnacle system and Monte Carlo (MC) calculation for 3 patient cases. For the artifact-free CT scan, an acrylic shield machined as the same size as that of the tungsten shield was used. For the MC calculation, BEAMnrc and DOSXYZnrc were used for the 6-MeV electron beam of the Varian 21EX, in which information for the tungsten, stainless steel, and aluminum material for the eye shieldmore » was used. The same plan was generated on the Pinnacle system and both were compared. The use of the acrylic shield produced clear CT images, enabling delineation of the regions of interest, and yielded CT-based dose calculation for the metallic shield. Both the MC and the Pinnacle systems showed a similar dose distribution downstream of the eye shield, reflecting the blocking effect of the metallic eye shield. The major difference between the MC and the Pinnacle results was the target eyelid dose upstream of the shield such that the Pinnacle system underestimated the dose by 19 to 28% and 11 to 18% for the maximum and the mean doses, respectively. The pattern of dose difference between the MC and the Pinnacle systems was similar to that in the previous phantom study. In conclusion, the metallic eye shield was successfully incorporated into the CT-based planning, and the accurate dose calculation requires MC simulation.« less

Evaluation of hybrid inverse planning and optimization (HIPO) algorithm for optimization in real-time, high-dose-rate (HDR) brachytherapy for prostate.

PubMed

Pokharel, Shyam; Rana, Suresh; Blikenstaff, Joseph; Sadeghi, Amir; Prestidge, Bradley

2013-07-08

The purpose of this study is to investigate the effectiveness of the HIPO planning and optimization algorithm for real-time prostate HDR brachytherapy. This study consists of 20 patients who underwent ultrasound-based real-time HDR brachytherapy of the prostate using the treatment planning system called Oncentra Prostate (SWIFT version 3.0). The treatment plans for all patients were optimized using inverse dose-volume histogram-based optimization followed by graphical optimization (GRO) in real time. The GRO is manual manipulation of isodose lines slice by slice. The quality of the plan heavily depends on planner expertise and experience. The data for all patients were retrieved later, and treatment plans were created and optimized using HIPO algorithm with the same set of dose constraints, number of catheters, and set of contours as in the real-time optimization algorithm. The HIPO algorithm is a hybrid because it combines both stochastic and deterministic algorithms. The stochastic algorithm, called simulated annealing, searches the optimal catheter distributions for a given set of dose objectives. The deterministic algorithm, called dose-volume histogram-based optimization (DVHO), optimizes three-dimensional dose distribution quickly by moving straight downhill once it is in the advantageous region of the search space given by the stochastic algorithm. The PTV receiving 100% of the prescription dose (V100) was 97.56% and 95.38% with GRO and HIPO, respectively. The mean dose (D(mean)) and minimum dose to 10% volume (D10) for the urethra, rectum, and bladder were all statistically lower with HIPO compared to GRO using the student pair t-test at 5% significance level. HIPO can provide treatment plans with comparable target coverage to that of GRO with a reduction in dose to the critical structures.

Reproductive Alterations in Chronically Exposed Female Mice to Environmentally Relevant Doses of a Mixture of Phthalates and Alkylphenols.

PubMed

Patiño-García, Daniel; Cruz-Fernandes, Leonor; Buñay, Julio; Palomino, Jaime; Moreno, Ricardo D

2018-02-01

Endocrine-disrupting chemicals (EDCs) are exogenous compounds that modify hormone biosynthesis, causing adverse effects to human health. Among them, phthalates and alkylphenols are important due to their wide use in plastics, detergents, personal care products, cosmetics, and food packaging. However, their conjoint effects over reproductive female health have not been addressed. The aim of this work was to test the effect of chronically exposed female mice to a mixture of three phthalates [bis (2-ethylhexyl), dibutyl, and benzyl butyl] and two alkylphenols (4-nonylphenol and 4-tert-octylphenol) from conception to adulthood at environmentally relevant doses. These EDCs were administered in two doses: one below the minimal risk dose to cause adverse effects on human development and reproduction [1 mg/kg body weight (BW)/d of the total mixture] and the other one based on the reference value close to occupational exposure in humans (10 mg/kg BW/d of the total mixture). Our results show that both doses had similar effects regarding the uterus and ovary relative weight, estrous cyclicity, serum levels of progesterone and 17β-estradiol, and expression of key elements in the steroidogenesis pathway (acute steroidogenic regulatory protein and CYP19A1). However, only the 1-mg/kg BW/d dose delayed the onset of puberty and the transition from preantral to antral follicles, whereas the 10-mg/kg BW/d dose decreased the number of antral follicles and gonadotropin receptor expression. In addition, we observed changes in several fertility parameters in exposed females and in their progeny (F2 generation). In conclusion, our results indicate that chronic exposure to a complex EDC mixture, at environmentally relevant doses, modifies reproductive parameters in female mice. Copyright © 2018 Endocrine Society.

Simultaneous determination of equivalent dose to organs and tissues of the patient and of the physician in interventional radiology using the Monte Carlo method

NASA Astrophysics Data System (ADS)

Bozkurt, A.; Bor, D.

2007-01-01

This study presents the results of computations of organ equivalent doses and effective doses for the patient and the primary physician during an interventional cardiological examination. The simulations were carried out for seven x-ray spectra (between 60 kVp and 120 kVp) using the Monte Carlo code MCNP. The voxel-based whole-body model VIP-Man was employed to represent both the patient and the physician, the former lying on the operation table while the latter standing 15 cm from the patient at about waist level behind a lead apron. The x-rays, which were generated by a point source positioned around the table and were directed with a conical distribution, irradiated the patient's heart under five major projections used in a coronary angiography examination. The mean effective doses under LAO45, PA, RAO30, LAO45/CAUD30 and LLAT irradiation conditions were calculated as 0.092, 0.163, 0.161, 0.133 and 0.118 mSv/(Gy cm2) for the patient and 1.153, 0.159, 0.145, 0.164 and 0.027 μSv/(Gy cm2) for the shielded physician. The effective doses for the patient determined in this study were usually lower than the literature data obtained through measurements and/or calculations and the discrepancies could be attributed to the fact that this study computes the effective doses specific to the VIP-Man body model, which lacks an ovarian contribution to the gonadal equivalent dose. The effective doses for the physician agreed reasonably well with the literature data.

A Review of the Cognitive Effects Observed in Humans Following Acute Supplementation with Flavonoids, and Their Associated Mechanisms of Action.

PubMed

Bell, Lynne; Lamport, Daniel J; Butler, Laurie T; Williams, Claire M

2015-12-09

Flavonoids are polyphenolic compounds found in varying concentrations in many plant-based foods. Recent studies suggest that flavonoids can be beneficial to both cognitive and physiological health. Long term flavonoid supplementation over a period of weeks or months has been extensively investigated and reviewed, particularly with respect to cognitive ageing and neurodegenerative disease. Significantly less focus has been directed towards the short term effects of single doses of flavonoids on cognition. Here, we review 21 such studies with particular emphasis on the subclass and dose of flavonoids administered, the cognitive domains affected by flavonoid supplementation, and the effect size of the response. The emerging evidence suggests that flavonoids may be beneficial to attention, working memory, and psychomotor processing speed in a general population. Episodic memory effects are less well defined and may be restricted to child or older adult populations. The evidence also points towards a dose-dependent effect of flavonoids, but the physiological mechanisms of action remain unclear. Overall, there is encouraging evidence that flavonoid supplementation can benefit cognitive outcomes within an acute time frame of 0-6 h. But larger studies, combining cognitive and physiological measures, are needed to strengthen the evidence base.

Impact of Number of Human Papillomavirus Vaccine Doses on Genital Warts Diagnoses Among a National Cohort of U.S. Adolescents.

PubMed

Perkins, Rebecca B; Lin, Mengyun; Wallington, Sherrie F; Hanchate, Amresh

2017-06-01

The impact of fewer than 3 doses of human papillomavirus (HPV) vaccine on genital warts is uncertain. Using the Truven Health Analytics Marketscan administrative database, we compared rates of genital warts among women receiving 0, 1, 2, or 3 doses of HPV vaccine. Females aged 9 to 18 years on January 1, 2007, who were continuously enrolled in the database through December 31, 2013, were included. Patients were assigned an HPV dose state (0, 1, 2, or 3) based on the last recorded dose. The exposure period began on January 1, 2007, or the date of the final HPV dose, and lasted until the first diagnosis of genital warts or December 31, 2013. Multivariable Poisson regression was performed to determine the risk of genital warts associated with vaccine doses. Among 387,906 subjects, mean age and exposure period were 14.73 and 5.64 years, respectively. The proportions of doses received were: 52.1%, 7.8%, 9.4%, and 30.7% for 0, 1, 2, and 3 doses, respectively. The rate of genital warts was 1.97/1000 person-years. Receipt of 0 or 1 dose was associated with more genital warts than 3 doses. The effectiveness of 2 doses following current Centers for Disease Control and Prevention guidelines was similar to 3 doses. The risk of genital warts rose with age. Prevention of genital warts is higher with completion of 3 vaccine doses than with 1 dose, though 2-dose recommendations appear to provide similar protection. Prospective effectiveness studies of recommended 2-dose schedules against clinical endpoints including persistent infection, genital warts, and cervical dysplasia are necessary to ensure long-term protection of vaccinated cohorts.

Usefulness of model-based iterative reconstruction in semi-automatic volumetry for ground-glass nodules at ultra-low-dose CT: a phantom study.

PubMed

Maruyama, Shuki; Fukushima, Yasuhiro; Miyamae, Yuta; Koizumi, Koji

2018-06-01

This study aimed to investigate the effects of parameter presets of the forward projected model-based iterative reconstruction solution (FIRST) on the accuracy of pulmonary nodule volume measurement. A torso phantom with simulated nodules [diameter: 5, 8, 10, and 12 mm; computed tomography (CT) density: - 630 HU] was scanned with a multi-detector CT at tube currents of 10 mA (ultra-low-dose: UL-dose) and 270 mA (standard-dose: Std-dose). Images were reconstructed with filtered back projection [FBP; standard (Std-FBP), ultra-low-dose (UL-FBP)], FIRST Lung (UL-Lung), and FIRST Body (UL-Body), and analyzed with a semi-automatic software. The error in the volume measurement was determined. The errors with UL-Lung and UL-Body were smaller than that with UL-FBP. The smallest error was 5.8% ± 0.3 for the 12-mm nodule with UL-Body (middle lung). Our results indicated that FIRST Body would be superior to FIRST Lung in terms of accuracy of nodule measurement with UL-dose CT.

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.

Aripiprazole Lauroxil: Pharmacokinetic Profile of This Long-Acting Injectable Antipsychotic in Persons With Schizophrenia.

PubMed

Hard, Marjie L; Mills, Richard J; Sadler, Brian M; Turncliff, Ryan Z; Citrome, Leslie

2017-06-01

Aripiprazole lauroxil is an extended-release prodrug of aripiprazole for intramuscular injection, approved for schizophrenia treatment. We developed a population pharmacokinetic (PopPK) model to characterize aripiprazole lauroxil PK and evaluate dosing scenarios likely to be encountered in clinical practice. Data from 616 patients with schizophrenia, collected from 5 clinical studies, were used to construct the PopPK model. The model was subsequently used to evaluate various dose levels and frequency and the impact of dosing delay on aripiprazole concentrations. The results of the model indicate that aripiprazole is released into the systemic circulation after 5 to 6 days, and release continues for an additional 36 days. The slow increase in aripiprazole concentration after injection necessitates the coadministration of oral aripiprazole for 21 days with the first injection. Based on the PopPK model simulations, a dosing interval of 882 mg every 6 weeks results in aripiprazole concentrations that fall within the concentration range associated with the efficacious aripiprazole lauroxil dose range (441-882 mg dosed monthly). A 662-mg monthly dose also resulted in aripiprazole concentrations within the efficacious dose range. Aripiprazole lauroxil administration results in prolonged exposure, such that dose delays of 2 to 4 weeks, depending on the dose regimen, do not require oral aripiprazole supplementation upon resumption of dosing. This PopPK model and model-based simulations were effective means for evaluating aripiprazole lauroxil dosing regimens and management of missed doses. Such analyses play an important role in determining the use of this long-acting antipsychotic in clinical practice.

SU-F-T-53: Treatment Planning with Inhomogeneity Correction for Intraoperative Radiotherapy Using KV X-Ray Beams

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

Chen, Y; Ghaly, M; Souri, S

Purpose: The current standard in dose calculation for intraoperative radiotherapy (IORT) using the ZEISS Intrabeam 50 kV x-ray system is based on depth dose measurements in water and no heterogeneous tissue effect has been taken into account. We propose an algorithm for pre-treatment planning including inhomogeneity correction based on data of depth dose measurements in various tissue phantoms for kV x-rays. Methods: Direct depth dose measurements were made in air, water, inner bone and cortical bone phantoms for the Intrabeam 50 kV x-rays with a needle applicator. The data were modelled by a function of power law combining exponential withmore » different parameters. Those phantom slabs used in the measurements were scanned to obtain CT numbers. The x-ray beam initiated from the source isocenter is ray-traced through tissues. The corresponding doses will be deposited/assigned at different depths. On the boundary of tissue/organ changes, the x-ray beam will be re-traced in new tissue/organ starting at an equivalent depth with the same dose. In principle, a volumetric dose distribution can be generated if enough directional beams are traced. In practice, a several typical rays traced may be adequate in providing estimates of maximum dose to the organ at risk and minimum dose in the target volume. Results: Depth dose measurements and modeling are shown in Figure 1. The dose versus CT number is shown in Figure 2. A computer program has been written for Kypho-IORT planning using those data. A direct measurement through 2 mm solid water, 2 mm inner bone, and 1 mm solid water yields a dose rate of 7.7 Gy/min. Our calculation shows 8.1±0.4 Gy/min, consistent with the measurement within 5%. Conclusion: The proposed method can be used to more accurately calculate the dose by taking into account the heterogeneous effect. The further validation includes comparison with Monte Carlo simulation.« less

CIE, Vitamin D and DNA Damage: A Synergetic Study in Thessaloniki, Greece

NASA Astrophysics Data System (ADS)

Zempila, Melina Maria; Taylor, Michael; Fountoulakis, Ilias; Koukouli, Maria Elissavet; Bais, Alkiviadis; Arola, Antii; van Geffen, Jos; van Weele, Michiel; van der A, Ronald; Kouremeti, Natalia; Kazadzis, Stelios; Meleti, Chariklia; Balis, Dimitrios

2016-08-01

The present study aims to validate different approaches for the estimation of three photobiological effective doses: the erythemal UV, the vitamin D and that for DNA damage, using high temporal resolution surface- based measurements of solar UV from 2005-2015. Data from a UV spectrophotometer, a multi-filter radiometer, and a UV radiation pyranometer that are located in Thessaloniki, Greece are used together with empirical relations, algorithms and models in order to calculate the desired quantities. In addition to the surface-based dose retrievals, OMI/Aura and the combined SCIAMACHY/Envisat and GOME/MetopA satellite products are also used in order to assess the accuracy of each method for deriving the photobiological doses.

Antitumor Activities of Rauwolfia vomitoria Extract and Potentiation of Carboplatin Effects Against Ovarian Cancer☆

PubMed Central

Yu, Jun; Ma, Yan; Drisko, Jeanne; Chen, Qi

2013-01-01

Background Tumor resistance to platinum-based drugs has been an obstacle to the treatment of ovarian cancer. Extract of the plant Rauwolfia vomitoria has long been used by cancer patients. However, there have not been systematic studies of its anticancer activity. Objective In an effort to enhance the effectiveness of platinum-based drugs, we investigated the anticancer effect of a Rauwolfia vomitoria extract (Rau), both alone and in combination with carboplatin (Cp). Methods In vitro cytotoxicity and colony formation were evaluated in several ovarian cancer cell lines. In vivo effects were evaluated in an intraperitoneal ovarian cancer mouse model. The combination of Rau and Cp was assessed using Chou-Talalay’s constant ratio design and median effect analysis based on the isobologram principle to determine the combination index values. Results Rau decreased cell growth in all 3 tested ovarian cancer cell lines dose dependently and completely inhibited formation of colonies in soft agar. Apoptosis was induced in a time- and dose-dependent manner and was the predominant form of Rau-induced cell death. Synergy of Rau with Cp was detected, with combination index values <1 and dose reduction index values for Cp ranging from 1.7- to 7-fold. Tumor growth in mice was significantly suppressed by 36% or 66% with Rau treatment alone at a low (20 mg/kg) or a high dose (50 mg/kg), respectively, an effect comparable to that of Cp alone. The volume of ascitic fluid and the number of nonblood cells in ascites were also significantly decreased. Combining Rau with Cp remarkably enhanced the effect of Cp and reduced tumor burden by 87% to 90% and ascites volume by 89% to 97%. Conclusions Rau has potent antitumor activity and in combination significantly enhances the effect of Cp against ovarian cancer. PMID:24465036

Opioid analgesics: does potency matter?

PubMed

Passik, Steven D; Webster, Lynn

2014-01-01

Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that less-potent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.

Moderators of intervention dose effects on diet quality and physical activity changes in a church-based, multicomponent, lifestyle study: Delta Body and Soul III

USDA-ARS?s Scientific Manuscript database

Many community-based lifestyle interventions targeting African Americans have reported positive effects on participant’s dietary choices and physical activity habits. However, these effects vary and not all participants will have outcome changes. Moderation analysis can help explain differential e...

A clinical trial designed to evaluate the safety and effectiveness of a thermosensitive hydrogel-type cultured epidermal allograft for deep second-degree burns.

PubMed

Yim, Haejun; Yang, Hyeong-Tae; Cho, Yong-Suk; Kim, Dohern; Kim, Jong-Hyun; Chun, Wook; Hur, Jun

2014-12-01

This study is a phase 1 and 2 clinical trial for investigating the safety profile, effective treatment dose and effectiveness of the newly developed thermosensitive hydrogel-type cultured epidermal allograft. For phase 1, the keratinocytes were divided into 3 groups as follows, with 5 patients in each group: (1) low-dose group (6.7×10(6)/1.5mL), (2) medium-dose group (2×10(7)/1.5mL), and (3) high-dose group (6.0×10(7)/1.5mL). The second phase of the trial proceeded with 10 cases after choosing the most effective dose based on the analysis of the first phase. When comparing re-epithelialization time, medium- and high-dose group showed significantly shorter re-epithelialization time than low-dose group (p=0.003 and p=0.002). A total of 15 cases, 5 cases selected from phase 1 and 10 cases test in phase 2 with the medium dose, were compared with the re-epithelialization period. The re-epithelialization period was 9.6±4.0 days in the test site and 12.4±4.8 days in the control site. In the test site, re-epithelialization was 2.8±1.8 days faster than in the control site (p<0.0001). There was no significant adverse reaction in our clinical trial. In conclusion, this new type of CEAllo accelerates wound healing time and shows the safety. Copyright © 2014 Elsevier Ltd and ISBI. All rights reserved.

Pharmaco-EEG-based assessment of the interaction between ethanol and oxcarbazepine.

PubMed

Pietrzak, Bogusława; Czarnecka, Elzbieta

2010-01-01

Oxcarbazepine is a representative molecule for a new class of anticonvulsant drugs that can treat alcohol dependence in addition to other disorders. Interestingly, the central mechanism of action in oxcarbazepine is very similar to ethanol, suggesting that these two agents may interact and cause enhanced effects in the central nervous system. In this study, we used a pharmaco-EEG method to examine the influence of oxcarbazepine on the effect of ethanol on the EEG of rabbits (midbrain reticular formation, hippocampus, frontal cortex). Oxcarbazepine was administered po as a single dose (20 mg/kg or 80 mg/kg) or repeatedly at a dose of 40 mg/kg/day for 14 days. Ethanol was injected iv at a dose of 0.8 g/kg 60 min after the administration of oxcarbazepine. Ethanol caused an increase in the low frequencies (0.5-4 Hz) in the recordings, and it caused a marked decrease in higher frequencies (13-30 Hz and 30-45 Hz). Oxcarbazepine altered the EEG pattern in rabbits; this interaction was dependent on the dose of the drug and whether it was administered as a single dose or as multiple doses. Oxcarbazepine administered at a lower dose had a synergistic effect with ethanol in the frontal cortex and midbrain reticular formation, and a similar effect was observed in the hippocampus at a higher dose. Changes in EEG recordings after the administration of oxcarbazepine alone were more pronounced after multiple administrations. The drug decreased the sensitivity of the hippocampus to ethanol, an observation that may be important for the treatment of alcohol addiction.

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

PubMed Central

Tomita, Masanori; Maeda, Munetoshi

2015-01-01

Abstract Elucidating the biological effect of low linear energy transfer (LET), low-dose and/or low-dose-rate ionizing radiation is essential in ensuring radiation safety. Over the past two decades, non-targeted effects, which are not only a direct consequence of radiation-induced initial lesions produced in cellular DNA but also of intra- and inter-cellular communications involving both targeted and non-targeted cells, have been reported and are currently defining a new paradigm in radiation biology. These effects include radiation-induced adaptive response, low-dose hypersensitivity, genomic instability, and radiation-induced bystander response (RIBR). RIBR is generally defined as a cellular response that is induced in non-irradiated cells that receive bystander signals from directly irradiated cells. RIBR could thus play an important biological role in low-dose irradiation conditions. However, this suggestion was mainly based on findings obtained using high-LET charged-particle radiations. The human population (especially the Japanese, who are exposed to lower doses of radon than the world average) is more frequently exposed to low-LET photons (X-rays or γ-rays) than to high-LET charged-particle radiation on a daily basis. There are currently a growing number of reports describing a distinguishing feature between photon-induced bystander response and high-LET RIBR. In particular, photon-induced bystander response is strongly influenced by irradiation dose, the irradiated region of the targeted cells, and p53 status. The present review focuses on the photon-induced bystander response, and discusses its impact on the low-dose radiation effect. PMID:25361549

The dose-effect relationship of baclofen in alcohol dependence: A 1-year cohort study.

PubMed

Pignon, Baptiste; Labreuche, Julien; Auffret, Marine; Gautier, Sophie; Deheul, Sylvie; Simioni, Nicolas; Cottencin, Olivier; Bordet, Régis; Duhamel, Alain; Rolland, Benjamin

2017-07-01

Our aim is to study the relationship between dose of baclofen and effectiveness in alcohol dependence. Two hundred two patients with alcohol dependence, who received baclofen treatment for drinking reduction, were followed up for 1 year. For each patient-month of treatment, the maximum daily dose of baclofen (DDB) and average weekly alcohol consumption (AWAC) were calculated. We defined a favorable drinking outcome as an AWAC under 200 g/w for at least 2 consecutive months. We divided the DDB of each patient-month into 3 categories (low dose: <90 mg/d, medium dose: 90-150 mg/d, and high dose: >150 mg/d) and investigated the relationship between reaching a favorable outcome and the concurrent DDB category in a time-varying Cox regression analysis. Hazard ratios (HRs) were adjusted based on age, sex, and initial AWAC. One hundred forty subjects were followed during at least 1 month. Of these patients, 58 (41%) had a favorable drinking outcome. In comparison to low dose, medium dose was associated with a decreased rate of favorable drinking outcome (HR = 0.42; 95% CI [0.20, 0.88]), whereas no difference was found with high dose (HR = 1.31; 95% CI [0.65, 2.64]). The relationship between dose of baclofen and favorable drinking outcome was U-shaped, that is, was increased at low and high doses compared to medium doses. Copyright © 2017 John Wiley & Sons, Ltd.

Enhanced Medial Collateral Ligament Healing using Mesenchymal Stem Cells: Dosage Effects on Cellular Response and Cytokine Profile

PubMed Central

Saether, Erin E.; Chamberlain, Connie S.; Leiferman, Ellen M.; Kondratko-Mittnacht, Jaclyn R.; Li, Wan Ju; Brickson, Stacey L.; Vanderby, Ray

2013-01-01

Mesenchymal stem cells (MSCs) have potential therapeutic applications for musculoskeletal injuries due to their ability to differentiate into several tissue cell types and modulate immune and inflammatory responses. These immune-modulatory properties were examined in vivo during early stage rat medial collateral ligament healing. Two different cell doses (low dose 1×106 or high dose 4×106 MSCs) were administered at the time of injury and compared with normal ligament healing at days 5 and 14 post-injury. At both times, the high dose MSC group demonstrated a significant decrease in M2 macrophages compared to controls. At day 14, fewer M1 macrophages were detected in the low dose group compared to the high dose group. These results, along with significant changes in procollagen I, proliferating cells, and endothelialization suggest that MSCs can alter the cellular response during healing in a dose-dependent manner. The higher dose ligaments also had increased expression of several pro-inflammatory cytokines at day 5 (IL-1β, IFNγ, IL-2) and increased expression of IL-12 at day 14. Mechanical testing at day 14 revealed increased failure strength and stiffness in low dose ligaments compared to controls. Based on these improved mechanical properties, MSCs enhanced functional healing when applied at a lower dose. Different doses of MSCs uniquely affected the cellular response and cytokine expression in healing ligaments. Interestingly, the lower dose of cells proved to be most effective in improving functional properties. PMID:24174129

Dosimetry study of diagnostic X-ray using doped iodide normoxic polymer gels

NASA Astrophysics Data System (ADS)

Huang, Y. R.; Chang, Y. J.; Hsieh, L. L.; Liu, M. H.; Liu, J. S.; Chu, C. H.; Hsieh, B. T.

2014-11-01

In radiotherapy, polymer gel dosimeters are used for three-dimensional (3D) dose distribution. However, the doses are within the Gy range. In this study, we attempted to develop a low-dose 3D dosimeter within the mGy range for diagnostic radiology. The effect of the iodinated compound was used as a dose enhancement sensitizer to enhance the dose sensitivity of normoxic polymer gel dosimeters. This study aims to use N-isopropylacrylamide(NIPAM)-based and methacrylic acid (MAGAT)-based gels to evaluate the potential dose enhancement sensitizer, as well as to compare two gels that may be suitable for measuring diagnostic radiation doses. The suitable formulation of NIPAM gel [5% (w/w) gelatin, 5% (w/w) NIPAM, 3% (w/w) N,N‧-methylenebisacrylamide (BIS), 5 mM tetrakis (hydroxymethyl) phosphonium chloride (THPC), and 87% (w/w) deionized distilled water] and MAGAT gel (4% MAA, 9% gelatin, 87% deionized water, and 10 mM THPC) were used and loaded with clinical iodinated contrast medium agent (Iobitridol, Xenetix® 350). Irradiation was conducted using X-ray computed tomography. The irradiation doses ranged from 0 mGy to 80 mGy. Optical computed tomography was the employed gel measurement system. The results indicate that the iodinated contrast agent yields a quantifiable dose enhancement ratio. The dose enhancement ratios of NIPAM and MAGAT gels are 3.35±0.6 and 1.36±0.3, respectively. The developed NIPAM gel in this study could be suitable for measuring diagnostic radiation doses.

Modeling the acute health effects of astronauts from exposure to large solar particle events.

PubMed

Hu, Shaowen; Kim, Myung-Hee Y; McClellan, Gene E; Cucinotta, Francis A

2009-04-01

Radiation exposure from Solar Particle Events (SPE) presents a significant health concern for astronauts for exploration missions outside the protection of the Earth's magnetic field, which could impair their performance and result in the possibility of failure of the mission. Assessing the potential for early radiation effects under such adverse conditions is of prime importance. Here we apply a biologically based mathematical model that describes the dose- and time-dependent early human responses that constitute the prodromal syndromes to consider acute risks from SPEs. We examine the possible early effects on crews from exposure to some historically large solar events on lunar and/or Mars missions. The doses and dose rates of specific organs were calculated using the Baryon radiation transport (BRYNTRN) code and a computerized anatomical man model, while the hazard of the early radiation effects and performance reduction were calculated using the Radiation-Induced Performance Decrement (RIPD) code. Based on model assumptions we show that exposure to these historical events would cause moderate early health effects to crew members inside a typical spacecraft or during extra-vehicular activities, if effective shielding and medical countermeasure tactics were not provided. We also calculate possible even worse cases (double intensity, multiple occurrences in a short period of time, etc.) to estimate the severity, onset and duration of various types of early illness. Uncertainties in the calculation due to limited data on relative biological effectiveness and dose-rate modifying factors for protons and secondary radiation, and the identification of sensitive sites in critical organs are discussed.

Potentiation of omega-3 fatty acid antidepressant-like effects with low non-antidepressant doses of fluoxetine and mirtazapine.

PubMed

Laino, Carlos Horacio; Fonseca, Cristina; Sterin-Speziale, Norma; Slobodianik, Nora; Reinés, Analía

2010-12-01

Despite the advances in psychopharmacology, the treatment of depressive disorders is still not satisfactory. Side effects and resistance to antidepressant drugs are the greatest complications during treatment. Based on recent evidence, omega-3 fatty acids may influence vulnerability and outcome in depressive disorders. The aim of this study was to further characterize the omega-3 antidepressant-like effect in rats in terms of its behavioral features in the depression model forced swimming test either alone or in combination with antidepressants fluoxetine or mirtazapine. Ultimately, we prompted to determine the lowest dose at which omega-3 fatty acids and antidepressant drugs may still represent a pharmacological advantage when employed in combined treatments. Chronic diet supplementation with omega-3 fatty acids produced concentration-dependent antidepressant-like effects in the forced swimming test displaying a behavioral profile similar to fluoxetine but different from mirtazapine. Fluoxetine or mirtazapine at antidepressant doses (10 and 20 mg/kg/day, respectively) rendered additive effects in combination with omega-3 fatty acid supplementation (720 mg/kg/day). Beneficial effects of combined treatment were also observed at sub-effective doses (1 mg/kg/day) of fluoxetine or mirtazapine, since in combination with omega-3 fatty acids (720 mg/kg/day), antidepressants potentiated omega-3 antidepressant-like effects. The antidepressant-like effects occurred in the absence of changes in brain phospholipid classes. The therapeutic approach of combining omega-3 fatty acids with low ineffective doses of antidepressants might represent benefits in the treatment of depression, especially in patients with depression resistant to conventional treatments and even may contribute to patient compliance by decreasing the magnitude of some antidepressant dose-dependent side effects. Copyright © 2010 Elsevier B.V. All rights reserved.

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

PubMed

Lee, Lucia H; Blake, Milan S

2012-04-01

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

SU-F-T-288: Impact of Trajectory Log Files for Clarkson-Based Independent Dose Verification of IMRT and VMAT

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

Takahashi, R; Kamima, T; Tachibana, H

2016-06-15

Purpose: To investigate the effect of the trajectory files from linear accelerator for Clarkson-based independent dose verification in IMRT and VMAT plans. Methods: A CT-based independent dose verification software (Simple MU Analysis: SMU, Triangle Products, Japan) with a Clarksonbased algorithm was modified to calculate dose using the trajectory log files. Eclipse with the three techniques of step and shoot (SS), sliding window (SW) and Rapid Arc (RA) was used as treatment planning system (TPS). In this study, clinically approved IMRT and VMAT plans for prostate and head and neck (HN) at two institutions were retrospectively analyzed to assess the dosemore » deviation between DICOM-RT plan (PL) and trajectory log file (TJ). An additional analysis was performed to evaluate MLC error detection capability of SMU when the trajectory log files was modified by adding systematic errors (0.2, 0.5, 1.0 mm) and random errors (5, 10, 30 mm) to actual MLC position. Results: The dose deviations for prostate and HN in the two sites were 0.0% and 0.0% in SS, 0.1±0.0%, 0.1±0.1% in SW and 0.6±0.5%, 0.7±0.9% in RA, respectively. The MLC error detection capability shows the plans for HN IMRT were the most sensitive and 0.2 mm of systematic error affected 0.7% dose deviation on average. Effect of the MLC random error did not affect dose error. Conclusion: The use of trajectory log files including actual information of MLC location, gantry angle, etc should be more effective for an independent verification. The tolerance level for the secondary check using the trajectory file may be similar to that of the verification using DICOM-RT plan file. From the view of the resolution of MLC positional error detection, the secondary check could detect the MLC position error corresponding to the treatment sites and techniques. This research is partially supported by Japan Agency for Medical Research and Development (AMED)« less

SU-E-T-759: To Replan Or Not To Replan for Each Fraction Using Inverse Optimization for Multichannel Vaginal Cylinder

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

Balik, M; Rybak, M; Strongosky, M

2015-06-15

Purpose: This study investigates whether replanning each fraction for vaginal cuff HDR therapy using a multichannel cylinder (MC) and brachytherapy inverse optimization (BIO) provides dosimetric benefits to organs-at-risk (OAR). The goal was to appropriately cover the target and limit dose to OAR, as well as evaluate dosimetric changes for each fraction, while doing this in a timely and cost effective manner. Methods: From an initial selection of 57 patients that were treated with 3 fractions using a MC and BIO, a subset of n=12 patients was selected based on the criterion that one plan was used for all 3 fractions.more » A simulation CT was acquired prior to each fraction. CT scans for fractions 2 and 3 were fused to the initial CT. Contours for the bladder and rectum were manually drawn on CTs for all 3 fractions, and the clinical treatment volume (PTVeval) was defined. Cylinders were reconstructed using applicator modeling library, influencing time and cost effectiveness. Planning objectives were at least 95% prescription dose to 95% (D95%) of target volume and limiting high dose to OAR. Dose to 2 cm{sup 3} (D2cc) for each OAR was analyzed using a t-test. Results: This study concentrated on comparing 2cm{sup 3} of highest dose to OAR (D2cc), for each fraction for the plans that were used to treat all 3 fraction. Based on statistical analysis, using the initial plan for fractions 2 and 3 resulted in approximately 6% change to the highest D2cc of the bladder (p=0.03). Conclusion: Performing CT fusion and contours of each OAR on each fraction allows objective plan evaluation and supports decision making on the necessity of replanning based on improved dose sparing for OAR. Future studies will investigate the effects of replanning on maximum dose (D0.1cc) using the same physician-drawn OAR contours to avoid subjectivity.« less

Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides

PubMed Central

Schuchardt, Christiane; Kulkarni, Harshad R.; Shahinfar, Mostafa; Singh, Aviral; Glatting, Gerhard; Baum, Richard P.; Beer, Ambros J.

2016-01-01

In molecular radiotherapy with 177Lu-labeled prostate specific membrane antigen (PSMA) peptides, kidney and/or salivary glands doses limit the activity which can be administered. The aim of this work was to investigate the effect of the ligand amount and injected activity on the tumor-to-normal tissue biologically effective dose (BED) ratio for 177Lu-labeled PSMA peptides. For this retrospective study, a recently developed physiologically based pharmacokinetic model was adapted for PSMA targeting peptides. General physiological parameters were taken from the literature. Individual parameters were fitted to planar gamma camera measurements (177Lu-PSMA I&T) of five patients with metastasizing prostate cancer. Based on the estimated parameters, the pharmacokinetics of tumor, salivary glands, kidneys, total body and red marrow was simulated and time-integrated activity coefficients were calculated for different peptide amounts. Based on these simulations, the absorbed doses and BEDs for normal tissue and tumor were calculated for all activities leading to a maximal tolerable kidney BED of 10 Gy2.5/cycle, a maximal salivary gland absorbed dose of 7.5 Gy/cycle and a maximal red marrow BED of 0.25 Gy15/cycle. The fits yielded coefficients of determination > 0.85, acceptable relative standard errors and low parameter correlations. All estimated parameters were in a physiologically reasonable range. The amounts (for 25−29 nmol) and pertaining activities leading to a maximal tumor dose, considering the defined maximal tolerable doses to organs of risk, were calculated to be 272±253 nmol (452±420 μg) and 7.3±5.1 GBq. Using the actually injected amount (235±155 μg) and the same maximal tolerable doses, the potential improvement for the tumor BED was 1–3 fold. The results suggest that currently given amounts for therapy are in the appropriate order of magnitude for many lesions. However, for lesions with high binding site density or lower perfusion, optimizing the peptide amount and activity might improve the tumor-to-kidney and tumor-to-salivary glands BED ratio considerably. PMID:27611841

Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides.

PubMed

Kletting, Peter; Schuchardt, Christiane; Kulkarni, Harshad R; Shahinfar, Mostafa; Singh, Aviral; Glatting, Gerhard; Baum, Richard P; Beer, Ambros J

2016-01-01

In molecular radiotherapy with 177Lu-labeled prostate specific membrane antigen (PSMA) peptides, kidney and/or salivary glands doses limit the activity which can be administered. The aim of this work was to investigate the effect of the ligand amount and injected activity on the tumor-to-normal tissue biologically effective dose (BED) ratio for 177Lu-labeled PSMA peptides. For this retrospective study, a recently developed physiologically based pharmacokinetic model was adapted for PSMA targeting peptides. General physiological parameters were taken from the literature. Individual parameters were fitted to planar gamma camera measurements (177Lu-PSMA I&T) of five patients with metastasizing prostate cancer. Based on the estimated parameters, the pharmacokinetics of tumor, salivary glands, kidneys, total body and red marrow was simulated and time-integrated activity coefficients were calculated for different peptide amounts. Based on these simulations, the absorbed doses and BEDs for normal tissue and tumor were calculated for all activities leading to a maximal tolerable kidney BED of 10 Gy2.5/cycle, a maximal salivary gland absorbed dose of 7.5 Gy/cycle and a maximal red marrow BED of 0.25 Gy15/cycle. The fits yielded coefficients of determination > 0.85, acceptable relative standard errors and low parameter correlations. All estimated parameters were in a physiologically reasonable range. The amounts (for 25-29 nmol) and pertaining activities leading to a maximal tumor dose, considering the defined maximal tolerable doses to organs of risk, were calculated to be 272±253 nmol (452±420 μg) and 7.3±5.1 GBq. Using the actually injected amount (235±155 μg) and the same maximal tolerable doses, the potential improvement for the tumor BED was 1-3 fold. The results suggest that currently given amounts for therapy are in the appropriate order of magnitude for many lesions. However, for lesions with high binding site density or lower perfusion, optimizing the peptide amount and activity might improve the tumor-to-kidney and tumor-to-salivary glands BED ratio considerably.

Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation.

PubMed

Olipitz, Werner; Wiktor-Brown, Dominika; Shuga, Joe; Pang, Bo; McFaline, Jose; Lonkar, Pallavi; Thomas, Aline; Mutamba, James T; Greenberger, Joel S; Samson, Leona D; Dedon, Peter C; Yanch, Jacquelyn C; Engelward, Bevin P

2012-08-01

In the event of a nuclear accident, people are exposed to elevated levels of continuous low dose-rate radiation. Nevertheless, most of the literature describes the biological effects of acute radiation. DNA damage and mutations are well established for their carcinogenic effects. We assessed several key markers of DNA damage and DNA damage responses in mice exposed to low dose-rate radiation to reveal potential genotoxic effects associated with low dose-rate radiation. We studied low dose-rate radiation using a variable low dose-rate irradiator consisting of flood phantoms filled with 125Iodine-containing buffer. Mice were exposed to 0.0002 cGy/min (~ 400-fold background radiation) continuously over 5 weeks. We assessed base lesions, micronuclei, homologous recombination (HR; using fluorescent yellow direct repeat mice), and transcript levels for several radiation-sensitive genes. We did not observe any changes in the levels of the DNA nucleobase damage products hypoxanthine, 8-oxo-7,8-dihydroguanine, 1,N6-ethenoadenine, or 3,N4-ethenocytosine above background levels under low dose-rate conditions. The micronucleus assay revealed no evidence that low dose-rate radiation induced DNA fragmentation, and there was no evidence of double strand break-induced HR. Furthermore, low dose-rate radiation did not induce Cdkn1a, Gadd45a, Mdm2, Atm, or Dbd2. Importantly, the same total dose, when delivered acutely, induced micronuclei and transcriptional responses. These results demonstrate in an in vivo animal model that lowering the dose-rate suppresses the potentially deleterious impact of radiation and calls attention to the need for a deeper understanding of the biological impact of low dose-rate radiation.

Prospective ECG-Triggered Coronary CT Angiography: Clinical Value of Noise-Based Tube Current Reduction Method with Iterative Reconstruction

PubMed Central

Shen, Junlin; Du, Xiangying; Guo, Daode; Cao, Lizhen; Gao, Yan; Yang, Qi; Li, Pengyu; Liu, Jiabin; Li, Kuncheng

2013-01-01

Objectives To evaluate the clinical value of noise-based tube current reduction method with iterative reconstruction for obtaining consistent image quality with dose optimization in prospective electrocardiogram (ECG)-triggered coronary CT angiography (CCTA). Materials and Methods We performed a prospective randomized study evaluating 338 patients undergoing CCTA with prospective ECG-triggering. Patients were randomly assigned to fixed tube current with filtered back projection (Group 1, n = 113), noise-based tube current with filtered back projection (Group 2, n = 109) or with iterative reconstruction (Group 3, n = 116). Tube voltage was fixed at 120 kV. Qualitative image quality was rated on a 5-point scale (1 = impaired, to 5 = excellent, with 3–5 defined as diagnostic). Image noise and signal intensity were measured; signal-to-noise ratio was calculated; radiation dose parameters were recorded. Statistical analyses included one-way analysis of variance, chi-square test, Kruskal-Wallis test and multivariable linear regression. Results Image noise was maintained at the target value of 35HU with small interquartile range for Group 2 (35.00–35.03HU) and Group 3 (34.99–35.02HU), while from 28.73 to 37.87HU for Group 1. All images in the three groups were acceptable for diagnosis. A relative 20% and 51% reduction in effective dose for Group 2 (2.9 mSv) and Group 3 (1.8 mSv) were achieved compared with Group 1 (3.7 mSv). After adjustment for scan characteristics, iterative reconstruction was associated with 26% reduction in effective dose. Conclusion Noise-based tube current reduction method with iterative reconstruction maintains image noise precisely at the desired level and achieves consistent image quality. Meanwhile, effective dose can be reduced by more than 50%. PMID:23741444

The impact of the oxygen scavenger on the dose-rate dependence and dose sensitivity of MAGIC type polymer gels

NASA Astrophysics Data System (ADS)

Khan, Muzafar; Heilemann, Gerd; Kuess, Peter; Georg, Dietmar; Berg, Andreas

2018-03-01

Recent developments in radiation therapy aimed at more precise dose delivery along with higher dose gradients (dose painting) and more efficient dose delivery with higher dose rates e.g. flattening filter free (FFF) irradiation. Magnetic-resonance-imaging based polymer gel dosimetry offers 3D information for precise dose delivery techniques. Many of the proposed polymer gels have been reported to exhibit a dose response, measured as relaxation rate ΔR2(D), which is dose rate dependent. A lack of or a reduced dose-rate sensitivity is very important for dosimetric accuracy, especially with regard to the increasing clinical use of FFF irradiation protocols with LINACs at high dose rates. Some commonly used polymer gels are based on Methacrylic-Acid-Gel-Initiated-by-Copper (MAGIC). Here, we report on the dose sensitivity (ΔR2/ΔD) of MAGIC-type gels with different oxygen scavenger concentration for their specific dependence on the applied dose rate in order to improve the dosimetric performance, especially for high dose rates. A preclinical x-ray machine (‘Yxlon’, E  =  200 kV) was used for irradiation to cover a range of dose rates from low \\dot{D} min  =  0.6 Gy min-1 to high \\dot{D} max  =  18 Gy min-1. The dose response was evaluated using R2-imaging of the gel on a human high-field (7T) MR-scanner. The results indicate that all of the investigated dose rates had an impact on the dose response in polymer gel dosimeters, being strongest in the high dose region and less effective for low dose levels. The absolute dose rate dependence \\frac{(Δ R2/Δ D)}{Δ \\dot{D}} of the dose response in MAGIC-type gel is significantly reduced using higher concentrations of oxygen scavenger at the expense of reduced dose sensitivity. For quantitative dose evaluations the relative dose rate dependence of a polymer gel, normalized to its sensitivity is important. Based on this normalized sensitivity the dose rate sensitivity was reduced distinctly using an increased oxygen scavenger concentration with reference to standard MAGIC-type gel formulation at high dose rate levels. The proposed gel composition with high oxygen scavenger concentration exhibits a larger linear active dose response and might be used especially in FFF-radiation applications and preclinical dosimetry at high dose rates. We propose in general to use high dose rates for calibration and evaluation as the change in relative dose sensitivity is reduced at higher dose rates in all of the investigated gel types.

SEMICONDUCTOR PHYSICS Dose-rate dependence of optically stimulated luminescence signal

NASA Astrophysics Data System (ADS)

Pingqiang, Wei; Zhaoyang, Chen; Yanwei, Fan; Yurun, Sun; Yun, Zhao

2010-10-01

Optically stimulated luminescence (OSL) is the luminescence emitted from a semiconductor during its exposure to light. The OSL intensity is a function of the total dose absorbed by the sample. The dose-rate dependence of the OSL signal of the semiconductor CaS doped Ce and Sm was studied by numerical simulation and experiments. Based on a one-trap/one-center model, the whole OSL process was represented by a series of differential equations. The dose-rate properties of the materials were acquired theoretically by solving the equations. Good coherence was achieved between numerical simulation and experiments, both of which showed that the OSL signal was independent of dose rate. This result validates that when using OSL as a dosimetry technique, the dose-rate effect can be neglected.

Poster — Thur Eve — 53: Novel Technique for the Measurement of Ultra-Superficial Doses Using Gafchromic Film

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

Marcos, M.; Devic, S.

2014-08-15

Purpose: Dose build-up and electron contamination are two closely related quantities with important implications in radiotherapy, yet they are quite difficult to measure with great certainty. We present a novel technique for measuring ultra-superficial doses. Method and Materials: We used Gafchromic EBT-3 film which have an effective point of measurement of roughly 153 micros (effective depth in water). By peeling off one of the polyester layers, the active layer becomes the top layer and we obtain a film with a effective point of measurement of 15 microns (effective depth in water). A film calibration was performed using a 180 kVpmore » orthovoltage beam. Since the active layer of the film may have been compressed or perturbed during the peeling of clear polyester we use a triple-channel film calibration technique to minimize the effects of non-uniformity in the active layer. We measured surface doses of orthovoltage beams with lead cutouts in place to introduce contaminant photoelectrons. Results: Our measurements show that the dose enhancement near the edges of the lead were about 125% relative to central axis for 6 cm diameter cutouts up to 170% for 2 cm diameter cutouts, which were within 5% of our EGSnrc based Monte Carlo simulations.« less

Effect of (+)-Methamphetamine on Path Integration Learning, Novel Object Recognition, and Neurotoxicity in Rats

PubMed Central

Herring, Nicole R.; Schaefer, Tori L.; Gudelsky, Gary A.; Vorhees, Charles V.; Williams, Michael T.

2008-01-01

Rationale Methamphetamine (MA) has been implicated in cognitive deficits in humans after chronic use. Animal models of neurotoxic MA exposure reveal persistent damage to monoaminergic systems, but few associated cognitive effects. Objectives Since, questions have been raised about the typical neurotoxic dosing regimen used in animals and whether it adequately models human cumulative drug exposure, these experiments examined two different dosing regimens. Methods Rats were treated with one of two regimens, one the typical neurotoxic regimen (4 × 10 mg/kg every 2 h) and one based on pharmacokinetic modeling (Cho et al. 2001) designed to better represent accumulating plasma concentrations of MA as seen in human users (24 ×1.67 mg/kg once every 15 min); matched for total daily dose. In two separate experiments, dosing regimens were compared for their effects on markers of neurotoxicity or on behavior. Results On markers of neurotoxicity, MA showed decreased DA and 5-HT, and increased glial fibrillary acidic protein and increased corticosterone levels regardless of dosing regimen 3 days post-treatment. Behaviorally, MA-treated groups, regardless of dosing regimen, showed hypoactivity, increased initial hyperactivity to a subsequent MA challenge, impaired novel object recognition, impaired learning in a multiple-T water maze test of path integration, and no differences on spatial navigation or reference memory in the Morris water maze. After behavioral testing, reductions of DA and 5-HT remained. Conclusions MA treatment induces an effect on path integration learning not previously reported. Dosing regimen had no differential effects on behavior or neurotoxicity. PMID:18509623

PATIENT RADIATION DOSE FROM CHEST X-RAY EXAMINATIONS IN THE WEST BANK-PALESTINE.

PubMed

Lahham, Adnan; Issa, Ahlam; ALMasri, Hussein

2018-02-01

Radiation doses to patients resulting from chest X-ray examinations were evaluated in four medical centers in the West Bank and East Jerusalem-Palestine. Absorbed organ and effective doses were calculated for a total of 428 adult male and female patients by using commercially available Monte Carlo based softwares; CALDOSE-X5 and PCXMC-2.0, and hermaphrodite mathematical adult phantoms. Patients were selected randomly from medical records in the time period from November 2014 to February 2015. A database of surveyed patients and exposure factors has been established and includes: patient's height, weight, age, gender, X-ray tube voltage, electric current (mAs), examination projection (anterior posterior (AP), posterior anterior (PA), lateral), X-ray tube filtration thickness in each X-ray equipment, anode angle, focus to skin distance and X-ray beam size. The average absorbed doses in the whole body from different projections were: 0.06, 0.07 and 0.11 mGy from AP, PA and lateral projections, respectively. The average effective dose for all surveyed patients was 0.14 mSv for all chest X-ray examinations and projections in the four investigated medical centers. The effect of projection geometry was also investigated. The average effective doses for AP, PA and lateral projections were 0.14, 0.07 and 0.22 mSv, respectively. The collective effective dose estimated for the exposed population was ~60 man-mSv. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Evaluation of the effect of patient dose from cone beam computed tomography on prostate IMRT using Monte Carlo simulation.

PubMed

Chow, James C L; Leung, Michael K K; Islam, Mohammad K; Norrlinger, Bernhard D; Jaffray, David A

2008-01-01

The aim of this study is to evaluate the impact of the patient dose due to the kilovoltage cone beam computed tomography (kV-CBCT) in a prostate intensity-modulated radiation therapy (IMRT). The dose distributions for the five prostate IMRTs were calculated using the Pinnacle treatment planning system. To calculate the patient dose from CBCT, phase-space beams of a CBCT head based on the ELEKTA x-ray volume imaging system were generated using the Monte Carlo BEAMnr code for 100, 120, 130, and 140 kVp energies. An in-house graphical user interface called DOSCTP (DOSXYZnrc-based) developed using MATLAB was used to calculate the dose distributions due to a 360 degrees photon arc from the CBCT beam with the same patient CT image sets as used in Pinnacle. The two calculated dose distributions were added together by setting the CBCT doses equal to 1%, 1.5%, 2%, and 2.5% of the prescription dose of the prostate IMRT. The prostate plan and the summed dose distributions were then processed in the CERR platform to determine the dose-volume histograms (DVHs) of the regions of interest. Moreover, dose profiles along the x- and y-axes crossing the isocenter with and without addition of the CBCT dose were determined. It was found that the added doses due to CBCT are most significant at the femur heads. Higher doses were found at the bones for a relatively low energy CBCT beam such as 100 kVp. Apart from the bones, the CBCT dose was observed to be most concentrated on the anterior and posterior side of the patient anatomy. Analysis of the DVHs for the prostate and other critical tissues showed that they vary only slightly with the added CBCT dose at different beam energies. On the other hand, the changes of the DVHs for the femur heads due to the CBCT dose and beam energy were more significant than those of rectal and bladder wall. By analyzing the vertical and horizontal dose profiles crossing the femur heads and isocenter, with and without the CBCT dose equal to 2% of the prescribed dose, it was found that there is about a 5% increase of dose at the femur head. Still, such an increase in the femur head dose is well below the dose limit of the bone in our IMRT plans. Therefore, under these dose fractionation conditions, it is concluded that, though CBCT causes a higher dose deposited at the bones, there may be no significant effect in the DVHs of critical tissues in the prostate IMRT.

Less is more: Patient-level meta-analysis reveals paradoxical dose-response effects of a computer-based social anxiety intervention targeting attentional bias.

PubMed

Price, Rebecca B; Kuckertz, Jennie M; Amir, Nader; Bar-Haim, Yair; Carlbring, Per; Wallace, Meredith L

2017-12-01

The past decade of research has seen considerable interest in computer-based approaches designed to directly target cognitive mechanisms of anxiety, such as attention bias modification (ABM). By pooling patient-level datasets from randomized controlled trials of ABM that utilized a dot-probe training procedure, we assessed the impact of training "dose" on relevant outcomes among a pooled sample of 693 socially anxious adults. A paradoxical effect of the number of training trials administered was observed for both posttraining social anxiety symptoms and behavioral attentional bias (AB) toward threat (the target mechanism of ABM). Studies administering a large (>1,280) number of training trials showed no benefit of ABM over control conditions, while those administering fewer training trials showed significant benefit for ABM in reducing social anxiety (P = .02). These moderating effects of dose were not better explained by other examined variables and previously identified moderators, including patient age, training setting (laboratory vs. home), or type of anxiety assessment (clinician vs. self-report). Findings inform the optimal dosing for future dot-probe style ABM applications in both research and clinical settings, and suggest several novel avenues for further research. © 2017 Wiley Periodicals, Inc.

Measuring and statistically testing the size of the effect of a chemical compound on a continuous in-vitro pharmacological response through a new statistical model of response detection limit

PubMed Central

Diaz, Francisco J.; McDonald, Peter R.; Pinter, Abraham; Chaguturu, Rathnam

2018-01-01

Biomolecular screening research frequently searches for the chemical compounds that are most likely to make a biochemical or cell-based assay system produce a strong continuous response. Several doses are tested with each compound and it is assumed that, if there is a dose-response relationship, the relationship follows a monotonic curve, usually a version of the median-effect equation. However, the null hypothesis of no relationship cannot be statistically tested using this equation. We used a linearized version of this equation to define a measure of pharmacological effect size, and use this measure to rank the investigated compounds in order of their overall capability to produce strong responses. The null hypothesis that none of the examined doses of a particular compound produced a strong response can be tested with this approach. The proposed approach is based on a new statistical model of the important concept of response detection limit, a concept that is usually neglected in the analysis of dose-response data with continuous responses. The methodology is illustrated with data from a study searching for compounds that neutralize the infection by a human immunodeficiency virus of brain glioblastoma cells. PMID:24905187

SU-D-BRC-05: Effects of Motion and Variable RBE in a Lung Patient Treated with Passively Scattered Protons

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

Mirkovic, D; Titt, U; Mohan, R

2016-06-15

Purpose: To evaluate effects of motion and variable relative biological effectiveness (RBE) in a lung cancer patient treated with passively scattered proton therapy using dose volume histograms associated with patient dose computed using three different methods. Methods: A proton treatment plan of a lung cancer patient optimized using clinical treatment planning system (TPS) was used to construct a detailed Monte Carlo (MC) model of the beam delivery system and the patient specific aperture and compensator. A phase space file containing all particles transported through the beam line was collected at the distal surface of the range compensator and subsequently transportedmore » through two different patient models. The first model was based on the average CT used by the TPS and the second model included all 10 phases of the corresponding 4DCT. The physical dose and proton linear energy transfer (LET) were computed in each voxel of two models and used to compute constant and variable RBE MC dose on average CT and 4D CT. The MC computed doses were compared to the TPS dose using dose volume histograms for relevant structures. Results: The results show significant differences in doses to the target and critical structures suggesting the need for more accurate proton dose computation methods. In particular, the 4D dose shows reduced coverage of the target and higher dose to the spinal cord, while variable RBE dose shows higher lung dose. Conclusion: The methodology developed in this pilot study is currently used for the analysis of a cohort of ∼90 lung patients from a clinical trial comparing proton and photon therapy for lung cancer. The results from this study will help us in determining the clinical significance of more accurate dose computation models in proton therapy.« less

Nuclear Radiation Degradation Study on HD Camera Based on CMOS Image Sensor at Different Dose Rates.

PubMed

Wang, Congzheng; Hu, Song; Gao, Chunming; Feng, Chang

2018-02-08

In this work, we irradiated a high-definition (HD) industrial camera based on a commercial-off-the-shelf (COTS) CMOS image sensor (CIS) with Cobalt-60 gamma-rays. All components of the camera under test were fabricated without radiation hardening, except for the lens. The irradiation experiments of the HD camera under biased conditions were carried out at 1.0, 10.0, 20.0, 50.0 and 100.0 Gy/h. During the experiment, we found that the tested camera showed a remarkable degradation after irradiation and differed in the dose rates. With the increase of dose rate, the same target images become brighter. Under the same dose rate, the radiation effect in bright area is lower than that in dark area. Under different dose rates, the higher the dose rate is, the worse the radiation effect will be in both bright and dark areas. And the standard deviations of bright and dark areas become greater. Furthermore, through the progressive degradation analysis of the captured image, experimental results demonstrate that the attenuation of signal to noise ratio (SNR) versus radiation time is not obvious at the same dose rate, and the degradation is more and more serious with increasing dose rate. Additionally, the decrease rate of SNR at 20.0, 50.0 and 100.0 Gy/h is far greater than that at 1.0 and 10.0 Gy/h. Even so, we confirm that the HD industrial camera is still working at 10.0 Gy/h during the 8 h of measurements, with a moderate decrease of the SNR (5 dB). The work is valuable and can provide suggestion for camera users in the radiation field.

Nuclear Radiation Degradation Study on HD Camera Based on CMOS Image Sensor at Different Dose Rates

PubMed Central

Wang, Congzheng; Hu, Song; Gao, Chunming; Feng, Chang

2018-01-01

In this work, we irradiated a high-definition (HD) industrial camera based on a commercial-off-the-shelf (COTS) CMOS image sensor (CIS) with Cobalt-60 gamma-rays. All components of the camera under test were fabricated without radiation hardening, except for the lens. The irradiation experiments of the HD camera under biased conditions were carried out at 1.0, 10.0, 20.0, 50.0 and 100.0 Gy/h. During the experiment, we found that the tested camera showed a remarkable degradation after irradiation and differed in the dose rates. With the increase of dose rate, the same target images become brighter. Under the same dose rate, the radiation effect in bright area is lower than that in dark area. Under different dose rates, the higher the dose rate is, the worse the radiation effect will be in both bright and dark areas. And the standard deviations of bright and dark areas become greater. Furthermore, through the progressive degradation analysis of the captured image, experimental results demonstrate that the attenuation of signal to noise ratio (SNR) versus radiation time is not obvious at the same dose rate, and the degradation is more and more serious with increasing dose rate. Additionally, the decrease rate of SNR at 20.0, 50.0 and 100.0 Gy/h is far greater than that at 1.0 and 10.0 Gy/h. Even so, we confirm that the HD industrial camera is still working at 10.0 Gy/h during the 8 h of measurements, with a moderate decrease of the SNR (5 dB). The work is valuable and can provide suggestion for camera users in the radiation field. PMID:29419782

Comparison of Points of Departure for Health Risk Assessment Based on High-Throughput Screening Data

PubMed Central

Sand, Salomon; Parham, Fred; Portier, Christopher J.; Tice, Raymond R.; Krewski, Daniel

2016-01-01

Background: The National Research Council’s vision for toxicity testing in the 21st century anticipates that points of departure (PODs) for establishing human exposure guidelines in future risk assessments will increasingly be based on in vitro high-throughput screening (HTS) data. Objectives: The aim of this study was to compare different PODs for HTS data. Specifically, benchmark doses (BMDs) were compared to the signal-to-noise crossover dose (SNCD), which has been suggested as the lowest dose applicable as a POD. Methods: Hill models were fit to > 10,000 in vitro concentration–response curves, obtained for > 1,400 chemicals tested as part of the U.S. Tox21 Phase I effort. BMDs and lower confidence limits on the BMDs (BMDLs) corresponding to extra effects (i.e., changes in response relative to the maximum response) of 5%, 10%, 20%, 30%, and 40% were estimated for > 8,000 curves, along with BMDs and BMDLs corresponding to additional effects (i.e., absolute changes in response) of 5%, 10%, 15%, 20%, and 25%. The SNCD, defined as the dose where the ratio between the additional effect and the difference between the upper and lower bounds of the two-sided 90% confidence interval on absolute effect was 1, 0.67, and 0.5, respectively, was also calculated and compared with the BMDLs. Results: The BMDL40, BMDL25, and BMDL18, defined in terms of extra effect, corresponded to the SNCD1.0, SNCD0.67, and SNCD0.5, respectively, at the median. Similarly, the BMDL25, BMDL17, and BMDL13, defined in terms of additional effect, corresponded to the SNCD1.0, SNCD0.67, and SNCD0.5, respectively, at the median. Conclusions: The SNCD may serve as a reference level that guides the determination of standardized BMDs for risk assessment based on HTS concentration–response data. The SNCD may also have application as a POD for low-dose extrapolation. Citation: Sand S, Parham F, Portier CJ, Tice RR, Krewski D. 2017. Comparison of points of departure for health risk assessment based on high-throughput screening data. Environ Health Perspect 125:623–633; http://dx.doi.org/10.1289/EHP408 PMID:27384688

Fibrinolytic Activity and Dose-Dependent Effect of Incubating Human Blood Clots in Caffeic Acid Phenethyl Ester: In Vitro Assays

PubMed Central

Elnager, Abuzar; Hassan, Rosline; Idris, Zamzuri; Mustafa, Zulkifli; Wan-Arfah, Nadiah; Sulaiman, S. A.; Gan, Siew Hua; Abdullah, Wan Zaidah

2015-01-01

Background. Caffeic acid phenethyl ester (CAPE) has been reported to possess time-dependent fibrinolytic activity by in vitro assay. This study is aimed at investigating fibrinolytic dose-dependent activity of CAPE using in vitro assays. Methods. Standardized human whole blood (WB) clots were incubated in either blank controls or different concentrations of CAPE (3.75, 7.50, 15.00, 22.50, and 30.00 mM). After 3 hours, D-dimer (DD) levels and WB clot weights were measured for each concentration. Thromboelastography (TEG) parameters were recorded following CAPE incubation, and fibrin morphology was examined under a confocal microscope. Results. Overall, mean DD (μg/mL) levels were significantly different across samples incubated with different CAPE concentrations, and the median pre- and postincubation WB clot weights (grams) were significantly decreased for each CAPE concentration. Fibrin removal was observed microscopically and indicated dose-dependent effects. Based on the TEG test, the Ly30 fibrinolytic parameter was significantly different between samples incubated with two different CAPE concentrations (15.0 and 22.50 mM). The 50% effective dose (ED50) of CAPE (based on DD) was 1.99 mg/mL. Conclusions. This study suggests that CAPE possesses fibrinolytic activity following in vitro incubation and that it has dose-dependent activities. Therefore, further investigation into CAPE as a potential alternative thrombolytic agent should be conducted. PMID:25664321

Cost-effectiveness of HPV vaccination regime: comparing twice versus thrice vaccinations dose regime among adolescent girls in Malaysia.

PubMed

Aljunid, Syed; Maimaiti, Namaitijiang; Nur, Amrizal M; Noor, Mohd Rushdan Md; Wan Puteh, Sharifa Ezat

2016-01-23

The HPV vaccine was introduced to Malaysian national immunization programme in 2010. The current implementation age of HPV vaccination in Malaysian is at the age of 13 years school girls, given according to a 3 doses protocol which may complicate implementation and compliance. Aim of the study is to determine the cost-effectiveness of HPV vaccination regime comparing twice versus thrice HPV vaccinations dose regime among adolescent girls in Malaysia. A Markov cohort model reflecting the natural history of HPV infection accounting for oncogenic and low-risk HPV was adapted for 13 year old Malaysian girls cohort (n = 274,050). Transition probabilities, utilities values, epidemiological and cost data were sourced from published literature and local data. Vaccine effectiveness was based on overall efficacy reported from 3-doses clinical trials, with the assumption that the 2-doses is non-inferior to the 3-doses allowing overall efficacy to be inferred from the 3-doses immunogenicity data. Price parity and life-long protection were assumed. The payer perspective was adopted, with appropriate discounting for costs (3 %) and outcomes (3 %). One way sensitivity analysis was conducted. The sensitivity analysis on cost of vaccine, vaccine coverage and discount rate with a 2-doses protocol was performed. The 3-doses and 2-doses regimes showed same number of Cervical Cancers averted (361 cases); QALYs saved at 7,732,266. However, the lifetime protection under the 2-doses regime, showed a significant cost-savings of RM 36, 722,700 compared to the 3-doses scheme. The MOH Malaysia could vaccinate 137,025 more girls in this country using saving 2-doses regime vaccination programme. The model predicted that 2-doses HPV vaccination schemes can avoid additional 180 Cervical Cancers and 63 deaths compare to 3-doses. A 2-doses HPV vaccination scheme may enable Malaysian women to be protected at a lower cost than that achievable under a 3-doses scheme, while avoiding the same number of Cervical Cancer cases and deaths. Using the saving money with 2-doses, more Cervical Cancers and deaths can be avoided.

SU-F-18C-01: Minimum Detectability Analysis for Comprehensive Sized Based Optimization of Image Quality and Radiation Dose Across CT Protocols

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

Smitherman, C; Chen, B; Samei, E

2014-06-15

Purpose: This work involved a comprehensive modeling of task-based performance of CT across a wide range of protocols. The approach was used for optimization and consistency of dose and image quality within a large multi-vendor clinical facility. Methods: 150 adult protocols from the Duke University Medical Center were grouped into sub-protocols with similar acquisition characteristics. A size based image quality phantom (Duke Mercury Phantom) was imaged using these sub-protocols for a range of clinically relevant doses on two CT manufacturer platforms (Siemens, GE). The images were analyzed to extract task-based image quality metrics such as the Task Transfer Function (TTF),more » Noise Power Spectrum, and Az based on designer nodule task functions. The data were analyzed in terms of the detectability of a lesion size/contrast as a function of dose, patient size, and protocol. A graphical user interface (GUI) was developed to predict image quality and dose to achieve a minimum level of detectability. Results: Image quality trends with variations in dose, patient size, and lesion contrast/size were evaluated and calculated data behaved as predicted. The GUI proved effective to predict the Az values representing radiologist confidence for a targeted lesion, patient size, and dose. As an example, an abdomen pelvis exam for the GE scanner, with a task size/contrast of 5-mm/50-HU, and an Az of 0.9 requires a dose of 4.0, 8.9, and 16.9 mGy for patient diameters of 25, 30, and 35 cm, respectively. For a constant patient diameter of 30 cm, the minimum detected lesion size at those dose levels would be 8.4, 5, and 3.9 mm, respectively. Conclusion: The designed CT protocol optimization platform can be used to evaluate minimum detectability across dose levels and patient diameters. The method can be used to improve individual protocols as well as to improve protocol consistency across CT scanners.« less

Agonistic TAM-163 antibody targeting tyrosine kinase receptor-B: applying mechanistic modeling to enable preclinical to clinical translation and guide clinical trial design.

PubMed

Vugmeyster, Yulia; Rohde, Cynthia; Perreault, Mylene; Gimeno, Ruth E; Singh, Pratap

2013-01-01

TAM-163, an agonist monoclonal antibody targeting tyrosine receptor kinase-B (TrkB), is currently being investigated as a potential body weight modulatory agent in humans. To support the selection of the dose range for the first-in-human (FIH) trial of TAM-163, we conducted a mechanistic analysis of the pharmacokinetic (PK) and pharmacodynamic (PD) data (e.g., body weight gain) obtained in lean cynomolgus and obese rhesus monkeys following single doses ranging from 0.3 to 60 mg/kg. A target-mediated drug disposition (TMDD) model was used to describe the observed nonlinear PK and Emax approach was used to describe the observed dose-dependent PD effect. The TMDD model development was supported by the experimental determination of the binding affinity constant (9.4 nM) and internalization rate of the drug-target complex (2.08 h(-1)). These mechanistic analyses enabled linking of exposure, target (TrkB) coverage, and pharmacological activity (e.g., PD) in monkeys, and indicated that ≥ 38% target coverage (time-average) was required to achieve significant body weight gain in monkeys. Based on the scaling of the TMDD model from monkeys to humans and assuming similar relationship between the target coverage and pharmacological activity between monkey and humans, subcutaneous (SC) doses of 1 and 15 mg/kg in humans were projected to be the minimally and the fully pharmacologically active doses, respectively. Based on the minimal anticipated biological effect level (MABEL) approach for starting dose selection, the dose of 0.05 mg/kg (3 mg for a 60 kg human) SC was recommended as the starting dose for FIH trials, because at this dose level<10% target coverage was projected at Cmax (and all other time points). This study illustrates a rational mechanistic approach for the selection of FIH dose range for a therapeutic protein with a complex model of action.

Estimating the effective radiation dose imparted to patients by intraoperative cone-beam computed tomography in thoracolumbar spinal surgery.

PubMed

Lange, Jeffrey; Karellas, Andrew; Street, John; Eck, Jason C; Lapinsky, Anthony; Connolly, Patrick J; Dipaola, Christian P

2013-03-01

Observational. To estimate the radiation dose imparted to patients during typical thoracolumbar spinal surgical scenarios. Minimally invasive techniques continue to become more common in spine surgery. Computer-assisted navigation systems coupled with intraoperative cone-beam computed tomography (CT) represent one such method used to aid in instrumented spinal procedures. Some studies indicate that cone-beam CT technology delivers a relatively low dose of radiation to patients compared with other x-ray-based imaging modalities. The goal of this study was to estimate the radiation exposure to the patient imparted during typical posterior thoracolumbar instrumented spinal procedures, using intraoperative cone-beam CT and to place these values in the context of standard CT doses. Cone-beam CT scans were obtained using Medtronic O-arm (Medtronic, Minneapolis, MN). Thermoluminescence dosimeters were placed in a linear array on a foam-plastic thoracolumbar spine model centered above the radiation source for O-arm presets of lumbar scans for small or large patients. In-air dosimeter measurements were converted to skin surface measurements, using published conversion factors. Dose-length product was calculated from these values. Effective dose was estimated using published effective dose to dose-length product conversion factors. Calculated dosages for many full-length procedures using the small-patient setting fell within the range of published effective doses of abdominal CT scans (1-31 mSv). Calculated dosages for many full-length procedures using the large-patient setting fell within the range of published effective doses of abdominal CT scans when the number of scans did not exceed 3. We have demonstrated that single cone-beam CT scans and most full-length posterior instrumented spinal procedures using O-arm in standard mode would likely impart a radiation dose within the range of those imparted by a single standard CT scan of the abdomen. Radiation dose increases with patient size, and the radiation dose received by larger patients as a result of more than 3 O-arm scans in standard mode may exceed the dose received during standard CT of the abdomen. Understanding radiation imparted to patients by cone-beam CT is important for assessing risks and benefits of this technology, especially when spinal surgical procedures require multiple intraoperative scans.

Individualized FSH dosing based on ovarian reserve testing in women starting IVF/ICSI: a multicentre trial and cost-effectiveness analysis.

PubMed

van Tilborg, Theodora C; Oudshoorn, Simone C; Eijkemans, Marinus J C; Mochtar, Monique H; van Golde, Ron J T; Hoek, Annemieke; Kuchenbecker, Walter K H; Fleischer, Kathrin; de Bruin, Jan Peter; Groen, Henk; van Wely, Madelon; Lambalk, Cornelis B; Laven, Joop S E; Mol, Ben Willem J; Broekmans, Frank J M; Torrance, Helen L

2017-12-01

Is there a difference in live birth rate and/or cost-effectiveness between antral follicle count (AFC)-based individualized FSH dosing or standard FSH dosing in women starting IVF or ICSI treatment? In women initiating IVF/ICSI, AFC-based individualized FSH dosing does not improve live birth rates or reduce costs as compared to a standard FSH dose. In IVF or ICSI, ovarian reserve testing is often used to adjust the FSH dose in order to normalize ovarian response and optimize live birth rates. However, no robust evidence for the (cost-)effectiveness of this practice exists. Between May 2011 and May 2014 we performed a multicentre prospective cohort study with two embedded RCTs in women scheduled for IVF/ICSI. Based on the AFC, women entered into one of the two RCTs (RCT1: AFC < 11; RCT2: AFC > 15) or the cohort (AFC 11-15). The primary outcome was ongoing pregnancy achieved within 18 months after randomization resulting in a live birth (delivery of at least one live foetus after 24 weeks of gestation). Data from the cohort with weight 0.5 were combined with both RCTs in order to conduct a strategy analysis. Potential half-integer numbers were rounded up. Differences in costs and effects between the two treatment strategies were compared by bootstrapping. In both RCTs women were randomized to an individualized (RCT1:450/225 IU, RCT2:100 IU) or standard FSH dose (150 IU). Women in the cohort all received the standard dose (150 IU). Anti-Müllerian hormone (AMH) was measured to assess AMH post-hoc as a biomarker to individualize treatment. For RCT1 dose adjustment was allowed in subsequent cycles based on pre-specified criteria in the standard group only. For RCT2 dose adjustment was allowed in subsequent cycles in both groups. Both effectiveness and cost-effectiveness of the strategies were evaluated from an intention-to-treat perspective. We included 1515 women, of whom 483 (31.9%) entered the cohort, 511 (33.7%) RCT1 and 521 (34.4%) RCT2. Live births occurred in 420/747 (56.3%) women in the individualized strategy and 447/769 (58.2%) women in the standard strategy (risk difference -0.019 (95% CI, -0.06 to 0.02), P = 0.39; a total of 1516 women due to rounding up the half integer numbers). The individualized strategy was more expensive (delta costs/woman = €275 (95% CI, 40 to 499)). Individualized dosing reduced the occurrence of mild and moderate ovarian hyperstimulation syndrome (OHSS) and subsequently the costs for management of these OHSS categories (costs saved/woman were €35). The analysis based on AMH as a tool for dose individualization suggested comparable results. Despite a training programme, the AFC might have suffered from inter-observer variation. In addition, although strict cancel criteria were provided, selective cancelling in the individualized dose group (for poor response in particular) cannot be excluded as observers were not blinded for the FSH dose and small dose adjustments were allowed in subsequent cycles. However, as both first cycle live birth rates and cumulative live birth rates show no difference between strategies, the open design probably did not mask a potential benefit for the individualized group. Despite increasing consensus on using GnRH antagonist co-treatment in women predicted for a hyper response in particular, GnRH agonists were used in almost 80% of the women in this study. Hence, in those women, the AFC and bloodsampling for the post-hoc AMH analysis were performed during pituitary suppression. As the correlation between AFC and ovarian response is not compromised during GnRH agonist use, this will probably not have influenced classification of response. Individualized FSH dosing for the IVF/ICSI population as a whole should not be pursued as it does not improve live birth rates and it increases costs. Women scheduled for IVF/ICSI with a regular menstrual cycle are therefore recommended a standard FSH starting dose of 150 IU per day. Still, safety management by individualized dosing in predicted hyper responders is open for further research. This study was funded by The Netherlands Organisation for Health Research and Development (ZonMW number 171102020). AMH measurements were performed free of charge by Roche Diagnostics. TCT, HLT and SCO received an unrestricted personal grant from Merck BV. AH declares that the department of Obstetrics and Gynecology, University Medical Centre Groningen receives an unrestricted research grant from Ferring pharmaceutics BV, The Netherlands. CBL receives grants from Merck, Ferring and Guerbet. BWJM is supported by a NHMRC Practitioner Fellowship (GNT1082548) and reports consultancy for OvsEva, Merck and Guerbet. FJMB receives monetary compensation as a member of the external advisory board for Ferring pharmaceutics BV (the Netherlands) and Merck Serono (the Netherlands) for consultancy work for Gedeon Richter (Belgium) and Roche Diagnostics on automated AMH assay development (Switzerland) and for a research cooperation with Ansh Labs (USA). All other autors have nothing to declare. Registered at the ICMJE-recognized Dutch Trial Registry (www.trialregister.nl). Registration number: NTR2657. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Pathology effects at radiation doses below those causing increased mortality

NASA Technical Reports Server (NTRS)

Carnes, Bruce A.; Gavrilova, Natalia; Grahn, Douglas

2002-01-01

Mortality data from experiments conducted at the Argonne National Laboratory (ANL) on the long-term effects of external whole-body irradiation on B6CF(1) mice were used to investigate radiation-induced effects at intermediate doses of (60)Co gamma rays or fission-spectrum neutrons either delivered as a single exposure or protracted over 60 once-weekly exposures. Kaplan-Meier analyses were used to identify the lowest dose in the ANL data (within radiation quality, pattern of exposure, and sex) at which radiation-induced mortality caused by primary tumors could be detected (approximately 1-2 Gy for gamma rays and 10-15 cGy for neutrons). Doses at and below these levels were then examined for radiation-induced shifts in the spectrum of pathology detected at death. To do this, specific pathology events were pooled into larger assemblages based on whether they were cancer, cardiovascular disease or non-neoplastic diseases detected within the lungs and pleura, liver and biliary tract, reproductive organs, or urinary tract. Cancer and cardiovascular disease were further subdivided into categories based on whether they caused death, contributed to death, or were simply observed at death. Counts of how often events falling within each of these combined pathology categories occurred within a mouse were then used as predictor variables in logistic regression to determine whether irradiated mice could be distinguished from control mice. Increased pathology burdens were detected in irradiated mice at doses lower than those causing detectable shifts in mortality-22 cGy for gamma rays and 2 cGy for neutrons. These findings suggest that (1) models based on mortality data alone may underestimate radiation effects, (2) radiation may have adverse health consequences (i.e. elevated health risks) even when mortality risks are not detected, and (3) radiation-induced pathologies other than cancer do occur, and they involve multiple organ systems.

Cost-effectiveness of CT screening in the National Lung Screening Trial.

PubMed

Black, William C; Gareen, Ilana F; Soneji, Samir S; Sicks, JoRean D; Keeler, Emmett B; Aberle, Denise R; Naeim, Arash; Church, Timothy R; Silvestri, Gerard A; Gorelick, Jeremy; Gatsonis, Constantine

2014-11-06

The National Lung Screening Trial (NLST) showed that screening with low-dose computed tomography (CT) as compared with chest radiography reduced lung-cancer mortality. We examined the cost-effectiveness of screening with low-dose CT in the NLST. We estimated mean life-years, quality-adjusted life-years (QALYs), costs per person, and incremental cost-effectiveness ratios (ICERs) for three alternative strategies: screening with low-dose CT, screening with radiography, and no screening. Estimations of life-years were based on the number of observed deaths that occurred during the trial and the projected survival of persons who were alive at the end of the trial. Quality adjustments were derived from a subgroup of participants who were selected to complete quality-of-life surveys. Costs were based on utilization rates and Medicare reimbursements. We also performed analyses of subgroups defined according to age, sex, smoking history, and risk of lung cancer and performed sensitivity analyses based on several assumptions. As compared with no screening, screening with low-dose CT cost an additional $1,631 per person (95% confidence interval [CI], 1,557 to 1,709) and provided an additional 0.0316 life-years per person (95% CI, 0.0154 to 0.0478) and 0.0201 QALYs per person (95% CI, 0.0088 to 0.0314). The corresponding ICERs were $52,000 per life-year gained (95% CI, 34,000 to 106,000) and $81,000 per QALY gained (95% CI, 52,000 to 186,000). However, the ICERs varied widely in subgroup and sensitivity analyses. We estimated that screening for lung cancer with low-dose CT would cost $81,000 per QALY gained, but we also determined that modest changes in our assumptions would greatly alter this figure. The determination of whether screening outside the trial will be cost-effective will depend on how screening is implemented. (Funded by the National Cancer Institute; NLST ClinicalTrials.gov number, NCT00047385.).

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

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

Gillmann, Clarissa, E-mail: clarissa.gillmann@med.uni-heidelberg.de; Jäkel, Oliver; Heidelberg Ion Beam Therapy Center

2014-04-01

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

SU-G-206-15: Effects of Dose Reduction On Emphysema Score

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

Lo, P; Wahi-Anwar, M; Kim, H

Purpose: The purpose of this study was to investigate the effects of reducing radiation dose levels on emphysema scores from lung cancer screening CT exams. Methods: 52 cases were selected from the National Lung Screening Trial (NLST) patients for which we had both the image series and the raw CT data. All scans were acquired with fixed effective mAs (25 for standard-sized patients, 40 for large patients) on a 64-slice scanner (Sensation 64, Siemens Healthcare) using 120kV, 64×0.6mm collimation and pitch 1.0. All images were reconstructed with 1mm slice thickness, B50 kernel. Based on a previously-published technique, we added noisemore » to the raw data to simulate reduced-dose versions at 50% and 25% of the original dose (approximately 1.0- and 0.5-mGy CTDIvol). Lung segmentations were obtained via region growing from manual seed point at a threshold of 600HU followed by manual removal of trachea and major airways. Lung segmentations were only performed on original dose scans, and mapped to simulated reduced-dose scans. Emphysema scores based on relative area of lung with attenuation values lower than −950HU (RA950) were computed for all cases. Results: Average RA950 of all 50 cases were 31.6 (±5.5), 32.5 (±4.9) and 32.8 (±4.6) for 100%, 50% and 25% dose level respectively. The average absolute difference in RA950 between simulated and original dose scans were 1.0 (±0.7) and 1.4 (±1.1) for 50% and 25% dose level respectively. Conclusion: RA950 is relatively robust to dose level, with a difference of no more than 5 from the original dose scans. The average RA950 of this population was high for a two reasons: This was a high risk population of patients with substantial smoking history; The use of B50 kernel, which may be biased towards high emphysema scores. Further exploration with smoother kernels will be conducted in the future. Institutional research agreement, Siemens Healthcare; Past recipient, research grant support, Siemens Healthcare; Consultant, Toshiba America Medical Systems; Consultant, Samsung Electronics; NIH grant support from U01 CA181156.« less

Effectiveness of Haemophilus influenzae type b vaccines administered according to various schedules: systematic review and meta-analysis of observational data.

PubMed

Jackson, Charlotte; Mann, Andrea; Mangtani, Punam; Fine, Paul

2013-11-01

Conjugate vaccines against Haemophilus influenzae type b (Hib) are widely used. The full implications of Hib vaccination schedule for vaccine effectiveness (VE) are unclear. We searched the literature for observational studies reporting the effectiveness of conjugate Hib vaccines administered according to different schedules. We summarized dose-specific VE estimates, where appropriate, using random effects meta-analysis. Thirty-one eligible articles (reporting 30 studies conducted in 17 countries) were identified. Meta-analysis of case-control studies using community controls produced VE estimates against Hib meningitis of 55% (95% confidence interval: 2-80%, based on 3 studies), 96% (86-99%, 3 studies) and 96% (86-99%, 4 studies) after 1, 2 and 3 doses of vaccines other than the polyribosyl ribitol phosphate outer membrane protein vaccine. Estimates were similar using hospital controls. VE against invasive Hib disease in case-control studies was estimated as 59% (30-76%, 3 studies) and 97% (87-99%, 3 studies) for 1 and 3 doses (insufficient data were identified to estimate 2-dose VE). Point estimates from 2 studies suggested VE>90% after 1 dose of the polyribosyl ribitol phosphate outer membrane protein vaccine, but meta-analysis was not possible. Using data from 4 cohort studies, 3-dose VE was estimated as 94% (88-97%). There was some evidence that Hib vaccine was less effective when administered with acellular (rather than whole cell) pertussis vaccine. Weak evidence from 2 studies suggested that a booster confers some additional protection following full primary vaccination and may compensate for an incomplete primary series. Observational data suggest that ≥2 doses of Hib vaccine are required for high effectiveness, but do not strongly favor any particular schedule.

Combination Treatment of Glioblastoma by Low-Dose Radiation and Genistein.

PubMed

Atefeh, Zamanian; Vahid, Changizi; Hasan, Nedaie; Saeed, Amanpour; Mahnaz, Haddadi

2016-01-01

Gioblastoma multiforme as a chemoresistant and radioresistant malignant cell line needs to novel strategies to treatment. Low-dose hyper-radiosensitivity (LDHRS) seems to be an effective phenomenon to irradiation that can save normal brain fibroblasts. Genistein which is a soy isoflavone can be cytotoxic in some tumor cell lines. So we determined to study the effect of combining these two treatment modalities. After 30 hours incubation with Genistein in different concentrations on U87MG cell line, proliferation and clonogenicity were conducted by both clonogenic and MTT assays. A conventional 2Gy radiation dose was compared with 10 doses of 0.2Gy gamma irradiation with 3 minutes and 1 hour intervals. Finally, concurrent effect of these modalities was assessed. Based on acquired cell doubling time (30 hours), one doubling time treatment by Genistein could decrease clonogenicity. U87MG cell line exhibited HRS at low dose irradiations. 2Gy irradiation was more effective than ultra-fractionation methods in comparison with control group. All groups with 50uM concentration of Genistein showed decrease in the survival. This decrease compared with control group, in 10x0.2Gy with 3 minutes intervals plus 50uM Genistein was significant and for groups with the same dose of Genistein but along with continuous 2Gy was more significant. In one day treatment regimen, 10x0.2Gy ultra-fractionation with 3 minutes and 1 hour intervals seems to be less effective than conventional 2Gy irradiation, however adding 50uM Genistein can decrease survival more. Although 2Gy conventional dose plus 50uM Genistein was the most effective regimen. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

[Comparative study on promoting blood effects of Danshen-Honghua herb pair with different preparations based on chemometrics and multi-attribute comprehensive index methods].

PubMed

Qu, Cheng; Tang, Yu-Ping; Shi, Xu-Qin; Zhou, Gui-Sheng; Shang, Er-Xin; Shang, Li-Li; Guo, Jian-Ming; Liu, Pei; Zhao, Jing; Zhao, Bu-Chang; Duan, Jin-Ao

2017-08-01

To evaluate the promoting blood circulation and removing blood stasis effects of Danshen-Honghua(DH) herb pair with different preparations (alcohol, 50% alcohol and water) on blood rheology and coagulation functions in acute blood stasis rats, and optimize the best preparation method of DH based on principal component analysis(PCA), hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods. Ice water bath and subcutaneous injection of adrenaline were both used to establish the acute blood stasis rat model. Then the blood stasis rats were administrated intragastrically with DH (alcohol, 50% alcohol and water) extracts. The whole blood viscosity(WBV), plasma viscosity(PV), erythrocyte sedimentation rate(ESR) and haematocrit(HCT) were tested to observe the effects of DH herb pair with different preparations and doses on hemorheology of blood stasis rats; the activated partial thromboplastin time(APTT), thrombin time(TT), prothrombin time(PT), and plasma fibrinogen(FIB) were tested to observe the effects of DH herb pair with different preparations on blood coagulation function and platelet aggregation of blood stasis rats. Then PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods were all used to comprehensively evaluate the total promoting blood circulation and removing blood stasis effects of DH herb pair with different preparations. The hemorheological indexes and coagulation parameters of model group had significant differences with normal blank group. As compared with the model group, the DH herb pair with different preparations at low, middle and high doses could improve the blood hemorheology indexes and coagulation parameters in acute blood stasis rats with dose-effect relation. Based on the PCA, hierarchical cluster heatmap analysis and multi-attribute comprehensive index methods, the high dose group of 50% alcohol extract had the best effect of promoting blood circulation and removing blood stasis. Under the same dose but different preparations, 50% alcohol DH could obviously improve the hemorheology and blood coagulation function in acute blood stasis rats. These results suggested that DH herb pair with different preparations could obviously ameliorate the abnormality of hemorheology and blood coagulation function in acute blood stasis rats, and the optimized preparation of DH herb pair on promoting blood effects was 50% alcohol extract, providing scientific basis for more effective application of the DH herb pair in modern clinic medicine. Copyright© by the Chinese Pharmaceutical Association.

Prediction of Drug-Drug Interactions with Crizotinib as the CYP3A Substrate Using a Physiologically Based Pharmacokinetic Model.

PubMed

Yamazaki, Shinji; Johnson, Theodore R; Smith, Bill J

2015-10-01

An orally available multiple tyrosine kinase inhibitor, crizotinib (Xalkori), is a CYP3A substrate, moderate time-dependent inhibitor, and weak inducer. The main objectives of the present study were to: 1) develop and refine a physiologically based pharmacokinetic (PBPK) model of crizotinib on the basis of clinical single- and multiple-dose results, 2) verify the crizotinib PBPK model from crizotinib single-dose drug-drug interaction (DDI) results with multiple-dose coadministration of ketoconazole or rifampin, and 3) apply the crizotinib PBPK model to predict crizotinib multiple-dose DDI outcomes. We also focused on gaining insights into the underlying mechanisms mediating crizotinib DDIs using a dynamic PBPK model, the Simcyp population-based simulator. First, PBPK model-predicted crizotinib exposures adequately matched clinically observed results in the single- and multiple-dose studies. Second, the model-predicted crizotinib exposures sufficiently matched clinically observed results in the crizotinib single-dose DDI studies with ketoconazole or rifampin, resulting in the reasonably predicted fold-increases in crizotinib exposures. Finally, the predicted fold-increases in crizotinib exposures in the multiple-dose DDI studies were roughly comparable to those in the single-dose DDI studies, suggesting that the effects of crizotinib CYP3A time-dependent inhibition (net inhibition) on the multiple-dose DDI outcomes would be negligible. Therefore, crizotinib dose-adjustment in the multiple-dose DDI studies could be made on the basis of currently available single-dose results. Overall, we believe that the crizotinib PBPK model developed, refined, and verified in the present study would adequately predict crizotinib oral exposures in other clinical studies, such as DDIs with weak/moderate CYP3A inhibitors/inducers and drug-disease interactions in patients with hepatic or renal impairment. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Development of a dual phantom technique for measuring the fast neutron component of dose in boron neutron capture therapy

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

Sakurai, Yoshinori, E-mail: yosakura@rri.kyoto-u.ac.jp; Tanaka, Hiroki; Kondo, Natsuko

2015-11-15

Purpose: Research and development of various accelerator-based irradiation systems for boron neutron capture therapy (BNCT) is underway throughout the world. Many of these systems are nearing or have started clinical trials. Before the start of treatment with BNCT, the relative biological effectiveness (RBE) for the fast neutrons (over 10 keV) incident to the irradiation field must be estimated. Measurements of RBE are typically performed by biological experiments with a phantom. Although the dose deposition due to secondary gamma rays is dominant, the relative contributions of thermal neutrons (below 0.5 eV) and fast neutrons are virtually equivalent under typical irradiation conditionsmore » in a water and/or acrylic phantom. Uniform contributions to the dose deposited from thermal and fast neutrons are based in part on relatively inaccurate dose information for fast neutrons. This study sought to improve the accuracy in the dose estimation for fast neutrons by using two phantoms made of different materials in which the dose components can be separated according to differences in the interaction cross sections. The development of a “dual phantom technique” for measuring the fast neutron component of dose is reported. Methods: One phantom was filled with pure water. The other phantom was filled with a water solution of lithium hydroxide (LiOH) capitalizing on the absorbing characteristics of lithium-6 (Li-6) for thermal neutrons. Monte Carlo simulations were used to determine the ideal mixing ratio of Li-6 in LiOH solution. Changes in the depth dose distributions for each respective dose component along the central beam axis were used to assess the LiOH concentration at the 0, 0.001, 0.01, 0.1, 1, and 10 wt. % levels. Simulations were also performed with the phantom filled with 10 wt. % {sup 6}LiOH solution for 95%-enriched Li-6. A phantom was constructed containing 10 wt. % {sup 6}LiOH solution based on the simulation results. Experimental characterization of the depth dose distributions of the neutron and gamma-ray components along the central axis was performed at Heavy Water Neutron Irradiation Facility installed at Kyoto University Reactor using activation foils and thermoluminescent dosimeters, respectively. Results: Simulation results demonstrated that the absorbing effect for thermal neutrons occurred when the LiOH concentration was over 1%. The most effective Li-6 concentration was determined to be enriched {sup 6}LiOH with a solubility approaching its upper limit. Experiments confirmed that the thermal neutron flux and secondary gamma-ray dose rate decreased substantially; however, the fast neutron flux and primary gamma-ray dose rate were hardly affected in the 10%-{sup 6}LiOH phantom. It was confirmed that the dose contribution of fast neutrons is improved from approximately 10% in the pure water phantom to approximately 50% in the 10%-{sup 6}LiOH phantom. Conclusions: The dual phantom technique using the combination of a pure water phantom and a 10%-{sup 6}LiOH phantom developed in this work provides an effective method for dose estimation of the fast neutron component in BNCT. Improvement in the accuracy achieved with the proposed technique results in improved RBE estimation for biological experiments and clinical practice.« less

Preclinical Toxicological Evaluation of IDM01: The Botanical Composition of 4-Hydroxyisoleucine- and Trigonelline-based Standardized Fenugreek Seed Extract.

PubMed

Deshpande, Pallavi O; Mohan, Vishwaraman; Thakurdesai, Prasad Arvind

2017-01-01

To evaluate acute oral toxicity (AOT), subchronic (90-day repeated dose) toxicity, mutagenicity, and genotoxicity potential of IDM01, the botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek ( Trigonella foenum-graecum L) seed extract in laboratory rats. The AOT and subchronic (90-day repeated dose) toxicity were evaluated using Sprague-Dawley rats as per the Organisation for Economic Co-operation and Development (OECD) guidelines No. 423 and No. 408, respectively. During the subchronic study, the effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenicity and genotoxicity of IDM01 were evaluated by reverse mutation assay (Ames test, OECD guideline No. 471) and chromosome aberration test (OECD guideline No. 473), respectively. The IDM01 did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-day repeated dose of 250, 500, and 1000 mg/kg with 28 days of recovery period) administration. The IDM01 showed oral median lethal dose (LD50) >2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg. IDM01 did not show mutagenicity up to a concentration of 5000 μg/plate during Ames test and did not induce structural chromosomal aberrations up to 50 mg/culture. IDM01 was found safe during preclinical acute and subchronic (90-day repeated dose) toxicity in rats without mutagenicity or genotoxicity. Acute oral toxicity, subchronic (90-day) oral toxicity, mutagenicity and genotoxicity of IDM01 (4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract) was evaluated.The median lethal dose, LD50, of IDM01 was more than 2000 mg/kg of body weight in rats.No observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg of body weight in rats.IDM01 was found safe during acute and subchronic oral toxicity studies in rats without mutagenicity or genotoxicity potetial. Abbreviations Used: 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control. 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control.

Preclinical Toxicological Evaluation of IDM01: The Botanical Composition of 4-Hydroxyisoleucine- and Trigonelline-based Standardized Fenugreek Seed Extract

PubMed Central

Deshpande, Pallavi O.; Mohan, Vishwaraman; Thakurdesai, Prasad Arvind

2017-01-01

Objective: To evaluate acute oral toxicity (AOT), subchronic (90-day repeated dose) toxicity, mutagenicity, and genotoxicity potential of IDM01, the botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek (Trigonella foenum-graecum L) seed extract in laboratory rats. Materials and Methods: The AOT and subchronic (90-day repeated dose) toxicity were evaluated using Sprague-Dawley rats as per the Organisation for Economic Co-operation and Development (OECD) guidelines No. 423 and No. 408, respectively. During the subchronic study, the effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenicity and genotoxicity of IDM01 were evaluated by reverse mutation assay (Ames test, OECD guideline No. 471) and chromosome aberration test (OECD guideline No. 473), respectively. Results: The IDM01 did not show mortality or treatment-related adverse signs during acute (limit dose of 2000 mg/kg) and subchronic (90-day repeated dose of 250, 500, and 1000 mg/kg with 28 days of recovery period) administration. The IDM01 showed oral median lethal dose (LD50) >2000 mg/kg during AOT study. The no-observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg. IDM01 did not show mutagenicity up to a concentration of 5000 μg/plate during Ames test and did not induce structural chromosomal aberrations up to 50 mg/culture. Conclusions: IDM01 was found safe during preclinical acute and subchronic (90-day repeated dose) toxicity in rats without mutagenicity or genotoxicity. SUMMARY Acute oral toxicity, subchronic (90-day) oral toxicity, mutagenicity and genotoxicity of IDM01 (4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract) was evaluated.The median lethal dose, LD50, of IDM01 was more than 2000 mg/kg of body weight in rats.No observed adverse effect level (NOAEL) of IDM01 was 500 mg/kg of body weight in rats.IDM01 was found safe during acute and subchronic oral toxicity studies in rats without mutagenicity or genotoxicity potetial. Abbreviations Used: 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control. 2-AA: 2-aminoanthracene; 2-AF: 2-aminofluorene; 4 NQNO: 4-nitroquinolene-N-oxide; 4HI: 4-hydroxyisoleucine; ANOVA: Analysis of variance; AOT: Acute oral toxicity; DM: Diabetes mellitus; IDM01: The Botanical composition of 4-hydroxyisoleucine- and trigonelline-based standardized fenugreek seed extract; LD50: Median lethal dose; MMS: Methyl methanesulfonate; NAD: No abnormality detected; OECD: Organisation for Economic Co-operation and Development; SD: Standard deviation; UV: Ultraviolet; VC: Vehicle control PMID:28539737

Model-based Iterative Reconstruction: Effect on Patient Radiation Dose and Image Quality in Pediatric Body CT

PubMed Central

Dillman, Jonathan R.; Goodsitt, Mitchell M.; Christodoulou, Emmanuel G.; Keshavarzi, Nahid; Strouse, Peter J.

2014-01-01

Purpose To retrospectively compare image quality and radiation dose between a reduced-dose computed tomographic (CT) protocol that uses model-based iterative reconstruction (MBIR) and a standard-dose CT protocol that uses 30% adaptive statistical iterative reconstruction (ASIR) with filtered back projection. Materials and Methods Institutional review board approval was obtained. Clinical CT images of the chest, abdomen, and pelvis obtained with a reduced-dose protocol were identified. Images were reconstructed with two algorithms: MBIR and 100% ASIR. All subjects had undergone standard-dose CT within the prior year, and the images were reconstructed with 30% ASIR. Reduced- and standard-dose images were evaluated objectively and subjectively. Reduced-dose images were evaluated for lesion detectability. Spatial resolution was assessed in a phantom. Radiation dose was estimated by using volumetric CT dose index (CTDIvol) and calculated size-specific dose estimates (SSDE). A combination of descriptive statistics, analysis of variance, and t tests was used for statistical analysis. Results In the 25 patients who underwent the reduced-dose protocol, mean decrease in CTDIvol was 46% (range, 19%–65%) and mean decrease in SSDE was 44% (range, 19%–64%). Reduced-dose MBIR images had less noise (P > .004). Spatial resolution was superior for reduced-dose MBIR images. Reduced-dose MBIR images were equivalent to standard-dose images for lungs and soft tissues (P > .05) but were inferior for bones (P = .004). Reduced-dose 100% ASIR images were inferior for soft tissues (P < .002), lungs (P < .001), and bones (P < .001). By using the same reduced-dose acquisition, lesion detectability was better (38% [32 of 84 rated lesions]) or the same (62% [52 of 84 rated lesions]) with MBIR as compared with 100% ASIR. Conclusion CT performed with a reduced-dose protocol and MBIR is feasible in the pediatric population, and it maintains diagnostic quality. © RSNA, 2013 Online supplemental material is available for this article. PMID:24091359