Characterization of a gated fiber-optic-coupled detector for application in clinical electron beam dosimetry

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

Tanyi, James A.; Nitzling, Kevin D.; Lodwick, Camille J.

2011-02-15

Purpose: Assessment of the fundamental dosimetric characteristics of a novel gated fiber-optic-coupled dosimetry system for clinical electron beam irradiation. Methods: The response of fiber-optic-coupled dosimetry system to clinical electron beam, with nominal energy range of 6-20 MeV, was evaluated for reproducibility, linearity, and output dependence on dose rate, dose per pulse, energy, and field size. The validity of the detector system's response was assessed in correspondence with a reference ionization chamber. Results: The fiber-optic-coupled dosimetry system showed little dependence to dose rate variations (coefficient of variation {+-}0.37%) and dose per pulse changes (with 0.54% of reference chamber measurements). The reproducibilitymore » of the system was {+-}0.55% for dose fractions of {approx}100 cGy. Energy dependence was within {+-}1.67% relative to the reference ionization chamber for the 6-20 MeV nominal electron beam energy range. The system exhibited excellent linear response (R{sup 2}=1.000) compared to reference ionization chamber in the dose range of 1-1000 cGy. The output factors were within {+-}0.54% of the corresponding reference ionization chamber measurements. Conclusions: The dosimetric properties of the gated fiber-optic-coupled dosimetry system compare favorably to the corresponding reference ionization chamber measurements and show considerable potential for applications in clinical electron beam radiotherapy.« less

IRIS Toxicological Review of 2,2',4,4'-Tetrabromodiphenyl ...

EPA Pesticide Factsheets

The U.S. EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessments of congeners of polybrominated diphenyl ethers (PDBEs), this review is about 2,2',4,4'-Tetrabromodiphenyl Ether, or commonly referred to as tetraBDE (BDE-47). Following the external peer review this assessment will appear in the Integrated Risk Information System (IRIS) database. Peer review will ensure that science is used credibly and appropriately in derivation of the dose-response assessments and toxicological characterization. EPA is updating the Integrated Risk Information System (IRIS) health assessments for the PBDEs.

INTERCOMPARISON ON THE MEASUREMENT OF THE QUANTITY PERSONAL DOSE EQUIVALENT HP(10) IN PHOTON FIELDS. LINEARITY DEPENDENCE, LOWER LIMIT OF DETECTION AND UNCERTAINTY IN MEASUREMENT OF DOSIMETRY SYSTEMS OF INDIVIDUAL MONITORING SERVICES IN GABON AND GHANA.

PubMed

Ondo Meye, P; Schandorf, C; Amoako, J K; Manteaw, P O; Amoatey, E A; Adjei, D N

2017-12-01

An inter-comparison study was conducted to assess the capability of dosimetry systems of individual monitoring services (IMSs) in Gabon and Ghana to measure personal dose equivalent Hp(10) in photon fields. The performance indicators assessed were the lower limit of detection, linearity and uncertainty in measurement. Monthly and quarterly recording levels were proposed with corresponding values of 0.08 and 0.025 mSv, and 0.05 and 0.15 mSv for the TLD and OSL systems, respectively. The linearity dependence of the dosimetry systems was performed following the requirement given in the Standard IEC 62387 of the International Electrotechnical Commission (IEC). The results obtained for the two systems were satisfactory. The procedure followed for the uncertainty assessment is the one given in the IEC technical report TR62461. The maximum relative overall uncertainties, in absolute value, expressed in terms of Hp(10), for the TL dosimetry system Harshaw 6600, are 44. 35% for true doses below 0.40 mSv and 36.33% for true doses ≥0.40 mSv. For the OSL dosimetry system microStar, the maximum relative overall uncertainties, in absolute value, are 52.17% for true doses below 0.40 mSv and 37.43% for true doses ≥0.40 mSv. These results are in good agreement with the requirements for accuracy of the International Commission on Radiological protection. When expressing the uncertainties in terms of response, comparison with the IAEA requirements for overall accuracy showed that the uncertainty results were also acceptable. The values of Hp(10) directly measured by the two dosimetry systems showed a significant underestimation for the Harshaw 6600 system, and a slight overestimation for the microStar system. After correction for linearity of the measured doses, the two dosimetry systems gave better and comparable results. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

The grout/glass performance assessment code system (GPACS) with verification and benchmarking

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

Piepho, M.G.; Sutherland, W.H.; Rittmann, P.D.

1994-12-01

GPACS is a computer code system for calculating water flow (unsaturated or saturated), solute transport, and human doses due to the slow release of contaminants from a waste form (in particular grout or glass) through an engineered system and through a vadose zone to an aquifer, well and river. This dual-purpose document is intended to serve as a user`s guide and verification/benchmark document for the Grout/Glass Performance Assessment Code system (GPACS). GPACS can be used for low-level-waste (LLW) Glass Performance Assessment and many other applications including other low-level-waste performance assessments and risk assessments. Based on all the cses presented, GPACSmore » is adequate (verified) for calculating water flow and contaminant transport in unsaturated-zone sediments and for calculating human doses via the groundwater pathway.« less

IRIS Toxicological Review of Dichloromethane (Methylene ...

EPA Pesticide Factsheets

EPA has finalized the Toxicological Review of Dichloromethane (Methylene Chloride): In support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health. This document presents background information and justification for the Intergrated Risk Information System (IRIS) Summary of the hazard and dose-response assessment of dichloromethane. IRIS Summaries may include oral reference dose (RfD) and inhalation reference concentration (RfC) values for chronic and other exposure durations, and a carcinogencity assessment. Internet/NCEA web site

IRIS Toxicological Review of Methanol (Non-Cancer) ...

EPA Pesticide Factsheets

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of methanol (non-cancer) that when finalized will appear on the Integrated Risk Information System (IRIS) database. EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of methanol (non-cancer) that will appear in the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Acrylamide (External Review ...

EPA Pesticide Factsheets

EPA has conducted a peer review by EPA’s Science Advisory Board (SAB) of the scientific basis supporting the human health hazard and dose-response assessment of acrylamide that once finalized will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that the science is used credibly and appropriately in derivation of the dose-response assessments and toxicological characterization. The draft Toxicological Review of Acrylamide provides scientific support and rationale for the hazard identification and dose-response assessment pertaining to a chronic exposure to acrylamide.

SIMULATING LOCAL DENSE AREAS USING PMMA TO ASSESS AUTOMATIC EXPOSURE CONTROL IN DIGITAL MAMMOGRAPHY.

PubMed

Bouwman, R W; Binst, J; Dance, D R; Young, K C; Broeders, M J M; den Heeten, G J; Veldkamp, W J H; Bosmans, H; van Engen, R E

2016-06-01

Current digital mammography (DM) X-ray systems are equipped with advanced automatic exposure control (AEC) systems, which determine the exposure factors depending on breast composition. In the supplement of the European guidelines for quality assurance in breast cancer screening and diagnosis, a phantom-based test is included to evaluate the AEC response to local dense areas in terms of signal-to-noise ratio (SNR). This study evaluates the proposed test in terms of SNR and dose for four DM systems. The glandular fraction represented by the local dense area was assessed by analytic calculations. It was found that the proposed test simulates adipose to fully glandular breast compositions in attenuation. The doses associated with the phantoms were found to match well with the patient dose distribution. In conclusion, after some small adaptations, the test is valuable for the assessment of the AEC performance in terms of both SNR and dose. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

An adaptive algorithm for the detection of microcalcifications in simulated low-dose mammography.

PubMed

Treiber, O; Wanninger, F; Führ, H; Panzer, W; Regulla, D; Winkler, G

2003-02-21

This paper uses the task of microcalcification detection as a benchmark problem to assess the potential for dose reduction in x-ray mammography. We present the results of a newly developed algorithm for detection of microcalcifications as a case study for a typical commercial film-screen system (Kodak Min-R 2000/2190). The first part of the paper deals with the simulation of dose reduction for film-screen mammography based on a physical model of the imaging process. Use of a more sensitive film-screen system is expected to result in additional smoothing of the image. We introduce two different models of that behaviour, called moderate and strong smoothing. We then present an adaptive, model-based microcalcification detection algorithm. Comparing detection results with ground-truth images obtained under the supervision of an expert radiologist allows us to establish the soundness of the detection algorithm. We measure the performance on the dose-reduced images in order to assess the loss of information due to dose reduction. It turns out that the smoothing behaviour has a strong influence on detection rates. For moderate smoothing. a dose reduction by 25% has no serious influence on the detection results. whereas a dose reduction by 50% already entails a marked deterioration of the performance. Strong smoothing generally leads to an unacceptable loss of image quality. The test results emphasize the impact of the more sensitive film-screen system and its characteristics on the problem of assessing the potential for dose reduction in film-screen mammography. The general approach presented in the paper can be adapted to fully digital mammography.

An adaptive algorithm for the detection of microcalcifications in simulated low-dose mammography

NASA Astrophysics Data System (ADS)

Treiber, O.; Wanninger, F.; Führ, H.; Panzer, W.; Regulla, D.; Winkler, G.

2003-02-01

This paper uses the task of microcalcification detection as a benchmark problem to assess the potential for dose reduction in x-ray mammography. We present the results of a newly developed algorithm for detection of microcalcifications as a case study for a typical commercial film-screen system (Kodak Min-R 2000/2190). The first part of the paper deals with the simulation of dose reduction for film-screen mammography based on a physical model of the imaging process. Use of a more sensitive film-screen system is expected to result in additional smoothing of the image. We introduce two different models of that behaviour, called moderate and strong smoothing. We then present an adaptive, model-based microcalcification detection algorithm. Comparing detection results with ground-truth images obtained under the supervision of an expert radiologist allows us to establish the soundness of the detection algorithm. We measure the performance on the dose-reduced images in order to assess the loss of information due to dose reduction. It turns out that the smoothing behaviour has a strong influence on detection rates. For moderate smoothing, a dose reduction by 25% has no serious influence on the detection results, whereas a dose reduction by 50% already entails a marked deterioration of the performance. Strong smoothing generally leads to an unacceptable loss of image quality. The test results emphasize the impact of the more sensitive film-screen system and its characteristics on the problem of assessing the potential for dose reduction in film-screen mammography. The general approach presented in the paper can be adapted to fully digital mammography.

[Methodology for an assessment of derived radiation levels for agrocenoses].

PubMed

Udalova, A A; Ul'ianenko, L N; Aleksakhin, R M; Geras'kin, S A; Filipas, A S

2010-01-01

Radiation protection of agrarian ecosystems should be considered as an integral part of a system for radiation protection of environment, with a special concern to agroecosystems' features. A methodology is proposed for an assessment of maximum permissible doses of radiation impact for agrocenoses based on an unified analysis of available data about effects of radiation in cultivated plants. It is considered as a component of radiation protection system for agricultural ecosystems. Critical doses and dose rates are estimated for crops under different exposure situations. It is shown that doses that could result in decreasing indexes of productivity and survival for main crops below 50% are unlikely up to 170-200 Gy and 15-17 Gy at an acute exposure of dormant seeds and vegetative plants, correspondingly. At chronic exposure, above 10% loss of productivity in crops is not expected at dose rates below 3-10 mGy/h.

MOSFET assessment of radiation dose delivered to mice using the Small Animal Radiation Research Platform (SARRP).

PubMed

Ngwa, Wilfred; Korideck, Houari; Chin, Lee M; Makrigiorgos, G Mike; Berbeco, Ross I

2011-12-01

The Small Animal Radiation Research Platform (SARRP) is a novel isocentric irradiation system that enables state-of-the-art image-guided radiotherapy research to be performed with animal models. This paper reports the results obtained from investigations assessing the radiation dose delivered by the SARRP to different anatomical target volumes in mice. Surgically implanted metal oxide semiconductor field effect transistors (MOSFET) dosimeters were employed for the dose assessment. The results reveal differences between the calculated and measured dose of -3.5 to 0.5%, -5.2 to -0.7%, -3.9 to 0.5%, -5.9 to 2.5%, -5.5 to 0.5%, and -4.3 to 0% for the left kidney, liver, pancreas, prostate, left lung, and brain, respectively. Overall, the findings show less than 6% difference between the delivered and calculated dose, without tissue heterogeneity corrections. These results provide a useful assessment of the need for tissue heterogeneity corrections in SARRP dose calculations for clinically relevant tumor model sites.

Technology Assessment and Roadmap for the Emergency Radiation Dose Assessment Program (ERDAP)

DTIC Science & Technology

2005-06-01

l2O3:C OSL dosimeters . Overall design is based on similar systems described earlier by Justus et al. (1999) and Huston et al. (2001). Similar apparatus...Radioisotope Contamination 4. Pre-Positioned Physical Dosimeters C. Assessment of Emerging Dosimetry Technologies 1. Biological Measurements 2. Physico...architectures for radiation dose assessment tools. • Focus initial studies on defining the role of pre-positioned dosimeters , optimizing the size and

[Dosimetric system for assessing doses received by people occupationally exposed to external sources of ionizing radiation].

PubMed

Brodecki, Marcin; Domienik, Joanna U; Zmyślony, Marek

2012-01-01

The current system of dosimetric quantities has been defined by the International Commission on Radiological Protection (ICRP) and the International Commission on Radiation Units and Measurements (ICRU). Complexity of the system implies the physical nature of ionizing radiation, resulting from the presence of different types of radiation of different ionization capabilities, as well as the individual radiation sensitivity of biological material exposed. According to the latest recommendations, there are three types of dosimeter quantities relevant to radiation protection and radiological assessment of occupational exposure. These are the basic quantities, safety quantities and operational quantities. Dose limits for occupational exposure relate directly to the protection quantities, i.e. the equivalent dose and effective dose, while these quantities are practically unmeasurable in real measurement conditions. For this reason, in the system of dosimetric quantities directly measurable operating volumes were defined. They represent equivalents of the protection quantities that allow for a reliable assessment of equivalent and effective dose by conducting routine monitoring of occupational exposure. This paper presents the characteristics of these quantities, their relationships and importance in assessing individual effects of radiation. Also the methods for their implementation in personal and environmental dosimetry were showcased. The material contained in the article is a compendium of essential information about dosimetric quantities with reference to the contemporary requirements of the law, including the changed annual occupational exposure limit for the lens of the eye. The material is especially addressed to those responsible for dosimetry monitoring in the workplace, radiation protection inspectors and occupational health physicians.

Verification of eye lens dose in IMRT by MOSFET measurement.

PubMed

Wang, Xuetao; Li, Guangjun; Zhao, Jianling; Song, Ying; Xiao, Jianghong; Bai, Sen

2018-04-17

The eye lens is recognized as one of the most radiosensitive structures in the human body. The widespread use of intensity-modulated radiotherapy (IMRT) complicates dose verification and necessitates high standards of dose computation. The purpose of this work was to assess the computed dose accuracy of eye lens through measurements using a metal-oxide-semiconductor field-effect transistor (MOSFET) dosimetry system. Sixteen clinical IMRT plans of head and neck patients were copied to an anthropomorphic head phantom. Measurements were performed using the MOSFET dosimetry system based on the head phantom. Two MOSFET detectors were imbedded in the eyes of the head phantom as the left and the right lens, covered by approximately 5-mm-thick paraffin wax. The measurement results were compared with the calculated values with a dose grid size of 1 mm. Sixteen IMRT plans were delivered, and 32 measured lens doses were obtained for analysis. The MOSFET dosimetry system can be used to verify the lens dose, and our measurements showed that the treatment planning system used in our clinic can provide adequate dose assessment in eye lenses. The average discrepancy between measurement and calculation was 6.7 ± 3.4%, and the largest discrepancy was 14.3%, which met the acceptability criterion set by the American Association of Physicists in Medicine Task Group 53 for external beam calculation for multileaf collimator-shaped fields in buildup regions. Copyright © 2018 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Dose accumulation of multiple high dose rate prostate brachytherapy treatments in two commercially available image registration systems.

PubMed

Poder, Joel; Yuen, Johnson; Howie, Andrew; Bece, Andrej; Bucci, Joseph

2017-11-01

The purpose of this study was to assess whether deformable image registration (DIR) is required for dose accumulation of multiple high dose rate prostate brachytherapy (HDRPBT) plans treated with the same catheter pattern on two different CT datasets. DIR was applied to 20 HDRPBT patients' planning CT images who received two treatment fractions on sequential days, on two different CT datasets, with the same implant. Quality of DIR in Velocity and MIM image registration systems was assessed by calculating the Dice Similarity Coefficient (DSC) and mean distance to agreement (MDA) for the prostate, urethra and rectum contours. Accumulated doses from each system were then calculated using the same DIR technique and dose volume histogram (DVH) parameters compared to manual addition with no DIR. The average DSC was found to be 0.83 (Velocity) and 0.84 (MIM), 0.80 (Velocity) and 0.80 (MIM), 0.80 (Velocity) and 0.81 (MIM), for the prostate, rectum and urethra contours, respectively. The average difference in calculated DVH parameters between the two systems using dose accumulation was less than 1%, and there was no statistically significant difference found between deformably accumulated doses in the two systems versus manual DVH addition with no DIR. Contour propagation using DIR in velocity and MIM was shown to be at least equivalent to inter-observer contouring variability on CT. The results also indicate that dose accumulation through manual addition of DVH parameters may be sufficient for HDRPBT treatments treated with the same catheter pattern on two different CT datasets. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Radiation biodosimetry: applications for spaceflight

NASA Astrophysics Data System (ADS)

Blakely, W.; Miller, A.; Grace, M.; Prasanna, P.; Muderhwa, J.

The multiparametric dosimetry system that we are developing for medical radiological defense applications could be adapted for spaceflight environments. The system complements the internationally accepted cytogenetic analysis of chromosome aberrations, considered the best means of documenting radiation doses for health records. Our system consists of a dose assessment software application, a portable blood cell counter, and molecular biodosimetry using miniaturized equipment. The Biodosimetry Assessment Tool (BAT) software application calculates radiation dose based on a patient's physical signs and symptoms and blood analysis, annotates location of personnel dosimeters, displays a summary of a patient's dosimetric information to healthcare professionals, and archives the data for further use. The dry reagent centrifuge-based blood cell counter (QBC Autoread Plus, Beckon Dickinson Bioscience) measures peripheral blood lymphocytes and monocytes, which could determine radiation dose based on the kinetics of blood cell depletion. Molecular biomarkers for ionizing radiation exposure (gene expression changes, blood proteins), once dose-dependent targets are identified, optimized, and validated, will make use of miniaturized diagnostic equipment for nucleic acid sequence and antigen-based biosensor detection technologies. These radiation assessment diagnostic technologies can have dual use for other medical related applications. [The Armed Forces Radiobiology Research Institute, under work unit AFRRI-01-3, and the Defense Threat Reduction Agency, under contract GG4661, supported this research.

Doses per vaccine vial container: An understated and underestimated driver of performance that needs more evidence.

PubMed

Heaton, Alexis; Krudwig, Kirstin; Lorenson, Tina; Burgess, Craig; Cunningham, Andrew; Steinglass, Robert

2017-04-19

The widespread use of multidose vaccine containers in low and middle income countries' immunization programs is assumed to have multiple benefits and efficiencies for health systems, yet the broader impacts on immunization coverage, costs, and safety are not well understood. To document what is known on this topic, how it has been studied, and confirm the gaps in evidence that allow us to assess the complex system interactions, the authors undertook a review of published literature that explored the relationship between doses per container and immunization systems. The relationships examined in this study are organized within a systems framework consisting of operational costs, timely coverage, safety, product costs/wastage, and policy/correct use, with the idea that a change in dose per container affects all of them, and the optimal solution will depend on what is prioritized and used to measure performance. Studies on this topic are limited and largely rely on modeling to assess the relationship between doses per container and other aspects of immunization systems. Very few studies attempt to look at how a change in doses per container affects vaccination coverage rates and other systems components simultaneously. This article summarizes the published knowledge on this topic to date and suggests areas of current and future research to ultimately improve decision making around vaccine doses per container and increase understanding of how this decision relates to other program goals. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Evaluation of Accuracy of Six Blood Glucose Monitoring Systems and Modeling of Possibly Related Insulin Dosing Errors.

PubMed

Baumstark, Annette; Jendrike, Nina; Pleus, Stefan; Haug, Cornelia; Freckmann, Guido

2017-10-01

Self-monitoring of blood glucose (BG) is an essential part of diabetes therapy. Accurate and reliable results from BG monitoring systems (BGMS) are important especially when they are used to calculate insulin doses. This study aimed at assessing system accuracy of BGMS and possibly related insulin dosing errors. System accuracy of six different BGMS (Accu-Chek ® Aviva Nano, Accu-Chek Mobile, Accu-Chek Performa Nano, CONTOUR ® NEXT LINK 2.4, FreeStyle Lite, OneTouch ® Verio ® IQ) was assessed in comparison to a glucose oxidase and a hexokinase method. Study procedures and analysis were based on ISO 15197:2013/EN ISO 15197:2015, clause 6.3. In addition, insulin dosing error was modeled. In the comparison against the glucose oxidase method, five out of six BGMS fulfilled ISO 15197:2013 accuracy criteria. Up to 14.3%/4.3%/0.3% of modeled doses resulted in errors exceeding ±0.5/±1.0/±1.5 U and missing the modeled target by 20 mg/dL/40 mg/dL/60 mg/dL, respectively. Compared against the hexokinase method, five out of six BGMS fulfilled ISO 15197:2013 accuracy criteria. Up to 25.0%/10.5%/3.2% of modeled doses resulted in errors exceeding ±0.5/±1.0/±1.5 U, respectively. Differences in system accuracy were found, even among BGMS that fulfilled the minimum system accuracy criteria of ISO 15197:2013. In the error model, considerable insulin dosing errors resulted for some of the investigated systems. Diabetes patients on insulin therapy should be able to rely on their BGMS' readings; therefore, they require highly accurate BGMS, in particular, when making therapeutic decisions.

Assessment of diurnal systemic dose of agrochemicals in regulatory toxicity testing--an integrated approach without additional animal use.

PubMed

Saghir, Shakil A; Bartels, Michael J; Rick, David L; McCoy, Alene T; Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Sue Marty, M; Terry, Claire; Bailey, Jason P; Billington, Richard; Bus, James S

2012-07-01

Integrated toxicokinetics (TK) data provide information on the rate, extent and duration of systemic exposure across doses, species, strains, gender, and life stages within a toxicology program. While routine for pharmaceuticals, TK assessments of non-pharmaceuticals are still relatively rare, and have never before been included in a full range of guideline studies for a new agrochemical. In order to better understand the relationship between diurnal systemic dose (AUC(24h)) and toxicity of agrochemicals, TK analyses in the study animals is now included in all short- (excluding acute), medium- and long-term guideline mammalian toxicity studies including reproduction/developmental tests. This paper describes a detailed procedure for the implementation of TK in short-, medium- and long-term regulatory toxicity studies, without the use of satellite animals, conducted on three agrochemicals (X11422208, 2,4-D and X574175). In these studies, kinetically-derived maximum doses (KMD) from short-term studies instead of, or along with, maximum tolerated doses (MTD) were used for the selection of the high dose in subsequent longer-term studies. In addition to leveraging TK data to guide dose level selection, the integrated program was also used to select the most appropriate method of oral administration (i.e., gavage versus dietary) of test materials for rat and rabbit developmental toxicity studies. The integrated TK data obtained across toxicity studies (without the use of additional/satellite animals) provided data critical to understanding differences in response across doses, species, strains, sexes, and life stages. Such data should also be useful in mode of action studies and to improve human risk assessments. Copyright © 2012 Elsevier Inc. All rights reserved.

IRIS Toxicological Review of Dichloromethane (Methylene ...

EPA Pesticide Factsheets

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Dichloromethane that when finalized will appear on the Integrated Risk Information System (IRIS) database. The draft Toxicological Review of Dichloromethane provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to dichloromethane.

[The reduction of the radiation dosage by means of storage phosphor-film radiography compared to a conventional film-screen system with a grid cassette on a skull phantom].

PubMed

Heyne, J P; Merbold, H; Sehner, J; Neumann, R; Freesmeyer, M; Jonetz-Mentzel, L; Kaiser, W A

1999-07-01

How much can the radiation dose be reduced for skull radiography by using digital luminescence radiography (DLR) compared to a conventional screen film system with a grid cassette? A skull phantom (3M) was x-rayed in anterior-posterior orientation using both a conventional screen film system with grid cassette and DLR (ADC-70, Agfa). The tube current time product (mAs) was diminished gradually while keeping the voltage constant. The surface entrance dose was measured by a sensor of Dosimax (Wellhöfer). Five investigators evaluated the images by characteristic and critical features, spatial resolution and contrast. The surface entrance dose at 73 kV/22 mAs was 0.432 mGy in conventional screen film system and 0.435 mGy in DLR. The images could be evaluated very well down to an average dose of 71% (0.308 mGy; SD 0.050); sufficient images were obtained down to an average dose of 31% (0.136 mGy; SD 0.065). The resolution of the line pairs were reduced down to 2 levels depending on the investigator. Contrast was assessed as being very good to sufficient. The acceptance of the postprocessed images (MUSICA-software) was individually different and resulted in an improvement of the assessment of bone structures and contrast in higher dose ranges only. For the sufficient assessment of a possible fracture/of paranasal sinuses/of measurement of the skull the dose can be reduced to at least 56% (phi 31%; SD 14.9%)/40% (phi 27%; SD 9.3%)/18% (phi 14%; SD 4.4%). Digital radiography allows question-referred exposure parameters with clearly reduced dose, so e.g. for fracture exclusion 73 kV/12.5 mAs and to skull measurement 73 kV/4 mAs.

IRIS Toxicological Review of Ammonia (External Review Draft ...

EPA Pesticide Factsheets

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of ammonia that will appear in the Integrated Risk Information System (IRIS) database. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for ammonia. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

IRIS Toxicological Review of n-Butanol (External Review Draft ...

EPA Pesticide Factsheets

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of n-butanol that will appear in the Integrated Risk Information System (IRIS) database. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for n-butanol. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

An operational approach for aircraft crew dosimetry: the SIEVERT system.

PubMed

Bottollier-Depois, J F; Blanchard, P; Clairand, I; Dessarps, P; Fuller, N; Lantos, P; Saint-Lô, D; Trompier, F

2007-01-01

The study of naturally occurring radiation and its associated risk is one of the preoccupations of bodies responsible for radiation protection. Cosmic particle flux is significantly higher on-board the aircraft that at ground level. Furthermore, its intensity depends on solar activity and eruptions. Due to their professional activity, flight crews and frequent flyers may receive an annual dose of some millisieverts. This is why the European directive adopted in 1996 requires the aircraft operators to assess the dose and to inform their flight crews about the risk. The effective dose is to be estimated using various experimental and calculation means. In France, the computerised system for flight assessment of exposure to cosmic radiation in air transport (SIEVERT) is delivered to airlines for assisting them in the application of the European directive. This professional service is available on an Internet server accessible to companies with a public section. The system provides doses that consider the routes flown by aircraft. Various results obtained are presented.

Image quality evaluation and patient dose assessment of medical fluoroscopic X-ray systems: a national study.

PubMed

Economides, S; Hourdakis, C J; Kalivas, N; Kalathaki, M; Simantirakis, G; Tritakis, P; Manousaridis, G; Vogiatzi, S; Kipouros, P; Boziari, A; Kamenopoulou, V

2008-01-01

This study presents the results from a survey conducted by the Greek Atomic Energy Commission (GAEC), during the period 1998-2003, in 530 public and private owned fluoroscopic X-ray systems in Greece. Certain operational parameters for conventional and remote control systems were assessed, according to a quality control protocol developed by GAEC on the basis of the current literature. Public (91.5%) and private (81.5%) owned fluoroscopic units exhibit high-contrast resolution values over 1 lp mm(-1). Moreover, 88.5 and 87.1% of the fluoroscopic units installed in the public and private sector, respectively, present Maximum Patient Entrance Kerma Rate values lower than 100 mGy min(-1). Additionally, 68.3% of the units assessed were found to perform within the acceptance limits. Finally, the third quartile of the Entrance Surface Dose Rate distribution was estimated according to the Dose Reference Level definition and found equal to 35 mGy min(-1).

75 FR 40729 - Residues of Quaternary Ammonium Compounds, N-Alkyl (C12-14

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-14

.... Systemic toxicity occurs after absorption and distribution of the chemical to tissues in the body. Such... identified (the LOAEL) or a Benchmark Dose (BMD) approach is sometimes used for risk assessment. Uncertainty.... No systemic effects observed up to 20 mg/ kg/day, highest dose of technical that could be tested...

Evaluation of the Emergency Response Dose Assessment System(ERDAS)

NASA Technical Reports Server (NTRS)

Evans, Randolph J.; Lambert, Winifred C.; Manobianco, John T.; Taylor, Gregory E.; Wheeler, Mark M.; Yersavich, Ann M.

1996-01-01

The emergency response dose assessment system (ERDAS) is a protype software and hardware system configured to produce routine mesoscale meteorological forecasts and enhanced dispersion estimates on an operational basis for the Kennedy Space Center (KSC)/Cape Canaveral Air Station (CCAS) region. ERDAS provides emergency response guidance to operations at KSC/CCAS in the case of an accidental hazardous material release or an aborted vehicle launch. This report describes the evaluation of ERDAS including: evaluation of sea breeze predictions, comparison of launch plume location and concentration predictions, case study of a toxic release, evaluation of model sensitivity to varying input parameters, evaluation of the user interface, assessment of ERDA's operational capabilities, and a comparison of ERDAS models to the ocean breeze dry gultch diffusion model.

Commissioning and quality assurance for VMAT delivery systems: An efficient time-resolved system using real-time EPID imaging.

PubMed

Zwan, Benjamin J; Barnes, Michael P; Hindmarsh, Jonathan; Lim, Seng B; Lovelock, Dale M; Fuangrod, Todsaporn; O'Connor, Daryl J; Keall, Paul J; Greer, Peter B

2017-08-01

An ideal commissioning and quality assurance (QA) program for Volumetric Modulated Arc Therapy (VMAT) delivery systems should assess the performance of each individual dynamic component as a function of gantry angle. Procedures within such a program should also be time-efficient, independent of the delivery system and be sensitive to all types of errors. The purpose of this work is to develop a system for automated time-resolved commissioning and QA of VMAT control systems which meets these criteria. The procedures developed within this work rely solely on images obtained, using an electronic portal imaging device (EPID) without the presence of a phantom. During the delivery of specially designed VMAT test plans, EPID frames were acquired at 9.5 Hz, using a frame grabber. The set of test plans was developed to individually assess the performance of the dose delivery and multileaf collimator (MLC) control systems under varying levels of delivery complexities. An in-house software tool was developed to automatically extract features from the EPID images and evaluate the following characteristics as a function of gantry angle: dose delivery accuracy, dose rate constancy, beam profile constancy, gantry speed constancy, dynamic MLC positioning accuracy, MLC speed and acceleration constancy, and synchronization between gantry angle, MLC positioning and dose rate. Machine log files were also acquired during each delivery and subsequently compared to information extracted from EPID image frames. The largest difference between measured and planned dose at any gantry angle was 0.8% which correlated with rapid changes in dose rate and gantry speed. For all other test plans, the dose delivered was within 0.25% of the planned dose for all gantry angles. Profile constancy was not found to vary with gantry angle for tests where gantry speed and dose rate were constant, however, for tests with varying dose rate and gantry speed, segments with lower dose rate and higher gantry speed exhibited less profile stability. MLC positional accuracy was not observed to be dependent on the degree of interdigitation. MLC speed was measured for each individual leaf and slower leaf speeds were shown to be compensated for by lower dose rates. The test procedures were found to be sensitive to 1 mm systematic MLC errors, 1 mm random MLC errors, 0.4 mm MLC gap errors and synchronization errors between the MLC, dose rate and gantry angle controls systems of 1°. In general, parameters measured by both EPID and log files agreed with the plan, however, a greater average departure from the plan was evidenced by the EPID measurements. QA test plans and analysis methods have been developed to assess the performance of each dynamic component of VMAT deliveries individually and as a function of gantry angle. This methodology relies solely on time-resolved EPID imaging without the presence of a phantom and has been shown to be sensitive to a range of delivery errors. The procedures developed in this work are both comprehensive and time-efficient and can be used for streamlined commissioning and QA of VMAT delivery systems. © 2017 American Association of Physicists in Medicine.

IRIS Toxicological Review of Tetrahydrofuran (THF) (External ...

EPA Pesticide Factsheets

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of tetrahydrofuran (THF) that when finalized will appear on the Integrated Risk Information System (IRIS) database. EPA is undertaking an Integrated Risk Information System (IRIS) health assessment for tetrahydrofuran. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

Local and Systemic Inflammation May Mediate Diesel Engine Exhaust-Induced Lung Function Impairment in a Chinese Occupational Cohort.

PubMed

Wang, Haitao; Duan, Huawei; Meng, Tao; Yang, Mo; Cui, Lianhua; Bin, Ping; Dai, Yufei; Niu, Yong; Shen, Meili; Zhang, Liping; Zheng, Yuxin; Leng, Shuguang

2018-04-01

Diesel exhaust (DE) as the major source of vehicle-emitted particle matter in ambient air impairs lung function. The objectives were to assess the contribution of local (eg, the fraction of exhaled nitric oxide [FeNO] and serum Club cell secretory protein [CC16]) and systemic (eg, serum C-reaction protein [CRP] and interleukin-6 [IL-6]) inflammation to DE-induced lung function impairment using a unique cohort of diesel engine testers (DETs, n = 137) and non-DETs (n = 127), made up of current and noncurrent smokers. Urinary metabolites, FeNO, serum markers, and spirometry were assessed. A 19% reduction in CC16 and a 94% increase in CRP were identified in DETs compared with non-DETs (all p values <10-4), which were further corroborated by showing a dose-response relationship with internal dose for DE exposure (all p values <.04) and a time-course relationship with DE exposure history (all p values <.005). Mediation analysis showed that 43% of the difference in FEV1 between DETs and non-DETs can be explained by circulating CC16 and CRP (permuted p < .001). An inverse dose-dependent relationship between FeNO and internal dose for cigarette smoke was identified (p = .0003). A range of 95% lower bounds of benchmark dose of 1.0261-1.4513 μg phenanthrols/g creatinine in urine as an internal dose was recommended for regulatory risk assessment. Local and systemic inflammation may be key processes that contribute to the subsequent development of obstructive lung disease in DE-exposed populations.

Dose computation for therapeutic electron beams

NASA Astrophysics Data System (ADS)

Glegg, Martin Mackenzie

The accuracy of electron dose calculations performed by two commercially available treatment planning computers, Varian Cadplan and Helax TMS, has been assessed. Measured values of absorbed dose delivered by a Varian 2100C linear accelerator, under a wide variety of irradiation conditions, were compared with doses calculated by the treatment planning computers. Much of the motivation for this work was provided by a requirement to verify the accuracy of calculated electron dose distributions in situations encountered clinically at Glasgow's Beatson Oncology Centre. Calculated dose distributions are required in a significant minority of electron treatments, usually in cases involving treatment to the head and neck. Here, therapeutic electron beams are subject to factors which may cause non-uniformity in the distribution of dose, and which may complicate the calculation of dose. The beam shape is often irregular, the beam may enter the patient at an oblique angle or at an extended source to skin distance (SSD), tissue inhomogeneities can alter the dose distribution, and tissue equivalent material (such as wax) may be added to reduce dose to critical organs. Technological advances have allowed the current generation of treatment planning computers to implement dose calculation algorithms with the ability to model electron beams in these complex situations. These calculations have, however, yet to be verified by measurement. This work has assessed the accuracy of calculations in a number of specific instances. Chapter two contains a comparison of measured and calculated planar electron isodose distributions. Three situations were considered: oblique incidence, incidence on an irregular surface (such as that which would be arise from the use of wax to reduce dose to spinal cord), and incidence on a phantom containing a small air cavity. Calculations were compared with measurements made by thermoluminescent dosimetry (TLD) in a WTe electron solid water phantom. Chapter three assesses the planning computers' ability to model electron beam penumbra at extended SSD. Calculations were compared with diode measurements in a water phantom. Further measurements assessed doses in the junction region produced by abutting an extended SSD electron field with opposed photon fields. Chapter four describes an investigation of the size and shape of the region enclosed by the 90% isodose line when produced by limiting the electron beam with square and elliptical apertures. The 90% isodose line was chosen because clinical treatments are often prescribed such that a given volume receives at least 90% dose. Calculated and measured dose distributions were compared in a plane normal to the beam central axis. Measurements were made by film dosimetry. While chapters two to four examine relative doses, chapter five assesses the accuracy of absolute dose (or output) calculations performed by the planning computers. Output variation with SSD and field size was examined. Two further situations already assessed for the distribution of relative dose were also considered: an obliquely incident field, and a field incident on an irregular surface. The accuracy of calculations was assessed against criteria stipulated by the International Commission on Radiation Units and Measurement (ICRU). The Varian Cadplan and Helax TMS treatment planning systems produce acceptable accuracy in the calculation of relative dose from therapeutic electron beams in most commonly encountered situations. When interpreting clinical dose distributions, however, knowledge of the limitations of the calculation algorithm employed by each system is required in order to identify the minority of situations where results are not accurate. The calculation of absolute dose is too inaccurate to implement in a clinical environment. (Abstract shortened by ProQuest.).

Commissioning and quality assurance for the treatment delivery components of the AccuBoost system.

PubMed

Iftimia, Ileana; Talmadge, Mike; Ladd, Ron; Halvorsen, Per

2015-03-08

The objective for this work was to develop a commissioning methodology for the treatment delivery components of the AccuBoost system, as well as to establish a routine quality assurance program and appropriate guidance for clinical use based on the commissioning results. Various tests were developed: 1) assessment of the accuracy of the displayed separation value; 2) validation of the dwell positions within each applicator; 3) assessment of the accuracy and precision of the applicator localization system; 4) assessment of the combined dose profile of two opposed applicators to confirm that they are coaxial; 5) measurement of the absolute dose delivered with each applicator to confirm acceptable agreement with dose based on Monte Carlo modeling; 6) measurements of the skin-to-center dose ratio using optically stimulated luminescence dosimeters; and 7) assessment of the mammopad cushion's effect on the center dose. We found that the difference between the measured and the actual paddle separation is < 0.1 cm for the separation range of 3 cm to 7.5 cm. Radiochromic film measurements demonstrated that the number of dwell positions inside the applicators agree with the values from the vendor, for each applicator type and size. The shift needed for a good applicator-grid alignment was within 0.2 cm. The dry-run test using film demonstrated that the shift of the dosimetric center is within 0.15 cm. Dose measurements in water converted to polystyrene agreed within 5.0% with the Monte Carlo data in polystyrene for the same applicator type, size, and depth. A solid water-to-water (phantom) factor was obtained for each applicator, and all future annual quality assurance tests will be performed in solid water using an average value of 1.07 for the solid water-to-water factor. The skin-to-center dose ratio measurements support the Monte Carlo-based values within 5.0% agreement. For the treatment separation range of 4 cm to 8cm, the change in center dose would be < 1.0% for all applicators when using a compressed pad of 0.2 cm to 0.3 cm. The tests performed ensured that all treatment components of the AccuBoost system are functional and that a treatment plan can be delivered with acceptable accuracy. Based on the commissioning results, a quality assurance manual and guidance documents for clinical use were developed.

IRIS Toxicological Review of Urea (External Review Draft) ...

EPA Pesticide Factsheets

EPA conducted a peer review and public comment of the scientific basis of a draft report supporting the human health hazard and dose-response assessment of Urea that when finalized will appear on the Integrated Risk Information System (IRIS) database. The draft Toxicological Review of Urea provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to Urea.

IRIS Toxicological Review of Trichloroacetic Acid (TCA) ...

EPA Pesticide Factsheets

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Trichloroacetic acid (TCA) that when finalized will appear on the Integrated Risk Information System (IRIS) database. The draft Toxicological Review of trichloroacetic acid provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to trichloroacetic acid.

Nonclinical Safety Assessment of Anti-Factor D: Key Strategies and Challenges for the Nonclinical Development of Intravitreal Biologics.

PubMed

Bantseev, Vladimir; Erickson, Rebecca; Leipold, Douglas; Amaya, Caroline; Miller, Paul E; Booler, Helen; Thackaberry, Evan A

The nonclinical toxicology program described here was designed to characterize the safety profile of anti-factor D (AFD; FCFD4514S, lampalizumab) to support intravitreal (ITV) administration in patients with geographic atrophy (GA). The toxicity of AFD was assessed in a single-dose and 6-month repeat-dose study in monkeys at doses up to 10 mg/eye. Toxicity was assessed by clinical ophthalmic examinations, intraocular pressure measurements, ocular photography, electroretinography, fluorescein angiography, optical coherence tomography, and anatomic pathology. Systemic exposure to AFD generally increased with the increase in dose level. The increases in mean maximal concentration and area under the curve values were roughly dose proportional. No accumulation of AFD was observed following 10 doses, and drug exposures were not affected by anti-drug antibodies. AFD was locally and systemically well tolerated in monkeys following ITV doses of up to 10 mg/eye. Ocular effects associated with AFD were limited to transient, reversible, dose-related, aqueous cell responses and injection-related, mild, vitreal cell responses. In the 6-month repeat-dose study, 2 monkeys had a nonspecific immune response to AFD that resulted in severe ocular inflammation, attributed to administration of a heterologous (humanized) protein. The comprehensive toxicology program in monkeys described here was designed to evaluate the safety profile of AFD and to support multiple ITV injections in the clinic. Administration of a heterologous (humanized) protein presents a challenge, and immunogenicity in nonclinical species is not predictive of immunogenicity in humans. Taken together, the results of the nonclinical program described here support the use of AFD in patients with GA.

IRIS Toxicological Review of 2-Hexanone (External Review ...

EPA Pesticide Factsheets

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of 2-hexanone that will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that science is used credibly and appropriately in derivation of the dose-response assessments and toxicological characterization. 2-Hexanone was nominated for IRIS assessment because of its frequent detection at sites nation-wide and its occurrence as a byproduct of certain industrial processes.

TU-H-CAMPUS-JeP3-02: Automated Dose Accumulation and Dose Accuracy Assessment for Online Or Offline Adaptive Replanning

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

Chen, G; Ahunbay, E; Li, X

Purpose: With introduction of high-quality treatment imaging during radiation therapy (RT) delivery, e.g., MR-Linac, adaptive replanning of either online or offline becomes appealing. Dose accumulation of delivered fractions, a prerequisite for the adaptive replanning, can be cumbersome and inaccurate. The purpose of this work is to develop an automated process to accumulate daily doses and to assess the dose accumulation accuracy voxel-by-voxel for adaptive replanning. Methods: The process includes the following main steps: 1) reconstructing daily dose for each delivered fraction with a treatment planning system (Monaco, Elekta) based on the daily images using machine delivery log file and consideringmore » patient repositioning if applicable, 2) overlaying the daily dose to the planning image based on deformable image registering (DIR) (ADMIRE, Elekta), 3) assessing voxel dose deformation accuracy based on deformation field using predetermined criteria, and 4) outputting accumulated dose and dose-accuracy volume histograms and parameters. Daily CTs acquired using a CT-on-rails during routine CT-guided RT for sample patients with head and neck and prostate cancers were used to test the process. Results: Daily and accumulated doses (dose-volume histograms, etc) along with their accuracies (dose-accuracy volume histogram) can be robustly generated using the proposed process. The test data for a head and neck cancer case shows that the gross tumor volume decreased by 20% towards the end of treatment course, and the parotid gland mean dose increased by 10%. Such information would trigger adaptive replanning for the subsequent fractions. The voxel-based accuracy in the accumulated dose showed that errors in accumulated dose near rigid structures were small. Conclusion: A procedure as well as necessary tools to automatically accumulate daily dose and assess dose accumulation accuracy is developed and is useful for adaptive replanning. Partially supported by Elekta, Inc.« less

A Randomized, Double-Blind, Placebo-Controlled, Laboratory Classroom Assessment of Methylphenidate Transdermal System in Children with ADHD

ERIC Educational Resources Information Center

McGough, James J.; Wigal, Sharon B.; Abikoff, Howard; Turnbow, John M.; Posner, Kelly; Moon, Eliot

2006-01-01

Objective: This study evaluates the efficacy, duration of action, and tolerability of methylphenidate transdermal system (MTS) in children with ADHD. Method: Participants were dose optimized over 5 weeks utilizing patch doses of 10, 16, 20, and 27 mg applied in the morning and worn for 9 hours. Following optimization, 80 participants were…

Assessment of ixekizumab, an interleukin-17A monoclonal antibody, for potential effects on reproduction and development, including immune system function, in cynomolgus monkeys.

PubMed

Clarke, D O; Hilbish, K G; Waters, D G; Newcomb, D L; Chellman, G J

2015-12-01

The reproductive and developmental toxicity of ixekizumab, a selective inhibitor of interleukin-17A (IL-17A), was assessed in the following studies in cynomolgus monkeys: fertility (3-month dosing), embryo-fetal development (EFD; dosing from gestation day (GD) 20 through 139), and pre-postnatal development (PPND; dosing from GD 20 through parturition). Because IL-17A has functional roles in innate and humoral immunity, immune system modulation was evaluated in the EFD and PPND studies; immunological evaluations in infants comprised peripheral blood immunophenotyping, Natural Killer cell cytolytic activity, and T-cell-dependent antibody (IgG and IgM) primary and secondary responses to antigen challenge. Ixekizumab exposure was sustained during the dosing periods in most adult monkeys. Fetal exposure at Cesarean section (GD 140-142; EFD study) was 18-25% of maternal exposure and ixekizumab was present in infants for up to 29 weeks postpartum. There were no adverse effects attributed to ixekizumab in any study. Importantly, immune system development and maturation were unaffected. Copyright © 2015 Elsevier Inc. All rights reserved.

ISDD: A computational model of particle sedimentation, diffusion and target cell dosimetry for in vitro toxicity studies

PubMed Central

2010-01-01

Background The difficulty of directly measuring cellular dose is a significant obstacle to application of target tissue dosimetry for nanoparticle and microparticle toxicity assessment, particularly for in vitro systems. As a consequence, the target tissue paradigm for dosimetry and hazard assessment of nanoparticles has largely been ignored in favor of using metrics of exposure (e.g. μg particle/mL culture medium, particle surface area/mL, particle number/mL). We have developed a computational model of solution particokinetics (sedimentation, diffusion) and dosimetry for non-interacting spherical particles and their agglomerates in monolayer cell culture systems. Particle transport to cells is calculated by simultaneous solution of Stokes Law (sedimentation) and the Stokes-Einstein equation (diffusion). Results The In vitro Sedimentation, Diffusion and Dosimetry model (ISDD) was tested against measured transport rates or cellular doses for multiple sizes of polystyrene spheres (20-1100 nm), 35 nm amorphous silica, and large agglomerates of 30 nm iron oxide particles. Overall, without adjusting any parameters, model predicted cellular doses were in close agreement with the experimental data, differing from as little as 5% to as much as three-fold, but in most cases approximately two-fold, within the limits of the accuracy of the measurement systems. Applying the model, we generalize the effects of particle size, particle density, agglomeration state and agglomerate characteristics on target cell dosimetry in vitro. Conclusions Our results confirm our hypothesis that for liquid-based in vitro systems, the dose-rates and target cell doses for all particles are not equal; they can vary significantly, in direct contrast to the assumption of dose-equivalency implicit in the use of mass-based media concentrations as metrics of exposure for dose-response assessment. The difference between equivalent nominal media concentration exposures on a μg/mL basis and target cell doses on a particle surface area or number basis can be as high as three to six orders of magnitude. As a consequence, in vitro hazard assessments utilizing mass-based exposure metrics have inherently high errors where particle number or surface areas target cells doses are believed to drive response. The gold standard for particle dosimetry for in vitro nanotoxicology studies should be direct experimental measurement of the cellular content of the studied particle. However, where such measurements are impractical, unfeasible, and before such measurements become common, particle dosimetry models such as ISDD provide a valuable, immediately useful alternative, and eventually, an adjunct to such measurements. PMID:21118529

An evaluation of voluntary 2-dose varicella vaccination coverage in New York City public schools.

PubMed

Doll, Margaret K; Rosen, Jennifer B; Bialek, Stephanie R; Szeto, Hiram; Zimmerman, Christopher M

2015-05-01

We assessed coverage for 2-dose varicella vaccination, which is not required for school entry, among New York City public school students and examined characteristics associated with receipt of 2 doses. We measured receipt of either at least 1 or 2 doses of varicella vaccine among students aged 4 years and older in a sample of 336 public schools (n = 223 864 students) during the 2010 to 2011 school year. Data came from merged student vaccination records from 2 administrative data systems. We conducted multivariable regression to assess associations of age, gender, race/ethnicity, and school location with 2-dose prevalence. Coverage with at least 1 varicella dose was 96.2% (95% confidence interval [CI] = 96.2%, 96.3%); coverage with at least 2 doses was 64.8% (95% CI = 64.6%, 64.9%). Increasing student age, non-Hispanic White race/ethnicity, and attendance at school in Staten Island were associated with lower 2-dose coverage. A 2-dose varicella vaccine requirement for school entry would likely improve 2-dose coverage, eliminate coverage disparities, and prevent disease.

Application of the ELDO approach to assess cumulative eye lens doses for interventional cardiologists.

PubMed

Farah, J; Struelens, L; Auvinen, A; Jacob, S; Koukorava, C; Schnelzer, M; Vanhavere, F; Clairand, I

2015-04-01

In preparation of a large European epidemiological study on the relation between eye lens dose and the occurrence of lens opacities, the European ELDO project focused on the development of practical methods to estimate retrospectively cumulative eye lens dose for interventional medical professionals exposed to radiation. The present paper applies one of the ELDO approaches, correlating eye lens dose to whole-body doses, to assess cumulative eye lens dose for 14 different Finnish interventional cardiologists for whom annual whole-body dose records were available for their entire working period. The estimated cumulative left and right eye lens dose ranged from 8 to 264 mSv and 6 to 225 mSv, respectively. In addition, calculations showed annual eye lens doses sometimes exceeding the new ICRP annual limit of 20 mSv. The work also highlights the large uncertainties associated with the application of such an approach proving the need for dedicated dosimetry systems in the routine monitoring of the eye lens dose. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Numerical Analysis of Organ Doses Delivered During Computed Tomography Examinations Using Japanese Adult Phantoms with the WAZA-ARI Dosimetry System.

PubMed

Takahashi, Fumiaki; Sato, Kaoru; Endo, Akira; Ono, Koji; Ban, Nobuhiko; Hasegawa, Takayuki; Katsunuma, Yasushi; Yoshitake, Takayasu; Kai, Michiaki

2015-08-01

A dosimetry system for computed tomography (CT) examinations, named WAZA-ARI, is being developed to accurately assess radiation doses to patients in Japan. For dose calculations in WAZA-ARI, organ doses were numerically analyzed using average adult Japanese male (JM) and female (JF) phantoms with the Particle and Heavy Ion Transport code System (PHITS). Experimental studies clarified the photon energy distribution of emitted photons and dose profiles on the table for some multi-detector row CT (MDCT) devices. Numerical analyses using a source model in PHITS could specifically take into account emissions of x rays from the tube to the table with attenuation of photons through a beam-shaping filter for each MDCT device based on the experiment results. The source model was validated by measuring the CT dose index (CTDI). Numerical analyses with PHITS revealed a concordance of organ doses with body sizes of the JM and JF phantoms. The organ doses in the JM phantoms were compared with data obtained using previously developed systems. In addition, the dose calculations in WAZA-ARI were verified with previously reported results by realistic NUBAS phantoms and radiation dose measurement using a physical Japanese model (THRA1 phantom). The results imply that numerical analyses using the Japanese phantoms and specified source models can give reasonable estimates of dose for MDCT devices for typical Japanese adults.

A compact in vivo neutron activation analysis system to quantify manganese in human hand bone

NASA Astrophysics Data System (ADS)

Liu, Yingzi

As an urgent issue of correlating cumulative manganese (Mn) exposure to neurotoxicity, bone has emerged as an attractive biomarker for long-term Mn deposition and storage. A novel Deuterium-Deuterium (DD) neutron generator irradiation system has been simulated and constructed, incorporating moderator, reflector and shielding. This neutron activation analysis (NAA) irradiation assembly presents several desirable features, including high neutron flux, improved detection limit and acceptable neutron & photon dose, which would allow it be ready for clinical measurement. Key steps include simulation modeling and verifying, irradiation system design, detector characterization, and neutron flux and dose assessment. Activation foils were also analyzed to reveal the accurate neutron spectrum in the irradiation cave. The detection limit with this system is 0.428 ppm with 36 mSv equivalent hand dose and 52 microSv whole body effective dose.

TH-EF-BRB-11: Volumetric Modulated Arc Therapy for Total Body Irradiation

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

Ouyang, L; Folkerts, M; Hrycushko, B

Purpose: To develop a modern, patient-comfortable total body irradiation (TBI) technique suitable for standard-sized linac vaults. Methods: An indexed rotatable immobilization system (IRIS) was developed to make possible total-body CT imaging and radiation delivery on conventional couches. Treatment consists of multi-isocentric volumetric modulated arc therapy (VMAT) to the upper body and parallel-opposed fields to the lower body. Each isocenter is indexed to the couch and includes a 180° IRIS rotation between the upper and lower body fields. VMAT fields are optimized to satisfy lung dose objectives while achieving a uniform therapeutic dose to the torso. End-to-end tests with a randomore » phantom were used to verify dosimetric characteristics. Treatment plan robustness regarding setup uncertainty was assessed by simulating global and regional isocenter setup shifts on patient data sets. Dosimetric comparisons were made with conventional extended distance, standing TBI (cTBI) plans using a Monte Carlo-based calculation. Treatment efficiency was assessed for eight courses of patient treatment. Results: The IRIS system is level and orthogonal to the scanned CT image plane, with lateral shifts <2mm following rotation. End-to-end tests showed surface doses within ±10% of the prescription dose, field junction doses within ±15% of prescription dose. Plan robustness tests showed <15% changes in dose with global setup errors up to 5mm in each direction. Local 5mm relative setup errors in the chest resulted in < 5% dose changes. Local 5mm shift errors in the pelvic and upper leg junction resulted in <10% dose changes while a 10mm shift error causes dose changes up to 25%. Dosimetric comparison with cTBI showed VMAT-TBI has advantages in preserving chest wall dose with flexibility in leveraging the PTV-body and PTV-lung dose. Conclusion: VMAT-TBI with the IRIS system was shown clinically feasible as a cost-effective approach to TBI for standard-sized linac vaults.« less

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.

Primary DNA damage assessed with the comet assay and comparison to the absorbed dose of diagnostic X-rays in children.

PubMed

Milkovic, Durdica; Garaj-Vrhovac, Vera; Ranogajec-Komor, Mária; Miljanic, Saveta; Gajski, Goran; Knezevic, Zeljka; Beck, Natko

2009-01-01

The aim of this work is to assess DNA damage in peripheral blood lymphocytes of children prior to and following airway X-ray examinations of the chest using the alkaline comet assay and to compare data with the measured absorbed dose. Twenty children with pulmonary diseases, between the ages of 5 and 14 years, are assessed. Absorbed dose measurements are conducted for posterior-anterior projection on the forehead, thyroid gland, gonads, chest, and back. Doses are measured using thermoluminescent and radiophotoluminescent dosimetry systems. Differences between tail lengths, tail intensity, and tail moments as well as for the long-tailed nuclei before and after exposures are statistically significant and are dependent on the individual. The results demonstrate the usefulness of the comet assay as a measure of X-ray damage to lymphocytes in a clinical setting. Doses measured with both dosimeters show satisfactory agreement (0.01 mSv) and are suitable for dosimetric measurements in X-ray diagnostics.

Developing and implementing a high precision setup system

NASA Astrophysics Data System (ADS)

Peng, Lee-Cheng

The demand for high-precision radiotherapy (HPRT) was first implemented in stereotactic radiosurgery using a rigid, invasive stereotactic head frame. Fractionated stereotactic radiotherapy (SRT) with a frameless device was developed along a growing interest in sophisticated treatment with a tight margin and high-dose gradient. This dissertation establishes the complete management for HPRT in the process of frameless SRT, including image-guided localization, immobilization, and dose evaluation. The most ideal and precise positioning system can allow for ease of relocation, real-time patient movement assessment, high accuracy, and no additional dose in daily use. A new image-guided stereotactic positioning system (IGSPS), the Align RT3C 3D surface camera system (ART, VisionRT), which combines 3D surface images and uses a real-time tracking technique, was developed to ensure accurate positioning at the first place. The uncertainties of current optical tracking system, which causes patient discomfort due to additional bite plates using the dental impression technique and external markers, are found. The accuracy and feasibility of ART is validated by comparisons with the optical tracking and cone-beam computed tomography (CBCT) systems. Additionally, an effective daily quality assurance (QA) program for the linear accelerator and multiple IGSPSs is the most important factor to ensure system performance in daily use. Currently, systematic errors from the phantom variety and long measurement time caused by switching phantoms were discovered. We investigated the use of a commercially available daily QA device to improve the efficiency and thoroughness. Reasonable action level has been established by considering dosimetric relevance and clinic flow. As for intricate treatments, the effect of dose deviation caused by setup errors remains uncertain on tumor coverage and toxicity on OARs. The lack of adequate dosimetric simulations based on the true treatment coordinates from the treatment planning system (TPS) has limited adaptive treatments. A reliable and accurate dosimetric simulation using TPS and in-house software in uncorrected errors has been developed. In SRT, the calculated dose deviation is compared to the original treatment dose with the dose-volume histogram to investigate the dose effect of rotational errors. In summary, this work performed a quality assessment to investigate the overall accuracy of current setup systems. To reach the ideal HPRT, the reliable dosimetric simulation, an effective daily QA program and effective, precise setup systems were developed and validated.

Reducing absorbed dose to eye lenses in head CT examinations: the effect of bismuth shielding.

PubMed

Ciarmatori, Alberto; Nocetti, L; Mistretta, G; Zambelli, G; Costi, T

2016-06-01

The eye lens is considered to be among the most radiosensitive human tissues. Brain CT scans may unnecessarily expose it to radiation even if the area of clinical interest is far from the eyes. The aim of this study is to implement a bismuth eye lens shielding system for Head-CT acquisitions in these cases. The study is focused on the assessment of the dosimetric characteristics of the shielding system as well as on its effect on image quality. The shielding system was tested in two set-ups which differ for distance ("contact" and "4 cm" Set up respectively). Scans were performed on a CTDI phantom and an anthropomorphic phantom. A reference set up without shielding system was acquired to establish a baseline. Image quality was assessed by signal (not HU converted), noise and contrast-to-noise ratio (CNR) evaluation. The overall dose reduction was evaluated by measuring the CTDIvol while the eye lens dose reduction was assessed by placing thermoluminescent dosimeters (TLDs) on an anthropomorphic phantom. The image quality analysis exhibits the presence of an artefact that mildly increases the CT number up to 3 cm below the shielding system. Below the artefact, the difference of the Signal and the CNR are negligible between the three different set-ups. Regarding the CTDI, the analysis demonstrates a decrease by almost 12 % (in the "contact" set-up) and 9 % (in the "4 cm" set-up). TLD measurements exhibit an eye lens dose reduction by 28.5 ± 5 and 21.1 ± 5 % respectively at the "contact" and the "4 cm" distance. No relevant artefact was found and image quality was not affected by the shielding system. Significant dose reductions were measured. These features make the shielding set-up useful for clinical implementation in both studied positions.

Multi-component assessment of chronic obstructive pulmonary disease: an evaluation of the ADO and DOSE indices and the global obstructive lung disease categories in international primary care data sets

PubMed Central

Jones, Rupert C; Price, David; Chavannes, Niels H; Lee, Amanda J; Hyland, Michael E; Ställberg, Björn; Lisspers, Karin; Sundh, Josefin; van der Molen, Thys; Tsiligianni, Ioanna

2016-01-01

Suitable tools for assessing the severity of chronic obstructive pulmonary disease (COPD) include multi-component indices and the global initiative for chronic obstructive lung disease (GOLD) categories. The aim of this study was to evaluate the dyspnoea, obstruction, smoking, exacerbation (DOSE) and the age, dyspnoea, obstruction (ADO) indices and GOLD categories as measures of current health status and future outcomes in COPD patients. This was an observational cohort study comprising 5,114 primary care COPD patients across three databases from UK, Sweden and Holland. The associations of DOSE and ADO indices with (i) health status using the Clinical COPD Questionnaire (CCQ) and St George’s Respiratory Questionnaire (SGRQ) and COPD Assessment test (CAT) and with (ii) current and future exacerbations, admissions and mortality were assessed in GOLD categories and DOSE and ADO indices. DOSE and ADO indices were significant predictors of future exacerbations: incident rate ratio was 1.52 (95% confidence intervals 1.46–1.57) for DOSE, 1.16 (1.12–1.20) for ADO index and 1.50 (1.33–1.68) and 1.23 (1.10–1.39), respectively, for hospitalisations. Negative binomial regression showed that the DOSE index was a better predictor of future admissions than were its component items. The hazard ratios for mortality were generally higher for ADO index groups than for DOSE index groups. The GOLD categories produced widely differing assessments for future exacerbation risk or for hospitalisation depending on the methods used to calculate them. None of the assessment systems were excellent at predicting future risk in COPD; the DOSE index appears better than the ADO index for predicting many outcomes, but not mortality. The GOLD categories predict future risk inconsistently. The DOSE index and the GOLD categories using exacerbation frequency may be used to identify those at high risk for exacerbations and admissions. PMID:27053297

Multi-component assessment of chronic obstructive pulmonary disease: an evaluation of the ADO and DOSE indices and the global obstructive lung disease categories in international primary care data sets.

PubMed

Jones, Rupert C; Price, David; Chavannes, Niels H; Lee, Amanda J; Hyland, Michael E; Ställberg, Björn; Lisspers, Karin; Sundh, Josefin; van der Molen, Thys; Tsiligianni, Ioanna

2016-04-07

Suitable tools for assessing the severity of chronic obstructive pulmonary disease (COPD) include multi-component indices and the global initiative for chronic obstructive lung disease (GOLD) categories. The aim of this study was to evaluate the dyspnoea, obstruction, smoking, exacerbation (DOSE) and the age, dyspnoea, obstruction (ADO) indices and GOLD categories as measures of current health status and future outcomes in COPD patients. This was an observational cohort study comprising 5,114 primary care COPD patients across three databases from UK, Sweden and Holland. The associations of DOSE and ADO indices with (i) health status using the Clinical COPD Questionnaire (CCQ) and St George's Respiratory Questionnaire (SGRQ) and COPD Assessment test (CAT) and with (ii) current and future exacerbations, admissions and mortality were assessed in GOLD categories and DOSE and ADO indices. DOSE and ADO indices were significant predictors of future exacerbations: incident rate ratio was 1.52 (95% confidence intervals 1.46-1.57) for DOSE, 1.16 (1.12-1.20) for ADO index and 1.50 (1.33-1.68) and 1.23 (1.10-1.39), respectively, for hospitalisations. Negative binomial regression showed that the DOSE index was a better predictor of future admissions than were its component items. The hazard ratios for mortality were generally higher for ADO index groups than for DOSE index groups. The GOLD categories produced widely differing assessments for future exacerbation risk or for hospitalisation depending on the methods used to calculate them. None of the assessment systems were excellent at predicting future risk in COPD; the DOSE index appears better than the ADO index for predicting many outcomes, but not mortality. The GOLD categories predict future risk inconsistently. The DOSE index and the GOLD categories using exacerbation frequency may be used to identify those at high risk for exacerbations and admissions.

IRIS Toxicological Review of Tetrachloroethylene ...

EPA Pesticide Factsheets

EPA conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of tetrachloroethylene that will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that science is used credibly and appropriately in derivation of the toxicological characterization and dose-response assessments. This draft health assessment addresses both non-cancer and cancer human health effects that may result from chronic exposure to tetrachloroethylene (also called Perchloroethylene or Perc) . This is an update of an existing assessment posted on IRIS in 1988. This draft Toxicological Review includes a chronic Reference Concentration (RfC) and carcinogenicity assessment, which are not currently available on IRIS, as well as an update of the 1988 IRIS Reference Dose (RfD). Tetrachloroethylene is a chemical solvent that is widely used for dry cleaning of fabrics, metal degreasing, and in making some consumer products and other chemicals.

Patient-specific radiation dose and cancer risk estimation in CT: Part I. Development and validation of a Monte Carlo program

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: Radiation-dose awareness and optimization in CT can greatly benefit from a dose-reporting system that provides dose and risk estimates specific to each patient and each CT examination. As the first step toward patient-specific dose and risk estimation, this article aimed to develop a method for accurately assessing radiation dose from CT examinations. Methods: A Monte Carlo program was developed to model a CT system (LightSpeed VCT, GE Healthcare). The geometry of the system, the energy spectra of the x-ray source, the three-dimensional geometry of the bowtie filters, and the trajectories of source motions during axial and helical scans were explicitly modeled. To validate the accuracy of the program, a cylindrical phantom was built to enable dose measurements at seven different radial distances from its central axis. Simulated radial dose distributions in the cylindrical phantom were validated against ion chamber measurements for single axial scans at all combinations of tube potential and bowtie filter settings. The accuracy of the program was further validated using two anthropomorphic phantoms (a pediatric one-year-old phantom and an adult female phantom). Computer models of the two phantoms were created based on their CT data and were voxelized for input into the Monte Carlo program. Simulated dose at various organ locations was compared against measurements made with thermoluminescent dosimetry chips for both single axial and helical scans. Results: For the cylindrical phantom, simulations differed from measurements by −4.8% to 2.2%. For the two anthropomorphic phantoms, the discrepancies between simulations and measurements ranged between (−8.1%, 8.1%) and (−17.2%, 13.0%) for the single axial scans and the helical scans, respectively. Conclusions: The authors developed an accurate Monte Carlo program for assessing radiation dose from CT examinations. When combined with computer models of actual patients, the program can provide accurate dose estimates for specific patients. PMID:21361208

IRIS Toxicological Review of Beryllium and Compounds (2008 ...

EPA Pesticide Factsheets

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Beryllium that when finalized will appear on the Integrated Risk Information System (IRIS) database. An IRIS Toxicological Review of Beryllium and Compounds was published in 1988 and reassessed in 1998. The current draft (2007) only focuses on the cancer assessment and does not re-evaluate posted reference doses or reference concentrations.

Prediction of Individual Serum Infliximab Concentrations in Inflammatory Bowel Disease by a Bayesian Dashboard System.

PubMed

Eser, Alexander; Primas, Christian; Reinisch, Sieglinde; Vogelsang, Harald; Novacek, Gottfried; Mould, Diane R; Reinisch, Walter

2018-01-30

Despite a robust exposure-response relationship of infliximab in inflammatory bowel disease (IBD), attempts to adjust dosing to individually predicted serum concentrations of infliximab (SICs) are lacking. Compared with labor-intensive conventional software for pharmacokinetic (PK) modeling (eg, NONMEM) dashboards are easy-to-use programs incorporating complex Bayesian statistics to determine individual pharmacokinetics. We evaluated various infliximab detection assays and the number of samples needed to precisely forecast individual SICs using a Bayesian dashboard. We assessed long-term infliximab retention in patients being dosed concordantly versus discordantly with Bayesian dashboard recommendations. Three hundred eighty-two serum samples from 117 adult IBD patients on infliximab maintenance therapy were analyzed by 3 commercially available assays. Data from each assay was modeled using NONMEM and a Bayesian dashboard. PK parameter precision and residual variability were assessed. Forecast concentrations from both systems were compared with observed concentrations. Infliximab retention was assessed by prediction for dose intensification via Bayesian dashboard versus real-life practice. Forecast precision of SICs varied between detection assays. At least 3 SICs from a reliable assay are needed for an accurate forecast. The Bayesian dashboard performed similarly to NONMEM to predict SICs. Patients dosed concordantly with Bayesian dashboard recommendations had a significantly longer median drug survival than those dosed discordantly (51.5 versus 4.6 months, P < .0001). The Bayesian dashboard helps to assess the diagnostic performance of infliximab detection assays. Three, not single, SICs provide sufficient information for individualized dose adjustment when incorporated into the Bayesian dashboard. Treatment adjusted to forecasted SICs is associated with longer drug retention of infliximab. © 2018, The American College of Clinical Pharmacology.

Commissioning and quality assurance for the treatment delivery components of the AccuBoost system

PubMed Central

Talmadge, Mike; Ladd, Ron; Halvorsen, Per

2015-01-01

The objective for this work was to develop a commissioning methodology for the treatment delivery components of the AccuBoost system, as well as to establish a routine quality assurance program and appropriate guidance for clinical use based on the commissioning results. Various tests were developed: 1) assessment of the accuracy of the displayed separation value; 2) validation of the dwell positions within each applicator; 3) assessment of the accuracy and precision of the applicator localization system; 4) assessment of the combined dose profile of two opposed applicators to confirm that they are coaxial; 5) measurement of the absolute dose delivered with each applicator to confirm acceptable agreement with dose based on Monte Carlo modeling; 6) measurements of the skin‐to‐center dose ratio using optically stimulated luminescence dosimeters; and 7) assessment of the mammopad cushion's effect on the center dose. We found that the difference between the measured and the actual paddle separation is <0.1 cm for the separation range of 3 cm to 7.5 cm. Radiochromic film measurements demonstrated that the number of dwell positions inside the applicators agree with the values from the vendor, for each applicator type and size. The shift needed for a good applicator‐grid alignment was within 0.2 cm. The dry‐run test using film demonstrated that the shift of the dosimetric center is within 0.15 cm. Dose measurements in water converted to polystyrene agreed within 5.0% with the Monte Carlo data in polystyrene for the same applicator type, size, and depth. A solid water‐to‐water (phantom) factor was obtained for each applicator, and all future annual quality assurance tests will be performed in solid water using an average value of 1.07 for the solid water‐to‐water factor. The skin‐to‐center dose ratio measurements support the Monte Carlo‐based values within 5.0% agreement. For the treatment separation range of 4 cm to 8 cm, the change in center dose would be <1.0% for all applicators when using a compressed pad of 0.2 cm to 0.3 cm. The tests performed ensured that all treatment components of the AccuBoost system are functional and that a treatment plan can be delivered with acceptable accuracy. Based on the commissioning results, a quality assurance manual and guidance documents for clinical use were developed. PACS numbers: 87.55.Qr, 87.56.Da, 87.90.+y PMID:26103184

Benchmarking pediatric cranial CT protocols using a dose tracking software system: a multicenter study.

PubMed

De Bondt, Timo; Mulkens, Tom; Zanca, Federica; Pyfferoen, Lotte; Casselman, Jan W; Parizel, Paul M

2017-02-01

To benchmark regional standard practice for paediatric cranial CT-procedures in terms of radiation dose and acquisition parameters. Paediatric cranial CT-data were retrospectively collected during a 1-year period, in 3 different hospitals of the same country. A dose tracking system was used to automatically gather information. Dose (CTDI and DLP), scan length, amount of retakes and demographic data were stratified by age and clinical indication; appropriate use of child-specific protocols was assessed. In total, 296 paediatric cranial CT-procedures were collected. Although the median dose of each hospital was below national and international diagnostic reference level (DRL) for all age categories, statistically significant (p-value < 0.001) dose differences among hospitals were observed. The hospital with lowest dose levels showed smallest dose variability and used age-stratified protocols for standardizing paediatric head exams. Erroneous selection of adult protocols for children still occurred, mostly in the oldest age-group. Even though all hospitals complied with national and international DRLs, dose tracking and benchmarking showed that further dose optimization and standardization is possible by using age-stratified protocols for paediatric cranial CT. Moreover, having a dose tracking system revealed that adult protocols are still applied for paediatric CT, a practice that must be avoided. • Significant differences were observed in the delivered dose between age-groups and hospitals. • Using age-adapted scanning protocols gives a nearly linear dose increase. • Sharing dose-data can be a trigger for hospitals to reduce dose levels.

Patient dose, gray level and exposure index with a computed radiography system

NASA Astrophysics Data System (ADS)

Silva, T. R.; Yoshimura, E. M.

2014-02-01

Computed radiography (CR) is gradually replacing conventional screen-film system in Brazil. To assess image quality, manufactures provide the calculation of an exposure index through the acquisition software of the CR system. The objective of this study is to verify if the CR image can be used as an evaluator of patient absorbed dose too, through a relationship between the entrance skin dose and the exposure index or the gray level values obtained in the image. The CR system used for this study (Agfa model 30-X with NX acquisition software) calculates an exposure index called Log of the Median (lgM), related to the absorbed dose to the IP. The lgM value depends on the average gray level (called Scan Average Level (SAL)) of the segmented pixel value histogram of the whole image. A Rando male phantom was used to simulate a human body (chest and head), and was irradiated with an X-ray equipment, using usual radiologic techniques for chest exams. Thermoluminescent dosimeters (LiF, TLD100) were used to evaluate entrance skin dose and exit dose. The results showed a logarithm relation between entrance dose and SAL in the image center, regardless of the beam filtration. The exposure index varies linearly with the entrance dose, but the angular coefficient is beam quality dependent. We conclude that, with an adequate calibration, the CR system can be used to evaluate the patient absorbed dose.

An Evaluation of Voluntary 2-Dose Varicella Vaccination Coverage in New York City Public Schools

PubMed Central

Rosen, Jennifer B.; Bialek, Stephanie R.; Szeto, Hiram; Zimmerman, Christopher M.

2015-01-01

Objectives. We assessed coverage for 2-dose varicella vaccination, which is not required for school entry, among New York City public school students and examined characteristics associated with receipt of 2 doses. Methods. We measured receipt of either at least 1 or 2 doses of varicella vaccine among students aged 4 years and older in a sample of 336 public schools (n = 223 864 students) during the 2010 to 2011 school year. Data came from merged student vaccination records from 2 administrative data systems. We conducted multivariable regression to assess associations of age, gender, race/ethnicity, and school location with 2-dose prevalence. Results. Coverage with at least 1 varicella dose was 96.2% (95% confidence interval [CI] = 96.2%, 96.3%); coverage with at least 2 doses was 64.8% (95% CI = 64.6%, 64.9%). Increasing student age, non-Hispanic White race/ethnicity, and attendance at school in Staten Island were associated with lower 2-dose coverage. Conclusions. A 2-dose varicella vaccine requirement for school entry would likely improve 2-dose coverage, eliminate coverage disparities, and prevent disease. PMID:25521904

Assessing dose of the representative person for the purpose of radiation protection of the public. ICRP publication 101. Approved by the Commission in September 2005.

PubMed

2006-01-01

The Commission intended that its revised recommendations should be based on a simple, but widely applicable, system of protection that would clarify its objectives and provide a basis for the more formal systems needed by operating managers and regulators. The recommendations would establish quantified constraints, or limits, on individual dose from specified sources. These dose constraints apply to actual or representative people who encounter occupational, medical, and public exposures. This report updates the previous guidance for estimating dose to the public. Dose to the public cannot be measured directly and, in some cases, it cannot be measured at all. Therefore, for the purpose of protection of the public, it is necessary to characterise an individual, either hypothetical or specific, whose dose can be used for determining compliance with the relevant dose constraint. This individual is defined as the 'representative person'. The Commission's goal of protection of the public is achieved if the relevant dose constraint for this individual for a single source is met and radiological protection is optimised. This report explains the process of estimating annual dose and recognises that a number of different methods are available for this purpose. These methods range from deterministic calculations to more complex probabilistic techniques. In addition, a mixture of these techniques may be applied. In selecting characteristics of the representative person, three important concepts should be borne in mind: reasonableness, sustainability, and homogeneity. Each concept is explained and examples are provided to illustrate their roles. Doses to the public are prospective (may occur in the future) or retrospective (occurred in the past). Prospective doses are for hypothetical individuals who may or may not exist in the future, while retrospective doses are generally calculated for specific individuals. The Commission recognises that the level of detail afforded by its provision of dose coefficients for six age categories is not necessary in making prospective assessments of dose, given the inherent uncertainties usually associated with estimating dose to the public and with identification of the representative person. It now recommends the use of three age categories for estimating annual dose to the representative person for prospective assessments. These categories are 0-5 years (infant), 6-15 years (child), and 16-70 years (adult). For practical implementation of this recommendation, dose coefficients and habit data for a 1-year-old infant, a 10-year-old child, and an adult should be used to represent the three age categories. In a probabilistic assessment of dose, whether from a planned facility or an existing situation, the Commission recommends that the representative person should be defined such that the probability is less than about 5% that a person drawn at random from the population will receive a greater dose. If such an assessment indicates that a few tens of people or more could receive doses above the relevant constraint, the characteristics of these people need to be explored. If, following further analysis, it is shown that doses to a few tens of people are indeed likely to exceed the relevant dose constraint, actions to modify the exposure should be considered. The Commission recognises the role that stakeholders can play in identifying characteristics of the representative person. Involvement of stakeholders can significantly improve the quality, understanding, and acceptability of the characteristics of the representative person and the resulting estimated dose.

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

Heintz, P; Heintz, B; Sandoval, D

Purpose: Computerized radiation therapy treatment planning is performed on almost all patients today. However it is seldom used for laboratory irradiations. The first objective is to assess whether modern radiation therapy treatment planning (RTP) systems accurately predict the subject dose by comparing in vivo and decedent dose measurements to calculated doses. The other objective is determine the importance of using a RTP system for laboratory irradiations. Methods: 5 MOSFET radiation dosimeters were placed enterically in each subject (2 sedated Rhesus Macaques) to measure the absorbed dose at 5 levels (carina, lung, heart, liver and rectum) during whole body irradiation. Themore » subjects were treated with large opposed lateral fields and extended distances to cover the entire subject using a Varian 600C linac. CT simulation was performed ante-mortem (AM) and post-mortem (PM). To compare AM and PM doses, calculation points were placed at the location of each dosimeter in the treatment plan. The measured results were compared to the results using Varian Eclipse and Prowess Panther RTP systems. Results: The Varian and Prowess treatment planning system agreed to within in +1.5% for both subjects. However there were significant differences between the measured and calculated doses. For both animals the calculated central axis dose was higher than prescribed by 3–5%. This was caused in part by inaccurate measurement of animal thickness at the time of irradiation. For one subject the doses ranged from 4% to 7% high and the other subject the doses ranged 7% to 14% high when compared to the RTP doses. Conclusions: Our results suggest that using proper CT RTP system can more accurately deliver the prescribed dose to laboratory subjects. It also shows that there is significant dose variation in such subjects when inhomogeneities are not considered in the planning process.« less

Consolidation Radiotherapy in Primary Central Nervous System Lymphomas: Impact on Outcome of Different Fields and Doses in Patients in Complete Remission After Upfront Chemotherapy

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

Ferreri, Andres Jose Maria, E-mail: andres.ferreri@hsr.i; Medical Oncology Unit, Department of Oncology, San Raffaele Scientific Institute, Milan; Verona, Chiara

Purpose: Avoidance radiotherapy or reduction of irradiation doses in patients with primary central nervous system lymphoma (PCNSL) in complete remission (CR) after high-dose methotrexate (HD-MTX)-based chemotherapy has been proposed to minimize the neurotoxicity risk. Nevertheless, no study has focused on the survival impact of radiation parameters, as far as we know, and the optimal radiation schedule remains to be defined. Methods and Materials: The impact on outcome and neurologic performance of different radiation fields and doses was assessed in 33 patients with PCNSL who achieved CR after MTX-containing chemotherapy and were referred to consolidation whole-brain irradiation (WBRT). Patterns of relapsemore » were analyzed on computed tomography-guided treatment planning, and neurologic impairment was assessed by the Mini Mental Status Examination. Results: At a median follow-up of 50 months, 21 patients are relapse-free (5-year failure-free survival [FFS], 51%). WBRT doses {>=}40 Gy were not associated with improved disease control in comparison with a WBRT dose of 30 to 36 Gy (relapse rate, 46% vs. 30%; 5-year FFS, 51% vs. 50%; p = 0.26). Disease control was not significantly different between patients irradiated to the tumor bed with 45 to 54 Gy or with 36 to 44 Gy, with a 5-year FFS of 35% and 44% (p = 0.43), respectively. Twenty patients are alive (5-year overall survival, 54%); WB and tumor bed doses did not have an impact on survival. Impairment as assessed by the Mini Mental Status Examination was significantly more common in patients treated with a WBRT dose {>=}40 Gy. Conclusion: Consolidation with WBRT 36 Gy is advisable in patients with PCNSL in CR after HD-MTX-based chemotherapy. Higher doses do not change the outcome and could increase the risk of neurotoxicity.« less

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.

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

McKenzie-Carter, M.A.; Lyon, R.E.; Rope, S.K.

This report contains information to support the Environmental Assessment for the Burning Plasma Experiment (BPX) Project proposed for the Princeton Plasma Physics Laboratory (PPPL). The assumptions and methodology used to assess the impact to members of the public from operational and accidental releases of radioactive material from the proposed BPX during the operational period of the project are described. A description of the tracer release tests conducted at PPPL by NOAA is included; dispersion values from these tests are used in the dose calculations. Radiological releases, doses, and resulting health risks are calculated and summarized. The computer code AIRDOS- EPA,more » which is part of the computer code system CAP-88, is used to calculate the individual and population doses for routine releases; FUSCRAC3 is used to calculate doses resulting from off-normal releases where direct application of the NOAA tracer test data is not practical. Where applicable, doses are compared to regulatory limits and guideline values. 48 refs., 16 tabs.« less

Preliminary assessment of the impact of incorporating a detailed algorithm for the effects of nuclear irradiation on combat crew performance into the Janus combat simulation

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

Warshawsky, A.S.; Uzelac, M.J.; Pimper, J.E.

The Crew III algorithm for assessing time and dose dependent combat crew performance subsequent to nuclear irradiation was incorporated into the Janus combat simulation system. Battle outcomes using this algorithm were compared to outcomes based on the currently used time-independent cookie-cutter'' assessment methodology. The results illustrate quantifiable differences in battle outcome between the two assessment techniques. Results suggest that tactical nuclear weapons are more effective than currently assumed if performance degradation attributed to radiation doses between 150 to 3000 rad are taken into account. 6 refs., 9 figs.

Usefulness of a new online patient-specific quality assurance system for respiratory-gated radiotherapy.

PubMed

Kurosawa, Tomoyuki; Tachibana, Hidenobu; Moriya, Shunsuke; Miyakawa, Shin; Nishio, Teiji; Sato, Masanori

2017-11-01

The accuracy of gated irradiation may decrease when treatment is performed with short "beam-on" times. Also, the dose is subject to variation between treatment sessions if the respiratory rate is irregular. We therefore evaluated the impact of the differences between gated and non-gated treatment on doses using a new online quality assurance (QA) system for respiratory-gated radiotherapy. We generated dose estimation models to associate dose and pulse information using a 0.6 cc Farmer chamber and our QA system. During gated irradiation with each of seven regular and irregular respiratory patterns, with the Farmer chamber readings as references, we evaluated our QA system's accuracy. We then used the QA system to assess the impact of respiratory patterns on dose distribution for three lung and three liver radiotherapy plans. Gated and non-gated plans were generated and compared. There was agreement within 1.7% between the ionization chamber and our system for several regular and irregular motion patterns. For dose distributions with measured errors, there were larger differences between gated and non-gated treatment for high-dose regions within the planned treatment volume (PTV). Compared with a non-gated plan, PTV D 95% for a gated plan decreased by -1.5% to -2.6%. Doses to organs at risk were similar with both plans. Our simple system estimated the radiation dose to the patient using only pulse information from the linac, even during irregular respiration. The quality of gated irradiation for each patient can be verified fraction by fraction. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Systems Biology and Biomarkers of Early Effects for Occupational Exposure Limit Setting

PubMed Central

DeBord, D. Gayle; Burgoon, Lyle; Edwards, Stephen W.; Haber, Lynne T.; Kanitz, M. Helen; Kuempel, Eileen; Thomas, Russell S.; Yucesoy, Berran

2015-01-01

In a recent National Research Council document, new strategies for risk assessment were described to enable more accurate and quicker assessments.( 1 ) This report suggested that evaluating individual responses through increased use of bio-monitoring could improve dose-response estimations. Identi-fication of specific biomarkers may be useful for diagnostics or risk prediction as they have the potential to improve exposure assessments. This paper discusses systems biology, biomarkers of effect, and computational toxicology approaches and their relevance to the occupational exposure limit setting process. The systems biology approach evaluates the integration of biological processes and how disruption of these processes by chemicals or other hazards affects disease outcomes. This type of approach could provide information used in delineating the mode of action of the response or toxicity, and may be useful to define the low adverse and no adverse effect levels. Biomarkers of effect are changes measured in biological systems and are considered to be preclinical in nature. Advances in computational methods and experimental -omics methods that allow the simultaneous measurement of families of macromolecules such as DNA, RNA, and proteins in a single analysis have made these systems approaches feasible for broad application. The utility of the information for risk assessments from -omics approaches has shown promise and can provide information on mode of action and dose-response relationships. As these techniques evolve, estimation of internal dose and response biomarkers will be a critical test of these new technologies for application in risk assessment strategies. While proof of concept studies have been conducted that provide evidence of their value, challenges with standardization and harmonization still need to be overcome before these methods are used routinely. PMID:26132979

Systems Biology and Biomarkers of Early Effects for Occupational Exposure Limit Setting.

PubMed

DeBord, D Gayle; Burgoon, Lyle; Edwards, Stephen W; Haber, Lynne T; Kanitz, M Helen; Kuempel, Eileen; Thomas, Russell S; Yucesoy, Berran

2015-01-01

In a recent National Research Council document, new strategies for risk assessment were described to enable more accurate and quicker assessments. This report suggested that evaluating individual responses through increased use of bio-monitoring could improve dose-response estimations. Identification of specific biomarkers may be useful for diagnostics or risk prediction as they have the potential to improve exposure assessments. This paper discusses systems biology, biomarkers of effect, and computational toxicology approaches and their relevance to the occupational exposure limit setting process. The systems biology approach evaluates the integration of biological processes and how disruption of these processes by chemicals or other hazards affects disease outcomes. This type of approach could provide information used in delineating the mode of action of the response or toxicity, and may be useful to define the low adverse and no adverse effect levels. Biomarkers of effect are changes measured in biological systems and are considered to be preclinical in nature. Advances in computational methods and experimental -omics methods that allow the simultaneous measurement of families of macromolecules such as DNA, RNA, and proteins in a single analysis have made these systems approaches feasible for broad application. The utility of the information for risk assessments from -omics approaches has shown promise and can provide information on mode of action and dose-response relationships. As these techniques evolve, estimation of internal dose and response biomarkers will be a critical test of these new technologies for application in risk assessment strategies. While proof of concept studies have been conducted that provide evidence of their value, challenges with standardization and harmonization still need to be overcome before these methods are used routinely.

Use of epidemiologic data in Integrated Risk Information System (IRIS) assessments

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

Persad, Amanda S.; Cooper, Glinda S.

2008-11-15

In human health risk assessment, information from epidemiologic studies is typically utilized in the hazard identification step of the risk assessment paradigm. However, in the assessment of many chemicals by the Integrated Risk Information System (IRIS), epidemiologic data, both observational and experimental, have also been used in the derivation of toxicological risk estimates (i.e., reference doses [RfD], reference concentrations [RfC], oral cancer slope factors [CSF] and inhalation unit risks [IUR]). Of the 545 health assessments posted on the IRIS database as of June 2007, 44 assessments derived non-cancer or cancer risk estimates based on human data. RfD and RfC calculationsmore » were based on a spectrum of endpoints from changes in enzyme activity to specific neurological or dermal effects. There are 12 assessments with IURs based on human data, two assessments that extrapolated human inhalation data to derive CSFs and one that used human data to directly derive a CSF. Lung or respiratory cancer is the most common endpoint for cancer assessments based on human data. To date, only one chemical, benzene, has utilized human data for derivation of all three quantitative risk estimates (i.e., RfC, RfD, and dose-response modeling for cancer assessment). Through examples from the IRIS database, this paper will demonstrate how epidemiologic data have been used in IRIS assessments for both adding to the body of evidence in the hazard identification process and in the quantification of risk estimates in the dose-response component of the risk assessment paradigm.« less

Dosimetry and image quality assessment in a direct radiography system

PubMed Central

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

2014-01-01

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

Real-time intraoperative evaluation of implant quality and dose correction during prostate brachytherapy consistently improves target coverage using a novel image fusion and optimization program.

PubMed

Zelefsky, Michael J; Cohen, Gilad N; Taggar, Amandeep S; Kollmeier, Marisa; McBride, Sean; Mageras, Gig; Zaider, Marco

Our purpose was to describe the process and outcome of performing postimplantation dosimetric assessment and intraoperative dose correction during prostate brachytherapy using a novel image fusion-based treatment-planning program. Twenty-six consecutive patients underwent intraoperative real-time corrections of their dose distributions at the end of their permanent seed interstitial procedures. After intraoperatively planned seeds were implanted and while the patient remained in the lithotomy position, a cone beam computed tomography scan was obtained to assess adequacy of the prescription dose coverage. The implanted seed positions were automatically segmented from the cone-beam images, fused onto a new set of acquired ultrasound images, reimported into the planning system, and recontoured. Dose distributions were recalculated based upon actual implanted seed coordinates and recontoured ultrasound images and were reviewed. If any dose deficiencies within the prostate target were identified, additional needles and seeds were added. Once an implant was deemed acceptable, the procedure was completed, and anesthesia was reversed. When the intraoperative ultrasound-based quality assurance assessment was performed after seed placement, the median volume receiving 100% of the dose (V100) was 93% (range, 74% to 98%). Before seed correction, 23% (6/26) of cases were noted to have V100 <90%. Based on this intraoperative assessment and replanning, additional seeds were placed into dose-deficient regions within the target to improve target dose distributions. Postcorrection, the median V100 was 97% (range, 93% to 99%). Following intraoperative dose corrections, all implants achieved V100 >90%. In these patients, postimplantation evaluation during the actual prostate seed implant procedure was successfully applied to determine the need for additional seeds to correct dose deficiencies before anesthesia reversal. When applied, this approach should significantly reduce intraoperative errors and chances for suboptimal dose delivery during prostate brachytherapy. Copyright © 2017 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Nonuniform Irradiation of the Canine Intestine. 2. Dosimetry

DTIC Science & Technology

1990-01-01

irradiation is accurate assessment In vivo dosimetry was done using Harshaw (Solon, Ohio) TLD - 100 lith- of the injury after either accidental or... vivo TLD dosimetry system allowed measure- 5 and 6. The dose was determined from the median TLD ment of the °Co dose deposited in the canine small...provide replicate measurements. Two separate dosimetry tubes were deveoped (Fig. 1). The first contained 30 TLD cap- doses (1). Nevertheless, current

3D treatment planning systems.

PubMed

Saw, Cheng B; Li, Sicong

2018-01-01

Three-dimensional (3D) treatment planning systems have evolved and become crucial components of modern radiation therapy. The systems are computer-aided designing or planning softwares that speed up the treatment planning processes to arrive at the best dose plans for the patients undergoing radiation therapy. Furthermore, the systems provide new technology to solve problems that would not have been considered without the use of computers such as conformal radiation therapy (CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). The 3D treatment planning systems vary amongst the vendors and also the dose delivery systems they are designed to support. As such these systems have different planning tools to generate the treatment plans and convert the treatment plans into executable instructions that can be implemented by the dose delivery systems. The rapid advancements in computer technology and accelerators have facilitated constant upgrades and the introduction of different and unique dose delivery systems than the traditional C-arm type medical linear accelerators. The focus of this special issue is to gather relevant 3D treatment planning systems for the radiation oncology community to keep abreast of technology advancement by assess the planning tools available as well as those unique "tricks or tips" used to support the different dose delivery systems. Copyright © 2018 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

An assessment of the use of skin flashes in helical tomotherapy using phantom and in-vivo dosimetry.

PubMed

Tournel, Koen; Verellen, Dirk; Duchateau, Michael; Fierens, Yves; Linthout, Nadine; Reynders, Truus; Voordeckers, Mia; Storme, Guy

2007-07-01

In helical tomotherapy the nature of the optimizing and planning systems allows the delivery of dose on the skin using a build-up compensating technique (skin flash). However, positioning errors or changes in the patient's contour can influence the correct dosage in these regions. This work studies the behavior of skin-flash regions using phantom and in-vivo dosimetry. The dosimetric accuracy of the tomotherapy planning system in skin-flash regions is checked using film and TLD on phantom. Positioning errors are induced and the effect on the skin dose is investigated. Further a volume decrease is simulated using bolus material and the results are compared. Results show that the tomotherapy planning system calculates dose on skin regions within 2 SD using TLD measurements. Film measurements show drops of dose of 2.8% and 26% for, respectively, a 5mm and 10mm mispositioning of the phantom towards air and a dose increase of 9% for a 5mm shift towards tissue. These measurements are confirmed by TLD measurements. A simulated volume reduction shows a similar behavior with a 2.6% and 19.4% drop in dose, measured with TLDs. The tomotherapy system allows adequate planning and delivery of dose using skin flashes. However, exact positioning is crucial to deliver the dose at the exact location.

A method for the assessment of specific energy distribution in a model tumor system

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

Noska, M.A.

1996-12-31

Due to the short range of alpha particles in tissue, the calculation of dose from internally deposited alpha emitters requires a detailed analysis of the microscopic distribution of the radionuclide in order to determine the spatial distribution of energy emission events and, from this, the spatial distribution of dose. In the present study, the authors used quantitative autoradiography (QAR) to assess the microdistribution of a radiolabeled monoclonal antibody (MAb) fragment in human glioma xenografts in mice.

IRIS Toxicological Review of Trichloroethylene (TCE) ...

EPA Pesticide Factsheets

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Trichloroethylene (TCE) that when finalized will appear on the Integrated Risk Information System (IRIS) database. The purpose of this Toxicological Review is to provide scientific support and rationale for the hazard and dose-response assessment in IRIS pertaining to chronic exposure to trichloroethylene. It is not intended to be a comprehensive treatise on the chemical or toxicological nature of trichloroethylene.

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

Yu, S; Green, G; Sehgal, V

Purpose: The purpose of this study is to assess the dose response of radioembolization using yttrium-90 (Y-90) microspheres in patients treated for unresectable cholangiocarcinoma. This study utilized partition dosimetry model for the dose calculation. The results show survival benefit with dose escalation. Methods: Between February 2009 and March 2013, ten patients with pathology proven unresectable cholangiocarcinoma were radioembolized with Y-90 microspheres. Patients underwent initial pre-treatment angiographic assessment for blood flow and 99mTc- MAA for lung shunt evaluation. Activity of Y-90 administration was calculated using the Body Surface Area (BSA) and target volumes which were determined by contouring the pre-treatment MRI/CTmore » images using a radiation therapy treatment planning system. Medical Internal Radiation Dose (MIRD) method was used to assess the dosimetric results of Y90. Partition model based on the tumor to-liver activity uptake estimated from pretreatment 99mTc- MAA study was used to calculate the dose delivered to the target. The variables assessed included: administered dose, toxicity based on clinical changes, imaging based tumor response, and survival. Results: Ten patients were radioembolized with Y-90 microspheres to either one hepatic lobe or both left and right lobes. Patients were stratified by dose. Four patients who received dose greater than 140Gy (p < 0.05) all survived. The corresponding activity they received was greater than 35 mCi. Six out of ten patients died of disease with median survival of 18 weeks (range 12–81wks). Conclusion: Given the growing body of data for Y-90 microspheres in the context of cholangiocarcinoma, radioembolization may become an important treatment modality for an appropriately selected group of patients. Our study further substantiates past studies and shows additional evidence of a survival benefit with dose escalation.« less

Changes in Mipomersen Dosing Regimen Provide Similar Exposure With Improved Tolerability in Randomized Placebo‐Controlled Study of Healthy Volunteers

PubMed Central

Flaim, JoAnn D.; Grundy, John S.; Baker, Brenda F.; McGowan, Mary P.; Kastelein, John J. P.

2014-01-01

Background Mipomersen, an apolipoprotein B synthesis inhibitor, demonstrated significant reductions in low‐density lipoprotein (LDL) cholesterol, non‐high density lipoprotein cholesterol, and apolipoprotein B in 4 phase 3 studies at the FDA‐approved subcutaneous dose of 200 mg once weekly. Methods and Results A short‐term phase 1 study in healthy volunteers was conducted to evaluate the relative bioavailability, safety, and tolerability of mipomersen in 2 test dose regimens in reference to the 200 mg weekly dose regimen. Eighty‐four adults were randomized to 1 of 3 cohorts (30 mg once daily, 70 mg 3 times weekly, or 200 mg once weekly) and then mipomersen or placebo (3:1 ratio) for 3 weeks of treatment. Comparable mipomersen post‐distribution phase plasma concentrations were observed across the 3 dose regimens suggesting similar tissue exposure. Injection site reactions were reported, but did not lead to treatment discontinuation. The median incidence of these responses per injection was decreased by lowering the dose. Signals from a diverse panel of systemic inflammation markers were essentially indistinguishable between dose regimens and placebo treatment. The one exception was a modest transient post‐dose elevation of C‐reactive protein (CRP) in the mipomersen 200 mg weekly group. This elevation was not associated with an increase in other proinflammatory markers. Conclusions This study demonstrated a similar drug exposure and overall safety profile between the 3 dosing regimens. Exploratory assessment of a diverse panel of biomarkers found no indication of a systemic inflammatory response to mipomersen treatment. These results support assessment of alternative dose regimens in longer‐term studies. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01061814. PMID:24627419

Changes in mipomersen dosing regimen provide similar exposure with improved tolerability in randomized placebo-controlled study of healthy volunteers.

PubMed

Flaim, Joann D; Grundy, John S; Baker, Brenda F; McGowan, Mary P; Kastelein, John J P

2014-03-13

Mipomersen, an apolipoprotein B synthesis inhibitor, demonstrated significant reductions in low-density lipoprotein (LDL) cholesterol, non-high density lipoprotein cholesterol, and apolipoprotein B in 4 phase 3 studies at the FDA-approved subcutaneous dose of 200 mg once weekly. A short-term phase 1 study in healthy volunteers was conducted to evaluate the relative bioavailability, safety, and tolerability of mipomersen in 2 test dose regimens in reference to the 200 mg weekly dose regimen. Eighty-four adults were randomized to 1 of 3 cohorts (30 mg once daily, 70 mg 3 times weekly, or 200 mg once weekly) and then mipomersen or placebo (3:1 ratio) for 3 weeks of treatment. Comparable mipomersen post-distribution phase plasma concentrations were observed across the 3 dose regimens suggesting similar tissue exposure. Injection site reactions were reported, but did not lead to treatment discontinuation. The median incidence of these responses per injection was decreased by lowering the dose. Signals from a diverse panel of systemic inflammation markers were essentially indistinguishable between dose regimens and placebo treatment. The one exception was a modest transient post-dose elevation of C-reactive protein (CRP) in the mipomersen 200 mg weekly group. This elevation was not associated with an increase in other proinflammatory markers. This study demonstrated a similar drug exposure and overall safety profile between the 3 dosing regimens. Exploratory assessment of a diverse panel of biomarkers found no indication of a systemic inflammatory response to mipomersen treatment. These results support assessment of alternative dose regimens in longer-term studies. http://www.clinicaltrials.gov. Unique identifier: NCT01061814.

A tiered approach for integrating exposure and dosimetry with in vitro dose-response data in the modern risk assessment paradigm

EPA Science Inventory

High-throughput (HT) risk screening approaches apply in vitro dose-response data to estimate potential health risks that arise from exposure to chemicals. However, much uncertainty is inherent in relating bioactivities observed in an in vitro system to the perturbations of biolog...

A biosphere modeling methodology for dose assessments of the potential Yucca Mountain deep geological high level radioactive waste repository.

PubMed

Watkins, B M; Smith, G M; Little, R H; Kessler, J

1999-04-01

Recent developments in performance standards for proposed high level radioactive waste disposal at Yucca Mountain suggest that health risk or dose rate limits will likely be part of future standards. Approaches to the development of biosphere modeling and dose assessments for Yucca Mountain have been relatively lacking in previous performance assessments due to the absence of such a requirement. This paper describes a practical methodology used to develop a biosphere model appropriate for calculating doses from use of well water by hypothetical individuals due to discharges of contaminated groundwater into a deep well. The biosphere model methodology, developed in parallel with the BIOMOVS II international study, allows a transparent recording of the decisions at each step, from the specification of the biosphere assessment context through to model development and analysis of results. A list of features, events, and processes relevant to Yucca Mountain was recorded and an interaction matrix developed to help identify relationships between them. Special consideration was given to critical/potential exposure group issues and approaches. The conceptual model of the biosphere system was then developed, based on the interaction matrix, to show how radionuclides migrate and accumulate in the biosphere media and result in potential exposure pathways. A mathematical dose assessment model was specified using the flexible AMBER software application, which allows users to construct their own compartment models. The starting point for the biosphere calculations was a unit flux of each radionuclide from the groundwater in the geosphere into the drinking water in the well. For each of the 26 radionuclides considered, the most significant exposure pathways for hypothetical individuals were identified. For 14 of the radionuclides, the primary exposure pathways were identified as consumption of various crops and animal products following assumed agricultural use of the contaminated water derived from the deep well. Inhalation of dust (11 radionuclides) and external irradiation (1 radionuclide) were also identified as significant exposure modes. Contribution to the total flux to dose conversion factor from the drinking water pathway for each radionuclide was also assessed and for most radionuclides was found to be less than 10% of the total flux to dose conversion factor summed across all pathways. Some of the uncertainties related to the results were considered. The biosphere modeling results have been applied within an EPRI Total Systems Performance Assessment of Yucca Mountain. Conclusions and recommendations for future performance assessments are provided.

Allometric methodology for the assessment of radon exposures to terrestrial wildlife.

PubMed

Vives i Batlle, J; Copplestone, D; Jones, S R

2012-06-15

A practical approach to calculate (222)Rn daughter dose rates to terrestrial wildlife is presented. The method scales allometrically the relevant parameters for respiration in different species of wildlife, allowing inter-species calculation of the dose per unit radon concentration in air as simple base-and-exponent power functions of the mass. For plants, passive gas exchange through the leaf surface is assumed, also leading to specific power relationships with mass. The model generates conservative predictions in which the main contributor to the dose rate of target tissues of the respiratory system is from α radiation arising from (222)Rn daughters. Tabulated (222)Rn DPURn values are given for 69 species used by the England & Wales Environment Agency for habitats assessments. The approach is then applied to assess the authorised discharges of (222)Rn from sites in England, demonstrating that, from a whole-body dose perspective, the biota considered are protected from effects at the population level. Copyright © 2012 Elsevier B.V. All rights reserved.

Triadimefon

EPA Science Inventory

Triadimefon (CAS 43121-43-3) is a broad spectrum systemic fungicide. The nervous system is the most sensitive target and serves as the basis for most regulatory assessments. Triadimefon is also a carcinogen and reproductive toxicant at high doses in rodent models.

A quantitative three-dimensional dose attenuation analysis around Fletcher-Suit-Delclos due to stainless steel tube for high-dose-rate brachytherapy by Monte Carlo calculations.

PubMed

Parsai, E Ishmael; Zhang, Zhengdong; Feldmeier, John J

2009-01-01

The commercially available brachytherapy treatment-planning systems today, usually neglects the attenuation effect from stainless steel (SS) tube when Fletcher-Suit-Delclos (FSD) is used in treatment of cervical and endometrial cancers. This could lead to potential inaccuracies in computing dwell times and dose distribution. A more accurate analysis quantifying the level of attenuation for high-dose-rate (HDR) iridium 192 radionuclide ((192)Ir) source is presented through Monte Carlo simulation verified by measurement. In this investigation a general Monte Carlo N-Particles (MCNP) transport code was used to construct a typical geometry of FSD through simulation and compare the doses delivered to point A in Manchester System with and without the SS tubing. A quantitative assessment of inaccuracies in delivered dose vs. the computed dose is presented. In addition, this investigation expanded to examine the attenuation-corrected radial and anisotropy dose functions in a form parallel to the updated AAPM Task Group No. 43 Report (AAPM TG-43) formalism. This will delineate quantitatively the inaccuracies in dose distributions in three-dimensional space. The changes in dose deposition and distribution caused by increased attenuation coefficient resulted from presence of SS are quantified using MCNP Monte Carlo simulations in coupled photon/electron transport. The source geometry was that of the Vari Source wire model VS2000. The FSD was that of the Varian medical system. In this model, the bending angles of tandem and colpostats are 15 degrees and 120 degrees , respectively. We assigned 10 dwell positions to the tandem and 4 dwell positions to right and left colpostats or ovoids to represent a typical treatment case. Typical dose delivered to point A was determined according to Manchester dosimetry system. Based on our computations, the reduction of dose to point A was shown to be at least 3%. So this effect presented by SS-FSD systems on patient dose is of concern.

Guaifenesin Pharmacokinetics Following Single‐Dose Oral Administration in Children Aged 2 to 17 Years

PubMed Central

Thompson, Gary A.; Solomon, Gail; Albrecht, Helmut H.; Reitberg, Donald P.

2016-01-01

Abstract This study characterized guaifenesin pharmacokinetics in children aged 2 to 17 years (n = 40) who received a single oral dose of guaifenesin (age‐based doses of 100‐400 mg) 2 hours after breakfast. Plasma samples were obtained before and for 8 hours after dosing and analyzed for guaifenesin using liquid chromatography‐tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods, relationships with age were assessed using linear regression, and dose proportionality was assessed on 95% confidence intervals. Based on the upper dose recommended in the monograph (for both children and adolescents), area under the curve from time zero to infinity and maximum plasma concentration both increased with age. However, when comparing the upper dose for children aged 2 to 11 years with the lower dose for adolescents aged 12 to 17 years, similar systemic exposure was observed. As expected due to increasing body size, oral clearance (CLo) and terminal volume of distribution (Vz/F) increased with age. Due to a larger increase in Vz/F than CLo, an increase in terminal exponential half‐life was also observed. Allometric scaling indicated no maturation‐related changes in CLo and Vz/F. PMID:26632082

Biological characterization of a novel in vitro cell irradiator

PubMed Central

Fowler, Tyler L.; Fisher, Michael M.; Bailey, Alison M.; Bednarz, Bryan P.

2017-01-01

To evaluate the overall robustness of a novel cellular irradiator we performed a series of well-characterized, dose-responsive assays to assess the consequences of DNA damage. We used a previously described novel irradiation system and a traditional 137Cs source to irradiate a cell line. The generation of reactive oxygen species was assessed using chloromethyl-H2DCFDA dye, the induction of DNA DSBs was observed using the comet assay, and the initiation of DNA break repair was assessed through γH2AX image cytometry. A high correlation between physical absorbed dose and biologic dose was seen for the production of intracellular reactive oxygen species, physical DNA double strand breaks, and modulation of the cellular double stand break pathway. The results compared favorably to irradiation with a traditional 137Cs source. The rapid, straightforward tests described form a reasonable approach for biologic characterization of novel irradiators. These additional testing metrics go beyond standard physics testing such as Monte Carlo simulation and thermo-luminescent dosimeter evaluation to confirm that a novel irradiator can produce the desired dose effects in vitro. Further, assessment of these biological metrics confirms that the physical handling of the cells during the irradiation process results in biologic effects that scale appropriately with dose. PMID:29232400

Image quality and dose differences caused by vendor-specific image processing of neonatal radiographs.

PubMed

Sensakovic, William F; O'Dell, M Cody; Letter, Haley; Kohler, Nathan; Rop, Baiywo; Cook, Jane; Logsdon, Gregory; Varich, Laura

2016-10-01

Image processing plays an important role in optimizing image quality and radiation dose in projection radiography. Unfortunately commercial algorithms are black boxes that are often left at or near vendor default settings rather than being optimized. We hypothesize that different commercial image-processing systems, when left at or near default settings, create significant differences in image quality. We further hypothesize that image-quality differences can be exploited to produce images of equivalent quality but lower radiation dose. We used a portable radiography system to acquire images on a neonatal chest phantom and recorded the entrance surface air kerma (ESAK). We applied two image-processing systems (Optima XR220amx, by GE Healthcare, Waukesha, WI; and MUSICA(2) by Agfa HealthCare, Mortsel, Belgium) to the images. Seven observers (attending pediatric radiologists and radiology residents) independently assessed image quality using two methods: rating and matching. Image-quality ratings were independently assessed by each observer on a 10-point scale. Matching consisted of each observer matching GE-processed images and Agfa-processed images with equivalent image quality. A total of 210 rating tasks and 42 matching tasks were performed and effective dose was estimated. Median Agfa-processed image-quality ratings were higher than GE-processed ratings. Non-diagnostic ratings were seen over a wider range of doses for GE-processed images than for Agfa-processed images. During matching tasks, observers matched image quality between GE-processed images and Agfa-processed images acquired at a lower effective dose (11 ± 9 μSv; P < 0.0001). Image-processing methods significantly impact perceived image quality. These image-quality differences can be exploited to alter protocols and produce images of equivalent image quality but lower doses. Those purchasing projection radiography systems or third-party image-processing software should be aware that image processing can significantly impact image quality when settings are left near default values.

Safety, Tolerability and Pharmacokinetics of Single Doses of Oxytocin Administered via an Inhaled Route in Healthy Females: Randomized, Single-blind, Phase 1 Study.

PubMed

Fernando, Disala; Siederer, Sarah; Singh, Sunita; Schneider, Ian; Gupta, Ashutosh; Powell, Marcy; Richards, Duncan; McIntosh, Michelle P; Lambert, Peter; Fowles, Susan

2017-08-01

The utility of intramuscular (IM) oxytocin for the prevention of postpartum hemorrhage in resource-poor settings is limited by the requirement for temperature-controlled storage and skilled staff to administer the injection. We evaluated the safety, tolerability and pharmacokinetics (PK) of a heat-stable, inhaled (IH) oxytocin formulation. This phase 1, randomized, single-center, single-blind, dose-escalation, fixed-sequence study (NCT02542813) was conducted in healthy, premenopausal, non-pregnant, non-lactating women aged 18-45years. Subjects initially received IM oxytocin 10 international units (IU) on day 1, IH placebo on day 2, and IH oxytocin 50μg on day 3. Subjects were then randomized 4:1 using validated GSK internal software to IH placebo or ascending doses of IH oxytocin (200, 400, 600μg). PK was assessed by comparing systemic exposure (maximum observed plasma concentration, area under the concentration-time curve, and plasma concentrations at 10 and 30min post dose) for IH versus IM oxytocin. Adverse events (AEs), spirometry, laboratory tests, vital signs, electrocardiograms, physical examinations, and cardiac telemetry were assessed. Subjects were recruited between September 14, 2015 and October 12, 2015. Of the 16 subjects randomized following initial dosing, 15 (IH placebo n=3; IH oxytocin n=12) completed the study. IH (all doses) and IM oxytocin PK profiles were comparable in shape. However, systemic exposure with IH oxytocin 400μg most closely matched IM oxytocin 10IU. Systemic exposure was approximately dose proportional for IH oxytocin. No serious AEs were reported. No clinically significant findings were observed for any safety parameters. These data suggest that similar oxytocin systemic exposure can be achieved with IM and IH administration routes, and no safety concerns were identified with either route. The inhalation route may offer the opportunity to increase access to oxytocin for women giving birth in resource-poor settings. Copyright © 2017. Published by Elsevier B.V.

Medical dosimetry in Hungary

NASA Astrophysics Data System (ADS)

Turák, O.; Osvay, M.; Ballay, L.

2012-09-01

Radiation exposure of medical staff during cardiological and radiological procedures was investigated. The exposure of medical staff is directly connected to patient exposure. The aim of this study was to determine the distribution of doses on uncovered part of body of medical staff using LiF thermoluminescent (TL) dosimeters in seven locations. Individual Kodak film dosimeters (as authorized dosimetry system) were used for the assessment of medical staff's effective dose. Results achieved on dose distribution measurements confirm that wearing only one film badge under the lead apron does not provide enough information on the personal dose. The value of estimated annual doses on eye lens and extremities (fingers) were in good correlation with international publications.

Microdosemeter instrument (MIDN) for assessing risk in space.

PubMed

Pisacane, V L; Dolecek, Q E; Malak, H; Cucinotta, F A; Zaider, M; Rosenfeld, A B; Rusek, A; Sivertz, M; Dicello, J F

2011-02-01

Radiation in space generally produces higher dose rates than that on the Earth's surface, and contributions from primary galactic and solar events increase with altitude within the magnetosphere. Presently, no personnel monitor is available to astronauts for real-time monitoring of dose, radiation quality and regulatory risk. This group is developing a prototypic instrument for use in an unknown, time-varying radiation field. This microdosemeter-dosemeter nucleon instrument is for use in a spacesuit, spacecraft, remote rover and other applications. It provides absorbed dose, dose rate and dose equivalent in real time so that action can be taken to reduce exposure. Such a system has applications in health physics, anti-terrorism and radiation-hardening of electronics as well. The space system is described and results of ground-based studies are presented and compared with predictions of transport codes. An early prototype in 2007 was successfully launched, the only solid-state microdosemeter to have flown in space.

SU-G-IeP3-13: Real-Time Patient and Staff Dose Monitoring in Fluoroscopy Guided Interventions

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

Vergoossen, L; Sailer, A; Paulis, L

Purpose: Interventional radiology procedures involve the use of X-rays, which can pose a large radiation burden on both patients and staff. Although some reports on radiation dose are available, most studies focus on limited types of procedures and only report patient dose. In our cathlabs a dedicated real-time patient and staff monitoring system was installed in November 2015. The aim of this study was to investigate the patient and staff dose exposure for different types of interventions. Methods: Radiologists involved in fluoroscopy guided interventional radiology procedures wore personal dose meters (PDM, DoseAware, Philips) on their lead-apron that measured the personalmore » dose equivalent Hp(10), a measure for the effective dose (E). Furthermore, reference PDMs were installed in the C-arms of the fluoroscopy system (Allura XPer, Philips). Patient dose-area-product (DAP) and PDM doses were retrieved from the monitoring system (DoseWise, Philips) for each procedure. A total of 399 procedures performed between November 2015 and February 2016 were analyzed with respect to the type of intervention. Interventions were grouped by anatomy and radiologist position. Results: The mean DAP for the different types of interventions ranged from 2.86±2.96 Gycm{sup 2} (percutaneous gastrostomy) to 147±178 Gycm{sup 2} (aortic repair procedures). The radiologist dose (E) ranged from 5.39±7.38 µSv (cerebral interventions) to 84.7±106 µSv (abdominal interventions) and strongly correlated with DAP (R{sup 2}=0.83). The E normalized to DAP showed that the relative radiologist dose was higher for interventions in larger body parts (e.g. abdomen) compared to smaller body parts (e.g. head). Conclusion: Using a real-time dose monitoring system we were able to assess the staff and patient dose revealing that the relative staff dose strongly depended on the type of procedure and patient anatomy. This could be explained by the position of the radiologist with respect to the patient and X-ray tube. To facilitate this study L Vergoossen received a scholarship from Philips Medical Systems.« less

Statistical model based iterative reconstruction (MBIR) in clinical CT systems: experimental assessment of noise performance.

PubMed

Li, Ke; Tang, Jie; Chen, Guang-Hong

2014-04-01

To reduce radiation dose in CT imaging, the statistical model based iterative reconstruction (MBIR) method has been introduced for clinical use. Based on the principle of MBIR and its nonlinear nature, the noise performance of MBIR is expected to be different from that of the well-understood filtered backprojection (FBP) reconstruction method. The purpose of this work is to experimentally assess the unique noise characteristics of MBIR using a state-of-the-art clinical CT system. Three physical phantoms, including a water cylinder and two pediatric head phantoms, were scanned in axial scanning mode using a 64-slice CT scanner (Discovery CT750 HD, GE Healthcare, Waukesha, WI) at seven different mAs levels (5, 12.5, 25, 50, 100, 200, 300). At each mAs level, each phantom was repeatedly scanned 50 times to generate an image ensemble for noise analysis. Both the FBP method with a standard kernel and the MBIR method (Veo(®), GE Healthcare, Waukesha, WI) were used for CT image reconstruction. Three-dimensional (3D) noise power spectrum (NPS), two-dimensional (2D) NPS, and zero-dimensional NPS (noise variance) were assessed both globally and locally. Noise magnitude, noise spatial correlation, noise spatial uniformity and their dose dependence were examined for the two reconstruction methods. (1) At each dose level and at each frequency, the magnitude of the NPS of MBIR was smaller than that of FBP. (2) While the shape of the NPS of FBP was dose-independent, the shape of the NPS of MBIR was strongly dose-dependent; lower dose lead to a "redder" NPS with a lower mean frequency value. (3) The noise standard deviation (σ) of MBIR and dose were found to be related through a power law of σ ∝ (dose)(-β) with the component β ≈ 0.25, which violated the classical σ ∝ (dose)(-0.5) power law in FBP. (4) With MBIR, noise reduction was most prominent for thin image slices. (5) MBIR lead to better noise spatial uniformity when compared with FBP. (6) A composite image generated from two MBIR images acquired at two different dose levels (D1 and D2) demonstrated lower noise than that of an image acquired at a dose level of D1+D2. The noise characteristics of the MBIR method are significantly different from those of the FBP method. The well known tradeoff relationship between CT image noise and radiation dose has been modified by MBIR to establish a more gradual dependence of noise on dose. Additionally, some other CT noise properties that had been well understood based on the linear system theory have also been altered by MBIR. Clinical CT scan protocols that had been optimized based on the classical CT noise properties need to be carefully re-evaluated for systems equipped with MBIR in order to maximize the method's potential clinical benefits in dose reduction and/or in CT image quality improvement. © 2014 American Association of Physicists in Medicine.

Statistical model based iterative reconstruction (MBIR) in clinical CT systems: Experimental assessment of noise performance

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

Li, Ke; Tang, Jie; Chen, Guang-Hong, E-mail: gchen7@wisc.edu

Purpose: To reduce radiation dose in CT imaging, the statistical model based iterative reconstruction (MBIR) method has been introduced for clinical use. Based on the principle of MBIR and its nonlinear nature, the noise performance of MBIR is expected to be different from that of the well-understood filtered backprojection (FBP) reconstruction method. The purpose of this work is to experimentally assess the unique noise characteristics of MBIR using a state-of-the-art clinical CT system. Methods: Three physical phantoms, including a water cylinder and two pediatric head phantoms, were scanned in axial scanning mode using a 64-slice CT scanner (Discovery CT750 HD,more » GE Healthcare, Waukesha, WI) at seven different mAs levels (5, 12.5, 25, 50, 100, 200, 300). At each mAs level, each phantom was repeatedly scanned 50 times to generate an image ensemble for noise analysis. Both the FBP method with a standard kernel and the MBIR method (Veo{sup ®}, GE Healthcare, Waukesha, WI) were used for CT image reconstruction. Three-dimensional (3D) noise power spectrum (NPS), two-dimensional (2D) NPS, and zero-dimensional NPS (noise variance) were assessed both globally and locally. Noise magnitude, noise spatial correlation, noise spatial uniformity and their dose dependence were examined for the two reconstruction methods. Results: (1) At each dose level and at each frequency, the magnitude of the NPS of MBIR was smaller than that of FBP. (2) While the shape of the NPS of FBP was dose-independent, the shape of the NPS of MBIR was strongly dose-dependent; lower dose lead to a “redder” NPS with a lower mean frequency value. (3) The noise standard deviation (σ) of MBIR and dose were found to be related through a power law of σ ∝ (dose){sup −β} with the component β ≈ 0.25, which violated the classical σ ∝ (dose){sup −0.5} power law in FBP. (4) With MBIR, noise reduction was most prominent for thin image slices. (5) MBIR lead to better noise spatial uniformity when compared with FBP. (6) A composite image generated from two MBIR images acquired at two different dose levels (D1 and D2) demonstrated lower noise than that of an image acquired at a dose level of D1+D2. Conclusions: The noise characteristics of the MBIR method are significantly different from those of the FBP method. The well known tradeoff relationship between CT image noise and radiation dose has been modified by MBIR to establish a more gradual dependence of noise on dose. Additionally, some other CT noise properties that had been well understood based on the linear system theory have also been altered by MBIR. Clinical CT scan protocols that had been optimized based on the classical CT noise properties need to be carefully re-evaluated for systems equipped with MBIR in order to maximize the method's potential clinical benefits in dose reduction and/or in CT image quality improvement.« less

An assessment of mumps vaccine effectiveness by dose during an outbreak in Canada

PubMed Central

Deeks, Shelley L.; Lim, Gillian H.; Simpson, Mary Anne; Gagné, Louise; Gubbay, Jonathan; Kristjanson, Erik; Fung, Cecilia; Crowcroft, Natasha S.

2011-01-01

Background This investigation was done to assess vaccine effectiveness of one and two doses of the measles, mumps and rubella (MMR) vaccine during an outbreak of mumps in Ontario. The level of coverage required to reach herd immunity and interrupt community transmission of mumps was also estimated. Methods Information on confirmed cases of mumps was retrieved from Ontario’s integrated Public Health Information System. Cases that occurred between Sept. 1, 2009, and June 10, 2010, were included. Selected health units supplied coverage data from the Ontario Immunization Record Information System. Vaccine effectiveness by dose was calculated using the screening method. The basic reproductive number (R0) represents the average number of new infections per case in a fully susceptile population, and R0 values of between 4 and 10 were considered for varying levels of vaccine effectiveness. Results A total of 134 confirmed cases of mumps were identified. Information on receipt of MMR vaccine was available for 114 (85.1%) cases, of whom 63 (55.3%) reported having received only one dose of vaccine; 32 (28.1%) reported having received two doses. Vaccine effectiveness of one dose of the MMR vaccine ranged from 49.2% to 81.6%, whereas vaccine effectiveness of two doses ranged from 66.3% to 88.0%. If we assume vaccine effectiveness of 85% for two doses of the vaccine, vaccine coverage of 88.2% and 98.0% would be needed to interrupt community transmission of mumps if the corresponding reproductive values were four and six. Interpretation Our estimates of vaccine effectiveness of one and two doses of mumps-containing vaccine were consistent with the estimates that have been reported in other outbreaks. Outbreaks occurring in Ontario and elsewhere serve as a warning against complacency over vaccination programs. PMID:21576295

An assessment of mumps vaccine effectiveness by dose during an outbreak in Canada.

PubMed

Deeks, Shelley L; Lim, Gillian H; Simpson, Mary Anne; Gagné, Louise; Gubbay, Jonathan; Kristjanson, Erik; Fung, Cecilia; Crowcroft, Natasha S

2011-06-14

This investigation was done to assess vaccine effectiveness of one and two doses of the measles, mumps and rubella (MMR) vaccine during an outbreak of mumps in Ontario. The level of coverage required to reach herd immunity and interrupt community transmission of mumps was also estimated. Information on confirmed cases of mumps was retrieved from Ontario's integrated Public Health Information System. Cases that occurred between Sept. 1, 2009, and June 10, 2010, were included. Selected health units supplied coverage data from the Ontario Immunization Record Information System. Vaccine effectiveness by dose was calculated using the screening method. The basic reproductive number (R(0)) represents the average number of new infections per case in a fully susceptible population, and R(0) values of between 4 and 10 were considered for varying levels of vaccine effectiveness. A total of 134 confirmed cases of mumps were identified. Information on receipt of MMR vaccine was available for 114 (85.1%) cases, of whom 63 (55.3%) reported having received only one dose of vaccine; 32 (28.1%) reported having received two doses. Vaccine effectiveness of one dose of the MMR vaccine ranged from 49.2% to 81.6%, whereas vaccine effectiveness of two doses ranged from 66.3% to 88.0%. If we assume vaccine effectiveness of 85% for two doses of the vaccine, vaccine coverage of 88.2% and 98.0% would be needed to interrupt community transmission of mumps if the corresponding reproductive values were four and six. Our estimates of vaccine effectiveness of one and two doses of mumps-containing vaccine were consistent with the estimates that have been reported in other outbreaks. Outbreaks occurring in Ontario and elsewhere serve as a warning against complacency over vaccination programs.

Food irradiation dosimetry by opti-chromic technique

NASA Astrophysics Data System (ADS)

Zhan-Jun, Liu; Radak, B. B.; McLaughlin, W. L.

The measurement of gamma-radiation quantities, e.g., absorbed dose in materials such as water, plastics, foodstuffs, is a convenient means of quality assurance in radiation processing. A new dosimetry system, called the "Opti-Chromic" dosimeter, is commercially available in large batches for use as a routine measurement system in the absorbed dose range 10 to 2x10 4 Gy. This dose range covers most food irradiation applications. A statistical evaluation was made of the reproducibility of this dosimeter for measuring doses appropriate for the disinfestation and shelf-life extension of many foods, namely 10 to 2x10 3 Gy. In addition, the small dosimeters were used to map absorbed dose distributions in boxes of foods having four different bulk densities (grapefruit, lemons, peanuts, and wheat bran). It is demonstrated that the dosimeters are rugged and stable enough to be used over a wide temperature and humidity range, and, in fact, can be placed in such environments as the inside of citrus fruits without adverse effects on their ability to give satisfactory dose assessment.

Occupational and patient exposure as well as image quality for full spine examinations with the EOS imaging system

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

Damet, J., E-mail: jerome.damet@chuv.ch; Fournier, P.; Monnin, P.

Purpose: EOS (EOS imaging S.A, Paris, France) is an x-ray imaging system that uses slot-scanning technology in order to optimize the trade-off between image quality and dose. The goal of this study was to characterize the EOS system in terms of occupational exposure, organ doses to patients as well as image quality for full spine examinations. Methods: Occupational exposure was determined by measuring the ambient dose equivalents in the radiological room during a standard full spine examination. The patient dosimetry was performed using anthropomorphic phantoms representing an adolescent and a five-year-old child. The organ doses were measured with thermoluminescent detectorsmore » and then used to calculate effective doses. Patient exposure with EOS was then compared to dose levels reported for conventional radiological systems. Image quality was assessed in terms of spatial resolution and different noise contributions to evaluate the detector's performances of the system. The spatial-frequency signal transfer efficiency of the imaging system was quantified by the detective quantum efficiency (DQE). Results: The use of a protective apron when the medical staff or parents have to stand near to the cubicle in the radiological room is recommended. The estimated effective dose to patients undergoing a full spine examination with the EOS system was 290μSv for an adult and 200 μSv for a child. MTF and NPS are nonisotropic, with higher values in the scanning direction; they are in addition energy-dependent, but scanning speed independent. The system was shown to be quantum-limited, with a maximum DQE of 13%. The relevance of the DQE for slot-scanning system has been addressed. Conclusions: As a summary, the estimated effective dose was 290μSv for an adult; the image quality remains comparable to conventional systems.« less

[Monitoring medication errors in personalised dispensing using the Sentinel Surveillance System method].

PubMed

Pérez-Cebrián, M; Font-Noguera, I; Doménech-Moral, L; Bosó-Ribelles, V; Romero-Boyero, P; Poveda-Andrés, J L

2011-01-01

To assess the efficacy of a new quality control strategy based on daily randomised sampling and monitoring a Sentinel Surveillance System (SSS) medication cart, in order to identify medication errors and their origin at different levels of the process. Prospective quality control study with one year follow-up. A SSS medication cart was randomly selected once a week and double-checked before dispensing medication. Medication errors were recorded before it was taken to the relevant hospital ward. Information concerning complaints after receiving medication and 24-hour monitoring were also noted. Type and origin error data were assessed by a Unit Dose Quality Control Group, which proposed relevant improvement measures. Thirty-four SSS carts were assessed, including 5130 medication lines and 9952 dispensed doses, corresponding to 753 patients. Ninety erroneous lines (1.8%) and 142 mistaken doses (1.4%) were identified at the Pharmacy Department. The most frequent error was dose duplication (38%) and its main cause inappropriate management and forgetfulness (69%). Fifty medication complaints (6.6% of patients) were mainly due to new treatment at admission (52%), and 41 (0.8% of all medication lines), did not completely match the prescription (0.6% lines) as recorded by the Pharmacy Department. Thirty-seven (4.9% of patients) medication complaints due to changes at admission and 32 matching errors (0.6% medication lines) were recorded. The main cause also was inappropriate management and forgetfulness (24%). The simultaneous recording of incidences due to complaints and new medication coincided in 33.3%. In addition, 433 (4.3%) of dispensed doses were returned to the Pharmacy Department. After the Unit Dose Quality Control Group conducted their feedback analysis, 64 improvement measures for Pharmacy Department nurses, 37 for pharmacists, and 24 for the hospital ward were introduced. The SSS programme has proven to be useful as a quality control strategy to identify Unit Dose Distribution System errors at initial, intermediate and final stages of the process, improving the involvement of the Pharmacy Department and ward nurses. Copyright © 2009 SEFH. Published by Elsevier Espana. All rights reserved.

TL dosimetry for quality control of CR mammography imaging systems

NASA Astrophysics Data System (ADS)

Gaona, E.; Nieto, J. A.; Góngora, J. A. I. D.; Arreola, M.; Enríquez, J. G. F.

The aim of this work is to estimate the average glandular dose with thermoluminescent (TL) dosimetry and comparison with quality imaging in computed radiography (CR) mammography. For a measuring dose, the Food and Drug Administration (FDA) and the American College of Radiology (ACR) use a phantom, so that dose and image quality are assessed with the same test object. The mammography is a radiological image to visualize early biological manifestations of breast cancer. Digital systems have two types of image-capturing devices, full field digital mammography (FFDM) and CR mammography. In Mexico, there are several CR mammography systems in clinical use, but only one system has been approved for use by the FDA. Mammography CR uses a photostimulable phosphor detector (PSP) system. Most CR plates are made of 85% BaFBr and 15% BaFI doped with europium (Eu) commonly called barium flourohalideE We carry out an exploratory survey of six CR mammography units from three different manufacturers and six dedicated X-ray mammography units with fully automatic exposure. The results show three CR mammography units (50%) have a dose greater than 3.0 mGy without demonstrating improved image quality. The differences between doses averages from TLD system and dosimeter with ionization chamber are less than 10%. TLD system is a good option for average glandular dose measurement for X-rays with a HVL (0.35-0.38 mmAl) and kVp (24-26) used in quality control procedures with ACR Mammography Accreditation Phantom.

The individual and combined effects of phenmetrazine and mgluR2/3 agonist LY379268 on the motivation to self-administer cocaine.

PubMed

Karkhanis, Anushree N; Beveridge, Thomas J R; Blough, Bruce E; Jones, Sara R; Ferris, Mark J

2016-09-01

The US Food and Drug Administration has not approved a treatment for cocaine addiction, possibly due in part to the fact that repeated cocaine use results in dysregulation of multiple neurotransmitter systems, including glutamate and dopamine, and an emergence of increased negative affective states and heightening motivation to take cocaine despite negative consequences. We used a combination therapy approach to assess whether modulation of both glutamate and dopamine transmission would reduce the motivation to self- administer cocaine compared to modulation of either system alone. The metabotropic glutamate 2/3 receptor agonist, LY379268, and the monoamine releaser, phenmetrazine, were used to assess their individual and combined ability to decrease the reinforcing efficacy of cocaine because they modulate glutamate and dopamine levels, respectively. Cocaine breakpoints and cocaine intake was assessed, using a progressive ratio schedule, at baseline in three groups based on dose of cocaine (0.19, 0.38, 0.75mg/kg/infusion), and following LY379268 (0.03 or 0.30mg/kg; i.p.), phenmetrazine (25mg/kg/day; osmotic minipump), and a combination of the two drugs. LY379268 and phenmetrazine alone reduced breakpoints for all doses of cocaine. The combination of the two drugs showed a concerted effect in reducing breakpoints for all doses of cocaine, with the lowest dose of cocaine reduced by as much as 70%. These data support combination therapy of dopamine and glutamate systems as an effective means to reduce the motivation to take cocaine since a combination of drugs can address neurobiological dysfunction in multiple neurotransmitter systems compared to therapies using single drugs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A phase 1/2 dose-finding, safety, and activity study of cabazitaxel in pediatric patients with refractory solid tumors including tumors of the central nervous system.

PubMed

Manley, Peter E; Trippett, Tanya; Smith, Amy A; Macy, Margaret E; Leary, Sarah E S; Boklan, Jessica; Cohen, Kenneth J; Goldman, Stewart; Kilburn, Lindsay B; Dhall, Girish; Devin, Jeanne; Herzog, Cynthia E; Partap, Sonia; Fauchet, Floris; Badreddine, Emmy; Bernard, John P; Chi, Susan N

2018-05-11

This phase 1/2 study (NCT01751308) evaluated cabazitaxel in pediatric patients. Phase 1 determined the maximum tolerated dose (MTD) in patients with recurrent/refractory solid tumors, including central nervous system (CNS) tumors. Phase 2 evaluated activity in pediatric recurrent high-grade glioma (HGG) or diffuse intrinsic pontine glioma (DIPG). In phase 1, a 3 + 3 dose-escalation study design was followed. Cabazitaxel was administered at a starting dose of 20 mg/m 2 . Dose-limiting toxicities (DLTs) during cycle 1 were assessed to determine the MTD. Tumor response and cabazitaxel pharmacokinetics were also assessed. In phase 2, patients received cabazitaxel at the MTD determined in phase 1. Tumor responses were assessed every 9 weeks (modified Response Assessment in Neuro-oncology criteria). Progression-free survival and cabazitaxel pharmacokinetics were evaluated, and overall survival was estimated. In phase 1, 23 patients were treated, including 19 with CNS tumors. One patient had a partial response; five had stable disease for >3 cycles. Common adverse events included fatigue, diarrhea, nausea and vomiting, febrile neutropenia, and hypersensitivity reactions. Two of three DLTs (febrile neutropenia) occurred with a dose of 35 mg/m 2 ; the MTD was 30 mg/m 2 . Slightly higher cabazitaxel clearance was observed compared with adult trials. In phase 2, 16 patients (eight HGG and eight DIPG) were enrolled; 11 were evaluable for response and five withdrew (three due to anaphylaxis). All 11 patients progressed within four cycles. No responses were observed; the study was stopped due to futility. The safety profile of cabazitaxel was consistent with previous studies. The MTD (30 mg/m 2 ) was higher than the adult MTD. Cabazitaxel did not demonstrate activity in recurrent/refractory HGG or DIPG. © 2018 Wiley Periodicals, Inc.

EXPOSURE RELATED DOSE ESTIMATING MODEL ( ERDEM ) A PHYSIOLOGICALLY-BASED PHARMACOKINETIC AND PHARMACODYNAMIC ( PBPK/PD ) MODEL FOR ASSESSING HUMAN EXPOSURE AND RISK

EPA Science Inventory

The Exposure Related Dose Estimating Model (ERDEM) is a PBPK/PD modeling system that was developed by EPA's National Exposure Research Laboratory (NERL). The ERDEM framework provides the flexibility either to use existing models and to build new PBPK and PBPK/PD models to address...

Dose and image quality for a cone-beam C-arm CT system.

PubMed

Fahrig, Rebecca; Dixon, Robert; Payne, Thomas; Morin, Richard L; Ganguly, Arundhuti; Strobel, Norbert

2006-12-01

We assess dose and image quality of a state-of-the-art angiographic C-arm system (Axiom Artis dTA, Siemens Medical Solutions, Forchheim, Germany) for three-dimensional neuro-imaging at various dose levels and tube voltages and an associated measurement method. Unlike conventional CT, the beam length covers the entire phantom, hence, the concept of computed tomography dose index (CTDI) is not the metric of choice, and one can revert to conventional dosimetry methods by directly measuring the dose at various points using a small ion chamber. This method allows us to define and compute a new dose metric that is appropriate for a direct comparison with the familiar CTDIw of conventional CT. A perception study involving the CATPHAN 600 indicates that one can expect to see at least the 9 mm inset with 0.5% nominal contrast at the recommended head-scan dose (60 mGy) when using tube voltages ranging from 70 kVp to 125 kVp. When analyzing the impact of tube voltage on image quality at a fixed dose, we found that lower tube voltages gave improved low contrast detectability for small-diameter objects. The relationships between kVp, image noise, dose, and contrast perception are discussed.

Radiological assessment. A textbook on environmental dose analysis

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

Till, J.E.; Meyer, H.R.

1983-09-01

Radiological assessment is the quantitative process of estimating the consequences to humans resulting from the release of radionuclides to the biosphere. It is a multidisciplinary subject requiring the expertise of a number of individuals in order to predict source terms, describe environmental transport, calculate internal and external dose, and extrapolate dose to health effects. Up to this time there has been available no comprehensive book describing, on a uniform and comprehensive level, the techniques and models used in radiological assessment. Radiological Assessment is based on material presented at the 1980 Health Physics Society Summer School held in Seattle, Washington. Themore » material has been expanded and edited to make it comprehensive in scope and useful as a text. Topics covered include (1) source terms for nuclear facilities and Medical and Industrial sites; (2) transport of radionuclides in the atmosphere; (3) transport of radionuclides in surface waters; (4) transport of radionuclides in groundwater; (5) terrestrial and aquatic food chain pathways; (6) reference man; a system for internal dose calculations; (7) internal dosimetry; (8) external dosimetry; (9) models for special-case radionuclides; (10) calculation of health effects in irradiated populations; (11) evaluation of uncertainties in environmental radiological assessment models; (12) regulatory standards for environmental releases of radionuclides; (13) development of computer codes for radiological assessment; and (14) assessment of accidental releases of radionuclides.« less

Dosimetric impact in the dose-volume histograms of rectal and vesical wall contouring in prostate cancer IMRT treatments.

PubMed

Gómez, Laura; Andrés, Carlos; Ruiz, Antonio

2017-01-01

The main purpose of this study was to evaluate the differences in dose-volume histograms of IMRT treatments for prostate cancer based on the delineation of the main organs at risk (rectum and bladder) as solid organs or by contouring their wall. Rectum and bladder have typically been delineated as solid organs, including the waste material, which, in practice, can lead to an erroneous assessment of the risk of adverse effects. A retrospective study was made on 25 patients treated with IMRT radiotherapy for prostate adenocarcinoma. 76.32 Gy in 36 fractions was prescribed to the prostate and seminal vesicles. In addition to the delineation of the rectum and bladder as solid organs (including their content), the rectal and bladder wall were also delineated and the resulting dose-volume histograms were analyzed for the two groups of structures. Data analysis shows statistically significant differences in the main parameters used to assess the risk of toxicity of a prostate radiotherapy treatment. Higher doses were received on the rectal and bladder walls compared to doses received on the corresponding solid organs. The observed differences in terms of received doses to the rectum and bladder based on the method of contouring could gain greater importance in inverse planning treatments, where the treatment planning system optimizes the dose in these volumes. So, one should take into account the method of delineating of these structures to make a clinical decision regarding dose limitation and risk assessment of chronic toxicity.

Pharmacokinetic interactions of efavirenz and voriconazole in healthy volunteers

PubMed Central

Damle, Bharat; LaBadie, Robert; Crownover, Penelope; Glue, Paul

2008-01-01

AIMS Co-administration of standard-dose voriconazole and efavirenz results in a substantial decrease in voriconazole levels, while concurrently increasing efavirenz levels. Hence, concomitant use of standard doses of these drugs was initially contraindicated. This study assessed different dose combinations of efavirenz and voriconazole, with the goal of attaining a dose combination that provides systemic exposures similar to standard-dose monotherapy with each drug. METHODS This was an open-label, four-treatment, multiple-dose, fixed-sequence study in 16 healthy males. Steady-state pharmacokinetics were assessed following two test treatments (voriconazole 300 mg q12 h + efavirenz 300 mg q24 h and voriconazole 400 mg q12 h + efavirenz 300 mg q24 h) and compared with standard-dose monotherapy (voriconazole 200 mg q12 h or efavirenz 600 mg q24 h). RESULTS Dose adjustment to voriconazole 300 mg q12 h with efavirenz 300 mg q24 h decreased voriconazole area under the concentration–time curve (AUCτ) and maximum concentration (Cmax), with changes of −55% [90% confidence interval (CI) −62, −45] and −36% (90% CI −49, −21), respectively, when compared with monotherapy. Voriconazole 400 mg q12 h plus efavirenz 300 mg q24 h decreased voriconazole AUCτ (−7%; 90% CI −23, 13) and increased Cmax (23%; 90% CI −1, 53), while increasing efavirenz AUCτ (17%; 90% CI 6, 29) and not changing Cmax when compared with the respective monotherapy regimens. No serious adverse events were observed with voriconazole plus efavirenz. CONCLUSIONS When co-administered, voriconazole dose should be increased to 400 mg q12 h and efavirenz dose decreased to 300 mg q24 h in order to provide systemic exposures similar to standard-dose monotherapy. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Efavirenz 400 mg q24 h reduces exposure to voriconazole 200 mg q12 h when the two drugs are co-administered.Furthermore, voriconazole increases the systemic exposure of efavirenz.Co-administration was therefore initially contraindicated. WHAT THIS STUDY ADDS The doses of efavirenz and voriconazole can be adjusted to provide adequate exposure to both drugs when the two are co-administered, without compromising safety.Appropriate adjustment of doses for both drugs may thus represent an alternative to a mere contraindication. PMID:18294336

Comprehensive assessment of patient image quality and radiation dose in latest generation cardiac x-ray equipment for percutaneous coronary interventions

PubMed Central

Gislason-Lee, Amber J.; Keeble, Claire; Egleston, Daniel; Bexon, Josephine; Kengyelics, Stephen M.; Davies, Andrew G.

2017-01-01

Abstract. This study aimed to determine whether a reduction in radiation dose was found for percutaneous coronary interventional (PCI) patients using a cardiac interventional x-ray system with state-of-the-art image enhancement and x-ray optimization, compared to the current generation x-ray system, and to determine the corresponding impact on clinical image quality. Patient procedure dose area product (DAP) and fluoroscopy duration of 131 PCI patient cases from each x-ray system were compared using a Wilcoxon test on median values. Significant reductions in patient dose (p≪0.001) were found for the new system with no significant change in fluoroscopy duration (p=0.2); procedure DAP reduced by 64%, fluoroscopy DAP by 51%, and “cine” acquisition DAP by 76%. The image quality of 15 patient angiograms from each x-ray system (30 total) was scored by 75 clinical professionals on a continuous scale for the ability to determine the presence and severity of stenotic lesions; image quality scores were analyzed using a two-sample t-test. Image quality was reduced by 9% (p≪0.01) for the new x-ray system. This demonstrates a substantial reduction in patient dose, from acquisition more than fluoroscopy imaging, with slightly reduced image quality, for the new x-ray system compared to the current generation system. PMID:28491907

Adapting Concepts from Systems Biology to Develop Systems Exposure Event Networks for Exposure Science Research

EPA Science Inventory

Systems exposure science has emerged from the traditional environmental exposure assessment framework and incorporates new concepts that link sources of human exposure to internal dose and metabolic processes. Because many human environmental studies are designed for retrospectiv...

Efficacy of Lens Protection Systems: Dependency on Different Cranial CT Scans in The Acute Stroke Setting.

PubMed

Guberina, Nika; Forsting, Michael; Ringelstein, Adrian

2017-06-15

To evaluate the dose-reduction potential with different lens protectors for patients undergoing cranial computed tomography (CT) scans. Eye lens dose was assessed in vitro (α-Al2O3:C thermoluminescence dosemeters) using an Alderson-Rando phantom® in cranial CT protocols at different CT scanners (SOMATOM-Definition-AS+®(CT1) and SOMATOM-Definition-Flash® (CT2)) using two different lens-protection systems (Somatex® (SOM) and Medical Imaging Systems® (MIS)). Summarised percentage of the transmitted photons: (1) CT1 (a) unenhanced CT (nCT) with gantry angulation: SOM = 103%, MIS = 111%; (2) CT2 (a) nCT without gantry angulation: SOM = 81%, MIS = 91%; (b) CT angiography (CTA) with automatic dose-modulation technique: SOM = 39%, MIS = 74%; (c) CTA without dose-modulation technique: SOM = 22%, MIS = 48%; (d) CT perfusion: SOM = 44%, MIS = 69%. SOM showed a higher dose-reduction potential than MIS maintaining equal image quality. Lens-protection systems are most effective in CTA protocols without dose-reduction techniques. Lens-protection systems lower the average eye lens dose during CT scans up to 1/3 (MIS) and 2/3 (SOM), respectively, if the eye lens is exposed to the direct beam of radiation. Considering both the CT protocol and the material of lens protectors, they seem to be mandatory for reducing the radiation exposure of the eye lens. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Volume of interest CBCT and tube current modulation for image guidance using dynamic kV collimation

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

Parsons, David, E-mail: david.parsons@dal.ca, E-mail: james.robar@nshealth.ca; Robar, James L., E-mail: david.parsons@dal.ca, E-mail: james.robar@nshealth.ca

2016-04-15

Purpose: The focus of this work is the development of a novel blade collimation system enabling volume of interest (VOI) CBCT with tube current modulation using the kV image guidance source on a linear accelerator. Advantages of the system are assessed, particularly with regard to reduction and localization of dose and improvement of image quality. Methods: A four blade dynamic kV collimator was developed to track a VOI during a CBCT acquisition. The current prototype is capable of tracking an arbitrary volume defined by the treatment planner for subsequent CBCT guidance. During gantry rotation, the collimator tracks the VOI withmore » adjustment of position and dimension. CBCT image quality was investigated as a function of collimator dimension, while maintaining the same dose to the VOI, for a 22.2 cm diameter cylindrical water phantom with a 9 mm diameter bone insert centered on isocenter. Dose distributions were modeled using a dynamic BEAMnrc library and DOSXYZnrc. The resulting VOI dose distributions were compared to full-field CBCT distributions to quantify dose reduction and localization to the target volume. A novel method of optimizing x-ray tube current during CBCT acquisition was developed and assessed with regard to contrast-to-noise ratio (CNR) and imaging dose. Results: Measurements show that the VOI CBCT method using the dynamic blade system yields an increase in contrast-to-noise ratio by a factor of approximately 2.2. Depending upon the anatomical site, dose was reduced to 15%–80% of the full-field CBCT value along the central axis plane and down to less than 1% out of plane. The use of tube current modulation allowed for specification of a desired SNR within projection data. For approximately the same dose to the VOI, CNR was further increased by a factor of 1.2 for modulated VOI CBCT, giving a combined improvement of 2.6 compared to full-field CBCT. Conclusions: The present dynamic blade system provides significant improvements in CNR for the same imaging dose and localization of imaging dose to a predefined volume of interest. The approach is compatible with tube current modulation, allowing optimization of the imaging protocol.« less

Analyzing U.S. prescription lists with RxNorm and the ATC/DDD Index.

PubMed

Bodenreider, Olivier; Rodriguez, Laritza M

2014-01-01

To evaluate the suitability of the ATC/DDD Index (Anatomical Therapeutic Chemical (ATC) Classification System/Defined Daily Dose) for analyzing prescription lists in the U.S. We mapped RxNorm clinical drugs to ATC. We used this mapping to classify a large set of prescription drugs with ATC and compared the prescribed daily dose to the defined daily dose (DDD) in ATC. 64% of the 11,422 clinical drugs could be precisely mapped to ATC. 97% of the 87,001 RxNorm codes from the prescription dataset could be classified with ATC, and 97% of the prescribed daily doses could be assessed. Although the mapping of RxNorm ingredients to ATC appears to be largely incomplete, the most frequently prescribed drugs in the prescription dataset we analyzed were covered. This study demonstrates the feasibility of using ATC in conjunction with RxNorm for analyzing U.S. prescription datasets for drug classification and assessment of the prescribed daily doses.

Biplane interventional pediatric system with cone‐beam CT: dose and image quality characterization for the default protocols

PubMed Central

Vañó, Eliseo; Alejo, Luis; Ubeda, Carlos; Gutiérrez‐Larraya, Federico; Garayoa, Julia

2016-01-01

The aim of this study was to assess image quality and radiation dose of a biplane angiographic system with cone‐beam CT (CBCT) capability tuned for pediatric cardiac procedures. The results of this study can be used to explore dose reduction techniques. For pulsed fluoroscopy and cine modes, polymethyl methacrylate phantoms of various thicknesses and a Leeds TOR 18‐FG test object were employed. Various fields of view (FOV) were selected. For CBCT, the study employed head and body dose phantoms, Catphan 504, and an anthropomorphic cardiology phantom. The study also compared two 3D rotational angiography protocols. The entrance surface air kerma per frame increases by a factor of 3–12 when comparing cine and fluoroscopy frames. The biggest difference in the signal‐to‐noise ratio between fluoroscopy and cine modes occurs at FOV 32 cm because fluoroscopy is acquired at a 1440×1440 pixel matrix size and in unbinned mode, whereas cine is acquired at 720×720 pixels and in binned mode. The high‐contrast spatial resolution of cine is better than that of fluoroscopy, except for FOV 32 cm, because fluoroscopy mode with 32 cm FOV is unbinned. Acquiring CBCT series with a 16 cm head phantom using the standard dose protocol results in a threefold dose increase compared with the low‐dose protocol. Although the amount of noise present in the images acquired with the low‐dose protocol is much higher than that obtained with the standard mode, the images present better spatial resolution. A 1 mm diameter rod with 250 Hounsfield units can be distinguished in reconstructed images with an 8 mm slice width. Pediatric‐specific protocols provide lower doses while maintaining sufficient image quality. The system offers a novel 3D imaging mode. The acquisition of CBCT images results in increased doses administered to the patients, but also provides further diagnostic information contained in the volumetric images. The assessed CBCT protocols provide images that are noisy, but with very good spatial resolution. PACS number(s): 87.59.‐e, 87.59.‐C, 87.59.‐cf, 87.59.Dj, 87.57. uq PMID:27455474

Biplane interventional pediatric system with cone-beam CT: dose and image quality characterization for the default protocols.

PubMed

Corredoira, Eva; Vañó, Eliseo; Alejo, Luis; Ubeda, Carlos; Gutiérrez-Larraya, Federico; Garayoa, Julia

2016-07-08

The aim of this study was to assess image quality and radiation dose of a biplane angiographic system with cone-beam CT (CBCT) capability tuned for pediatric cardiac procedures. The results of this study can be used to explore dose reduction techniques. For pulsed fluoroscopy and cine modes, polymethyl methacrylate phantoms of various thicknesses and a Leeds TOR 18-FG test object were employed. Various fields of view (FOV) were selected. For CBCT, the study employed head and body dose phantoms, Catphan 504, and an anthropomorphic cardiology phantom. The study also compared two 3D rotational angiography protocols. The entrance surface air kerma per frame increases by a factor of 3-12 when comparing cine and fluoroscopy frames. The biggest difference in the signal-to- noise ratio between fluoroscopy and cine modes occurs at FOV 32 cm because fluoroscopy is acquired at a 1440 × 1440 pixel matrix size and in unbinned mode, whereas cine is acquired at 720 × 720 pixels and in binned mode. The high-contrast spatial resolution of cine is better than that of fluoroscopy, except for FOV 32 cm, because fluoroscopy mode with 32 cm FOV is unbinned. Acquiring CBCT series with a 16 cm head phantom using the standard dose protocol results in a threefold dose increase compared with the low-dose protocol. Although the amount of noise present in the images acquired with the low-dose protocol is much higher than that obtained with the standard mode, the images present better spatial resolution. A 1 mm diameter rod with 250 Hounsfield units can be distinguished in reconstructed images with an 8 mm slice width. Pediatric-specific protocols provide lower doses while maintaining sufficient image quality. The system offers a novel 3D imaging mode. The acquisition of CBCT images results in increased doses administered to the patients, but also provides further diagnostic information contained in the volumetric images. The assessed CBCT protocols provide images that are noisy, but with very good spatial resolution. © 2016 The Authors.

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

PubMed

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

1998-06-01

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

SU-D-213-05: Design, Evaluation and First Applications of a Off-Site State-Of-The-Art 3D Dosimetry System

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

Malcolm, J; Mein, S; McNiven, A

2015-06-15

Purpose: To design, construct and commission a prototype in-house three dimensional (3D) dose verification system for stereotatic body radiotherapy (SBRT) verification at an off-site partner institution. To investigate the potential of this system to achieve sufficient performance (1mm resolution, 3% noise, within 3% of true dose reading) for SBRT verification. Methods: The system was designed utilizing a parallel ray geometry instigated by precision telecentric lenses and an LED 630nm light source. Using a radiochromic dosimeter, a 3D dosimetric comparison with our gold-standard system and treatment planning software (Eclipse) was done for a four-field box treatment, under gamma passing criteria ofmore » 3%/3mm/10% dose threshold. Post off-site installation, deviations in the system’s dose readout performance was assessed by rescanning the four-field box irradiated dosimeter and using line-profiles to compare on-site and off-site mean and noise levels in four distinct dose regions. As a final step, an end-to-end test of the system was completed at the off-site location, including CT-simulation, irradiation of the dosimeter and a 3D dosimetric comparison of the planned (Pinnacle{sup 3}) to delivered dose for a spinal SBRT treatment(12 Gy per fraction). Results: The noise level in the high and medium dose regions of the four field box treatment was relatively 5% pre and post installation. This reflects the reduction in positional uncertainty through the new design. This At 1mm dose voxels, the gamma pass rates(3%,3mm) for our in-house gold standard system and the off-site system were comparable at 95.8% and 93.2% respectively. Conclusion: This work will describe the end-to-end process and results of designing, installing, and commissioning a state-of-the-art 3D dosimetry system created for verification of advanced radiation treatments including spinal radiosurgery.« less

SU-E-I-54: Effective Dose and Radiation Cancer Risks for Scoliosis Patients Undergoing Full Spine Radiography

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

Lin, Y; Hwang, Y; Tsai, H

2015-06-15

Purpose: Scoliotic patients underwent a lot of radiologic examinations during the control and treatment periods. This study used the PCXMC program to calculate the effective dose of the patients and assess the radiation cancer risks. Methods: Seventy five scoliotic patients were examined using CR or DR systems during the control and treatment periods in Chang Gung Memorial Hospital. The technical factors were recorded for each patient during his/her control and treatment period. The entrance surface dose was measured using thermoluminence dosimeters and derived from technical factors and irradiated geometry. The effective dose of patients and relative radiation cancer risks weremore » calculated by the PCXMC program. All required information regarding patient age and sex, the x-ray spectra, and the tube voltage and current were registered. The radiation risk were estimated using the model developed by the BEIR VII committee (2006). Results: The effective doses of full spine radiography with anteroposterior and lateral projections were 0.626 mSv for patients using DR systems, and 0.483mSv for patients using CR systems, respectively. The dose using DR system was 29.6% higher than those using CR system. The maximum organ dose was observed in the breast for both projections in all the systems. The risk of exposure—induced cancer death (REID) of patients for DR and CR systems were 0.009% and 0.007%, respectively. Conclusion: The risk estimates were regarded with healthy skepticism, placed more emphasis on the magnitude of the risk. The effective doses estimated in this study could be served as a reference for radiologists and technologists and demonstrate the necessity to optimize patient protection for full spine radiography though the effective doses are not at the level to induce deterministic effects and not significant in the stochastic effect. This study was supported by the grants from the Chang Gung Memorial Hospital (CMRPD1D0421)« less

Review of Chinese Environmental Risk Assessment Regulations and Case Studies

PubMed Central

Meng, Xiaojie; Zhang, Yan; Zhao, Yuchao; Lou, In Chio; Gao, Jixi

2012-01-01

Environmental risk assessment is an essential step in the development of solutions for pollution problems and new environmental regulations. An assessment system for environmental risks has been developed in China in recent decades. However, many of the Chinese technical guidelines, standards, and regulations were directly adapted from those of developed countries, and were not based on the Chinese environmental and socioeconomic context. Although existing environmental regulations for pollutants are usually obtained by extrapolations from high-dose toxicological data to low-dose scenarios using linear-non-threshold (LNT) models, toxicologists have argued that J-shaped or inverse J-shaped curves may dominate the dose–response relationships for environmental pollutants at low doses because low exposures stimulate biological protective mechanisms that are ineffective at higher doses. The costs of regulations based on LNT and J-shaped models could therefore be dramatically different. Since economic factors strongly affect the decision-making process, particularly for developing countries, it is time to strengthen basic research to provide more scientific support for Chinese environmental regulations. In this paper, we summarize current Chinese environmental policies and standards and the application of environmental risk assessment in China, and recommend a more scientific approach to the development of Chinese regulations. PMID:22740787

Controlled-release systemic delivery - a new concept in cancer chemoprevention

PubMed Central

2012-01-01

Many chemopreventive agents have encountered bioavailability issues in pre-clinical/clinical studies despite high oral doses. We report here a new concept utilizing polycaprolactone implants embedded with test compounds to obtain controlled systemic delivery, circumventing oral bioavailability issues and reducing the total administered dose. Compounds were released from the implants in vitro dose dependently and for long durations (months), which correlated with in vivo release. Polymeric implants of curcumin significantly inhibited tissue DNA adducts following the treatment of rats with benzo[a]pyrene, with the total administered dose being substantially lower than typical oral doses. A comparison of bioavailability of curcumin given by implants showed significantly higher levels of curcumin in the plasma, liver and brain 30 days after treatment compared with the dietary route. Withaferin A implants resulted in a nearly 60% inhibition of lung cancer A549 cell xenografts, but no inhibition occurred when the same total dose was administered intraperitoneally. More than 15 phytochemicals have been tested successfully by this formulation. Together, our data indicate that this novel implant-delivery system circumvents oral bioavailability issues, provides continuous delivery for long durations and lowers the total administered dose, eliciting both chemopreventive/chemotherapeutic activities. This would also allow the assessment of activity of minor constituents and synthetic metabolites, which otherwise remain uninvestigated in vivo. PMID:22696595

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

PubMed

Ahmad, M; Nath, R

2001-02-20

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

A Report of the Joint Development of a Prototype Communications Link to Share Nuclear Accident Dispersion and Dose Assessment Modeling Products Between JAERI/WSPEEDI and LLNL/NARAC

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

Sullivan, T J; Belles, R D; Ellis, J S

2001-05-01

In June of 1997, under an umbrella Memorandum of Understanding between the Japan Atomic Energy Research Institute (JAERI) and the U.S. Department of Energy (US/DOE) concerning matters of nuclear research and development, a Specific Memorandum of Agreement (SMA) entitled ''A Collaborative Programme of Development of a Prototype Communication Link to Share Atmospheric Dispersion and Dose Assessment Modelling Products'' was signed. This SMA formalized an informal collaborative exchange between the DOE's Lawrence Livermore National Laboratory (LLNL) Atmospheric Release Advisory Capability (ARAC) center and the Japan Atomic Energy Research Institute (JAERI) Worldwide System for Prediction of Environmental Emergency Dose Information (WSPEEDI). Themore » intended objective of this agreement was to explore various modes of information exchange, beyond facsimile transmission, which could provide for the quick exchange of information between two major nuclear emergency dose assessment and prediction national centers to provide consistency checks and data exchange before public release of their calculations. The extreme sensitivity of the general public to any nuclear accident information has been a strong motivation to seek peer preview prior to public release. Other intended objectives of this work are the development of an affordable/accessible system for distribution of prediction results to other countries having no prediction capabilities and utilization of the link for collaboration studies. To fulfill the objectives of this project JAERI and LLNL scientists determined to assess the evolving Internet and rapidly emerging communications application software. Our timing was a little early in 1997-1998 but nonetheless a few candidate software packages were found, evaluated and a selection was made for initial test and evaluation. Subsequently several new candidate software packages have arrived, albeit with limitations. This report outlines the ARAC and JAERI emergency response assessment systems, describes the prototype communications protocol system established and the tools evaluated in that process. Three real-time applications of the information exchange protocol and lessons learned are discussed and then some conclusions and future plans are presented.« less

A gamma-secretase inhibitor decreases amyloid-beta production in the central nervous system

PubMed Central

Bateman, Randall J.; Siemers, Eric R.; Mawuenyega, Kwasi G.; Wen, Guolin; Browning, Karen R.; Sigurdson, Wendy C.; Yarasheski, Kevin E.; Friedrich, Stuart W.; DeMattos, Ronald B.; May, Patrick C.; Paul, Steven M.; Holtzman, David M.

2009-01-01

Objective Accumulation of amyloid-β (Aβ) by over-production or under-clearance in the central nervous system is hypothesized to be a necessary event in the pathogenesis of Alzheimer Disease. However, previously there has not been a method to determine drug effects on Aβ production or clearance in the human central nervous system. The objective of this study was to determine the effects of a gamma-secretase inhibitor on the production of Aβ in the human CNS. Methods We utilized a recently developed method of stable-isotope labeling combined with cerebrospinal fluid sampling to directly measure Aβ production during treatment of a gamma-secretase inhibitor, LY450139. We assessed whether this drug could decrease central nervous system Aβ production in healthy men (age 21–50) at single oral doses of 100mg, 140mg, or 280mg (N=5 per group). Results LY450139 significantly decreased the production of central nervous system Aβ in a dose-dependent fashion, with inhibition of Aβ generation of 47%, 52%, and 84% over a 12 hour period with doses of 100 mg, 140, and 280 mg respectively. There was no difference in Aβ clearance. Interpretation Stable isotope labeling of central nervous system proteins can be utilized to assess the effects of drugs on the production and clearance rates of proteins targeted as potential disease modifying treatments for Alzheimer Disease and other central nervous system disorders. Results from this approach can assist in making decisions about drug dosing and frequency in the design of larger and longer clinical trials for diseases such as Alzheimer Disease, and may accelerate effective drug validation. PMID:19360898

Technical assessment of a cone-beam CT scanner for otolaryngology imaging: image quality, dose, and technique protocols.

PubMed

Xu, J; Reh, D D; Carey, J P; Mahesh, M; Siewerdsen, J H

2012-08-01

As cone-beam CT (CBCT) systems dedicated to various imaging specialties proliferate, technical assessment grounded in imaging physics is important to ensuring that image quality and radiation dose are quantified, understood, and justified. This paper involves technical assessment of a new CBCT scanner (CS 9300, Carestream Health, Rochester, NY) dedicated to imaging of the ear and sinuses for applications in otolaryngology-head and neck surgery (OHNS). The results guided evaluation of technique protocols to minimize radiation dose in a manner sufficient for OHNS imaging tasks. The technical assessment focused on the imaging performance and radiation dose for each of seven technique protocols recommended by the manufacturer: three sinus protocols and four ear (temporal bone) protocols. Absolute dose was measured using techniques adapted from AAPM Task Group Report No. 111, involving three stacked 16 cm diameter acrylic cylinders (CTDI phantoms) and a 0.6 cm(3) Farmer ionization chamber to measure central and peripheral dose. The central dose (D(o)) was also measured as a function of longitudinal position (z) within and beyond the primary radiation field to assess, for example, out-of-field dose to the neck. Signal-difference-to-noise ratio (SDNR) and Hounsfield unit (HU) accuracy were assessed in a commercially available quality assurance phantom (CATPHAN module CTP404, The Phantom Laboratory, Greenwich, NY) and a custom phantom with soft-tissue-simulating plastic inserts (Gammex RMI, Madison, WI). Spatial resolution was assessed both qualitatively (a line-pair pattern, CATPHAN module CTP528) and quantitatively (modulation transfer function, MTF, measured with a wire phantom). Imaging performance pertinent to various OHNS imaging tasks was qualitatively assessed using an anthropomorphic phantom as evaluated by two experienced OHNS specialists. The technical assessment motivated a variety of modifications to the manufacturer-specified protocols to provide reduced radiation dose without compromising pertinent task-based imaging performance. The revised protocols yielded D(o) ranging 2.9-5.7 mGy, representing a ∼30% reduction in dose from the original technique chart. Out-of-field dose was ∼10% of D(o) at a distance of ∼8 cm from the field edge. Soft-tissue contrast resolution was fairly limited (water-brain SDNR ∼0.4-0.7) while high-contrast performance was reasonably good (SDNR ∼2-4 for a polystyrene insert in the CATPHAN). The scanner does not demonstrate (or claim to provide) accurate HU and exhibits a systematic error in CT number that could potentially be addressed by further calibration. The spatial resolution is ∼10-16 lp∕cm as assessed in a line-pair phantom, with MTF exceeding 10% out to ∼20 lp∕cm. Qualitative assessment by expert readers suggested limited soft-tissue visibility but excellent high-contrast (bone) visualization with isotropic spatial resolution suitable to a broad spectrum of pertinent sinus and temporal bone imaging tasks. The CBCT scanner provided spatial and contrast resolution suitable to visualization of high-contrast morphology in sinus, maxillofacial, and otologic imaging applications. Rigorous technical assessment guided revision of technique protocols to reduce radiation dose while maintaining image quality sufficient for pertinent imaging tasks. The scanner appears well suited to high-contrast sinus and temporal bone imaging at doses comparable to or less than that reported for conventional diagnostic CT of the head.

The Development of a Beta-Gamma Personnel Dosimeter

NASA Astrophysics Data System (ADS)

Tsakeres, Frank Steven

The assessment of absorbed dose in mixed beta and gamma radiation fields is an extremely complex task. For many years, the assessment of the absorbed dose to tissue from the weakly penetrating components of a radiation field (i.e., beta particles, electrons) has been largely ignored. Beta radiation fields are encountered routinely in a nuclear facility and may represent the major radiation component under certain accident or emergency conditions. Many attempts have been made to develop an accurate mixed field personnel dosimeter. However, all of these dosimeters have exhibited numerous response problems which have limited their usefulness for personnel dose assessment. Consequently, the determination of the absorbed dose at the epidermal depth (i.e., 7 mg/cm('2)) has been difficult to measure accurately. The objective of this research project was to design, build, and test a sensitive and accurate personnel dosimeter for mixed field applications. The selection of the various dosimeter elements were determined by evaluating several types of phosphors, filters, and backscatter materials. After evaluating the various response characteristics of the badge components, a prototype dosimeter, the CHEMM (CaF(,2):Dy Highly Efficient Multiple Element Multiple Filter) personnel dosimeter, was developed and tested at Georgia Tech, Emory University and the National Bureau of Standards. This dosimeter was comprised of four large CaF(,2):Dy (TLD-200) TLD's and a standard LiF (TLD-100) chip. The weakly penetrating and penetrating components of a radiation field were separated using a series of TLD/filter combinations and a new dose assessment algorithm. The large TLD-200 chips, along with a series of tissue-equivalent filters, were used to determine the absorbed dose due to the weakly penetrating radiation while a LiF/filter combination was used to measure the penetrating component. In addition, a new backscatter material was included in the badge design to better simulate a tissue-equivalent response. The CHEMM personnel dosimeter performance tests were conducted to simulate actual mixed radiation field environments. This dosimeter provided a high degree of sensitivity with accuracies well within the ANSI recommended performance standards for personnel dosimeters. In addition, it was concluded that the CHEMM dosimetry system provided a practical dosimeter alternative with a higher dose assessment accuracy and measurement sensitivity than the personnel dosimetry systems presently used in the nuclear power industry.

Does the choice of mobile C-arms lead to a reduction of the intraoperative radiation dose?

PubMed

Richter, P H; Steinbrener, J; Schicho, A; Gebhard, F

2016-08-01

Mobile C-arm imaging is commonly used in operating rooms worldwide. Especially in orthopaedic surgery, intraoperative C-arms are used on a daily basis. Because of new minimally-invasive surgical procedures a development in intraoperative imaging is required. The purpose of this article is investigate if the choice of mobile C-arms with flat panel detector technology (Siemens Cios Alpha and Ziehm Vision RFD) influences image quality and dose using standard, commercially available test devices. For a total of four clinical application settings, two zoom formats, and all dose levels provided, the transmission dose was measured and representative images were recorded for each test device. The data was scored by four observers to assess low contrast and spatial resolution performance. The results were converted to a relative image quality figure allowing for a direct image quality and dose comparison of the two systems. For one test device, the Cios Alpha system achieved equivalent (within the inter-observer standard error) or better low contrast resolution scores at significantly lower dose levels, while the results of the other test device suggested that both systems achieved similar image quality at the same dose. The Cios Alpha system achieved equivalent or better spatial resolution at significantly lower dose for all application settings except for Cardiac, where a comparable spatial resolution was achieved at the same dose. The correct choice of a mobile C-arm is very important, because it can lead to a reduction of the intraoperative radiation dose without negative effects on image quality. This can be a big advantage to reduce intraoperative radiation not only for the patient but also for the entire OR-team. Copyright © 2016. Published by Elsevier Ltd.

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.

Endocrine-disrupting chemicals, epigenetics, and skeletal system dysfunction: exploration of links using bisphenol A as a model system

PubMed Central

Xin, Frances; Smith, Lauren M; Susiarjo, Martha; Jepsen, Karl J

2018-01-01

Abstract Early life exposures to endocrine-disrupting chemicals (EDCs) have been associated with physiological changes of endocrine-sensitive tissues throughout postnatal life. Although hormones play a critical role in skeletal growth and maintenance, the effects of prenatal EDC exposure on adult bone health are not well understood. Moreover, studies assessing skeletal changes across multiple generations are limited. In this article, we present previously unpublished data demonstrating dose-, sex-, and generation-specific changes in bone morphology and function in adult mice developmentally exposed to the model estrogenic EDC bisphenol A (BPA) at doses of 10 μg (lower dose) or 10 mg per kg bw/d (upper dose) throughout gestation and lactation. We show that F1 generation adult males, but not females, developmentally exposed to bisphenol A exhibit dose-dependent reductions in outer bone size resulting in compromised bone stiffness and strength. These structural alterations and weaker bone phenotypes in the F1 generation did not persist in the F2 generation. Instead, F2 generation males exhibited greater bone strength. The underlying mechanisms driving the EDC-induced physiological changes remain to be determined. We discuss potential molecular changes that could contribute to the EDC-induced skeletal effects, with an emphasis on epigenetic dysregulation. Furthermore, we assess the necessity of intact sex steroid receptors to mediate these effects. Expanding future assessments of EDC-induced effects to the skeleton may provide much needed insight into one of the many health effects of these chemicals and aid in regulatory decision making regarding exposure of vulnerable populations to these chemicals. PMID:29732168

Endocrine-disrupting chemicals, epigenetics, and skeletal system dysfunction: exploration of links using bisphenol A as a model system.

PubMed

Xin, Frances; Smith, Lauren M; Susiarjo, Martha; Bartolomei, Marisa S; Jepsen, Karl J

2018-04-01

Early life exposures to endocrine-disrupting chemicals (EDCs) have been associated with physiological changes of endocrine-sensitive tissues throughout postnatal life. Although hormones play a critical role in skeletal growth and maintenance, the effects of prenatal EDC exposure on adult bone health are not well understood. Moreover, studies assessing skeletal changes across multiple generations are limited. In this article, we present previously unpublished data demonstrating dose-, sex-, and generation-specific changes in bone morphology and function in adult mice developmentally exposed to the model estrogenic EDC bisphenol A (BPA) at doses of 10 μg (lower dose) or 10 mg per kg bw/d (upper dose) throughout gestation and lactation. We show that F1 generation adult males, but not females, developmentally exposed to bisphenol A exhibit dose-dependent reductions in outer bone size resulting in compromised bone stiffness and strength. These structural alterations and weaker bone phenotypes in the F1 generation did not persist in the F2 generation. Instead, F2 generation males exhibited greater bone strength. The underlying mechanisms driving the EDC-induced physiological changes remain to be determined. We discuss potential molecular changes that could contribute to the EDC-induced skeletal effects, with an emphasis on epigenetic dysregulation. Furthermore, we assess the necessity of intact sex steroid receptors to mediate these effects. Expanding future assessments of EDC-induced effects to the skeleton may provide much needed insight into one of the many health effects of these chemicals and aid in regulatory decision making regarding exposure of vulnerable populations to these chemicals.

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

Chen, Q; Read, P

Purpose: Multiple error pathways can lead to delivery errors during the treatment course that cannot be caught with pre-treatment QA. While in vivo solutions are being developed for linacs, no such solution exists for tomotherapy. The purpose of this study is to develop a near real-time system for tomotherapy that can monitor the delivery and dose accumulation process during the treatment-delivery, which enable the user to assess the impact of delivery variations and/or errors and to interrupt the treatment if necessary. Methods: A program running on a tomotherapy planning station fetches the raw DAS data during treatment. Exit detector datamore » is extracted as well as output, gantry angle, and other machine parameters. For each sample, the MLC open-close state is determined. The delivered plan is compared with the original plan via a Monte Carlo dose engine which transports fluence deviations from a pre-treatment Monte Carlo run. A report containing the difference in fluence, dose and DVH statistics is created in html format. This process is repeated until the treatment is completed. Results: Since we only need to compute the dose for the difference in fluence for a few projections each time, dose with 2% statistical uncertainty can be computed in less than 1 second on a 4-core cpu. However, the current bottleneck in this near real-time system is the repeated fetching and processing the growing DAS data file throughout the delivery. The frame rate drops from 10Hz at the beginning of treatment to 5Hz after 3 minutes and to 2Hz after 10 minutes. Conclusion: A during-treatment delivery monitor system has been built to monitor tomotherapy treatments. The system improves patient safety by allowing operators to assess the delivery variations and errors during treatment delivery and adopt appropriate actions.« less

Impact of external carbon dose on the removal of micropollutants using methanol and ethanol in post-denitrifying Moving Bed Biofilm Reactors.

PubMed

Torresi, Elena; Escolà Casas, Mònica; Polesel, Fabio; Plósz, Benedek G; Christensson, Magnus; Bester, Kai

2017-01-01

Addition of external carbon sources to post-denitrification systems is frequently used in wastewater treatment plants to enhance nitrate removal. However, little is known about the fate of micropollutants in post-denitrification systems and the influence of external carbon dosing on their removal. In this study, we assessed the effects of two different types and availability of commonly used carbon sources -methanol and ethanol- on the removal of micropollutants in biofilm systems. Two laboratory-scale moving bed biofilm reactors (MBBRs), containing AnoxKaldnes K1 carriers with acclimated biofilm from full-scale systems, were operated in continuous-flow using wastewater dosed with methanol and ethanol, respectively. Batch experiments with 22 spiked pharmaceuticals were performed to assess removal kinetics. Acetyl-sulfadiazine, atenolol, citalopram, propranolol and trimethoprim were easily biotransformed in both MBBRs (biotransformations rate constants k bio between 1.2 and 12.9 L g biomass -1  d -1 ), 13 compounds were moderately biotransformed (rate constants between 0.2 and 2 L g biomass -1  d -1 ) and 4 compounds were recalcitrant. The methanol-dosed MBBR showed higher k bio (e.g., 1.5-2.5-fold) than in the ethanol-dosed MBBR for 9 out of the 22 studied compounds, equal k bio for 10 compounds, while 3 compounds (i.e., targeted sulfonamides) were biotransformed faster in the ethanol-dosed MBBR. While biotransformation of most of the targeted compounds followed first-order kinetics, removal of venlafaxine, carbamazepine, sulfamethoxazole and sulfamethizole could be described with a cometabolic model. Analyses of the microbial composition in the biofilms using 16S rRNA amplicon sequencing revealed that the methanol-dosed MBBR contained higher microbial richness than the one dosed with ethanol, suggesting that improved biotransformation of targeted compounds could be associated with higher microbial richness. During continuous-flow operation, at conditions representative of full-scale denitrification systems (hydraulic residence time = 2 h), the removal efficiencies of micropollutants were below 35% in both MBBRs, with the exception of atenolol and trimethoprim (>80%). Overall, this study demonstrated that MBBRs used for post-denitrification could be optimized to enhance the biotransformation of a number of micropollutants by accounting for optimal carbon sources and extended residence time. Copyright © 2016 Elsevier Ltd. All rights reserved.

SU-D-204-06: Dose and Image Quality Evaluation of a Low-Dose Slot-Scanning X-Ray System for Pediatric Orthopedic Studies

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

Liu, Z; Hoerner, M; Lamoureux, R

Purpose: Children in early teens with scoliosis require repeated radiographic exams over a number of years. The EOS (EOS imaging S.A., Paris, France) is a novel low-dose slot-scanning digital radiographic system designed to produce full-spine images of a free-standing patient. The radiation dose and image quality characteristics of the EOS were evaluated relative to those of a Computed Radiography (CR) system for scoliosis imaging. Methods: For dose evaluation, a full-torso anthropomorphic phantom was scanned five times using the default standard clinical protocols for both the EOS and a CR system, which include both posteroanterior and lateral full-spine views. Optically stimulatedmore » luminescent dosimeters (OSLDs), also known as nanoDots™ (Landauer, Inc., Glenwood, IL), were placed on the phantom’s surface to measure entrance skin dose. To assess image quality, MTF curves were generated from sampling the noise levels within the high-contrast regions of a line-pair phantom. Vertical and horizontal distortions were measured for the square line-pair phantom with the EOS system to evaluate the effects of geometric magnification and misalignment with the indicated imaging plane. Results: The entrance skin dose was measured to be 0.4 to 1.1 mGy for the EOS, and 0.7 to 3.6 mGy for the CR study. MTF comparison shows that CR greatly outperforms the EOS, despite both systems having a limiting resolution at 1.8 line-pairs per mm. Vertical distortion was unaffected by phantom positioning, because of the EOS slot-scanning geometry. Horizontal distortion increased linearly with miscentering distance. Conclusion: The EOS system resulted in approximately 70% lower radiation dose than CR for full-spine images. Image quality was found to be inferior to CR. Further investigation is required to see if EOS system is an acceptable modality for performing clinically diagnostic scoliosis examinations.« less

IRIS Toxicological Review of Inorganic Arsenic (Cancer) (2010 External Review Draft)

EPA Science Inventory

EPA's Science Advisory Board (SAB) conducted a review of the scientific basis supporting the human health cancer hazard and dose-response assessment of inorganic arsenic that will appear on the Integrated Risk Information System (IRIS) database. EPA revised the assessment and is...

Evaluation of Measles-Mumps-Rubella Vaccination Among Newly Arrived Refugees.

PubMed

Lee, Deborah; Weinberg, Michelle; Benoit, Stephen

2017-05-01

To assess US availability and use of measles-mumps-rubella (MMR) vaccination documentation for refugees vaccinated overseas. We selected 1500 refugee records from 14 states from March 2013 through July 2015 to determine whether overseas vaccination records were available at the US postarrival health assessment and integrated into the Advisory Committee on Immunization Practices schedule. We assessed number of doses, dosing interval, and contraindications. Twelve of 14 (85.7%) states provided data on 1118 (74.5%) refugees. Overseas records for 972 (86.9%) refugees were available, most from the Centers for Disease Control and Prevention's Electronic Disease Notification system (66.9%). Most refugees (829; 85.3%) were assessed appropriately for MMR vaccination; 37 (3.8%) should have received MMR vaccine but did not; 106 (10.9%) did not need the MMR vaccine but were vaccinated. Overseas documentation was available at most clinics, and MMR vaccinations typically were given when needed. Further collaboration between refugee health clinics and state immunization information systems would improve accessibility of vaccination documentation.

Efficacy of lead foil for reducing doses in the head and neck: a simulation study using digital intraoral systems

PubMed Central

Silva, A I V; Brasil, D M; Vasconcelos, K F; Haiter Neto, F; Boscolo, F N

2015-01-01

Objectives: To assess the efficacy of lead foils in reducing the radiation dose received by different anatomical sites of the head and neck during periapical intraoral examinations performed with digital systems. Methods: Images were acquired through four different manners: phosphor plate (PSP; VistaScan® system; Dürr Dental GmbH, Bissingen, Germany) alone, PSP plus lead foil, complementary metal oxide semiconductor (CMOS; DIGORA® Toto, Soredex®, Tuusula, Finland) alone and CMOS plus lead foil. Radiation dose was measured after a full-mouth periapical series (14 radiographs) using the long-cone paralleling technique. Lithium fluoride (LiF 100) thermoluminescent dosemeters were placed in an anthropomorphic phantom at points corresponding to the tongue, thyroid, crystalline lenses, parotid glands and maxillary sinuses. Results: Dosemeter readings demonstrated the efficacy of the addition of lead foil in the intraoral digital X-ray systems provided in reducing organ doses in the selected structures, approximately 32% in the PSP system and 59% in the CMOS system. Conclusions: The use of lead foils associated with digital X-ray sensors is an effective alternative for the protection of different anatomical sites of the head and neck during full-mouth periapical series acquisition. PMID:26084474

Guaifenesin Pharmacokinetics Following Single-Dose Oral Administration in Children Aged 2 to 17 Years.

PubMed

Thompson, Gary A; Solomon, Gail; Albrecht, Helmut H; Reitberg, Donald P; Guenin, Eric

2016-07-01

This study characterized guaifenesin pharmacokinetics in children aged 2 to 17 years (n = 40) who received a single oral dose of guaifenesin (age-based doses of 100-400 mg) 2 hours after breakfast. Plasma samples were obtained before and for 8 hours after dosing and analyzed for guaifenesin using liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods, relationships with age were assessed using linear regression, and dose proportionality was assessed on 95% confidence intervals. Based on the upper dose recommended in the monograph (for both children and adolescents), area under the curve from time zero to infinity and maximum plasma concentration both increased with age. However, when comparing the upper dose for children aged 2 to 11 years with the lower dose for adolescents aged 12 to 17 years, similar systemic exposure was observed. As expected due to increasing body size, oral clearance (CLo ) and terminal volume of distribution (Vz /F) increased with age. Due to a larger increase in Vz /F than CLo , an increase in terminal exponential half-life was also observed. Allometric scaling indicated no maturation-related changes in CLo and Vz /F. © 2016, The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Clinical assessment of the jaw-tracking function in IMRT for a brain tumor

NASA Astrophysics Data System (ADS)

Kim, Jin-Young; Kim, Shin-Wook; Choe, Bo-Young; Suh, Tae-Suk; Park, Sung-Kwang; Jo, Sun-Mi; Oh, Won-Yong; Shin, Jung-Wook; Cho, Gyu-Seok; Nam, Sang-Hee; Chung, Jin-Beom; Kim, Jung-Ki; Lee, Young-Kyu

2015-01-01

Intensity-modulated radiotherapy (IMRT) improves dose conformity and saves critical organs. IMRT is widely used in cases of head and neck, prostate, and brain cancer due to the close location of the targets to critical structures. However, because IMRT has a larger amount of radiation exposure than 3 dimensional-conformal radiation therapy (3D-CRT), it has disadvantages such as increases in the low dose irradiation to normal tissues and in the accumulated dose for the whole volume due to leakage and transmission of the multi-leaf collimator (MLC). The increased accumulated dose and the larger low dose may increase the occurrence of secondary malignant neoplasms. For these reasons, the jaw-tracking function of the TrueBeam (Varian Medical Systems, Palo Alto, CA) was developed to reduce the leakage and the transmission dose of the MLC with linear accelerators. However, the change in the superficial dose has not been verified with a quantitative analysis of the dose reduction in a brain tumor. Therefore, in the present study, we intended to verify the clinical possibility of utilizing the jaw-tracking function for a brain tumor by comparing treatment plans and superficial doses. To accomplish this, we made three types of original treatment plans using Eclipse11 (Varian Medical Systems, Palo Alto, CA): 1) farther than 2 cm from the organs at risk (OAR); 2) within 2 cm of the OAR; and 3) intersecting with the OAR. Jaw-tracking treatment plans were also made with copies of the original treatment plan using Smart LMC Version 11.0.31 (Varian Medical Systems, Palo Alto, CA). A comparison between the original treatment plans and jaw-tracking treatment plans was performed using the difference of the mean dose and maximum dose to the OARs in cumulative Dose Volume Histogram (DVH). In addition, the dependencies of the effects of transmission and the scattering doses according to jaw motion were assessed through the difference in the surface doses. In the DVH comparison, a maximum dose difference of 0.4% was observed between the planning methods in the case of over 2 cm distance, and the maximum dose of 0.6% was obtained for within the 2 cm distance. For the case intersecting with the OAR, the maximum dose difference of 2.3% was achieved. According to these results, the differences in the mean doses and the maximum doses to the OARs ware larger when the OARs and the planning target volume (PTV) were closer. In addition, small differences in the surface dose measurements were observed. In the case of the inside field, the differences were under 2% of the prescription dose while the difference was under 0.1% in the case of the outside field. Therefore, treatment plans with the jaw-tracking function consistently affected the dose reduction for a brain tumor, and the clinical possibility could be verified as the surface dose was not increased.

SU-F-18C-09: Assessment of OSL Dosimeter Technology in the Validation of a Monte Carlo Radiation Transport Code for CT Dosimetry

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

Carver, D; Kost, S; Pickens, D

Purpose: To assess the utility of optically stimulated luminescent (OSL) dosimeter technology in calibrating and validating a Monte Carlo radiation transport code for computed tomography (CT). Methods: Exposure data were taken using both a standard CT 100-mm pencil ionization chamber and a series of 150-mm OSL CT dosimeters. Measurements were made at system isocenter in air as well as in standard 16-cm (head) and 32-cm (body) CTDI phantoms at isocenter and at the 12 o'clock positions. Scans were performed on a Philips Brilliance 64 CT scanner for 100 and 120 kVp at 300 mAs with a nominal beam width ofmore » 40 mm. A radiation transport code to simulate the CT scanner conditions was developed using the GEANT4 physics toolkit. The imaging geometry and associated parameters were simulated for each ionization chamber and phantom combination. Simulated absorbed doses were compared to both CTDI{sub 100} values determined from the ion chamber and to CTDI{sub 100} values reported from the OSLs. The dose profiles from each simulation were also compared to the physical OSL dose profiles. Results: CTDI{sub 100} values reported by the ion chamber and OSLs are generally in good agreement (average percent difference of 9%), and provide a suitable way to calibrate doses obtained from simulation to real absorbed doses. Simulated and real CTDI{sub 100} values agree to within 10% or less, and the simulated dose profiles also predict the physical profiles reported by the OSLs. Conclusion: Ionization chambers are generally considered the standard for absolute dose measurements. However, OSL dosimeters may also serve as a useful tool with the significant benefit of also assessing the radiation dose profile. This may offer an advantage to those developing simulations for assessing radiation dosimetry such as verification of spatial dose distribution and beam width.« less

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

Kienhuis, Anne S., E-mail: anne.kienhuis@rivm.nl; RIKILT, Institute of Food Safety, Wageningen UR, PO Box 230, 6700 AE, Wageningen; Netherlands Toxicogenomics Centre

Hepatic systems toxicology is the integrative analysis of toxicogenomic technologies, e.g., transcriptomics, proteomics, and metabolomics, in combination with traditional toxicology measures to improve the understanding of mechanisms of hepatotoxic action. Hepatic toxicology studies that have employed toxicogenomic technologies to date have already provided a proof of principle for the value of hepatic systems toxicology in hazard identification. In the present review, acetaminophen is used as a model compound to discuss the application of toxicogenomics in hepatic systems toxicology for its potential role in the risk assessment process, to progress from hazard identification towards hazard characterization. The toxicogenomics-based parallelogram is usedmore » to identify current achievements and limitations of acetaminophen toxicogenomic in vivo and in vitro studies for in vitro-to-in vivo and interspecies comparisons, with the ultimate aim to extrapolate animal studies to humans in vivo. This article provides a model for comparison of more species and more in vitro models enhancing the robustness of common toxicogenomic responses and their relevance to human risk assessment. To progress to quantitative dose-response analysis needed for hazard characterization, in hepatic systems toxicology studies, generation of toxicogenomic data of multiple doses/concentrations and time points is required. Newly developed bioinformatics tools for quantitative analysis of toxicogenomic data can aid in the elucidation of dose-responsive effects. The challenge herein is to assess which toxicogenomic responses are relevant for induction of the apical effect and whether perturbations are sufficient for the induction of downstream events, eventually causing toxicity.« less

Use of gadoxetic acid for computed tomographic cholangiography in healthy dogs.

PubMed

Chau, Jennifer; Podadera, Juan M; Young, Alex C; Makara, Mariano A

2017-07-01

OBJECTIVE To evaluate the effect of gadoxetic acid (contrast) dose on biliary tract enhancement, determine the optimal time after contrast injection for CT image acquisition, and assess the feasibility of CT cholangiography in sedated dogs. ANIMALS 8 healthy dogs. PROCEDURES The study had 2 parts. In part 1, 4 dogs were anesthetized and underwent CT cholangiography twice. Gadoxetic acid was administered IV at a low dose (0.025 mmol/kg) for the first procedure and high dose (0.3 mmol/kg) for the second procedure. Serial CT scans were obtained at predetermined times after contrast injection. In part 2, 4 dogs were sedated and underwent CT angiography 85 minutes after IV administration of the high contrast dose. Contrast enhancement of the biliary tract on all scans was objectively assessed by measurement of CT attenuation and qualitatively assessed by use of a subjective 4-point scoring system by 3 independent reviewers. All measurements were compared over time and between contrast doses for the dogs of part 1. Subjective measurements were compared between the sedated dogs of part 2 and anesthetized dogs of part 1. RESULTS Enhancement of the biliary tract was positively associated with contrast dose and time after contrast injection. Optimal enhancement was achieved 65 minutes after contrast injection. Subjective visualization of most biliary structures did not differ significantly between sedated and anesthetized dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated CT cholangiography with gadoxetic acid was feasible in sedated dogs. The high contrast dose provided better visualization of biliary structures than the low dose; CT scans should be obtained 65 minutes after contrast injection.

Safety and pharmacodynamics of venetoclax (ABT-199) in a randomized single and multiple ascending dose study in women with systemic lupus erythematosus.

PubMed

Lu, P; Fleischmann, R; Curtis, C; Ignatenko, S; Clarke, S H; Desai, M; Wong, S L; Grebe, K M; Black, K; Zeng, J; Stolzenbach, J; Medema, J K

2018-02-01

Objective The anti-apoptotic protein B-cell lymphoma 2 (Bcl-2) may contribute to the pathogenesis of systemic lupus erythematosus. The safety, tolerability, and pharmacodynamics of the selective Bcl-2 inhibitor venetoclax (ABT-199) were assessed in women with systemic lupus erythematosus. Methods A phase 1, double-blind, randomized, placebo controlled study evaluated single ascending doses (10, 30, 90, 180, 300, and 500 mg) and multiple ascending doses (2 cycles; 30, 60, 120, 240, 400, and 600 mg for 1 week, and then 3 weeks off per cycle) of orally administered venetoclax. Eligible participants were aged 18-65 years with a diagnosis of systemic lupus erythematosus for 6 months or more receiving stable therapy for systemic lupus erythematosus (which could have included corticosteroids and/or stable antimalarials). Results All patients (48/48) completed the single ascending dose, 25 continued into the multiple ascending dose, and 44/50 completed the multiple ascending dose; two of the withdrawals (venetoclax 60 mg and 600 mg cohorts) were due to adverse events. Adverse event incidences were slightly higher in the venetoclax groups compared with the placebo groups, with no dose dependence. There were no serious adverse events with venetoclax. The most common adverse events were headache, nausea, and fatigue. Venetoclax 600 mg multiple ascending dose treatment depleted total lymphocytes and B cells by approximately 50% and 80%, respectively. Naive, switched memory, and memory B-cell subsets enriched in autoreactive B cells exhibited dose-dependent reduction of up to approximately 80%. There were no consistent or marked changes in neutrophils, natural killer cells, hemoglobin, or platelets. Conclusions Venetoclax was generally well tolerated in women with systemic lupus erythematosus and reduced total lymphocytes and disease-relevant subsets of antigen-experienced B cells. Registration ClinicalTrials.gov: NCT01686555.

Microbial Risk Assessment

NASA Technical Reports Server (NTRS)

Ott, C. M.; Mena, K. D.; Nickerson, C.A.; Pierson, D. L.

2009-01-01

Historically, microbiological spaceflight requirements have been established in a subjective manner based upon expert opinion of both environmental and clinical monitoring results and the incidence of disease. The limited amount of data, especially from long-duration missions, has created very conservative requirements based primarily on the concentration of microorganisms. Periodic reevaluations of new data from later missions have allowed some relaxation of these stringent requirements. However, the requirements remain very conservative and subjective in nature, and the risk of crew illness due to infectious microorganisms is not well defined. The use of modeling techniques for microbial risk has been applied in the food and potable water industries and has exceptional potential for spaceflight applications. From a productivity standpoint, this type of modeling can (1) decrease unnecessary costs and resource usage and (2) prevent inadequate or inappropriate data for health assessment. In addition, a quantitative model has several advantages for risk management and communication. By identifying the variable components of the model and the knowledge associated with each component, this type of modeling can: (1) Systematically identify and close knowledge gaps, (2) Systematically identify acceptable and unacceptable risks, (3) Improve communication with stakeholders as to the reasons for resource use, and (4) Facilitate external scientific approval of the NASA requirements. The modeling of microbial risk involves the evaluation of several key factors including hazard identification, crew exposure assessment, dose-response assessment, and risk characterization. Many of these factors are similar to conditions found on Earth; however, the spaceflight environment is very specialized as the inhabitants live in a small, semi-closed environment that is often dependent on regenerative life support systems. To further complicate modeling efforts, microbial dose-response characteristics may be affected by a potentially dysfunctional crew immune system during a mission. In addition, microbial virulence has been shown to change under certain conditions during spaceflight, further complicating dose-response characterization. An initial study of the applicability of microbial risk assessment techniques was performed using Crew Health Care System (CHeCS) operational data from the International Space Station potable water systems. The risk of infection from potable water was selected as the flight systems and microbial ecology are well defined. This initial study confirmed the feasibility of using microbial risk assessment modeling for spaceflight systems. While no immediate threat was detected, the study identified several medically significant microorganisms that could pose a health risk if uncontrolled. The study also identified several specific knowledge gaps in making a risk assessment and noted that filling these knowledge gaps is essential as the risk estimates may change by orders of magnitude depending on the answers. The current phase of the microbial risk assessment studies focuses on the dose-response relationship of specific infectious agents, focusing on Salmonella enterica Typhimurium, Pseudomonas spp., and Escherichia coli, as their evaluation will provide a better baseline for determining the overall hazard characterization. The organisms were chosen as they either have been isolated on spacecraft or have an identified route of infection during a mission. The characterization will utilize dose-response models selected either from the peer-reviewed literature and/or by using statistical approaches. Development of these modeling and risk assessment techniques will help to optimize flight requirements and to protect the safety, health, and performance of the crew.

SU-F-T-08: Brachytherapy Film Dosimetry in a Water Phantom for a Ring and Tandem HDR Applicator

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

Lee, B; Grelewicz, Z; Kang, Z

2016-06-15

Purpose: The feasibility of dose measurement using new generation EBT3 film was explored in a water phantom for a ring and tandem HDR applicator for measurements tracking mucosal dose during cervical brachytherapy. Methods: An experimental fixture was assembled to position the applicator in a water phantom. Prior to measurement, calibration curves for EBT3 film in water and in solidwater were verified. EBT3 film was placed at different known locations around the applicator in the water tank. A CT scan of the phantom with applicator was performed using clinical protocol. A typical cervical cancer treatment plan was then generated by Oncentramore » brachytherapy planning system. A dose of 500 cGy was prescribed to point A (2 cm, 2 cm). Locations measured by film included the outer surface of the ring, measurement point A-m (2.2 cm, 2.2 cm), and profiles extending from point A-m parallel to the tandem. Three independent measurements were conducted. The doses recorded by film were carefully analyzed and compared with values calculated by the treatment planning system. Results: Assessment of the EBT3 films indicate that the dose at point A matches the values predicted by the planning system. Dose to the point A-m was 411.5 cGy, and the outer circumferential surface dose of the ring was between 500 and 1150 cGy. It was found that from the point A-m, the dose drops 60% within 4.5 cm on the line parallel to the tandem. The measurement doses agree with the treatment planning system. Conclusion: Use of EBT3 film is feasible for in-water measurements for brachytherapy. A carefully machined apparatus will likely improve measurement accuracy. In a typical plan, our study found that the ring surface dose can be 2.5 times larger than the point A prescription dose. EBT3 film can be used to monitor mucosal dose in brachytherapy treatments.« less

Real-time dosimetry in radiotherapy using tailored optical fibers

NASA Astrophysics Data System (ADS)

Rahman, A. K. M. Mizanur; Zubair, H. T.; Begum, Mahfuza; Abdul-Rashid, H. A.; Yusoff, Z.; Omar, Nasr Y. M.; Ung, N. M.; Mat-Sharif, K. A.; Bradley, D. A.

2016-05-01

Real-time dosimetry plays an important role for accurate patient-dose measurement during radiotherapy. A tiny piece of laboratory fabricated Ge-doped optical fiber has been investigated as a radioluminescence (RL) sensor for real-time dosimetry over the dose range from 1 Gy to 8 Gy under 6 MV photon beam by LINAC. Fiber-coupled software-based RL prototype system was used to assess essential dosimetric characteristics including dose response linearity, dose rate dependency, sensitivity, repeatability and output dependence on field sizes. The consistency level of RL photon counts versus dose rate was also compared with that of standard Al2O3:C chips. Sensitivity of Ge-doped fiber were found to be sufficiently sensitive for practical use and also provided linear dose responses for various dose rates from 100 cGy/min to 600 cGy/min using both 6 MV photon and 6 MeV electron beams. SEM-EDX analysis was performed to identify Ge-dopant concentration level within the optical fiber RL material. Accumulated doses were also estimated using simple integral technique and the error was found to be around less than 1% under dissimilar dose rates or repeat measurements. The evaluation of the Ge-doped optical fiber based RL dosimeter system indicates its potential in medical dosimetry.

Reactogenicity of tetanus, diphtheria, 5-component acellular pertussis vaccine administered as a sixth consecutive acellular pertussis vaccine dose to adolescents.

PubMed

Liese, Johannes G; Rieber, Nikolaus; Malzer, Thomas; Ocak, Marion; Johnson, David R; Decker, Michael D

2010-12-01

Safety of a sixth consecutive dose of acellular pertussis vaccine in adolescents was assessed in a 2-armed, randomized study. Adolescents who had received 5 doses of acellular pertussis vaccine combined with diphtheria and tetanus toxoids (6-dose group) received 1 dose of reduced 5-component acellular pertussis vaccine combined with tetanus toxoid and reduced diphtheria toxoid (Tdap). Adolescents who had received a primary series of 3 doses of whole-cell pertussis and 1 acellular or whole-cell pertussis booster received 1 dose of Tdap vaccine (5-dose group). Of 214 participants, 176 (82%) reported an injection-site reaction with pain (80%), erythema (22%), and swelling (19%) most frequently reported. A systemic reaction was reported by 169 of 214 (79%) with myalgia (66%), headache (42%), malaise (39%), and fever (9%) most frequently reported. The overall rate of solicited reactions was lower in the 6-dose group than in the 5-dose group (for injection-site reactions: 76.1% vs. 89.7%; for systemic reactions 72.6% vs. 86.6%). Significant differences were observed for injection-site pain, erythema, and for grade 1 or grade 2 increases in arm circumference. Fever, myalgia, and headache were reported at a significantly lower rate in the 6-dose group. Swelling >10 cm was observed in 5 patients (2%), 4 in the 5-dose group. Tdap vaccine was safe when given to adolescents who had received 5 prior doses of acellular pertussis vaccine.

Nebuliser systems for drug delivery in cystic fibrosis.

PubMed

Daniels, Tracey; Mills, Nicola; Whitaker, Paul

2013-04-30

Nebuliser systems are used to deliver medications to control the symptoms and the progression of lung disease in people with cystic fibrosis. Many types of nebuliser systems are available for use with various medications; however, there has been no previous systematic review which has evaluated these systems. To evaluate effectiveness, safety, burden of treatment and adherence to nebulised therapy using different nebuliser systems for people with cystic fibrosis. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches, handsearching of relevant journals and abstract books of conference proceedings. We searched the reference lists of each study for additional publications and approached the manufacturers of both nebuliser systems and nebulised medications for published and unpublished data. Date of the most recent search: 15 Oct 2012. Randomised controlled trials or quasi-randomised controlled trials comparing nebuliser systems including conventional nebulisers, vibrating mesh technology systems, adaptive aerosol delivery systems and ultrasonic nebuliser systems. Two authors independently assessed studies for inclusion. They also independently extracted data and assessed the risk of bias. A third author assessed studies where agreement could not be reached. The search identified 40 studies with 20 of these (1936 participants) included in the review. These studies compared the delivery of tobramycin, colistin, dornase alfa, hypertonic sodium chloride and other solutions through the different nebuliser systems. This review demonstrates variability in the delivery of medication depending on the nebuliser system used. Conventional nebuliser systems providing higher flows, higher respirable fractions and smaller particles decrease treatment time, increase deposition and may be preferred by people with CF, as compared to conventional nebuliser systems providing lower flows, lower respirable fractions and larger particles. Nebulisers using adaptive aerosol delivery or vibrating mesh technology reduce treatment time to a far greater extent. Deposition (as a percentage of priming dose) is greater than conventional with adaptive aerosol delivery. Vibrating mesh technology systems may give greater deposition than conventional when measuring sputum levels, but lower deposition when measuring serum levels or using gamma scintigraphy. The available data indicate that these newer systems are safe when used with an appropriate priming dose, which may be different to the priming dose used for conventional systems. There is an indication that adherence is maintained or improved with systems which use these newer technologies, but also that some nebuliser systems using vibrating mesh technology may be subject to increased failures. Clinicians should be aware of the variability in the performance of different nebuliser systems. Technologies such as adaptive aerosol delivery and vibrating mesh technology have advantages over conventional systems in terms of treatment time, deposition as a percentage of priming dose, patient preference and adherence. There is a need for long-term randomised controlled trials of these technologies to determine patient-focused outcomes (such as quality of life and burden of care), safe and effective dosing levels of medications and clinical outcomes (such as hospitalisations and need for antibiotics) and an economic evaluation of their use.

Influence of eye size and beam entry angle on dose to non-targeted tissues of the eye during stereotactic x-ray radiosurgery of AMD

NASA Astrophysics Data System (ADS)

Cantley, Justin L.; Hanlon, Justin; Chell, Erik; Lee, Choonsik; Smith, W. Clay; Bolch, Wesley E.

2013-10-01

Age-related macular degeneration is a leading cause of vision loss for the elderly population of industrialized nations. The IRay® Radiotherapy System, developed by Oraya® Therapeutics, Inc., is a stereotactic low-voltage irradiation system designed to treat the wet form of the disease. The IRay System uses three robotically positioned 100 kVp collimated photon beams to deliver an absorbed dose of up to 24 Gy to the macula. The present study uses the Monte Carlo radiation transport code MCNPX to assess absorbed dose to six non-targeted tissues within the eye—total lens, radiosensitive tissues of the lens, optic nerve, distal tip of the central retinal artery, non-targeted portion of the retina, and the ciliary body--all as a function of eye size and beam entry angle. The ocular axial length was ranged from 20 to 28 mm in 2 mm increments, with the polar entry angle of the delivery system varied from 18° to 34° in 2° increments. The resulting data showed insignificant variations in dose for all eye sizes. Slight variations in the dose to the optic nerve and the distal tip of the central retinal artery were noted as the polar beam angle changed. An increase in non-targeted retinal dose was noted as the entry angle increased, while the dose to the lens, sensitive volume of the lens, and ciliary body decreased as the treatment polar angle increased. Polar angles of 26° or greater resulted in no portion of the sensitive volume of the lens receiving an absorbed dose of 0.5 Gy or greater. All doses to non-targeted structures reported in this study were less than accepted thresholds for post-procedure complications.

A novel phantom model for mouse tumor dose assessment under MV beams

PubMed Central

Gossman, Michael S.; Das, Indra J.; Sharma, Subhash C.; Lopez, Jeffrey P.; Howard, Candace M.; Claudio, Pier P.

2011-01-01

Purpose In order to determine a mouse’s dose accurately and prior to engaging in live mouse radiobiological research, a tissue-equivalent tumor-bearing phantom mouse was constructed and bored to accommodate detectors. Methods and Materials Comparisons were made between four different types of radiation detectors, each inserted into the phantom mouse for radiation measurement under a 6 MV linear accelerator beam. Dose detection response from a diode, thermoluminescent dosimeters, metal-oxide semiconductor field-effect transistors were used and compared to that of a reference pin-point ionization chamber. Likewise, a computerized treatment planning system was also directly compared. Results Each detector system demonstrated results similar to the dose computed by the therapeutic treatment planning system, although some differences were noted. The average disagreement from a accelerator calibrated output dose prescription in the range of 200–400 cGy were −0.4% ± 0.5σ for the diode, −2.4% ± 2.6σ for the TLD, −2.9% ± 5.0σ for the MOSFET and +1.3% ± 1.4σ for the treatment planning system. Conclusions This phantom mouse design is unique, simple, reproducible and therefore recommended as a standard approach to dosimetry for radiobiological mouse studies by means of any of the detectors used in this study. We fully advocate for treatment planning modeling when possible prior to linac-based dose delivery. PMID:22048493

Assessing the use of school public address systems to deliver nutrition messages to children: Shape up Somerville--audio adventures.

PubMed

Folta, Sara C; Goldberg, Jeanne P; Economos, Christina; Bell, Rick; Landers, Stewart; Hyatt, Raymond

2006-11-01

Given the current childhood obesity epidemic, it is especially important to find effective ways to promote healthful foods to children. School public address (PA) systems represent an inexpensive and a replicable way of reaching children with health messages. To test the effectiveness of this channel, messages were created to promote 2 dried bean (legume) dishes that had been added to the school lunch menu. Six elementary schools were pair matched, and 1 school from each pair was randomly chosen to play the messages. The impact of the intervention on choice of the 2 new entrees was assessed. Results indicate that for all schools combined, choice was not significantly affected. However, compared to their matched control schools, choice was significantly higher in the school that received the highest dose of the intervention and was significantly lower in the school that received the lowest dose. Choice was not changed in the school that received an intermediate dose. These results suggest that PA systems show promise as an effective and appropriate communications channel but only in schools that are able to play messages frequently.

The effects of insecticide dose and herbivore density on tri-trophic effects of thiamethoxam in a system involving wheat, aphids, and lady beetles

USDA-ARS?s Scientific Manuscript database

We assess how herbivore density and insecticide dose affects the tri-trophic effects between thiamethoxam-treated wheat (Triticum sp.), Rhophalosiphum padi and the predatory Coleomegilla maculata DeGeer. In the first experiment 2nd and 4th instar C. maculata were fed aphids reared for 24 h on wheat ...

Non-Monotonic Dose Responses in Studies of Endocrine Disrupting Chemicals: Bisphenol A as a Case Study

PubMed Central

Vandenberg, Laura N.

2014-01-01

Non-monotonic dose response curves (NMDRCs) have been demonstrated for natural hormones and endocrine disrupting chemicals (EDCs) in a variety of biological systems including cultured cells, whole organ cultures, laboratory animals and human populations. The mechanisms responsible for these NMDRCs are well known, typically related to the interactions between the ligand (hormone or EDC) and a hormone receptor. Although there are hundreds of examples of NMDRCs in the EDC literature, there are claims that they are not ‘common enough’ to influence the use of high-to-low dose extrapolations in risk assessments. Here, we chose bisphenol A (BPA), a well-studied EDC, to assess the frequency of non-monotonic responses. Our results indicate that NMDRCs are common in the BPA literature, occurring in greater than 20% of all experiments and in at least one endpoint in more than 30% of all studies we examined. We also analyzed the types of endpoints that produce NMDRCs in vitro and factors related to study design that influence the ability to detect these kinds of responses. Taken together, these results provide strong evidence for NMDRCs in the EDC literature, specifically for BPA, and question the current risk assessment practice where ‘safe’ low doses are predicted from high dose exposures. PMID:24910584

Non-monotonic dose responses in studies of endocrine disrupting chemicals: bisphenol a as a case study.

PubMed

Vandenberg, Laura N

2014-05-01

Non-monotonic dose response curves (NMDRCs) have been demonstrated for natural hormones and endocrine disrupting chemicals (EDCs) in a variety of biological systems including cultured cells, whole organ cultures, laboratory animals and human populations. The mechanisms responsible for these NMDRCs are well known, typically related to the interactions between the ligand (hormone or EDC) and a hormone receptor. Although there are hundreds of examples of NMDRCs in the EDC literature, there are claims that they are not 'common enough' to influence the use of high-to-low dose extrapolations in risk assessments. Here, we chose bisphenol A (BPA), a well-studied EDC, to assess the frequency of non-monotonic responses. Our results indicate that NMDRCs are common in the BPA literature, occurring in greater than 20% of all experiments and in at least one endpoint in more than 30% of all studies we examined. We also analyzed the types of endpoints that produce NMDRCs in vitro and factors related to study design that influence the ability to detect these kinds of responses. Taken together, these results provide strong evidence for NMDRCs in the EDC literature, specifically for BPA, and question the current risk assessment practice where 'safe' low doses are predicted from high dose exposures.

SU-F-T-236: Comparison of Two IMRT/VMAT QA Systems Using Gamma Index Analysis

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

Dogan, N; Denissova, S

2016-06-15

Purpose: The goal of this study is to assess differences in the Gamma index pass rates when using two commercial QA systems and provide optimum Gamma index parameters for pre-treatment patient specific QA. Methods: Twenty-two VMAT cases that consisted of prostate, lung, head and neck, spine, brain and pancreas, were included in this study. The verification plans have been calculated using AcurosXB(V11) algorithm for different dose grids (1.5mm, 2.5mm, 3mm). The measurements were performed on TrueBeam(Varian) accelerator using both EPID(S1000) portal imager and ArcCheck(SunNuclearCorp) devices. Gamma index criteria variation of 3%/3mm, 2%/3mm, 2%/2mm and threshold (TH) doses of 5% tomore » 50% were used in analysis. Results: The differences in Gamma pass rates between two devices are not statistically significant for 3%/3mm, yielding pass rate higher than 95%. Increase of lower dose TH showed reduced pass rates for both devices. ArcCheck’s more pronounced effect can be attributed to higher contribution of lower dose region spread. As expected, tightening criteria to 2%/2mm (TH: 10%) decreased Gamma pass rates below 95%. Higher EPID (92%) pass rates compared to ArcCheck (86%) probably due to better spatial resolution. Portal Dosimetry results showed lower Gamma pass rates for composite plans compared to individual field pass rates. This may be due to the expansion in the analyzed region which includes pixels not included in the separate field analysis. Decreasing dose grid size from 2.5mm to 1.5mm did not show statistically significant (p<0.05) differences in Gamma pass rates for both QA devices. Conclusion: Overall, both system measurements agree well with calculated dose when using gamma index criteria of 3%/3mm for a variety of VMAT cases. Variability between two systems increases using different dose GRID, TH and tighter gamma criteria and must be carefully assessed prior to clinical use.« less

Dose commitments due to radioactive releases from nuclear power plant sites: Methodology and data base. Supplement 1

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

Baker, D.A.

1996-06-01

This manual describes a dose assessment system used to estimate the population or collective dose commitments received via both airborne and waterborne pathways by persons living within a 2- to 80-kilometer region of a commercial operating power reactor for a specific year of effluent releases. Computer programs, data files, and utility routines are included which can be used in conjunction with an IBM or compatible personal computer to produce the required dose commitments and their statistical distributions. In addition, maximum individual airborne and waterborne dose commitments are estimated and compared to 10 CFR Part 50, Appendix 1, design objectives. Thismore » supplement is the last report in the NUREG/CR-2850 series.« less

SU-F-T-323: A Post-Mastectomy Radiation Therapy Dose Distribution Study Using Nanodots and Films

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

Qian, X; Vaidya, K; Puckett, L

Purpose: In post-mastectomy radiation therapy (RT), skin dose must be accurately estimated to assess skin reactions such as erythema, desquamation and necrosis. Planning systems cannot always provide accurate dosimetry for target volumes distal to skin. Therefore, in-vivo dosimetry is necessary. A female anthropomorphic phantom was used with optically stimulated luminescence dosimeters (nanoDots) to measure dose to chest wall skin. In addition, EBT2 films was employed to measure dose to left lung and heart in post-mastectomy RT. Methods: Films and nanoDots were calibrated under full buildup conditions at 100cm SAD for 6MV photons. Five pieces of films were placed between slabsmore » of Rando phantom to assess dose to left lung and heart. Two layers of 0.5cm thick bolus were used to cover the whole left chest. Six pairs of nanoDots were placed at medical and lateral aspects on the bolus surface, between the 0.5cm bolus layers, and under the bolus. Three control nanoDots were placed on chest wall to quantify imaging dose. The phantom was CT scanned with all dosimeters in place, and treatment planning was performed with tangential fields (200cGy). All dosimeters were contoured on CT and dose was extracted. NanoDots were read using nanoDot reader and films were scanned using film scanner. The measured and calculated doses were tabulated. Results: Dose to 12 nanoDots were evaluated. Dose variance for surface nanoDots were +3.8%, +2.7%, −5% and −9.8%. Those at lateral positions, with greater beam obliquity had larger variance than the medial positions. A similar trend was observed for other nanoDots (Table1). Point doses from films for heart and the left lung were 112.7cGy and 108.7cGy, with +10.2% and +9.04% deviation from calculated values, respectively. Conclusion: Dosimetry provided by the advanced planning system was verified using NanoDots and films. Both nanoDots and films provided good estimation of dose distribution in post-mastectomy RT.« less

Predicting In Vivo Effect Levels for Repeat Dose Systemic Toxicity using Chemical, Biological, Kinetic and Study Covariates

EPA Science Inventory

In an effort to ensure chemical safety while reducing reliance on animal testing, USEPA and L’Oréal have collaborated to address a major challenge in chemical safety assessment using alternative approaches: the prediction of points-of-departure (POD) of systemic effects. Systemic...

10 CFR 963.16 - Postclosure suitability evaluation method.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 963.16 Energy DEPARTMENT OF ENERGY YUCCA MOUNTAIN SITE SUITABILITY GUIDELINES Site Suitability... assessment to evaluate the ability of the Yucca Mountain disposal system to limit radiological doses and... the performance of the Yucca Mountain disposal system using the method described in paragraph (b) of...

Effect of 2',3'-didehydro-3'-deoxythymidine in an in vitro hollow-fiber pharmacodynamic model system correlates with results of dose-ranging clinical studies.

PubMed Central

Bilello, J A; Bauer, G; Dudley, M N; Cole, G A; Drusano, G L

1994-01-01

We sought to validate an in vitro system which could predict the minimal effect dose of antiretroviral agents. Mixtures of uninfected CEM cells and CEM cells chronically infected with human immunodeficiency virus (HIV) type 1 MN were exposed to 2',3'-didehydro-3'-deoxythymidine (D4T) in vitro in a hollow-fiber model which simulates the plasma concentration-time profile of D4T in patients. Drug concentration was adjusted to simulate continuous intravenous infusion, or an intravenous bolus administered twice daily. The effect of the dosing regimen was measured with viral infectivity, p24 antigen, and reverse transcriptase or PCR for unintegrated HIV DNA. Dose deescalation studies on a twice-daily dosing schedule predicted a minimum effect dose of 0.5 mg/kg of body weight per day which correlated with the results of a clinical trial. Antiviral effect was demonstrated to be independent of schedule for every 12-h dosing versus continuous infusion. Finally, at or near the minimal effect dose, efficacy appeared to depend on the viral load. The ability of this in vitro pharmacodynamic model to assess the response of HIV-infected cells to different doses and schedules of antiviral agents may be useful in the design of optimal dosing regimens for clinical trials but requires validation with other types of antiretroviral agents. PMID:8092842

A systematic uncertainty analysis of an evaluative fate and exposure model.

PubMed

Hertwich, E G; McKone, T E; Pease, W S

2000-08-01

Multimedia fate and exposure models are widely used to regulate the release of toxic chemicals, to set cleanup standards for contaminated sites, and to evaluate emissions in life-cycle assessment. CalTOX, one of these models, is used to calculate the potential dose, an outcome that is combined with the toxicity of the chemical to determine the Human Toxicity Potential (HTP), used to aggregate and compare emissions. The comprehensive assessment of the uncertainty in the potential dose calculation in this article serves to provide the information necessary to evaluate the reliability of decisions based on the HTP A framework for uncertainty analysis in multimedia risk assessment is proposed and evaluated with four types of uncertainty. Parameter uncertainty is assessed through Monte Carlo analysis. The variability in landscape parameters is assessed through a comparison of potential dose calculations for different regions in the United States. Decision rule uncertainty is explored through a comparison of the HTP values under open and closed system boundaries. Model uncertainty is evaluated through two case studies, one using alternative formulations for calculating the plant concentration and the other testing the steady state assumption for wet deposition. This investigation shows that steady state conditions for the removal of chemicals from the atmosphere are not appropriate and result in an underestimate of the potential dose for 25% of the 336 chemicals evaluated.

Pharmacokinetics After Single Ascending Dose, Food Effect, and Safety of Sacubitril/Valsartan (LCZ696), an Angiotensin Receptor and Neprilysin Inhibitor, in Healthy Japanese Subjects.

PubMed

Akahori, Mizuki; Ayalasomayajula, Surya; Langenickel, Thomas; Pal, Parasar; Zhou, Wei; Sunkara, Gangadhar

2017-06-01

LCZ696 (sacubitril/valsartan) is a novel angiotensin receptor neprilysin inhibitor (ARNI) that has been developed for treatment of heart failure patients with reduced ejection fraction and approved in the US, Europe, and many other countries. This randomized, placebo-controlled study was conducted in healthy Japanese male subjects (N = 50) to assess the pharmacokinetics and safety of single ascending oral doses (20-600 mg) of LCZ696. Food effect was also evaluated following administration of 200 mg dose. Plasma and urine samples from 40 subjects receiving LCZ696 were collected to assess pharmacokinetics of LCZ696 analytes (sacubitril, sacubitrilat, and valsartan). Following single oral dose administration of LCZ696, sacubitril and valsartan rapidly appeared in systemic circulation with a dose-linear increase in the exposure to the LCZ696 analytes. Of the administered dose, approximately 0.85 %, 54.0 %, and 8.19 % of sacubitril, sacubitrilat, and valsartan, respectively, were recovered in urine. Food reduced AUC of sacubitril, sacubitrilat, and valsartan by 21, 8, and 40 %, respectively, and C max by 72, 27, and 51 %, respectively. Single oral doses of up to 600 mg of LCZ696 were safe and generally well tolerated in healthy Japanese male subjects.

Statistical methods for biodosimetry in the presence of both Berkson and classical measurement error

NASA Astrophysics Data System (ADS)

Miller, Austin

In radiation epidemiology, the true dose received by those exposed cannot be assessed directly. Physical dosimetry uses a deterministic function of the source term, distance and shielding to estimate dose. For the atomic bomb survivors, the physical dosimetry system is well established. The classical measurement errors plaguing the location and shielding inputs to the physical dosimetry system are well known. Adjusting for the associated biases requires an estimate for the classical measurement error variance, for which no data-driven estimate exists. In this case, an instrumental variable solution is the most viable option to overcome the classical measurement error indeterminacy. Biological indicators of dose may serve as instrumental variables. Specification of the biodosimeter dose-response model requires identification of the radiosensitivity variables, for which we develop statistical definitions and variables. More recently, researchers have recognized Berkson error in the dose estimates, introduced by averaging assumptions for many components in the physical dosimetry system. We show that Berkson error induces a bias in the instrumental variable estimate of the dose-response coefficient, and then address the estimation problem. This model is specified by developing an instrumental variable mixed measurement error likelihood function, which is then maximized using a Monte Carlo EM Algorithm. These methods produce dose estimates that incorporate information from both physical and biological indicators of dose, as well as the first instrumental variable based data-driven estimate for the classical measurement error variance.

A study on the indirect urea dosing method in the Selective Catalytic Reduction system

NASA Astrophysics Data System (ADS)

Brzeżański, M.; Sala, R.

2016-09-01

This article presents the results of studies on concept solution of dosing urea in a gas phase in a selective catalytic reduction system. The idea of the concept was to heat-up and evaporate the water urea solution before introducing it into the exhaust gas stream. The aim was to enhance the processes of urea converting into ammonia, what is the target reductant for nitrogen oxides treatment. The study was conducted on a medium-duty Euro 5 diesel engine with exhaust line consisting of DOC catalyst, DPF filter and an SCR system with a changeable setup allowing to dose the urea in liquid phase (regular solution) and to dose it in a gas phase (concept solution). The main criteria was to assess the effect of physical state of urea dosed on the NOx conversion ratio in the SCR catalyst. In order to compare both urea dosing methods a special test procedure was developed which consisted of six test steps covering a wide temperature range of exhaust gas generated at steady state engine operation condition. Tests were conducted for different urea dosing quantities defined by the a equivalence ratio. Based on the obtained results, a remarkable improvement in NOx reduction was found for gas urea application in comparison to the standard liquid urea dosing. Measured results indicate a high potential to increase an efficiency of the SCR catalyst by using a gas phase urea and provide the basis for further scientific research on this type of concept.

Space radiation risks to the central nervous system

NASA Astrophysics Data System (ADS)

Cucinotta, Francis A.; Alp, Murat; Sulzman, Frank M.; Wang, Minli

2014-07-01

Central nervous system (CNS) risks which include during space missions and lifetime risks due to space radiation exposure are of concern for long-term exploration missions to Mars or other destinations. Possible CNS risks during a mission are altered cognitive function, including detriments in short-term memory, reduced motor function, and behavioral changes, which may affect performance and human health. The late CNS risks are possible neurological disorders such as premature aging, and Alzheimer's disease (AD) or other dementia. Radiation safety requirements are intended to prevent all clinically significant acute risks. However the definition of clinically significant CNS risks and their dependences on dose, dose-rate and radiation quality is poorly understood at this time. For late CNS effects such as increased risk of AD, the occurrence of the disease is fatal with mean time from diagnosis of early stage AD to death about 8 years. Therefore if AD risk or other late CNS risks from space radiation occur at mission relevant doses, they would naturally be included in the overall acceptable risk of exposure induced death (REID) probability for space missions. Important progress has been made in understanding CNS risks due to space radiation exposure, however in general the doses used in experimental studies have been much higher than the annual galactic cosmic ray (GCR) dose (∼0.1 Gy/y at solar maximum and ∼0.2 Gy/y at solar minimum with less than 50% from HZE particles). In this report we summarize recent space radiobiology studies of CNS effects from particle accelerators simulating space radiation using experimental models, and make a critical assessment of their relevance relative to doses and dose-rates to be incurred on a Mars mission. Prospects for understanding dose, dose-rate and radiation quality dependencies of CNS effects and extrapolation to human risk assessments are described.

Uncertainty propagation for SPECT/CT-based renal dosimetry in 177Lu peptide receptor radionuclide therapy

NASA Astrophysics Data System (ADS)

Gustafsson, Johan; Brolin, Gustav; Cox, Maurice; Ljungberg, Michael; Johansson, Lena; Sjögreen Gleisner, Katarina

2015-11-01

A computer model of a patient-specific clinical 177Lu-DOTATATE therapy dosimetry system is constructed and used for investigating the variability of renal absorbed dose and biologically effective dose (BED) estimates. As patient models, three anthropomorphic computer phantoms coupled to a pharmacokinetic model of 177Lu-DOTATATE are used. Aspects included in the dosimetry-process model are the gamma-camera calibration via measurement of the system sensitivity, selection of imaging time points, generation of mass-density maps from CT, SPECT imaging, volume-of-interest delineation, calculation of absorbed-dose rate via a combination of local energy deposition for electrons and Monte Carlo simulations of photons, curve fitting and integration to absorbed dose and BED. By introducing variabilities in these steps the combined uncertainty in the output quantity is determined. The importance of different sources of uncertainty is assessed by observing the decrease in standard deviation when removing a particular source. The obtained absorbed dose and BED standard deviations are approximately 6% and slightly higher if considering the root mean square error. The most important sources of variability are the compensation for partial volume effects via a recovery coefficient and the gamma-camera calibration via the system sensitivity.

Human Papillomavirus Vaccine Coverage and Prevalence of Missed Opportunities for Vaccination in an Integrated Healthcare System.

PubMed

Irving, Stephanie A; Groom, Holly C; Stokley, Shannon; McNeil, Michael M; Gee, Julianne; Smith, Ning; Naleway, Allison L

2018-03-01

Human papillomavirus (HPV) vaccination has been recommended in the United States for female and male adolescents since 2006 and 2011, respectively. Coverage rates are lower than those for other adolescent vaccines. The objective of this study was to evaluate an assessment and feedback intervention designed to increase HPV vaccination coverage and quantify missed opportunities for HPV vaccine initiation at preventive care visits. We examined changes in HPV vaccination coverage and missed opportunities within the adolescent (11-17 years) population at 9 Oregon-based Kaiser Permanente Northwest outpatient clinics after an assessment and feedback intervention. Quarterly coverage rates were calculated for the adolescent populations at the clinics, according to age group (11-12 and 13-17 years), sex, and department (Pediatrics and Family Medicine). Comparison coverage assessments were calculated at 3 nonintervention (control) clinics. Missed opportunities for HPV vaccine initiation, defined as preventive care visits in which a patient eligible for HPV dose 1 remained unvaccinated, were examined according to sex and age group. An average of 29,021 adolescents were included in coverage assessments. Before the intervention, 1-dose and 3-dose quarterly coverage rates were increasing at intervention as well as at control clinics in both age groups. Postimplementation quarterly trends in 1-dose or 3-dose coverage did not differ significantly between intervention and control clinics for either age group. One-dose coverage rates among adolescents with Pediatrics providers were significantly higher than those with Family Medicine providers (56% vs 41% for 11- to 12-year-old and 82% vs 69% for 13- to 17-year-old girls; 55% vs 40% for 11- to 12-year-old and 78% vs 62% for 13- to 17-year-old boys). No significant differences in HPV vaccine coverage were identified at intervention clinics. However, coverage rates were increasing before the start of the intervention and might have been influenced by ongoing health system best practices. HPV vaccine coverage rates varied significantly according to department, which could allow for targeted improvement opportunities. Copyright © 2017 Academic Pediatric Association. All rights reserved.

SU-G-IeP3-12: Preliminary Report On the Experience of Patient Radiation Dose Monitoring and Tracking Systems; PEMNET, Radimetrics and DoseWatch

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

Lin, P; Corwin, F; Ghita, M

Purpose: Three patient radiation dose monitoring and tracking (PRDMT) systems have been in operation at this institution for the past 6 months. There are useful information that should be disseminated to those who are considering installation of PRDMT programs. In addition, there are “problems” uncovered in the process of estimating fluoroscopic “peak” skin dose (PSD), especially, for those patients who received interventional angiographic studies and in conjunction with surgical procedures. Methods: Upon exporting the PRDMT data to Microsoft Excel program, the peak skin dose can be estimated by applying various correction factors including; attenuation due to the tabletop and examinationmore » mattress, table height, tabletop translation, backscatter, etc. A procedure was established to screen and divide the PRDMT reported radiation dose and estimated PSD to three different levels of threshold to assess the potential skin injuries, to assist patient follow-up, risk management and provide radiation dosimetry information in case of “Sentinel Event”. Results: The Radiation Dose Structured Report (RDSR) was found to be the prerequisite for the PRDMT systems to work seamlessly. And, the geometrical parameters (gantry and table orientation) displayed by the equipment are not necessarily implemented in the “patient centric” manner which could result in a large error in the PSD estimation. Since, the PRDMT systems obtain their pertinent data from the DICOM tags including the polarity (+ and − signs), the geometrical parameters need to be verified. Conclusion: PRDMT systems provide a more accurate PSD estimation than previously possible as the air-kerma-area dose meter become widely implemented. However, care should be exercised to correctly apply the geometrical parameters in estimating the patient dose. In addition, further refinement is necessary for these software programs to account for all geometrical parameters such as the tabletop translation in the z-direction in particular.« less

Comparison of dose response functions for EBT3 model GafChromic™ film dosimetry system.

PubMed

Aldelaijan, Saad; Devic, Slobodan

2018-05-01

Different dose response functions of EBT3 model GafChromic™ film dosimetry system have been compared in terms of sensitivity as well as uncertainty vs. error analysis. We also made an assessment of the necessity of scanning film pieces before and after irradiation. Pieces of EBT3 film model were irradiated to different dose values in Solid Water (SW) phantom. Based on images scanned in both reflection and transmission mode before and after irradiation, twelve different response functions were calculated. For every response function, a reference radiochromic film dosimetry system was established by generating calibration curve and by performing the error vs. uncertainty analysis. Response functions using pixel values from the green channel demonstrated the highest sensitivity in both transmission and reflection mode. All functions were successfully fitted with rational functional form, and provided an overall one-sigma uncertainty of better than 2% for doses above 2 Gy. Use of pre-scanned images to calculate response functions resulted in negligible improvement in dose measurement accuracy. Although reflection scanning mode provides higher sensitivity and could lead to a more widespread use of radiochromic film dosimetry, it has fairly limited dose range and slightly increased uncertainty when compared to transmission scan based response functions. Double-scanning technique, either in transmission or reflection mode, shows negligible improvement in dose accuracy as well as a negligible increase in dose uncertainty. Normalized pixel value of the images scanned in transmission mode shows linear response in a dose range of up to 11 Gy. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Radiation dose and magnification in pelvic X-ray: EOS™ imaging system versus plain radiographs.

PubMed

Chiron, P; Demoulin, L; Wytrykowski, K; Cavaignac, E; Reina, N; Murgier, J

2017-12-01

In plain pelvic X-ray, magnification makes measurement unreliable. The EOS™ (EOS Imaging, Paris France) imaging system is reputed to reproduce patient anatomy exactly, with a lower radiation dose. This, however, has not been assessed according to patient weight, although both magnification and irradiation are known to vary with weight. We therefore conducted a prospective comparative study, to compare: (1) image magnification and (2) radiation dose between the EOS imaging system and plain X-ray. The EOS imaging system reproduces patient anatomy exactly, regardless of weight, unlike plain X-ray. A single-center comparative study of plain pelvic X-ray and 2D EOS radiography was performed in 183 patients: 186 arthroplasties; 104 male, 81 female; mean age 61.3±13.7years (range, 24-87years). Magnification and radiation dose (dose-area product [DAP]) were compared between the two systems in 186 hips in patients with a mean body-mass index (BMI) of 27.1±5.3kg/m 2 (range, 17.6-42.3kg/m 2 ), including 7 with morbid obesity. Mean magnification was zero using the EOS system, regardless of patient weight, compared to 1.15±0.05 (range, 1-1.32) on plain X-ray (P<10 -5 ). In patients with BMI<25, mean magnification on plain X-ray was 1.15±0.05 (range, 1-1.25) and, in patients with morbid obesity, 1.22±0.06 (range, 1.18-1.32). The mean radiation dose was 8.19±2.63dGy/cm 2 (range, 1.77-14.24) with the EOS system, versus 19.38±12.37dGy/cm 2 (range, 4.77-81.75) with plain X-ray (P<10 -4 ). For BMI >40, mean radiation dose was 9.36±2.57dGy/cm 2 (range, 7.4-14.2) with the EOS system, versus 44.76±22.21 (range, 25.2-81.7) with plain X-ray. Radiation dose increased by 0.20dGy with each extra BMI point for the EOS system, versus 0.74dGy for plain X-ray. Magnification did not vary with patient weight using the EOS system, unlike plain X-ray, and radiation dose was 2.5-fold lower. 3, prospective case-control study. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Verification of intensity modulated radiation therapy beams using a tissue equivalent plastic scintillator dosimetry system

NASA Astrophysics Data System (ADS)

Petric, Martin Peter

This thesis describes the development and implementation of a novel method for the dosimetric verification of intensity modulated radiation therapy (IMRT) fields with several advantages over current techniques. Through the use of a tissue equivalent plastic scintillator sheet viewed by a charge-coupled device (CCD) camera, this method provides a truly tissue equivalent dosimetry system capable of efficiently and accurately performing field-by-field verification of IMRT plans. This work was motivated by an initial study comparing two IMRT treatment planning systems. The clinical functionality of BrainLAB's BrainSCAN and Varian's Helios IMRT treatment planning systems were compared in terms of implementation and commissioning, dose optimization, and plan assessment. Implementation and commissioning revealed differences in the beam data required to characterize the beam prior to use with the BrainSCAN system requiring higher resolution data compared to Helios. This difference was found to impact on the ability of the systems to accurately calculate dose for highly modulated fields, with BrainSCAN being more successful than Helios. The dose optimization and plan assessment comparisons revealed that while both systems use considerably different optimization algorithms and user-control interfaces, they are both capable of producing substantially equivalent dose plans. The extensive use of dosimetric verification techniques in the IMRT treatment planning comparison study motivated the development and implementation of a novel IMRT dosimetric verification system. The system consists of a water-filled phantom with a tissue equivalent plastic scintillator sheet built into the top surface. Scintillation light is reflected by a plastic mirror within the phantom towards a viewing window where it is captured using a CCD camera. Optical photon spread is removed using a micro-louvre optical collimator and by deconvolving a glare kernel from the raw images. Characterization of this new dosimetric verification system indicates excellent dose response and spatial linearity, high spatial resolution, and good signal uniformity and reproducibility. Dosimetric results from square fields, dynamic wedged fields, and a 7-field head and neck IMRT treatment plan indicate good agreement with film dosimetry distributions. Efficiency analysis of the system reveals a 50% reduction in time requirements for field-by-field verification of a 7-field IMRT treatment plan compared to film dosimetry.

Performance assessment of the BEBIG MultiSource® high dose rate brachytherapy treatment unit

NASA Astrophysics Data System (ADS)

Palmer, Antony; Mzenda, Bongile

2009-12-01

A comprehensive system characterisation was performed of the Eckert & Ziegler BEBIG GmbH MultiSource® High Dose Rate (HDR) brachytherapy treatment unit with an 192Ir source. The unit is relatively new to the UK market, with the first installation in the country having been made in the summer of 2009. A detailed commissioning programme was devised and is reported including checks of the fundamental parameters of source positioning, dwell timing, transit doses and absolute dosimetry of the source. Well chamber measurements, autoradiography and video camera analysis techniques were all employed. The absolute dosimetry was verified by the National Physical Laboratory, UK, and compared to a measurement based on a calibration from PTB, Germany, and the supplied source certificate, as well as an independent assessment by a visiting UK centre. The use of the 'Krieger' dosimetry phantom has also been evaluated. Users of the BEBIG HDR system should take care to avoid any significant bend in the transfer tube, as this will lead to positioning errors of the source, of up to 1.0 mm for slight bends, 2.0 mm for moderate bends and 5.0 mm for extreme curvature (depending on applicators and transfer tube used) for the situations reported in this study. The reason for these errors and the potential clinical impact are discussed. Users should also note the methodology employed by the system for correction of transit doses, and that no correction is made for the initial and final transit doses. The results of this investigation found that the uncorrected transit doses lead to small errors in the delivered dose at the first dwell position, of up to 2.5 cGy at 2 cm (5.6 cGy at 1 cm) from a 10 Ci source, but the transit dose correction for other dwells was accurate within 0.2 cGy. The unit has been mechanically reliable, and source positioning accuracy and dwell timing have been reproducible, with overall performance similar to other existing HDR equipment. The unit is capable of high quality brachytherapy treatment delivery, taking the above factors into account.

Estimating systemic exposure to ethinyl estradiol from an oral contraceptive.

PubMed

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

2015-05-01

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

A 13-week dermal repeat-dose neurotoxicity study of hydrodesulfurized kerosene in rats.

PubMed

Breglia, Rudolph; Bui, Quang; Burnett, Donald; Koschier, Francis; Lapadula, Elizabeth; Podhasky, Paula; Schreiner, Ceinwen; White, Russell

2014-01-01

A 13-week dermal repeat-dose toxicity study was conducted with hydrodesulfurized (HDS) kerosene, a test material that also met the commercial specifications for aviation turbine fuel (jet A). The objectives were to assess the potential for target organ toxicity and neurotoxicity. The HDS kerosene was applied to the shaved backs of Sprague-Dawley CD rats, 12/sex/group, 6 h/d, 5 d/wk in doses of 0 (vehicle control), 165 mg/kg (20% HDS kerosene), 330 mg/kg (40% HDS kerosene), or 495 mg/kg (60% HDS kerosene). Additional rats (12/sex) from the control and the high-dose groups were held without treatment for 4 weeks to assess recovery. Standard parameters of toxicity were investigated during the in-life phase. At necropsy, organs were weighed and selected tissues were processed for microscopic evaluation. Neurobehavioral evaluations included tests of motor activity and functional observations that were conducted pretest, at intervals during the exposure period and after recovery. No test substance-related effects on mortality, clinical observations (except dermal irritation), body weight, or clinical chemistry values were observed. A dose-related increase in skin irritation, confirmed histologically as minimal, was evident at the dosing site. The only statistically significant change considered potentially treatment related was an increase in the neutrophil count in females at 13 weeks. No test article-related effects were observed in the neurobehavioral assessments or gross or microscopic findings in the peripheral or central nervous system tissues in any of the dose groups. Excluding skin irritation, the no observed adverse effect level value for all effects was considered 495 mg/kg/d.

Poster – 13: Evaluation of an in-house CCD camera film dosimetry imaging system for small field deliveries

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

Lalonde, Michel; Alexander, Kevin; Olding, Tim

Purpose: Radiochromic film dosimetry is a standard technique used in clinics to verify modern conformal radiation therapy delivery, and sometimes in research to validate other dosimeters. We are using film as a standard for comparison as we improve high-resolution three-dimensional gel systems for small field dosimetry; however, precise film dosimetry can be technically challenging. We report here measurements for fractionated stereotactic radiation therapy (FSRT) delivered using volumetric modulated arc therapy (VMAT) to investigate the accuracy and reproducibility of film measurements with a novel in-house readout system. We show that radiochromic film can accurately and reproducibly validate FSRT deliveries and alsomore » benchmark our gel dosimetry work. Methods: VMAT FSRT plans for metastases alone (PTV{sub MET}) and whole brain plus metastases (WB+PTV{sub MET}) were delivered onto a multi-configurational phantom with a sheet of EBT3 Gafchromic film inserted mid-plane. A dose of 400 cGy was prescribed to 4 small PTV{sub MET} structures in the phantom, while a WB structure was prescribed a dose of 200 cGy in the WB+PTV{sub MET} iterations. Doses generated from film readout with our in-house system were compared to treatment planned doses. Each delivery was repeated multiple times to assess reproducibility. Results and Conclusions: The reproducibility of film optical density readout was excellent throughout all experiments. Doses measured from the film agreed well with plans for the WB+PTV{sub MET} delivery. But, film doses for PTV{sub MET} only deliveries were significantly below planned doses. This discrepancy is due to stray/scattered light perturbations in our system during readout. Corrections schemes will be presented.« less

Effectiveness of one dose of mumps vaccine against clinically diagnosed mumps in Guangzhou, China, 2006–2012

PubMed Central

Fu, Chuanxi; Xu, Jianxiong; Cai, Yuanjun; He, Qing; Zhang, Chunhuan; Chen, Jian; Dong, Zhiqiang; Hu, Wensui; Wang, Hui; Zhu, Wei; Wang, Ming

2013-01-01

Although mumps-containing vaccines were introduced in China in 1990s, mumps continues to be a public health concern due to the lack of decline in reported mumps cases. To assess the mumps vaccine effectiveness (VE) in Guangzhou, China, we performed a 1:1 matched case-control study. Among children in Guangzhou aged 8 mo to 12 y during 2006 to 2012, we matched one healthy child to each child with clinically diagnosed mumps. Cases with clinically diagnosed mumps were identified from surveillance sites system and healthy controls were randomly sampled from the Children’s Expanded Programmed Immunization Administrative Computerized System in Guangzhou. Conditional logistic regression was used to calculate VE. We analyzed the vaccination information for 1983 mumps case subjects and 1983 matched controls and found that the overall VE for 1 dose of mumps vaccine, irrespective of the manufacture, was 53.6% (95% confidence interval [CI], 41.0–63.5%) to children aged 8 mo to 12 y. This post-marketing mumps VE study found that immunization with one dose of the mumps vaccine confers partial protection against mumps disease. Evaluation of the VE for the current mumps vaccines, introduction of a second dose of mumps vaccine, and assessment of modifications to childhood immunization schedules is essential. PMID:23955378

Effectiveness of one dose of mumps vaccine against clinically diagnosed mumps in Guangzhou, China, 2006-2012.

PubMed

Fu, Chuanxi; Xu, Jianxiong; Cai, Yuanjun; He, Qing; Zhang, Chunhuan; Chen, Jian; Dong, Zhiqiang; Hu, Wensui; Wang, Hui; Zhu, Wei; Wang, Ming

2013-12-01

Although mumps-containing vaccines were introduced in China in 1990s, mumps continues to be a public health concern due to the lack of decline in reported mumps cases. To assess the mumps vaccine effectiveness (VE) in Guangzhou, China, we performed a 1:1 matched case-control study. Among children in Guangzhou aged 8 mo to 12 y during 2006 to 2012, we matched one healthy child to each child with clinically diagnosed mumps. Cases with clinically diagnosed mumps were identified from surveillance sites system and healthy controls were randomly sampled from the Children's Expanded Programmed Immunization Administrative Computerized System in Guangzhou. Conditional logistic regression was used to calculate VE. We analyzed the vaccination information for 1983 mumps case subjects and 1983 matched controls and found that the overall VE for 1 dose of mumps vaccine, irrespective of the manufacture, was 53.6% (95% confidence interval [CI], 41.0-63.5%) to children aged 8 mo to 12 y. This post-marketing mumps VE study found that immunization with one dose of the mumps vaccine confers partial protection against mumps disease. Evaluation of the VE for the current mumps vaccines, introduction of a second dose of mumps vaccine, and assessment of modifications to childhood immunization schedules is essential.

Design of a transdermal delivery system for aspirin as an antithrombotic drug.

PubMed

Ammar, H O; Ghorab, M; El-Nahhas, S A; Kamel, R

2006-12-11

Aspirin has become the gold standard to which newer antiplatelet drugs are compared for reducing risks of cardiovascular diseases, while keeping low cost. Oral aspirin has a repertoire of gastrointestinal side effects even at low doses and requires high frequent dosing because it undergoes extensive presystemic metabolism. Transdermal delivery offers an alternative route that bypasses the gut and may be more convenient and safer for aspirin delivery especially during long-term use. This study comprised formulation of aspirin in different topical bases. Release studies revealed that hydrocarbon gel allowed highest drug release. In vitro permeation studies revealed high drug permeation from hydrocarbon gel. Several chemical penetration enhancers were monitored for augmenting the permeation from this base. Combination of propylene glycol and alcohol showed maximum enhancing effect and, hence, was selected for biological investigation. The biological performance of the selected formulation was assessed by measuring the inhibition of platelet aggregation relevant to different dosage regimens aiming to minimize both drug dose and frequency of application. The results demonstrated the feasibility of successfully influencing platelet function and revealed that the drug therapeutic efficacy in transdermal delivery system is dose independent. Biological performance was re-assessed after storage and the results revealed stability and persistent therapeutic efficacy.

STABILITY OF THE NEUTRON DOSE DETERMINATION ALGORITHM FOR PERSONAL NEUTRON DOSEMETERS AT DIFFERENT RADON GAS EXPOSURES.

PubMed

Mayer, Sabine; Boschung, Markus; Butterweck, Gernot; Assenmacher, Frank; Hohmann, Eike

2016-09-01

Since 2008 the Paul Scherrer Institute (PSI) has been using a microscope-based automatic scanning system for assessing personal neutron doses with a dosemeter based on PADC. This scanning system, known as TASLImage, includes a comprehensive characterisation of tracks. The distributions of several specific track characteristics such as size, shape and optical density are compared with a reference set to discriminate tracks of alpha particles and non-track background. Due to the dosemeter design at PSI, it is anticipated that radon should not significantly contribute to the creation of additional tracks in the PADC detector. The present study tests the stability of the neutron dose determination algorithm of the personal neutron dosemeter system in operation at PSI at different radon gas exposures. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Entrance surface dose distribution and organ dose assessment for cone-beam computed tomography using measurements and Monte Carlo simulations with voxel phantoms

NASA Astrophysics Data System (ADS)

Baptista, M.; Di Maria, S.; Vieira, S.; Vaz, P.

2017-11-01

Cone-Beam Computed Tomography (CBCT) enables high-resolution volumetric scanning of the bone and soft tissue anatomy under investigation at the treatment accelerator. This technique is extensively used in Image Guided Radiation Therapy (IGRT) for pre-treatment verification of patient position and target volume localization. When employed daily and several times per patient, CBCT imaging may lead to high cumulative imaging doses to the healthy tissues surrounding the exposed organs. This work aims at (1) evaluating the dose distribution during a CBCT scan and (2) calculating the organ doses involved in this image guiding procedure for clinically available scanning protocols. Both Monte Carlo (MC) simulations and measurements were performed. To model and simulate the kV imaging system mounted on a linear accelerator (Edge™, Varian Medical Systems) the state-of-the-art MC radiation transport program MCNPX 2.7.0 was used. In order to validate the simulation results, measurements of the Computed Tomography Dose Index (CTDI) were performed, using standard PMMA head and body phantoms, with 150 mm length and a standard pencil ionizing chamber (IC) 100 mm long. Measurements for head and pelvis scanning protocols, usually adopted in clinical environment were acquired, using two acquisition modes (full-fan and half fan). To calculate the organ doses, the implemented MC model of the CBCT scanner together with a male voxel phantom ("Golem") was used. The good agreement between the MCNPX simulations and the CTDIw measurements (differences up to 17%) presented in this work reveals that the CBCT MC model was successfully validated, taking into account the several uncertainties. The adequacy of the computational model to map dose distributions during a CBCT scan is discussed in order to identify ways to reduce the total CBCT imaging dose. The organ dose assessment highlights the need to evaluate the therapeutic and the CBCT imaging doses, in a more balanced approach, and the importance of improving awareness regarding the increased risk, arising from repeated exposures.

A computational method for estimating the dosimetric effect of intra-fraction motion on step-and-shoot IMRT and compensator plans

NASA Astrophysics Data System (ADS)

Waghorn, Ben J.; Shah, Amish P.; Ngwa, Wilfred; Meeks, Sanford L.; Moore, Joseph A.; Siebers, Jeffrey V.; Langen, Katja M.

2010-07-01

Intra-fraction organ motion during intensity-modulated radiation therapy (IMRT) treatment can cause differences between the planned and the delivered dose distribution. To investigate the extent of these dosimetric changes, a computational model was developed and validated. The computational method allows for calculation of the rigid motion perturbed three-dimensional dose distribution in the CT volume and therefore a dose volume histogram-based assessment of the dosimetric impact of intra-fraction motion on a rigidly moving body. The method was developed and validated for both step-and-shoot IMRT and solid compensator IMRT treatment plans. For each segment (or beam), fluence maps were exported from the treatment planning system. Fluence maps were shifted according to the target position deduced from a motion track. These shifted, motion-encoded fluence maps were then re-imported into the treatment planning system and were used to calculate the motion-encoded dose distribution. To validate the accuracy of the motion-encoded dose distribution the treatment plan was delivered to a moving cylindrical phantom using a programmed four-dimensional motion phantom. Extended dose response (EDR-2) film was used to measure a planar dose distribution for comparison with the calculated motion-encoded distribution using a gamma index analysis (3% dose difference, 3 mm distance-to-agreement). A series of motion tracks incorporating both inter-beam step-function shifts and continuous sinusoidal motion were tested. The method was shown to accurately predict the film's dose distribution for all of the tested motion tracks, both for the step-and-shoot IMRT and compensator plans. The average gamma analysis pass rate for the measured dose distribution with respect to the calculated motion-encoded distribution was 98.3 ± 0.7%. For static delivery the average film-to-calculation pass rate was 98.7 ± 0.2%. In summary, a computational technique has been developed to calculate the dosimetric effect of intra-fraction motion. This technique has the potential to evaluate a given plan's sensitivity to anticipated organ motion. With knowledge of the organ's motion it can also be used as a tool to assess the impact of measured intra-fraction motion after dose delivery.

Using the Monte Carlo method for assessing the tissue and organ doses of patients in dental radiography

NASA Astrophysics Data System (ADS)

Makarevich, K. O.; Minenko, V. F.; Verenich, K. A.; Kuten, S. A.

2016-05-01

This work is dedicated to modeling dental radiographic examinations to assess the absorbed doses of patients and effective doses. For simulating X-ray spectra, the TASMIP empirical model is used. Doses are assessed on the basis of the Monte Carlo method by using MCNP code for voxel phantoms of ICRP. The results of the assessment of doses to individual organs and effective doses for different types of dental examinations and features of X-ray tube are presented.

IRIS Toxicological Review of Propionaldehyde (External Review Draft)

EPA Science Inventory

EPA conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of propionaldehyde that will appear on the Integrated Risk Information System (IRIS) database.

IMRT head and neck treatment planning with a commercially available Monte Carlo based planning system

NASA Astrophysics Data System (ADS)

Boudreau, C.; Heath, E.; Seuntjens, J.; Ballivy, O.; Parker, W.

2005-03-01

The PEREGRINE Monte Carlo dose-calculation system (North American Scientific, Cranberry Township, PA) is the first commercially available Monte Carlo dose-calculation code intended specifically for intensity modulated radiotherapy (IMRT) treatment planning and quality assurance. In order to assess the impact of Monte Carlo based dose calculations for IMRT clinical cases, dose distributions for 11 head and neck patients were evaluated using both PEREGRINE and the CORVUS (North American Scientific, Cranberry Township, PA) finite size pencil beam (FSPB) algorithm with equivalent path-length (EPL) inhomogeneity correction. For the target volumes, PEREGRINE calculations predict, on average, a less than 2% difference in the calculated mean and maximum doses to the gross tumour volume (GTV) and clinical target volume (CTV). An average 16% ± 4% and 12% ± 2% reduction in the volume covered by the prescription isodose line was observed for the GTV and CTV, respectively. Overall, no significant differences were noted in the doses to the mandible and spinal cord. For the parotid glands, PEREGRINE predicted a 6% ± 1% increase in the volume of tissue receiving a dose greater than 25 Gy and an increase of 4% ± 1% in the mean dose. Similar results were noted for the brainstem where PEREGRINE predicted a 6% ± 2% increase in the mean dose. The observed differences between the PEREGRINE and CORVUS calculated dose distributions are attributed to secondary electron fluence perturbations, which are not modelled by the EPL correction, issues of organ outlining, particularly in the vicinity of air cavities, and differences in dose reporting (dose to water versus dose to tissue type).

Intussusception after monovalent rotavirus vaccine-United States, Vaccine Adverse Event Reporting System (VAERS), 2008-2014.

PubMed

Haber, Penina; Parashar, Umesh D; Haber, Michael; DeStefano, Frank

2015-09-11

In 2006 and 2008, two new rotavirus vaccines (RotaTeq [RV5] and Rotarix [RV1]) were introduced in the United States. US data on intussusception have been mostly related to RV5, with limited data on RV1. We assessed intussusception events following RV1 reported to the Vaccine Adverse Event Reporting System (VAERS), a US national passive surveillance system, during February 2008-December 2014. We conducted a self-controlled risk interval analysis using Poisson regression to estimate the daily reporting ratio (DRR) of intussusception after the first 2 doses of RV1 comparing average daily reports 3-6 versus 0-2 days after vaccination. We calculated the excess risk of intussusception per 100,000 vaccinations based on DRRs and background rates of intussusception. Sensitivity analyses were conducted to assess effects of differential reporting completeness and inaccuracy of baseline rates. VAERS received 108 confirmed insusceptible reports after RV1. A significant clustering was observed on days 3-8 after does1 (p=0.001) and days 2-7 after dose 2 (p=0.001). The DRR comparing the 3-6 day and the 0-2 day periods after RV1 dose 1 was 7.5 (95% CI=2.3, 24.6), translating to an excess risk of 1.6 (95% CI=0.3, 5.8) per 100,000 vaccinations. The DRR was elevated but not significant after dose 2 (2.4 [95% CI=0.8,7.5]). The excess risk ranged from 1.2 to 2.8 per 100,000 in sensitivity analysis. We observed a significant increased risk of intussusception 3-6 days after dose 1 of RV1. The estimated small number of intussusception cases attributable to RV1 is outweighed by the benefits of rotavirus vaccination. Published by Elsevier Ltd.

Dedicated Cone-Beam CT System for Extremity Imaging

PubMed Central

Al Muhit, Abdullah; Zbijewski, Wojciech; Thawait, Gaurav K.; Stayman, J. Webster; Packard, Nathan; Senn, Robert; Yang, Dong; Foos, David H.; Yorkston, John; Siewerdsen, Jeffrey H.

2014-01-01

Purpose To provide initial assessment of image quality and dose for a cone-beam computed tomographic (CT) scanner dedicated to extremity imaging. Materials and Methods A prototype cone-beam CT scanner has been developed for imaging the extremities, including the weight-bearing lower extremities. Initial technical assessment included evaluation of radiation dose measured as a function of kilovolt peak and tube output (in milliampere seconds), contrast resolution assessed in terms of the signal difference–to-noise ratio (SDNR), spatial resolution semiquantitatively assessed by using a line-pair module from a phantom, and qualitative evaluation of cadaver images for potential diagnostic value and image artifacts by an expert CT observer (musculoskeletal radiologist). Results The dose for a nominal scan protocol (80 kVp, 108 mAs) was 9 mGy (absolute dose measured at the center of a CT dose index phantom). SDNR was maximized with the 80-kVp scan technique, and contrast resolution was sufficient for visualization of muscle, fat, ligaments and/or tendons, cartilage joint space, and bone. Spatial resolution in the axial plane exceeded 15 line pairs per centimeter. Streaks associated with x-ray scatter (in thicker regions of the patient—eg, the knee), beam hardening (about cortical bone—eg, the femoral shaft), and cone-beam artifacts (at joint space surfaces oriented along the scanning plane—eg, the interphalangeal joints) presented a slight impediment to visualization. Cadaver images (elbow, hand, knee, and foot) demonstrated excellent visibility of bone detail and good soft-tissue visibility suitable to a broad spectrum of musculoskeletal indications. Conclusion A dedicated extremity cone-beam CT scanner capable of imaging upper and lower extremities (including weight-bearing examinations) provides sufficient image quality and favorable dose characteristics to warrant further evaluation for clinical use. © RSNA, 2013 Online supplemental material is available for this article. PMID:24475803

Radiological risks from irradiation of cargo contents with EURITRACK neutron inspection systems

NASA Astrophysics Data System (ADS)

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

2012-07-01

The radiological risk for the population related to the neutron irradiation of cargo containers with a tagged neutron inspection system has been studied. Two possible effects on the public health have been assessed: the modification of the nutritional and organoleptic properties of the irradiated materials, in particular foodstuff, and the neutron activation of consumer products (i.e. food and pharmaceuticals). The result of this study is that irradiation of food and foodstuff, pharmaceutical and medical devices in container cargoes would neither modify the properties of the irradiated material nor produce effective doses of concern for public health. Furthermore, the dose received by possible stowaways present inside the container during the inspection is less than the annual effective dose limit defined by European Legislation for the public.

A correlation study of eye lens dose and personal dose equivalent for interventional cardiologists.

PubMed

Farah, J; Struelens, L; Dabin, J; Koukorava, C; Donadille, L; Jacob, S; Schnelzer, M; Auvinen, A; Vanhavere, F; Clairand, I

2013-12-01

This paper presents the dosimetry part of the European ELDO project, funded by the DoReMi Network of Excellence, in which a method was developed to estimate cumulative eye lens doses for past practices based on personal dose equivalent values, H(p)(10), measured above the lead apron at several positions at the collar, chest and waist levels. Measurement campaigns on anthropomorphic phantoms were carried out in typical interventional settings considering different tube projections and configurations, beam energies and filtration, operator positions and access routes and using both mono-tube and biplane X-ray systems. Measurements showed that eye lens dose correlates best with H(p)(10) measured on the left side of the phantom at the level of the collar, although this correlation implicates high spreads (41 %). Nonetheless, for retrospective dose assessment, H(p)(10) records are often the only option for eye dose estimates and the typically used chest left whole-body dose measurement remains useful.

Ecological Dose Modeling of Aquatic and Riparian Receptors to Strontium-90 with an Emphasis on Radiosensitive Organs

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

Poston, Ted M.; Traub, Richard J.; Antonio, Ernest J.

2011-07-20

The 100-NR-2 site is the location of elevated releases of strontium-90 to the Columbia River via contaminated groundwater. The resulting dose to aquatic and riparian receptors was evaluated in 2005 (DOE 2009) and compared to U.S. Department of Energy (DOE) dose guidance values. We have conducted additional dose assessments for a broader spectrum of aquatic and riparian organisms using RESRAD Biota and specific exposure scenarios. Because strontium-90 accumulates in bone, we have also modeled the dose to the anterior kidney, a blood-forming and immune system organ that lies close to the spinal column of fish. The resulting dose is primarilymore » attributable to the yttrium-90 progeny of strontium-90 and very little of the dose is associated with the beta emission from strontium-90. All dose modeling results were calculated with an assumption of secular equilibrium between strontium-90 and yttrum-90.« less

IRIS Toxicological Review of Chloroprene (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of chloroprene that will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Chloroprene (2000 External Review Draft)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of chloroprene that will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Trimethylbenzenes (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of trimethylbenzenes that will appear in the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Ammonia (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of ammonia that will appear in the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Pentachlorophenol (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of pentachlorophenol that will appear in the Integrated Risk Information System (IRIS) database.

Characterization and control of EUV scanner dose uniformity and stability

NASA Astrophysics Data System (ADS)

Robinson, Chris; Corliss, Dan; Meli, Luciana; Johnson, Rick

2018-03-01

The EUV source is an impressive feat of engineering that provides 13.5 nm radiation by vaporizing tin droplets with a high power CO2 laser and focusing the photons produced in the resultant plasma into the scanner illumination system. Great strides have been made in addressing the many potential stability challenges, but there are still residual spatial and temporal dose non-uniformity signatures. Since even small dose errors can impact the yieldable process window for the advanced lithography products that are exposed on EUV scanners it is crucial to monitor and control the dose variability. Using on-board metrology, the EUV scanner outputs valuable metrics that provide real time insight into the dose performance. We have supplemented scanner data collection with a wafer based methodology that provides high throughput, high sensitivity, quantitative characterization of the EUV scanner dose delivery. The technique uses open frame EUV exposures, so it is exclusive of lithographic pattern imaging, exclusive of lithographic mask pattern and not limited by placement of metrology features. Processed wafers are inspected rapidly, providing 20,000 pixels of detail per exposure field in approximately one minute. Exposing the wafer on the scanner with a bit less than the resist E0 (open frame clearing dose) results in good sensitivity to small variations in the EUV dose delivered. The nominal exposure dose can be modulated by field to calibrate the inspection results and provide quantitative assessment of variations with < 1% sensitivity. This technique has been used for dose uniformity assessments. It is also being used for long term dose stability monitoring and has proven valuable for short term dose stability follow up investigations.

MDCT of acute pancreatitis: Intraindividual comparison of single-phase versus dual-phase MDCT for initial assessment of acute pancreatitis using different CT scoring systems.

PubMed

Avanesov, Maxim; Weinrich, Julius M; Kraus, Thomas; Derlin, Thorsten; Adam, Gerhard; Yamamura, Jin; Karul, Murat

2016-11-01

The purpose of the retrospective study was to evaluate the additional value of dual-phase multidetector computed tomography (MDCT) protocols over a single-phase protocol on initial MDCT in patients with acute pancreatitis using three CT-based pancreatitis severity scores with regard to radiation dose. In this retrospective, IRB approved study MDCT was performed in 102 consecutive patients (73 males; 55years, IQR48-64) with acute pancreatitis. Inclusion criteria were CT findings of interstitial edematous pancreatitis (IP) or necrotizing pancreatitis (NP) and a contrast-enhanced dual-phase (arterial phase and portal-venous phase) abdominal CT performed at ≥72h after onset of symptoms. The severity of pancreatic and extrapancreatic changes was independently assessed by 2 observers using 3 validated CT-based scoring systems (CTSI, mCTSI, EPIC). All scores were applied to arterial phase and portal venous phase scans and compared to score results of portal venous phase scans, assessed ≥14days after initial evaluation. For effective dose estimation, volume CT dose index (CTDIvol) and dose length product (DLP) were recorded in all examinations. In neither of the CT severity scores a significant difference was observed after application of a dual-phase protocol compared with a single-phase protocol (IP: CTSI: 2.7 vs. 2.5, p=0.25; mCTSI: 4.0 vs. 4.0, p=0.10; EPIC: 2.0 vs. 2.0, p=0.41; NP: CTSI: 8.0 vs. 7.0, p=0.64; mCTSI: 8.0 vs. 8.0, p=0.10; EPIC: 3.0 vs. 3.0, p=0.06). The application of a single-phase CT protocol was associated with a median effective dose reduction of 36% (mean dose reduction 31%) compared to a dual-phase CT scan. An initial dual-phase abdominal CT after ≥72h after onset of symptoms of acute pancreatitis was not superior to a single-phase protocol for evaluation of the severity of pancreatic and extrapancreatic changes. However, the effective radiation dose may be reduced by 36% using a single-phase protocol. Copyright © 2016. Published by Elsevier Ireland Ltd.

Rapid Acute Dose Assessment Using MCNP6

NASA Astrophysics Data System (ADS)

Owens, Andrew Steven

Acute radiation doses due to physical contact with a high-activity radioactive source have proven to be an occupational hazard. Multiple radiation injuries have been reported due to manipulating a radioactive source with bare hands or by placing a radioactive source inside a shirt or pants pocket. An effort to reconstruct the radiation dose must be performed to properly assess and medically manage the potential biological effects from such doses. Using the reference computational phantoms defined by the International Commission on Radiological Protection (ICRP) and the Monte Carlo N-Particle transport code (MCNP6), dose rate coefficients are calculated to assess doses for common acute doses due to beta and photon radiation sources. The research investigates doses due to having a radioactive source in either a breast pocket or pants back pocket. The dose rate coefficients are calculated for discrete energies and can be used to interpolate for any given energy of photon or beta emission. The dose rate coefficients allow for quick calculation of whole-body dose, organ dose, and/or skin dose if the source, activity, and time of exposure are known. Doses are calculated with the dose rate coefficients and compared to results from the International Atomic Energy Agency (IAEA) reports from accidents that occurred in Gilan, Iran and Yanango, Peru. Skin and organ doses calculated with the dose rate coefficients appear to agree, but there is a large discrepancy when comparing whole-body doses assessed using biodosimetry and whole-body doses assessed using the dose rate coefficients.

Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6–11 years-old than cumulative high doses of inhaled terbutaline

PubMed Central

Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

2004-01-01

Objectives To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Methods Twenty boys and girls (6–11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis®) 4.5 µg (F4.5) or terbutaline (Bricanyl®) 500 µg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler®) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Results Formoterol and terbutaline had significant β2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48–3.65) mmol l−1 on the day of no treatment to 2.98 (CI: 2.90–3.08) after 10 × F4.5 and 2.70 (CI: 2.61–2.78) mmol l−1 after 10 × T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422–435) ms on the day of no treatment, to 455 (CI: 448–462) ms after 10 × F4.5 and 470 (CI: 463–476) ms after 10 × T500. Estimates of relative dose potency indicated that F4.5 µg had the same systemic activity as the clinically less effective dose of 250 µg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 µg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h. Conclusions Multiple inhalations over 2.5 h of formoterol (4.5 µg) via Turbuhaler® are at least as safe as and associated with less systemic effects than multiple inhalations of the clinically equipotent dose of terbutaline (500 µg) in children with asthma. PMID:15373934

Cumulative high doses of inhaled formoterol have less systemic effects in asthmatic children 6-11 years-old than cumulative high doses of inhaled terbutaline.

PubMed

Kaae, Rikke; Agertoft, Lone; Pedersen, Sören; Nordvall, S Lennart; Pedroletti, Christophe; Bengtsson, Thomas; Johannes-Hellberg, Ingegerd; Rosenborg, Johan

2004-10-01

To evaluate high dose tolerability and relative systemic dose potency between inhaled clinically equipotent dose increments of formoterol and terbutaline in children. Twenty boys and girls (6-11 years-old) with asthma and normal ECGs were studied. Ten doses of formoterol (Oxis) 4.5 microg (F4.5) or terbutaline (Bricanyl) 500 microg (T500) were inhaled cumulatively via a dry powder inhaler (Turbuhaler) over 1 h (three patients) or 2.5 h (17 patients) and compared to a day of no treatment, in a randomised, double-blind (active treatments only), crossover trial. Blood pressure (BP), ECG, plasma potassium, glucose, lactate, and adverse events were monitored up to 10 h to assess tolerability and relative systemic dose potency. Formoterol and terbutaline had significant beta2-adrenergic effects on most outcomes. Apart from the effect on systolic BP, QRS duration and PR interval, the systemic effects were significantly more pronounced with terbutaline than with formoterol. Thus, mean minimum plasma potassium, was suppressed from 3.56 (95% confidence interval, CI: 3.48-3.65) mmol l(-1) on the day of no treatment to 2.98 (CI: 2.90-3.08) after 10 x F4.5 and 2.70 (CI: 2.61-2.78) mmol l(-1) after 10 x T500, and maximum Q-Tc (heart rate corrected Q-T interval [Bazett's formula]) was prolonged from 429 (CI: 422-435) ms on the day of no treatment, to 455 (CI: 448-462) ms after 10 x F4.5 and 470 (CI: 463-476) ms after 10 x T500. Estimates of relative dose potency indicated that F4.5 microg had the same systemic activity as the clinically less effective dose of 250 microg terbutaline. The duration of systemic effects differed marginally between treatments. Spontaneously reported adverse events (most frequently tremor) were fewer with formoterol (78% of the children) than with terbutaline (95%). A serious adverse event occurred after inhalation of 45 microg formoterol over the 1 h dosing time, that prompted the extension of dosing time to 2.5 h. Multiple inhalations over 2.5 h of formoterol (4.5 microg) via Turbuhaler) are at least as safe as and associated with less systemic effects than multiple inhalations of the clinically equipotent dose of terbutaline (500 microg) in children with asthma. Copyright 2004 Blackwell Publishing Ltd

Mixed species radioiodine air sampling readout and dose assessment system

DOEpatents

Distenfeld, Carl H.; Klemish, Jr., Joseph R.

1978-01-01

This invention provides a simple, reliable, inexpensive and portable means and method for determining the thyroid dose rate of mixed airborne species of solid and gaseous radioiodine without requiring highly skilled personnel, such as health physicists or electronics technicians. To this end, this invention provides a means and method for sampling a gas from a source of a mixed species of solid and gaseous radioiodine for collection of the mixed species and readout and assessment of the emissions therefrom by cylindrically, concentrically and annularly molding the respective species around a cylindrical passage for receiving a conventional probe-type Geiger-Mueller radiation detector.

Head-and-neck IMRT treatments assessed with a Monte Carlo dose calculation engine.

PubMed

Seco, J; Adams, E; Bidmead, M; Partridge, M; Verhaegen, F

2005-03-07

IMRT is frequently used in the head-and-neck region, which contains materials of widely differing densities (soft tissue, bone, air-cavities). Conventional methods of dose computation for these complex, inhomogeneous IMRT cases involve significant approximations. In the present work, a methodology for the development, commissioning and implementation of a Monte Carlo (MC) dose calculation engine for intensity modulated radiotherapy (MC-IMRT) is proposed which can be used by radiotherapy centres interested in developing MC-IMRT capabilities for research or clinical evaluations. The method proposes three levels for developing, commissioning and maintaining a MC-IMRT dose calculation engine: (a) development of a MC model of the linear accelerator, (b) validation of MC model for IMRT and (c) periodic quality assurance (QA) of the MC-IMRT system. The first step, level (a), in developing an MC-IMRT system is to build a model of the linac that correctly predicts standard open field measurements for percentage depth-dose and off-axis ratios. Validation of MC-IMRT, level (b), can be performed in a rando phantom and in a homogeneous water equivalent phantom. Ultimately, periodic quality assurance of the MC-IMRT system is needed to verify the MC-IMRT dose calculation system, level (c). Once the MC-IMRT dose calculation system is commissioned it can be applied to more complex clinical IMRT treatments. The MC-IMRT system implemented at the Royal Marsden Hospital was used for IMRT calculations for a patient undergoing treatment for primary disease with nodal involvement in the head-and-neck region (primary treated to 65 Gy and nodes to 54 Gy), while sparing the spinal cord, brain stem and parotid glands. Preliminary MC results predict a decrease of approximately 1-2 Gy in the median dose of both the primary tumour and nodal volumes (compared with both pencil beam and collapsed cone). This is possibly due to the large air-cavity (the larynx of the patient) situated in the centre of the primary PTV and the approximations present in the dose calculation.

Assessment of a New High-Performance Small-Animal X-Ray Tomograph

NASA Astrophysics Data System (ADS)

Vaquero, J. J.; Redondo, S.; Lage, E.; Abella, M.; Sisniega, A.; Tapias, G.; Montenegro, M. L. Soto; Desco, M.

2008-06-01

We have developed a new X-ray cone-beam tomograph for in vivo small-animal imaging using a flat panel detector (CMOS technology with a microcolumnar CsI scintillator plate) and a microfocus X-ray source. The geometrical configuration was designed to achieve a spatial resolution of about 12 lpmm with a field of view appropriate for laboratory rodents. In order to achieve high performance with regard to per-animal screening time and cost, the acquisition software takes advantage of the highest frame rate of the detector and performs on-the-fly corrections on the detector raw data. These corrections include geometrical misalignments, sensor non-uniformities, and defective elements. The resulting image is then converted to attenuation values. We measured detector modulation transfer function (MTF), detector stability, system resolution, quality of the reconstructed tomographic images and radiated dose. The system resolution was measured following the standard test method ASTM E 1695 -95. For image quality evaluation, we assessed signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as a function of the radiated dose. Dose studies for different imaging protocols were performed by introducing TLD dosimeters in representative organs of euthanized laboratory rats. Noise figure, measured as standard deviation, was 50 HU for a dose of 10 cGy. Effective dose with standard research protocols is below 200 mGy, confirming that the system is appropriate for in vivo imaging. Maximum spatial resolution achieved was better than 50 micron. Our experimental results obtained with image quality phantoms as well as with in-vivo studies show that the proposed configuration based on a CMOS flat panel detector and a small micro-focus X-ray tube leads to a compact design that provides good image quality and low radiated dose, and it could be used as an add-on for existing PET or SPECT scanners.

Meningococcal Serogroup B Bivalent rLP2086 Vaccine Elicits Broad and Robust Serum Bactericidal Responses in Healthy Adolescents

PubMed Central

Vesikari, Timo; Østergaard, Lars; Diez-Domingo, Javier; Wysocki, Jacek; Flodmark, Carl-Erik; Beeslaar, Johannes; Eiden, Joseph; Jiang, Qin; Jansen, Kathrin U.; Jones, Thomas R.; Harris, Shannon L.; O'Neill, Robert E.; York, Laura J.; Crowther, Graham; Perez, John L.

2016-01-01

Background Neisseria meningitidis serogroup B (MnB) is a leading cause of invasive meningococcal disease in adolescents and young adults. A recombinant factor H binding protein (fHBP) vaccine (Trumenba®; bivalent rLP2086) was recently approved in the United States in individuals aged 10–25 years. Immunogenicity and safety of 2- or 3-dose schedules of bivalent rLP2086 were assessed in adolescents. Methods Healthy adolescents (11 to <19 years) were randomized to 1 of 5 bivalent rLP2086 dosing regimens (0,1,6-month; 0,2,6-month; 0,2-month; 0,4-month; 0,6-month). Immunogenicity was assessed by serum bactericidal antibody assay using human complement (hSBA). Safety assessments included local and systemic reactions and adverse events. Results Bivalent rLP2086 was immunogenic when administered as 2 or 3 doses; the most robust hSBA responses occurred with 3 doses. The proportion of subjects with hSBA titers ≥1:8 after 3 doses ranged from 91.7% to 95.0%, 98.9% to 99.4%, 88.4% to 89.0%, and 86.1% to 88.5% for MnB test strains expressing vaccine­-heterologous fHBP variants A22, A56, B24, and B44, respectively. After 2 doses, responses ranged from 90.8% to 93.5%, 98.4% to 100%, 69.1% to 81.1%, and 70.1% to 77.5%. Geometric mean titers (GMTs) were highest among subjects receiving 3 doses and similar between the 2- and 3-dose regimens. After 2 doses, GMTs trended numerically higher among subjects with longer intervals between the first and second dose (6 months vs 2 and 4 months). Bivalent rLP2086 was well tolerated. Conclusions Bivalent rLP2086 was immunogenic and well tolerated when administered in 2 or 3 doses. Three doses yielded the most robust hSBA response rates against MnB strains expressing vaccine-heterologous subfamily B fHBPs. PMID:26407272

Air contamination measurements for the evaluation of internal dose to workers in nuclear medicine departments

NASA Astrophysics Data System (ADS)

De Massimi, B.; Bianchini, D.; Sarnelli, A.; D'Errico, V.; Marcocci, F.; Mezzenga, E.; Mostacci, D.

2017-11-01

Radionuclides handled in nuclear medicine departments are often characterized by high volatility and short half-life. It is generally difficult to monitor directly the intake of these short-lived radionuclides in hospital staff: this makes measuring air contamination of utmost interest. The aim of the present work is to provide a method for the evaluation of internal doses to workers in nuclear medicine, by means of an air activity sampling detector, to ensure that the limits prescribed by the relevant legislation are respected. A continuous air sampling system measures isotope concentration with a Nal(TI) detector. Energy efficiency of the system was assessed with GEANT4 and with known activities of 18F. Air is sampled in a number of areas of the nuclear medicine department of the IRST-IRCCS hospital (Meldola- Italy). To evaluate committed doses to hospital staff involved (doctors, technicians, nurses) different exposure situations (rooms, times, radionuclides etc) were considered. After estimating the intake, the committed effective dose has been evaluated, for the different radionuclides, using the dose coefficients mandated by the Italian legislation. Error propagation for the estimated intake and personal dose has been evaluated, starting from measurement statistics.

Measuring in vitro biotransformation rates of super hydrophobic chemicals in rat liver s9 fractions using thin-film sorbent-phase dosing.

PubMed

Lee, Yung-Shan; Otton, S Victoria; Campbell, David A; Moore, Margo M; Kennedy, Chris J; Gobas, Frank A P C

2012-01-03

Methods for rapid and cost-effective assessment of the biotransformation potential of very hydrophobic and potentially bioaccumulative chemicals in mammals are urgently needed for the ongoing global evaluation of the environmental behavior of commercial chemicals. We developed and tested a novel solvent-free, thin-film sorbent-phase in vitro dosing system to measure the in vitro biotransformation rates of very hydrophobic chemicals in male Sprague-Dawley rat liver S9 homogenates and compared the rates to those measured by conventional solvent-delivery dosing. The thin-film sorbent-phase dosing system using ethylene vinyl acetate coated vials was developed to eliminate the incomplete dissolution of very hydrophobic substances in largely aqueous liver homogenates, to determine biotransformation rates at low substrate concentrations, to measure the unbound fraction of substrate in solution, and to simplify chemical analysis by avoiding the difficult extraction of test chemicals from complex biological matrices. Biotransformation rates using sorbent-phase dosing were 2-fold greater than those measured using solvent-delivery dosing. Unbound concentrations of very hydrophobic test chemicals were found to decline with increasing S9 and protein concentrations, causing measured biotransformation rates to be independent of S9 or protein concentrations. The results emphasize the importance of specifying both protein content and unbound substrate fraction in the measurement and reporting of in vitro biotransformation rates of very hydrophobic substances, which can be achieved in a thin-film sorbent-phase dosing system.

Comparison of peripheral and central effects of single and repeated oral dose administrations of bilastine, a new H1 antihistamine: a dose-range study in healthy volunteers with hydroxyzine and placebo as control treatments.

PubMed

García-Gea, Consuelo; Martínez-Colomer, Joan; Antonijoan, Rosa M; Valiente, Román; Barbanoj, Manuel-José

2008-12-01

Peripheral anti-H1 and central nervous system (CNS) activities after single (day 1) and repeated (day 7) administrations of increasing doses of bilastine (BIL) were assessed in 20 healthy volunteers throughout a crossover, randomized, double-blind, placebo (PLA)-controlled study. Repeated doses of BIL 20, 40, or 80 mg and hydroxyzine 25 mg (HYD) as positive standard were administered on 7 consecutive days. Before and at several time points after drug intake, skin reactivity to the intradermal injection of histamine, objective tests of psychomotor performance, and subjective mood scales were evaluated. All active treatments led to a significant and similar reduction in the wheal reaction in relation to PLA after both the single (P < 0.001) and repeated administrations (P < 0.001). No delay was observed in the onset of its peripheral activity after the first dose of BIL as compared with HYD. No tolerance or sensitization was seen when comparing acute and repetitive assessments. Central nervous system effects showed that HYD induced the greatest psychomotor impairment (P < 0.05). Repeated HYD intake showed a lower number of significant alterations in comparison to acute administration. Bilastine 80 mg also showed some impairment (P < 0.05). Subjectively, the only active treatment that could not be differentiated from PLA was BIL 20 mg. Hydroxyzine 25 mg showed the greatest differentiation (P < 0.01). A clear dissociation between peripheral anti-H1 and CNS activity was found after BIL treatment. Significant and sustained peripheral H1-blocking effects were observed after both single and repeated administrations of the therapeutic dose of 20 mg BIL. The 40-mg dose of BIL produced subjective report of sedation, whereas unwanted objective CNS side effects were observed only with the 80-mg dose.

Suppression of ciprofloxacin-induced resistant Pseudomonas aeruginosa in a dynamic kill curve system.

PubMed

Wu, Benjamin M; Sabarinath, Sreedharan N; Rand, Kenneth; Johnson, Judith; Derendorf, Hartmut

2011-06-01

Current dosing approaches for treating microbial infections ignore resistant subpopulations. A clinical isolate of Pseudomonas aeruginosa was cultured in a dynamic in vitro kill curve system designed to simulate the half-lives of drugs in order to evaluate the drug-microbial response relationship. The first dose of ciprofloxacin (CIP) uses a concentration equivalent to the unbound fraction of a 200mg clinical dose. A second dose of 200mg or 600 mg CIP, or ceftriaxone (CFX) or gentamicin (GEN) was administered at 12h. Dynamics of the minimum inhibitory concentration (MIC) were assessed using Etest strips before and throughout the CIP treatment period. In addition, the microbroth dilution method was used to evaluate drug susceptibility across a wide range of antibiotics using samples from before and after CIP exposure. A significant loss of CIP effects was observed at the second dose. Cross-resistance to many antibiotics (cefoxitin, cefuroxime, cefotetan, ampicillin and ertapenem) was observed. GEN, but not CFX or high-dose CIP, was sufficient to suppress the developed resistant subpopulation following the initial CIP exposure. The CIP MIC increased substantially from 0.13 μg/mL pre dose to 4 μg/mL at 12h after a CIP dose. In addition, aztreonam induced a similar resistance pattern as CIP, indicating that induction of resistance was not limited to fluoroquinolones. In conclusion, the in vitro dynamic kill curve system revealed that aminoglycosides, more than other classes of antibiotics, were effective against the CIP-induced resistant subpopulations. Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

Pain point system scale (PPSS): a method for postoperative pain estimation in retrospective studies

PubMed Central

Gkotsi, Anastasia; Petsas, Dimosthenis; Sakalis, Vasilios; Fotas, Asterios; Triantafyllidis, Argyrios; Vouros, Ioannis; Saridakis, Evangelos; Salpiggidis, Georgios; Papathanasiou, Athanasios

2012-01-01

Purpose Pain rating scales are widely used for pain assessment. Nevertheless, a new tool is required for pain assessment needs in retrospective studies. Methods The postoperative pain episodes, during the first postoperative day, of three patient groups were analyzed. Each pain episode was assessed by a visual analog scale, numerical rating scale, verbal rating scale, and a new tool – pain point system scale (PPSS) – based on the analgesics administered. The type of analgesic was defined based on the authors’ clinic protocol, patient comorbidities, pain assessment tool scores, and preadministered medications by an artificial neural network system. At each pain episode, each patient was asked to fill the three pain scales. Bartlett’s test and Kaiser–Meyer–Olkin criterion were used to evaluate sample sufficiency. The proper scoring system was defined by varimax rotation. Spearman’s and Pearson’s coefficients assessed PPSS correlation to the known pain scales. Results A total of 262 pain episodes were evaluated in 124 patients. The PPSS scored one point for each dose of paracetamol, three points for each nonsteroidal antiinflammatory drug or codeine, and seven points for each dose of opioids. The correlation between the visual analog scale and PPSS was found to be strong and linear (rho: 0.715; P < 0.001 and Pearson: 0.631; P < 0.001). Conclusion PPSS correlated well with the known pain scale and could be used safely in the evaluation of postoperative pain in retrospective studies. PMID:23152699

SU-F-J-178: A Computer Simulation Model Observer for Task-Based Image Quality Assessment in Radiation Therapy

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

Dolly, S; Mutic, S; Anastasio, M

Purpose: Traditionally, image quality in radiation therapy is assessed subjectively or by utilizing physically-based metrics. Some model observers exist for task-based medical image quality assessment, but almost exclusively for diagnostic imaging tasks. As opposed to disease diagnosis, the task for image observers in radiation therapy is to utilize the available images to design and deliver a radiation dose which maximizes patient disease control while minimizing normal tissue damage. The purpose of this study was to design and implement a new computer simulation model observer to enable task-based image quality assessment in radiation therapy. Methods: A modular computer simulation framework wasmore » developed to resemble the radiotherapy observer by simulating an end-to-end radiation therapy treatment. Given images and the ground-truth organ boundaries from a numerical phantom as inputs, the framework simulates an external beam radiation therapy treatment and quantifies patient treatment outcomes using the previously defined therapeutic operating characteristic (TOC) curve. As a preliminary demonstration, TOC curves were calculated for various CT acquisition and reconstruction parameters, with the goal of assessing and optimizing simulation CT image quality for radiation therapy. Sources of randomness and bias within the system were analyzed. Results: The relationship between CT imaging dose and patient treatment outcome was objectively quantified in terms of a singular value, the area under the TOC (AUTOC) curve. The AUTOC decreases more rapidly for low-dose imaging protocols. AUTOC variation introduced by the dose optimization algorithm was approximately 0.02%, at the 95% confidence interval. Conclusion: A model observer has been developed and implemented to assess image quality based on radiation therapy treatment efficacy. It enables objective determination of appropriate imaging parameter values (e.g. imaging dose). Framework flexibility allows for incorporation of additional modules to include any aspect of the treatment process, and therefore has great potential for both assessment and optimization within radiation therapy.« less

Radiation dose exposure in patients affected by lymphoma undergoing repeat CT examinations: how to manage the radiation dose variability.

PubMed

Paolicchi, Fabio; Bastiani, Luca; Guido, Davide; Dore, Antonio; Aringhieri, Giacomo; Caramella, Davide

2018-03-01

To assess the variability of radiation dose exposure in patients affected by lymphoma undergoing repeat CT (computed tomography) examinations and to evaluate the influence of different scan parameters on the overall radiation dose. A series of 34 patients (12 men and 22 women with a median age of 34.4 years) with lymphoma, after the initial staging CT underwent repeat follow-up CT examinations. For each patient and each repeat examination, age, sex, use of AEC system (Automated Exposure Control, i.e. current modulation), scan length, kV value, number of acquired scans (i.e. number of phases), abdominal size diameter and dose length product (DLP) were recorded. The radiation dose of just one venous phase was singled out from the DLP of the entire examination. All scan data were retrieved by our PACS (Picture Archiving and Communication System) by means of a dose monitoring software. Among the variables we considered, no significant difference of radiation dose was observed among patients of different ages nor concerning tube voltage. On the contrary the dose delivered to the patients varied depending on sex, scan length and usage of AEC. No significant difference was observed depending on the behaviour of technologists, while radiologists' choices had indirectly an impact on the radiation dose due to the different number of scans requested by each of them. Our results demonstrate that patients affected by lymphoma who undergo repeat whole body CT scanning may receive unnecessary overexposure. We quantified and analyzed the most relevant variables in order to provide a useful tool to manage properly CT dose variability, estimating the amount of additional radiation dose for every single significant variable. Additional scans, incorrect scan length and incorrect usage of AEC system are the most relevant cause of patient radiation exposure.

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

PubMed

Makeev, Andrey; Glick, Stephen J

2017-12-01

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

Dose assessment in environmental radiological protection: State of the art and perspectives.

PubMed

Stark, Karolina; Goméz-Ros, José M; Vives I Batlle, Jordi; Lindbo Hansen, Elisabeth; Beaugelin-Seiller, Karine; Kapustka, Lawrence A; Wood, Michael D; Bradshaw, Clare; Real, Almudena; McGuire, Corynne; Hinton, Thomas G

2017-09-01

Exposure to radiation is a potential hazard to humans and the environment. The Fukushima accident reminded the world of the importance of a reliable risk management system that incorporates the dose received from radiation exposures. The dose to humans from exposure to radiation can be quantified using a well-defined system; its environmental equivalent, however, is still in a developmental state. Additionally, the results of several papers published over the last decade have been criticized because of poor dosimetry. Therefore, a workshop on environmental dosimetry was organized by the STAR (Strategy for Allied Radioecology) Network of Excellence to review the state of the art in environmental dosimetry and prioritize areas of methodological and guidance development. Herein, we report the key findings from that international workshop, summarise parameters that affect the dose animals and plants receive when exposed to radiation, and identify further research needs. Current dosimetry practices for determining environmental protection are based on simple screening dose assessments using knowledge of fundamental radiation physics, source-target geometry relationships, the influence of organism shape and size, and knowledge of how radionuclide distributions in the body and in the soil profile alter dose. In screening model calculations that estimate whole-body dose to biota the shapes of organisms are simply represented as ellipsoids, while recently developed complex voxel phantom models allow organ-specific dose estimates. We identified several research and guidance development priorities for dosimetry. For external exposures, the uncertainty in dose estimates due to spatially heterogeneous distributions of radionuclide contamination is currently being evaluated. Guidance is needed on the level of dosimetry that is required when screening benchmarks are exceeded and how to report exposure in dose-effect studies, including quantification of uncertainties. Further research is needed to establish whether and how dosimetry should account for differences in tissue physiology, organism life stages, seasonal variability (in ecology, physiology and radiation field), species life span, and the proportion of a population that is actually exposed. We contend that, although major advances have recently been made in environmental radiation protection, substantive improvements are required to reduce uncertainties and increase the reliability of environmental dosimetry. Copyright © 2017 Elsevier Ltd. All rights reserved.

Estimates of internal-dose equivalent from inhalation and ingestion of selected radionuclides

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

Dunning, D.E.

1982-01-01

This report presents internal radiation dose conversion factors for radionuclides of interest in environmental assessments of nuclear fuel cycles. This volume provides an updated summary of estimates of committed dose equivalent for radionuclides considered in three previous Oak Ridge National Laboratory (ORNL) reports. Intakes by inhalation and ingestion are considered. The International Commission on Radiological Protection (ICRP) Task Group Lung Model has been used to simulate the deposition and retention of particulate matter in the respiratory tract. Results corresponding to activity median aerodynamic diameters (AMAD) of 0.3, 1.0, and 5.0 ..mu..m are given. The gastorintestinal (GI) tract has been representedmore » by a four-segment catenary model with exponential transfer of radioactivity from one segment to the next. Retention of radionuclides in systemic organs is characterized by linear combinations of decaying exponential functions, recommended in ICRP Publication 30. The first-year annual dose rate, maximum annual dose rate, and fifty-year dose commitment per microcurie intake of each radionuclide is given for selected target organs and the effective dose equivalent. These estimates include contributions from specified source organs plus the systemic activity residing in the rest of the body; cross irradiation due to penetrating radiations has been incorporated into these estimates. 15 references.« less

Lesion detection performance: comparative analysis of low-dose CT data of the chest on two hybrid imaging systems.

PubMed

Jessop, Maryam; Thompson, John D; Coward, Joanne; Sanderud, Audun; Jorge, José; de Groot, Martijn; Lança, Luís; Hogg, Peter

2015-03-01

Incidental findings on low-dose CT images obtained during hybrid imaging are an increasing phenomenon as CT technology advances. Understanding the diagnostic value of incidental findings along with the technical limitations is important when reporting image results and recommending follow-up, which may result in an additional radiation dose from further diagnostic imaging and an increase in patient anxiety. This study assessed lesions incidentally detected on CT images acquired for attenuation correction on two SPECT/CT systems. An anthropomorphic chest phantom containing simulated lesions of varying size and density was imaged on an Infinia Hawkeye 4 and a Symbia T6 using the low-dose CT settings applied for attenuation correction acquisitions in myocardial perfusion imaging. Twenty-two interpreters assessed 46 images from each SPECT/CT system (15 normal images and 31 abnormal images; 41 lesions). Data were evaluated using a jackknife alternative free-response receiver-operating-characteristic analysis (JAFROC). JAFROC analysis showed a significant difference (P < 0.0001) in lesion detection, with the figures of merit being 0.599 (95% confidence interval, 0.568, 0.631) and 0.810 (95% confidence interval, 0.781, 0.839) for the Infinia Hawkeye 4 and Symbia T6, respectively. Lesion detection on the Infinia Hawkeye 4 was generally limited to larger, higher-density lesions. The Symbia T6 allowed improved detection rates for midsized lesions and some lower-density lesions. However, interpreters struggled to detect small (5 mm) lesions on both image sets, irrespective of density. Lesion detection is more reliable on low-dose CT images from the Symbia T6 than from the Infinia Hawkeye 4. This phantom-based study gives an indication of potential lesion detection in the clinical context as shown by two commonly used SPECT/CT systems, which may assist the clinician in determining whether further diagnostic imaging is justified. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Recommendations to harmonize European early warning dosimetry network systems

NASA Astrophysics Data System (ADS)

Dombrowski, H.; Bleher, M.; De Cort, M.; Dabrowski, R.; Neumaier, S.; Stöhlker, U.

2017-12-01

After the Chernobyl nuclear power plant accident in 1986, followed by the Fukushima Nuclear power plant accident 25 years later, it became obvious that real-time information is required to quickly gain radiological information. As a consequence, the European countries established early warning network systems with the aim to provide an immediate warning in case of a major radiological emergency, to supply reliable information on area dose rates, contamination levels, radioactivity concentrations in air and finally to assess public exposure. This is relevant for governmental decisions on intervention measures in an emergency situation. Since different methods are used by national environmental monitoring systems to measure area dose rate values and activity concentrations, there are significant differences in the results provided by different countries. Because European and neighboring countries report area dose rate data to a central data base operated on behalf of the European Commission, the comparability of the data is crucial for its meaningful interpretation, especially in the case of a nuclear accident with transboundary implications. Only by harmonizing measuring methods and data evaluation, is the comparability of the dose rate data ensured. This publication concentrates on technical requirements and methods with the goal to effectively harmonize area dose rate monitoring data provided by automatic early warning network systems. The requirements and procedures laid down in this publication are based on studies within the MetroERM project, taking into account realistic technical approaches and tested procedures.

IRIS Toxicological Review of Hexavalent Chromium (Peer Review Plan)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of hexavalent chromium that will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Biphenyl (External Review Draft) (September 2011)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of biphenyl that will appear in the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of n-Butanol (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of n-butanol that will appear in the Integrated Risk Information System (IRIS) database.

Long-term mesalamine maintenance in ulcerative colitis: which is more important? Adherence or daily dose.

PubMed

Khan, Nabeel; Abbas, Ali M; Koleva, Yordanka N; Bazzano, Lydia A

2013-05-01

There are limited data about the long-term follow-up of patients with ulcerative colitis (UC) maintained on high versus low doses of mesalamine. We evaluated the best long-term average daily dose that would keep the disease in remission. Nationwide ulcerative colitis data were obtained from the Veterans Affairs health care system for the period 2001 to 2011. Those who started mesalamine maintenance during this period were included. Average daily dose and the level of adherence were assessed for the period between the first mesalamine dispense and the date of first flare defined as the first filling of 40 mg/day or more of oral prednisone or any dose of intravenous steroids. Patients with ulcerative colitis maintained on an average daily dose 2.4 to 2.8 g/day (low dose) were compared with 4.4 to 4.8 g/day (high dose). Adherence was assessed using continuous single interval medication availability indicator. We included 4452 patients with a median follow-up of 6 years. There was no significant reduction in the risk of flares when comparing high versus low average mesalamine dose among patients with high [hazard ratio = 0.96, P = 0.8)] and medium (hazard ratio = 0.74, P = 0.17) adherence. However, there was a significant reduction in the risk of flares with high dose of mesalamine among patients with low adherence (hazard ratio = 0.28, P = 0.003). Our data show that when starting a patient on mesalamine, there is no difference in the long-term flare risk between low versus high average daily dose as long as the patients have a high to moderate level of adherence.

Effects of low to moderate acute doses of pramipexole on impulsivity and cognition in healthy volunteers.

PubMed

Hamidovic, Ajna; Kang, Un Jung; de Wit, Harriet

2008-02-01

The neurotransmitter dopamine is integrally involved in the rewarding effects of drugs, and it has also been thought to mediate impulsive behaviors in animal models. Most of the studies of drug effects on impulsive behaviors in humans have involved drugs with complex actions on different transmitter systems and different receptor subtypes. The present study was designed to characterize the effect of single doses of pramipexole, a D2/D3 agonist, on measures of cognitive and impulsive behavior, as well as on mood in healthy volunteers. Healthy men and women (N = 10) received placebo and 2 doses of pramipexole, 0.25 and 0.50 mg, in a within-subject, double-blinded study. Outcome measures included changes in cognitive performance, assessed by the Automated Neuropsychological Assessment Metrics, several behavioral measures related to impulsive behavior, including the Balloon Analogue Risk Task, Delay Discounting Task, Go/No-Go Task, Card Perseveration Task, and subjective ratings of mood assessed by Addiction Research Center Inventory, Profile of Mood States, and Drug Effects Questionnaire. Pramipexole decreased positive ratings of mood (euphoria, intellectual efficiency, and energy) and increased both subjectively reported sedation and behavioral sedation indicated by impaired cognitive performance on several measures of the Automated Neuropsychological Assessment Metrics. Single low to medium doses of this drug did not produce a decrease in impulsive responding on behavioral measures included in this study. The sedative-like effects observed in this study may reflect presynaptic actions of the drug. Higher doses with postsynaptic actions may be needed to produce either behavioral or subjective stimulant-like effects.

TU-AB-BRA-11: Indications for Online Adaptive Radiotherapy Based On Dosimetric Consequences of Interfractional Pancreas-To-Duodenum Motion in MRI-Guided Pancreatic Radiotherapy

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

Mittauer, K; Rosenberg, S; Geurts, M

Purpose: Dose limiting structures, such as the duodenum, render the treatment of pancreatic cancer challenging. In this multi-institutional study, we assess dosimetric differences caused by interfraction pancreas-to-duodenum motion using MR-IGRT to determine the potential impact of adaptive replanning. Methods: Ten patients from two institutions undergoing MRI-guided radiotherapy with conventional fractionation (n=5) or SBRT (n=5) for pancreatic cancer were included. Initial plans were limited by duodenal dose constraints of 50 Gy (0.5 cc)/31 Gy (0.1 cc) for conventional/SBRT with prescriptions of 30 Gy/5 fractions (SBRT) and 40–50 Gy/25 fractions (conventional). Daily volumetric MR images were acquired under treatment conditions on amore » clinical MR-IGRT system. The correlation was assessed between interfractional GTV-to-duodenum positional variation and daily recalculations of duodenal dose metrics. Positional variation was quantified as the interfraction difference in Hausdorff distance from simulation baseline (ΔHD) between the GTV and proximal duodenal surface, or volume overlap between GTV and duodenum for cases with HD{sub 0}=0 (GTV abutting duodenum). Adaptation was considered indicated when daily positional variations enabled dose escalation to the target while maintaining duodenal constraints. Results: For fractions with ΔHD>0 (n=14, SBRT only), the mean interfraction duodenum dose decrease from simulation to treatment was 44±53 cGy (maximum 136 cGy). A correlation was found between ΔHD and dosimetric difference (R{sup 2}=0.82). No correlation was found between volume of overlap and dosimetric difference (R{sup 2}=0.31). For 89% of fractions, the duodenum remained overlapped with the target and the duodenal dose difference was negligible. The maximum observed indication for adaptation was for interfraction ΔHD=11.6 mm with potential for adaptive dose escalation of 136 cGy. Conclusion: This assessment showed that Hausdorff distance was a reasonable metric to use to determine the indication for adaptation. Adaptation was potentially indicated in 11% of the treatments (fractions where GTV-to-duodenum distance increased from simulation), with a feasible average dose escalation of 7.0%. MB, LH, JO, RK, PP: research and/or travel funding from ViewRay Inc. PP: research grant from Varian Medical Systems and Philips Healthcare.« less

Assessment of dosimetric impact of system specific geometric distortion in an MRI only based radiotherapy workflow for prostate

NASA Astrophysics Data System (ADS)

Gustafsson, C.; Nordström, F.; Persson, E.; Brynolfsson, J.; Olsson, L. E.

2017-04-01

Dosimetric errors in a magnetic resonance imaging (MRI) only radiotherapy workflow may be caused by system specific geometric distortion from MRI. The aim of this study was to evaluate the impact on planned dose distribution and delineated structures for prostate patients, originating from this distortion. A method was developed, in which computer tomography (CT) images were distorted using the MRI distortion field. The displacement map for an optimized MRI treatment planning sequence was measured using a dedicated phantom in a 3 T MRI system. To simulate the distortion aspects of a synthetic CT (electron density derived from MR images), the displacement map was applied to CT images, referred to as distorted CT images. A volumetric modulated arc prostate treatment plan was applied to the original CT and the distorted CT, creating a reference and a distorted CT dose distribution. By applying the inverse of the displacement map to the distorted CT dose distribution, a dose distribution in the same geometry as the original CT images was created. For 10 prostate cancer patients, the dose difference between the reference dose distribution and inverse distorted CT dose distribution was analyzed in isodose level bins. The mean magnitude of the geometric distortion was 1.97 mm for the radial distance of 200-250 mm from isocenter. The mean percentage dose differences for all isodose level bins, were  ⩽0.02% and the radiotherapy structure mean volume deviations were  <0.2%. The method developed can quantify the dosimetric effects of MRI system specific distortion in a prostate MRI only radiotherapy workflow, separated from dosimetric effects originating from synthetic CT generation. No clinically relevant dose difference or structure deformation was found when 3D distortion correction and high acquisition bandwidth was used. The method could be used for any MRI sequence together with any anatomy of interest.

Assessment of dosimetric impact of system specific geometric distortion in an MRI only based radiotherapy workflow for prostate.

PubMed

Gustafsson, C; Nordström, F; Persson, E; Brynolfsson, J; Olsson, L E

2017-04-21

Dosimetric errors in a magnetic resonance imaging (MRI) only radiotherapy workflow may be caused by system specific geometric distortion from MRI. The aim of this study was to evaluate the impact on planned dose distribution and delineated structures for prostate patients, originating from this distortion. A method was developed, in which computer tomography (CT) images were distorted using the MRI distortion field. The displacement map for an optimized MRI treatment planning sequence was measured using a dedicated phantom in a 3 T MRI system. To simulate the distortion aspects of a synthetic CT (electron density derived from MR images), the displacement map was applied to CT images, referred to as distorted CT images. A volumetric modulated arc prostate treatment plan was applied to the original CT and the distorted CT, creating a reference and a distorted CT dose distribution. By applying the inverse of the displacement map to the distorted CT dose distribution, a dose distribution in the same geometry as the original CT images was created. For 10 prostate cancer patients, the dose difference between the reference dose distribution and inverse distorted CT dose distribution was analyzed in isodose level bins. The mean magnitude of the geometric distortion was 1.97 mm for the radial distance of 200-250 mm from isocenter. The mean percentage dose differences for all isodose level bins, were  ⩽0.02% and the radiotherapy structure mean volume deviations were  <0.2%. The method developed can quantify the dosimetric effects of MRI system specific distortion in a prostate MRI only radiotherapy workflow, separated from dosimetric effects originating from synthetic CT generation. No clinically relevant dose difference or structure deformation was found when 3D distortion correction and high acquisition bandwidth was used. The method could be used for any MRI sequence together with any anatomy of interest.

A Bayesian Model and Stochastic Exposure (Dose) Estimation for Relative Exposure Risk Comparison Involving Asbestos-Containing Dropped Ceiling Panel Installation and Maintenance Tasks.

PubMed

Boelter, Fred W; Xia, Yulin; Persky, Jacob D

2017-09-01

Assessing exposures to hazards in order to characterize risk is at the core of occupational hygiene. Our study examined dropped ceiling systems commonly used in schools and commercial buildings and lay-in ceiling panels that may have contained asbestos prior to the mid to late 1970s. However, most ceiling panels and tiles do not contain asbestos. Since asbestos risk relates to dose, we estimated the distribution of eight-hour TWA concentrations and one-year exposures (a one-year dose equivalent) to asbestos fibers (asbestos f/cc-years) for five groups of workers who may encounter dropped ceilings: specialists, generalists, maintenance workers, nonprofessional do-it-yourself (DIY) persons, and other tradespersons who are bystanders to ceiling work. Concentration data (asbestos f/cc) were obtained through two exposure assessment studies in the field and one chamber study. Bayesian and stochastic models were applied to estimate distributions of eight-hour TWAs and annual exposures (dose). The eight-hour TWAs for all work categories were below current and historic occupational exposure limits (OELs). Exposures to asbestos fibers from dropped ceiling work would be categorized as "highly controlled" for maintenance workers and "well controlled" for remaining work categories, according to the American Industrial Hygiene Association exposure control rating system. Annual exposures (dose) were found to be greatest for specialists, followed by maintenance workers, generalists, bystanders, and DIY. On a comparative basis, modeled dose and thus risk from dropped ceilings for all work categories were orders of magnitude lower than published exposures for other sources of banned friable asbestos-containing building material commonly encountered in construction trades. © 2016 The Authors Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

Dosing algorithm to target a predefined AUC in patients with primary central nervous system lymphoma receiving high dose methotrexate.

PubMed

Joerger, Markus; Ferreri, Andrés J M; Krähenbühl, Stephan; Schellens, Jan H M; Cerny, Thomas; Zucca, Emanuele; Huitema, Alwin D R

2012-02-01

There is no consensus regarding optimal dosing of high dose methotrexate (HDMTX) in patients with primary CNS lymphoma. Our aim was to develop a convenient dosing algorithm to target AUC(MTX) in the range between 1000 and 1100 µmol l(-1) h. A population covariate model from a pooled dataset of 131 patients receiving HDMTX was used to simulate concentration-time curves of 10,000 patients and test the efficacy of a dosing algorithm based on 24 h MTX plasma concentrations to target the prespecified AUC(MTX) . These data simulations included interindividual, interoccasion and residual unidentified variability. Patients received a total of four simulated cycles of HDMTX and adjusted MTX dosages were given for cycles two to four. The dosing algorithm proposes MTX dose adaptations ranging from +75% in patients with MTX C(24) < 0.5 µmol l(-1) up to -35% in patients with MTX C(24) > 12 µmol l(-1). The proposed dosing algorithm resulted in a marked improvement of the proportion of patients within the AUC(MTX) target between 1000 and 1100 µmol l(-1) h (11% with standard MTX dose, 35% with the adjusted dose) and a marked reduction of the interindividual variability of MTX exposure. A simple and practical dosing algorithm for HDMTX has been developed based on MTX 24 h plasma concentrations, and its potential efficacy in improving the proportion of patients within a prespecified target AUC(MTX) and reducing the interindividual variability of MTX exposure has been shown by data simulations. The clinical benefit of this dosing algorithm should be assessed in patients with primary central nervous system lymphoma (PCNSL). © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Joint minimization of uplink and downlink whole-body exposure dose in indoor wireless networks.

PubMed

Plets, D; Joseph, W; Vanhecke, K; Vermeeren, G; Wiart, J; Aerts, S; Varsier, N; Martens, L

2015-01-01

The total whole-body exposure dose in indoor wireless networks is minimized. For the first time, indoor wireless networks are designed and simulated for a minimal exposure dose, where both uplink and downlink are considered. The impact of the minimization is numerically assessed for four scenarios: two WiFi configurations with different throughputs, a Universal Mobile Telecommunications System (UMTS) configuration for phone call traffic, and a Long-Term Evolution (LTE) configuration with a high data rate. Also, the influence of the uplink usage on the total absorbed dose is characterized. Downlink dose reductions of at least 75% are observed when adding more base stations with a lower transmit power. Total dose reductions decrease with increasing uplink usage for WiFi due to the lack of uplink power control but are maintained for LTE and UMTS. Uplink doses become dominant over downlink doses for usages of only a few seconds for WiFi. For UMTS and LTE, an almost continuous uplink usage is required to have a significant effect on the total dose, thanks to the power control mechanism.

Joint Minimization of Uplink and Downlink Whole-Body Exposure Dose in Indoor Wireless Networks

PubMed Central

Plets, D.; Joseph, W.; Vanhecke, K.; Vermeeren, G.; Wiart, J.; Aerts, S.; Varsier, N.; Martens, L.

2015-01-01

The total whole-body exposure dose in indoor wireless networks is minimized. For the first time, indoor wireless networks are designed and simulated for a minimal exposure dose, where both uplink and downlink are considered. The impact of the minimization is numerically assessed for four scenarios: two WiFi configurations with different throughputs, a Universal Mobile Telecommunications System (UMTS) configuration for phone call traffic, and a Long-Term Evolution (LTE) configuration with a high data rate. Also, the influence of the uplink usage on the total absorbed dose is characterized. Downlink dose reductions of at least 75% are observed when adding more base stations with a lower transmit power. Total dose reductions decrease with increasing uplink usage for WiFi due to the lack of uplink power control but are maintained for LTE and UMTS. Uplink doses become dominant over downlink doses for usages of only a few seconds for WiFi. For UMTS and LTE, an almost continuous uplink usage is required to have a significant effect on the total dose, thanks to the power control mechanism. PMID:25793213

ESTIMATING SYSTEMIC EXPOSURE TO ETHINYL ESTRADIOL FROM AN ORAL CONTRACEPTIVE

PubMed Central

WESTHOFF, Carolyn L.; PIKE, Malcolm C.; TANG, Rosalind; DINAPOLI, Marianne N.; SULL, Monica; CREMERS, Serge

2015-01-01

Objectives This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive to steady-state values, and to assess whether any simpler measures could provide an adequate proxy of the ‘gold standard’ 24-hour steady-state area-under-the-curve. Identifying a simple, less expensive, measure of systemic ethinyl estradiol exposure would be useful for larger studies designed to assess the relationship between an individual’s ethinyl estradiol exposure and her side effects. Study Design We conducted a 13 samples over 24 hours pharmacokinetic analysis on day 1 and day 21 of the first cycle of a monophasic oral contraceptive containing 30 mcg ethinyl estradiol and 150 mcg levonorgestrel in 17 non-obese healthy white women. We also conducted an abbreviated single dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of full 13-sample steady-state pharmacokinetic analysis with results calculated using fewer samples (9 or 5) and following the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. Results The area-under-the-curve, maximum (Cmax), and 24-hour (C24) values were similar following the two single oral contraceptive doses (area-under-the-curve, r = 0.92). The steady-state 13-sample 24-hour area-under-the-curve was highly correlated with the average 9-sample area-under-the-curve after the two single doses (r = 0.81, p = 0.0002). This correlation remained the same if the number of samples was reduced to 4, taken at time 1, 2.5, 4 and 24 hours. The C24 at steady-state was highly correlated with the 24-hour steady-state area-under-the-curve (r = 0.92, p < 0.0001). The average of the C24 values following the two single doses was also quite highly correlated with the steady-state area-under-the-curve (r = 0.72, p = 0.0026). Conclusions Limited blood sampling, including results from two single doses, gave highly correlated estimates of an oral contraceptive user’s steady-state ethinyl estradiol exposure. PMID:25511238

An In-home Advanced Robotic System to Manage Elderly Home-care Patients' Medications: A Pilot Safety and Usability Study.

PubMed

Rantanen, Pekka; Parkkari, Timo; Leikola, Saija; Airaksinen, Marja; Lyles, Alan

2017-05-01

We examined the safety profile and usability of an integrated advanced robotic device and telecare system to promote medication adherence for elderly home-care patients. There were two phases. Phase I aimed to verify under controlled conditions in a single nursing home (n = 17 patients) that no robotic malfunctions would hinder the device's safe use. Phase II involved home-care patients from 3 sites (n = 27) who were on long-term medication. On-time dispensing and missed doses were recorded by the robotic system. Patients' and nurses' experiences were assessed with structured interviews. The 17 nursing home patients had 457 total days using the device (Phase I; mean, 26.9 per patient). On-time sachet retrieval occurred with 97.7% of the alerts, and no medication doses were missed. At baseline, Phase II home-dwelling patients reported difficulty remembering to take their medicines (23%), and 18% missed at least 2 doses per week. Most Phase II patients (78%) lived alone. The device delivered and patients retrieved medicine sachets for 99% of the alerts. All patients and 96% of nurses reported the device was easy to use. This trial demonstrated the safety profile and usability of an in-home advanced robotic device and telecare system and its acceptability to patients and nurses. It supports individualized patient dosing schedules, patient-provider communications, and on-time, in-home medication delivery to promote adherence. Real time dose-by-dose monitoring and communication with providers if a dose is missed provide oversight generally not seen in home care. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Design and implementation of wireless dose logger network for radiological emergency decision support system.

PubMed

Gopalakrishnan, V; Baskaran, R; Venkatraman, B

2016-08-01

A decision support system (DSS) is implemented in Radiological Safety Division, Indira Gandhi Centre for Atomic Research for providing guidance for emergency decision making in case of an inadvertent nuclear accident. Real time gamma dose rate measurement around the stack is used for estimating the radioactive release rate (source term) by using inverse calculation. Wireless gamma dose logging network is designed, implemented, and installed around the Madras Atomic Power Station reactor stack to continuously acquire the environmental gamma dose rate and the details are presented in the paper. The network uses XBee-Pro wireless modules and PSoC controller for wireless interfacing, and the data are logged at the base station. A LabView based program is developed to receive the data, display it on the Google Map, plot the data over the time scale, and register the data in a file to share with DSS software. The DSS at the base station evaluates the real time source term to assess radiation impact.

Design and implementation of wireless dose logger network for radiological emergency decision support system

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

Gopalakrishnan, V.; Baskaran, R.; Venkatraman, B.

A decision support system (DSS) is implemented in Radiological Safety Division, Indira Gandhi Centre for Atomic Research for providing guidance for emergency decision making in case of an inadvertent nuclear accident. Real time gamma dose rate measurement around the stack is used for estimating the radioactive release rate (source term) by using inverse calculation. Wireless gamma dose logging network is designed, implemented, and installed around the Madras Atomic Power Station reactor stack to continuously acquire the environmental gamma dose rate and the details are presented in the paper. The network uses XBee–Pro wireless modules and PSoC controller for wireless interfacing,more » and the data are logged at the base station. A LabView based program is developed to receive the data, display it on the Google Map, plot the data over the time scale, and register the data in a file to share with DSS software. The DSS at the base station evaluates the real time source term to assess radiation impact.« less

User Performance Evaluation of Four Blood Glucose Monitoring Systems Applying ISO 15197:2013 Accuracy Criteria and Calculation of Insulin Dosing Errors.

PubMed

Freckmann, Guido; Jendrike, Nina; Baumstark, Annette; Pleus, Stefan; Liebing, Christina; Haug, Cornelia

2018-04-01

The international standard ISO 15197:2013 requires a user performance evaluation to assess if intended users are able to obtain accurate blood glucose measurement results with a self-monitoring of blood glucose (SMBG) system. In this study, user performance was evaluated for four SMBG systems on the basis of ISO 15197:2013, and possibly related insulin dosing errors were calculated. Additionally, accuracy was assessed in the hands of study personnel. Accu-Chek ® Performa Connect (A), Contour ® plus ONE (B), FreeStyle Optium Neo (C), and OneTouch Select ® Plus (D) were evaluated with one test strip lot. After familiarization with the systems, subjects collected a capillary blood sample and performed an SMBG measurement. Study personnel observed the subjects' measurement technique. Then, study personnel performed SMBG measurements and comparison measurements. Number and percentage of SMBG measurements within ± 15 mg/dl and ± 15% of the comparison measurements at glucose concentrations < 100 and ≥ 100 mg/dl, respectively, were calculated. In addition, insulin dosing errors were modelled. In the hands of lay-users three systems fulfilled ISO 15197:2013 accuracy criteria with the investigated test strip lot showing 96% (A), 100% (B), and 98% (C) of results within the defined limits. All systems fulfilled minimum accuracy criteria in the hands of study personnel [99% (A), 100% (B), 99.5% (C), 96% (D)]. Measurements with all four systems were within zones of the consensus error grid and surveillance error grid associated with no or minimal risk. Regarding calculated insulin dosing errors, all 99% ranges were between dosing errors of - 2.7 and + 1.4 units for measurements in the hands of lay-users and between - 2.5 and + 1.4 units for study personnel. Frequent lay-user errors were not checking the test strips' expiry date and applying blood incorrectly. Data obtained in this study show that not all available SMBG systems complied with ISO 15197:2013 accuracy criteria when measurements were performed by lay-users. The study was registered at ClinicalTrials.gov (NCT02916576). Ascensia Diabetes Care Deutschland GmbH.

Skin dose mapping for fluoroscopically guided interventions.

PubMed

Johnson, Perry B; Borrego, David; Balter, Stephen; Johnson, Kevin; Siragusa, Daniel; Bolch, Wesley E

2011-10-01

To introduce a new skin dose mapping software system for interventional fluoroscopy dose assessment and to analyze the benefits and limitations of patient-phantom matching. In this study, a new software system was developed for visualizing patient skin dose during interventional fluoroscopy procedures. The system works by translating the reference point air kerma to the location of the patient's skin, which is represented by a computational model. In order to orient the model with the x-ray source, geometric parameters found within the radiation dose structured report (RDSR) are used along with a limited number of in-clinic measurements. The output of the system is a visual indication of skin dose mapped onto an anthropomorphic model at a resolution of 5 mm. In order to determine if patient-dependent and patient-sculpted models increase accuracy, peak skin dose was calculated for each of 26 patient-specific models and compared with doses calculated using an elliptical stylized model, a reference hybrid model, a matched patient-dependent model and one patient-sculpted model. Results were analyzed in terms of a percent difference using the doses calculated using the patient-specific model as the true standard. Anthropometric matching, including the use of both patient-dependent and patient-sculpted phantoms, was shown most beneficial for left lateral and anterior-posterior projections. In these cases, the percent difference using a reference model was between 8 and 20%, using a patient-dependent model between 7 and 15%, and using a patient-sculpted model between 3 and 7%. Under the table tube configurations produced errors less than 5% in most situations due to the flattening affects of the table and pad, and the fact that table height is the main determination of source-to-skin distance for these configurations. In addition to these results, several skin dose maps were produced and a prototype display system was placed on the in-clinic monitor of an interventional fluoroscopy system. The skin dose mapping program developed in this work represents a new tool that, as the RDSR becomes available through automated export or real-time streaming, can provide the interventional physician information needed to modify behavior when clinically appropriate. The program is nonproprietary and transferable, and also functions independent to the software systems already installed on the control room workstation. The next step will be clinical implementation where the workflow will be optimized along with further analysis of real-time capabilities.

Systemic and bronchodilator effects of inhaled rac-formoterol in subjects with chronic obstructive pulmonary disease: a dose–response study

PubMed Central

Whale, Christopher I; Sovani, Milind P; Mortimer, Kevin J; Harrison, Timothy W; Tattersfield, Anne E

2008-01-01

AIMS Rac-formoterol is effective as maintenance treatment for both asthma and chronic obstructive pulmonary disease (COPD) and is now used as relief therapy in asthma. Using rac-formoterol for relief and maintenance treatment could involve inhalation of high doses, and whether this is of benefit in COPD is uncertain. Our aim was to determine whether higher doses of inhaled rac-formoterol produce systemic adverse effects that outweigh the limited bronchodilator benefit seen in subjects with COPD. METHODS We examined airway and systemic effects of 6, 12, 24 and 48 μg rac-formoterol and placebo on separate days in 20 subjects with symptomatic COPD [forced expiratory volume in 1 s (FEV1) 47% predicted]. FEV1, oxygen saturation, dyspnoea, 6-min walk distance, patient satisfaction and systemic effects were measured and treatment was assessed against placebo and for dose–response effects. RESULTS FEV1[area under the time–response curve (AUC)] and satisfaction scores increased with all formoterol doses compared with placebo, as did AUC tremor with the 24- and 48-μg doses and AUC heart rate with the 48-μg dose. A dose–response relationship was seen with FEV1 and tremor, but not with satisfaction scores. There was no difference between placebo and rac-formoterol for other variables. CONCLUSIONS Our results show that in patients with COPD rac-formoterol improves FEV1 and patient satisfaction without a corresponding reduction in dyspnoea. Since the systemic effects from a relatively high dose were minimal, its use as relief medication in COPD merits further evaluation. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT The long-acting inhaled β2-agonist formoterol has systemic effects when taken in high doses. It can be used as relief medication in asthma and there is interest in this approach in chronic obstructive pulmonary disease (COPD). Relief medication can involve high doses, and in subjects with COPD who have limited ability to bronchodilate the adverse effects can outweigh the benefits. There are concerns with the overall safety of high-dose β2-agonists in subjects with COPD, and this study looks at the balance of beneficial and adverse effects of a range of doses of inhaled formoterol. WHAT THIS STUDY ADDS Among subjects with COPD, high-dose inhaled formoterol produced a dose-related increase in forced expiratory volume in 1 s without a corresponding reduction in dyspnoea or increase in walk distance.Systemic effects were modest, however, and high doses did not appear to reduce patient satisfaction.Although further safety data are needed, inhaled formoterol may have a role as relief medication in COPD. PMID:18394012

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

Chen, S; Guerrero, M; Zhang, B

Purpose: To implement a comprehensive non-measurement-based verification program for patient-specific IMRT QA Methods: Based on published guidelines, a robust IMRT QA program should assess the following components: 1) accuracy of dose calculation, 2) accuracy of data transfer from the treatment planning system (TPS) to the record-and-verify (RV) system, 3) treatment plan deliverability, and 4) accuracy of plan delivery. Results: We have implemented an IMRT QA program that consist of four components: 1) an independent re-calculation of the dose distribution in the patient anatomy with a commercial secondary dose calculation program: Mobius3D (Mobius Medical Systems, Houston, TX), with dose accuracy evaluationmore » using gamma analysis, PTV mean dose, PTV coverage to 95%, and organ-at-risk mean dose; 2) an automated in-house-developed plan comparison system that compares all relevant plan parameters such as MU, MLC position, beam iso-center position, collimator, gantry, couch, field size settings, and bolus placement, etc. between the plan and the RV system; 3) use of the RV system to check the plan deliverability and further confirm using “mode-up” function on treatment console for plans receiving warning; and 4) implementation of a comprehensive weekly MLC QA, in addition to routine accelerator monthly and daily QA. Among 1200 verifications, there were 9 cases of suspicious calculations, 5 cases of delivery failure, no data transfer errors, and no failure of weekly MLC QA. These 9 suspicious cases were due to the PTV extending to the skin or to heterogeneity correction effects, which would not have been caught using phantom measurement-based QA. The delivery failure was due to the rounding variation of MLC position between the planning system and RV system. Conclusion: A very efficient, yet comprehensive, non-measurement-based patient-specific QA program has been implemented and used clinically for about 18 months with excellent results.« less

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

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

Zhang Yibao; Yan Yulong; Nath, Ravinder

2012-08-01

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

[CLIMATE CHANGE AND ALLERGIC AIRWAY DISEASE] OBSERVATIONAL,LABORATORY, AND MODELING STUDIES OF THE IMPACTS OF CLIMATE CHANGE ONALLERGIC AIRWAY DISEASE

EPA Science Inventory

Based on these data and preliminary studies, this proposal will be composed of a multiscale source-to-dose analysis approach for assessing the exposure interactions of environmental and biological systems. Once the entire modeling system is validated, it will run f...

Assessment of copper nanoparticles (Cu-NPs) and copper (II) oxide (CuO) induced hemato- and hepatotoxicity in Cyprinus carpio

NASA Astrophysics Data System (ADS)

Noureen, Aasma; Jabeen, Farhat; Tabish, Tanveer A.; Yaqub, Sajid; Ali, Muhammad; Shakoor Chaudhry, Abdul

2018-04-01

Recently, Cu-based nanoparticles have drawn considerable attention for their various fascinating roles in multiple biological systems. It is recognized that their frequent use can create compatibility challenges for the recipient systems. Nevertheless, it is unclear how various biological interactions affect the compatibility of Cu oxide II (CuO) and Cu oxide nanoparticles (Cu-NPs) for different organisms. Consequently, it has been difficult to perform structured risk assessments for their use in biological systems. Therefore, this study compared the effects of different doses of waterborne Cu-NPs and CuO on the blood and liver of selected groups of Cyprinus (C) carpio. These fish while housed in suitable water tanks were exposed to one of the following treatments for 14 d: control (no added Cu) or 0.5 or 1 or 1.5 mg Cu as Cu-NPs or CuO l-1 of water. We found significant changes in all assessed blood parameters of fish in response to increasing doses from 0 to 1.5 mg of Cu-NPs or CuO. Similarly, increased levels of lipid peroxide and reduced glutathione (GSH) were also observed in the livers of C. carpio in Cu-NPs or CuO treated groups. Enhanced levels of lipid peroxidation and GSH were also recorded in the Cu-NP treated groups compared with the CuO treated groups in a dose dependent manner. The lowest catalase activity was observed in the liver of C. carpio treated with the higer dose of Cu-NPs. Cu-NP or CuO exposure induced significant histological alterations in the liver of C. carpio including focal necrosis, cloudy swelling of hepatocytes, degenerative hepatocytes, vacuolization, pyknotic nuclei, damaged central vein, nuclear hypertrophy, dilated sinusoid, vacuolated degeneration, congestion, and complete degeneration in a dose dependent manner. Substantial alterations in blood and liver specimens were observed in the Cu-NP treated fish when compared with the CuO treated fish. It appeared that the Cu-NPs were more toxic than the CuO as shown by the hemato- and hepatotoxicity in C. carpio of this study.

Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats.

PubMed

Cheng, Chen; Lin, Jia-zhen; Li, Li; Yang, Jun-ling; Jia, Wei-wei; Huang, Yu-hong; Du, Fei-fei; Wang, Feng-qing; Li, Mei-juan; Li, Yan-fen; Xu, Fang; Zhang, Na-ting; Olaleye, Olajide E; Sun, Yan; Li, Jian; Sun, Chang-hai; Zhang, Gui-ping; Li, Chuan

2016-04-01

Monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) are believed to be pharmacologically important for the antiseptic herbal injection XueBiJing. This study was designed to characterize the pharmacokinetics and disposition of monoterpene glycosides. Systemic exposure to Chishao monoterpene glycosides was assessed in human subjects receiving an intravenous infusion and multiple infusions of XueBiJing injection, followed by assessment of the pharmacokinetics of the major circulating compounds. Supportive rat studies were also performed. Membrane permeability and plasma-protein binding were assessed in vitro. A total of 18 monoterpene glycosides were detected in XueBiJing injection (content levels, 0.001-2.47 mmol/L), and paeoniflorin accounted for 85.5% of the total dose of monoterpene glycosides detected. In human subjects, unchanged paeoniflorin exhibited considerable levels of systemic exposure with elimination half-lives of 1.2-1.3 h; no significant metabolite was detected. Oxypaeoniflorin and albiflorin exhibited low exposure levels, and the remaining minor monoterpene glycosides were negligible or undetected. Glomerular-filtration-based renal excretion was the major elimination pathway of paeoniflorin, which was poorly bound to plasma protein. In rats, the systemic exposure level of paeoniflorin increased proportionally as the dose was increased. Rat lung, heart, and liver exposure levels of paeoniflorin were lower than the plasma level, with the exception of the kidney level, which was 4.3-fold greater than the plasma level; brain penetration was limited by the poor membrane permeability. Due to its significant systemic exposure and appropriate pharmacokinetic profile, as well as previously reported antiseptic properties, paeoniflorin is a promising XueBiJing constituent of therapeutic importance.

HEMODOSE: A Set of Multi-parameter Biodosimetry Tools

NASA Technical Reports Server (NTRS)

Hu, Shaowen; Blakely, William F.; Cucinotta, Francis A.

2014-01-01

There continues to be important concerns of the possibility of the occurrence of acute radiation syndromes following nuclear and radiological terrorism or accidents that may result in mass casualties in densely populated areas. To guide medical personnel in their clinical decisions for effective medical management and treatment of the exposed individuals, biological markers are usually applied to examine radiation induced biological changes to assess the severity of radiation injury to sensitive organ systems. Among these the peripheral blood cell counts are widely used to assess the extent of radiation induced bone marrow (BM) injury. This is due to the fact that hematopoietic system is a vulnerable part of the human body to radiation damage. Particularly, the lymphocyte, granulocyte, and platelet cells are the most radiosensitive of the blood elements, and monitoring their changes after exposure is regarded as a practical and recommended laboratory test to estimate radiation dose and injury. In this work we describe the HEMODOSE web tools, which are built upon solid physiological and pathophysiological understanding of mammalian hematopoietic systems, and rigorous coarse-grained biomathematical modeling and validation. Using single or serial granulocyte, lymphocyte, leukocyte, or platelet counts after exposure, these tools can estimate absorbed doses of adult victims very rapidly and accurately to assess the severity of BM radiation injury. Some patient data from historical accidents are utilized as examples to demonstrate the capabilities of these tools as a rapid point-of-care diagnostic or centralized high-throughput assay system in a large-scale radiological disaster scenario. HEMODOSE web tools establish robust correlations between the absorbed doses and victim's various types of blood cell counts not only in the early time window (1 or 2 days), but also in very late phase (up to 4 weeks) after exposure.

Independent calculation-based verification of IMRT plans using a 3D dose-calculation engine.

PubMed

Arumugam, Sankar; Xing, Aitang; Goozee, Gary; Holloway, Lois

2013-01-01

Independent monitor unit verification of intensity-modulated radiation therapy (IMRT) plans requires detailed 3-dimensional (3D) dose verification. The aim of this study was to investigate using a 3D dose engine in a second commercial treatment planning system (TPS) for this task, facilitated by in-house software. Our department has XiO and Pinnacle TPSs, both with IMRT planning capability and modeled for an Elekta-Synergy 6MV photon beam. These systems allow the transfer of computed tomography (CT) data and RT structures between them but do not allow IMRT plans to be transferred. To provide this connectivity, an in-house computer programme was developed to convert radiation therapy prescription (RTP) files as generated by many planning systems into either XiO or Pinnacle IMRT file formats. Utilization of the technique and software was assessed by transferring 14 IMRT plans from XiO and Pinnacle onto the other system and performing 3D dose verification. The accuracy of the conversion process was checked by comparing the 3D dose matrices and dose volume histograms (DVHs) of structures for the recalculated plan on the same system. The developed software successfully transferred IMRT plans generated by 1 planning system into the other. Comparison of planning target volume (TV) DVHs for the original and recalculated plans showed good agreement; a maximum difference of 2% in mean dose, - 2.5% in D95, and 2.9% in V95 was observed. Similarly, a DVH comparison of organs at risk showed a maximum difference of +7.7% between the original and recalculated plans for structures in both high- and medium-dose regions. However, for structures in low-dose regions (less than 15% of prescription dose) a difference in mean dose up to +21.1% was observed between XiO and Pinnacle calculations. A dose matrix comparison of original and recalculated plans in XiO and Pinnacle TPSs was performed using gamma analysis with 3%/3mm criteria. The mean and standard deviation of pixels passing gamma tolerance for XiO-generated IMRT plans was 96.1 ± 1.3, 96.6 ± 1.2, and 96.0 ± 1.5 in axial, coronal, and sagittal planes respectively. Corresponding results for Pinnacle-generated IMRT plans were 97.1 ± 1.5, 96.4 ± 1.2, and 96.5 ± 1.3 in axial, coronal, and sagittal planes respectively. © 2013 American Association of Medical Dosimetrists.

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

Suzuki, Minoru; Sakurai, Yoshinori; Masunaga, Shinichiro

Purpose: To investigate the feasibility of boron neutron capture therapy (BNCT) for malignant pleural mesothelioma (MPM) from a viewpoint of dose distribution analysis using Simulation Environment for Radiotherapy Applications (SERA), a currently available BNCT treatment planning system. Methods and Materials: The BNCT treatment plans were constructed for 3 patients with MPM using the SERA system, with 2 opposed anterior-posterior beams. The {sup 1}B concentrations in the tumor and normal lung in this study were assumed to be 84 and 24 ppm, respectively, and were derived from data observed in clinical trials. The maximum, mean, and minimum doses to the tumorsmore » and the normal lung were assessed for each plan. The doses delivered to 5% and 95% of the tumor volume, D{sub 05} and D{sub 95}, were adopted as the representative dose for the maximum and minimum dose, respectively. Results: When the D{sub 05} to the normal ipsilateral lung was 5 Gy-Eq, the D{sub 95} and mean doses delivered to the normal lung were 2.2-3.6 and 3.5-4.2 Gy-Eq, respectively. The mean doses delivered to the tumors were 22.4-27.2 Gy-Eq. The D{sub 05} and D{sub 95} doses to the tumors were 9.6-15.0 and 31.5-39.5 Gy-Eq, respectively. Conclusions: From a viewpoint of the dose-distribution analysis, BNCT has the possibility to be a promising treatment for MPM patients who are inoperable because of age and other medical illnesses.« less

Evaluation of lens dose from anterior electron beams: comparison of Pinnacle and Gafchromic EBT3 film.

PubMed

Sonier, Marcus; Wronski, Matt; Yeboah, Collins

2015-03-08

Lens dose is a concern during the treatment of facial lesions with anterior electron beams. Lead shielding is routinely employed to reduce lens dose and minimize late complications. The purpose of this work is twofold: 1) to measure dose pro-files under large-area lead shielding at the lens depth for clinical electron energies via film dosimetry; and 2) to assess the accuracy of the Pinnacle treatment planning system in calculating doses under lead shields. First, to simulate the clinical geometry, EBT3 film and 4 cm wide lead shields were incorporated into a Solid Water phantom. With the lead shield inside the phantom, the film was positioned at a depth of 0.7 cm below the lead, while a variable thickness of solid water, simulating bolus, was placed on top. This geometry was reproduced in Pinnacle to calculate dose profiles using the pencil beam electron algorithm. The measured and calculated dose profiles were normalized to the central-axis dose maximum in a homogeneous phantom with no lead shielding. The resulting measured profiles, functions of bolus thickness and incident electron energy, can be used to estimate the lens dose under various clinical scenarios. These profiles showed a minimum lead margin of 0.5 cm beyond the lens boundary is required to shield the lens to ≤ 10% of the dose maximum. Comparisons with Pinnacle showed a consistent overestimation of dose under the lead shield with discrepancies of ~ 25% occur-ring near the shield edge. This discrepancy was found to increase with electron energy and bolus thickness and decrease with distance from the lead edge. Thus, the Pinnacle electron algorithm is not recommended for estimating lens dose in this situation. The film measurements, however, allow for a reasonable estimate of lens dose from electron beams and for clinicians to assess the lead margin required to reduce the lens dose to an acceptable level.

SU-F-BRD-05: Robustness of Dose Painting by Numbers in Proton Therapy

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

Montero, A Barragan; Sterpin, E; Lee, J

Purpose: Proton range uncertainties may cause important dose perturbations within the target volume, especially when steep dose gradients are present as in dose painting. The aim of this study is to assess the robustness against setup and range errors for high heterogeneous dose prescriptions (i.e., dose painting by numbers), delivered by proton pencil beam scanning. Methods: An automatic workflow, based on MATLAB functions, was implemented through scripting in RayStation (RaySearch Laboratories). It performs a gradient-based segmentation of the dose painting volume from 18FDG-PET images (GTVPET), and calculates the dose prescription as a linear function of the FDG-uptake value on eachmore » voxel. The workflow was applied to two patients with head and neck cancer. Robustness against setup and range errors of the conventional PTV margin strategy (prescription dilated by 2.5 mm) versus CTV-based (minimax) robust optimization (2.5 mm setup, 3% range error) was assessed by comparing the prescription with the planned dose for a set of error scenarios. Results: In order to ensure dose coverage above 95% of the prescribed dose in more than 95% of the GTVPET voxels while compensating for the uncertainties, the plans with a PTV generated a high overdose. For the nominal case, up to 35% of the GTVPET received doses 5% beyond prescription. For the worst of the evaluated error scenarios, the volume with 5% overdose increased to 50%. In contrast, for CTV-based plans this 5% overdose was present only in a small fraction of the GTVPET, which ranged from 7% in the nominal case to 15% in the worst of the evaluated scenarios. Conclusion: The use of a PTV leads to non-robust dose distributions with excessive overdose in the painted volume. In contrast, robust optimization yields robust dose distributions with limited overdose. RaySearch Laboratories is sincerely acknowledged for providing us with RayStation treatment planning system and for the support provided.« less

Low-Dose Carcinogenicity Studies

EPA Science Inventory

One of the major deficiencies of cancer risk assessments is the lack of low-dose carcinogenicity data. Most assessments require extrapolation from high to low doses, which is subject to various uncertainties. Only 4 low-dose carcinogenicity studies and 5 low-dose biomarker/pre-n...

Modulation of cannabinoid signaling by amygdala α2-adrenergic system in fear conditioning.

PubMed

Nasehi, Mohammad; Zamanparvar, Majid; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

2016-03-01

The noradrenergic system plays a critical role in the modulation of emotional state, primarily related to anxiety, arousal, and stress. Growing evidence suggests that the endocannabinoid system mediates stress responses and emotional homeostasis, in part, by targeting noradrenergic circuits. In addition, there is an interaction between the cannabinoid and noradrenergic system that has significant functional and behavioral implications. Considering the importance of these systems in forming memories for fearful events, we have investigated the involvement of basolateral amygdala (BLA) α2-adrenoceptors on ACPA (as selective cannabinoid CB1 agonist)-induced inhibition of the acquisition of contextual and auditory conditioned fear. A contextual and auditory fear conditioning apparatus for assess fear memory in adult male NMRI mice was used. Pre-training, intraperitoneal administration of ACPA decreased the percentage freezing time in contextual (at doses of 0.05 and 0.1mg/kg) and auditory (at dose of 0.1 mg/kg) in the fear conditioning task, indicating memory acquisition deficit. The same result was observed with intra-BLA microinjection of clonidine (0.001-0.5 μg/mouse, for both memories), as α2-adrenoceptor agonist and yohimbine (at doses of 0.005 and 0.05 for contextual and at dose of 0.05 μg/mouse for auditory fear memory), as α2-adrenoceptor antagonist. In addition, intra-BLA microinjection of clonidine (0.0005 μg/mouse) did not alter ACPA response in both conditions, while the same dose of yohimbine potentiated ACPA response at the lower dose on contextual fear memory. It is concluded that BLA α2-adrenergic receptors may be involved in context- but not tone-dependent fear memory impairment induced by activation of CB1 receptors. Copyright © 2015. Published by Elsevier B.V.

IRIS Toxicological Review of Hexachloroethane (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of hexachloroethane that when finalized will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Libby Amphibole Asbestos (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of Libby Amphibole Asbestos that will appear in the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Hydrogen Cyanide (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of hydrogen cyanide and cyanide salts that will appear on the Integrated Risk Information System (IRIS) database.

Evaluation of nonrigid registration models for interfraction dose accumulation in radiotherapy

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

Janssens, Guillaume; Orban de Xivry, Jonathan; Fekkes, Stein

2009-09-15

Purpose: Interfraction dose accumulation is necessary to evaluate the dose distribution of an entire course of treatment by adding up multiple dose distributions of different treatment fractions. This accumulation of dose distributions is not straightforward as changes in the patient anatomy may occur during treatment. For this purpose, the accuracy of nonrigid registration methods is assessed for dose accumulation based on the calculated deformations fields. Methods: A phantom study using a deformable cubic silicon phantom with implanted markers and a cylindrical silicon phantom with MOSFET detectors has been performed. The phantoms were deformed and images were acquired using a cone-beammore » CT imager. Dose calculations were performed on these CT scans using the treatment planning system. Nonrigid CT-based registration was performed using two different methods, the Morphons and Demons. The resulting deformation field was applied on the dose distribution. For both phantoms, accuracy of the registered dose distribution was assessed. For the cylindrical phantom, also measured dose values in the deformed conditions were compared with the dose values of the registered dose distributions. Finally, interfraction dose accumulation for two treatment fractions of a patient with primary rectal cancer has been performed and evaluated using isodose lines and the dose volume histograms of the target volume and normal tissue. Results: A significant decrease in the difference in marker or MOSFET position was observed after nonrigid registration methods (p<0.001) for both phantoms and with both methods, as well as a significant decrease in the dose estimation error (p<0.01 for the cubic phantom and p<0.001 for the cylindrical) with both methods. Considering the whole data set at once, the difference between estimated and measured doses was also significantly decreased using registration (p<0.001 for both methods). The patient case showed a slightly underdosed planning target volume and an overdosed bladder volume due to anatomical deformations. Conclusions: Dose accumulation using nonrigid registration methods is possible using repeated CT imaging. This opens possibilities for interfraction dose accumulation and adaptive radiotherapy to incorporate possible differences in dose delivered to the target volume and organs at risk due to anatomical deformations.« less

SU-D-BRC-03: Development and Validation of an Online 2D Dose Verification System for Daily Patient Plan Delivery Accuracy Check

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

Zhao, J; Hu, W; Xing, Y

Purpose: All plan verification systems for particle therapy are designed to do plan verification before treatment. However, the actual dose distributions during patient treatment are not known. This study develops an online 2D dose verification tool to check the daily dose delivery accuracy. Methods: A Siemens particle treatment system with a modulated scanning spot beam is used in our center. In order to do online dose verification, we made a program to reconstruct the delivered 2D dose distributions based on the daily treatment log files and depth dose distributions. In the log files we can get the focus size, positionmore » and particle number for each spot. A gamma analysis is used to compare the reconstructed dose distributions with the dose distributions from the TPS to assess the daily dose delivery accuracy. To verify the dose reconstruction algorithm, we compared the reconstructed dose distributions to dose distributions measured using PTW 729XDR ion chamber matrix for 13 real patient plans. Then we analyzed 100 treatment beams (58 carbon and 42 proton) for prostate, lung, ACC, NPC and chordoma patients. Results: For algorithm verification, the gamma passing rate was 97.95% for the 3%/3mm and 92.36% for the 2%/2mm criteria. For patient treatment analysis,the results were 97.7%±1.1% and 91.7%±2.5% for carbon and 89.9%±4.8% and 79.7%±7.7% for proton using 3%/3mm and 2%/2mm criteria, respectively. The reason for the lower passing rate for the proton beam is that the focus size deviations were larger than for the carbon beam. The average focus size deviations were −14.27% and −6.73% for proton and −5.26% and −0.93% for carbon in the x and y direction respectively. Conclusion: The verification software meets our requirements to check for daily dose delivery discrepancies. Such tools can enhance the current treatment plan and delivery verification processes and improve safety of clinical treatments.« less

Clinical Experience and Evaluation of Patient Treatment Verification With a Transit Dosimeter

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

Ricketts, Kate, E-mail: k.ricketts@ucl.ac.uk; Department of Radiotherapy Physics, Royal Berkshire NHS Foundation Trust, Reading; Navarro, Clara

2016-08-01

Purpose: To prospectively evaluate a protocol for transit dosimetry on a patient population undergoing intensity modulated radiation therapy (IMRT) and to assess the issues in clinical implementation of electronic portal imaging devices (EPIDs) for treatment verification. Methods and Materials: Fifty-eight patients were enrolled in the study. Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. Measured EPID dose maps were back-projected using the planning computed tomographic (CT) images to calculate dose at prespecified points within the patient and compared with treatment planning system dose offline using point dose difference and point γ analysis. Themore » deviation of the results was used to inform future action levels. Results: Two hundred twenty-five transit images were analyzed, composed of breast, prostate, and head and neck IMRT fields. Patient measurements demonstrated the potential of the dose verification protocol to model dose well under complex conditions: 83.8% of all delivered beams achieved the initial set tolerance level of Δ{sub D} of 0 ± 5 cGy or %Δ{sub D} of 0% ± 5%. Importantly, the protocol was also sensitive to anatomic changes and spotted that 3 patients from 20 measured prostate patients had undergone anatomic change in comparison with the planning CT. Patient data suggested an EPID-reconstructed versus treatment planning system dose difference action level of 0% ± 7% for breast fields. Asymmetric action levels were more appropriate for inversed IMRT fields, using absolute dose difference (−2 ± 5 cGy) or summed field percentage dose difference (−6% ± 7%). Conclusions: The in vivo dose verification method was easy to use and simple to implement, and it could detect patient anatomic changes that impacted dose delivery. The system required no extra dose to the patient or treatment time delay and so could be used throughout the course of treatment to identify and limit systematic and random errors in dose delivery for patient groups.« less

Clinical Experience and Evaluation of Patient Treatment Verification With a Transit Dosimeter.

PubMed

Ricketts, Kate; Navarro, Clara; Lane, Katherine; Blowfield, Claire; Cotten, Gary; Tomala, Dee; Lord, Christine; Jones, Joanne; Adeyemi, Abiodun

2016-08-01

To prospectively evaluate a protocol for transit dosimetry on a patient population undergoing intensity modulated radiation therapy (IMRT) and to assess the issues in clinical implementation of electronic portal imaging devices (EPIDs) for treatment verification. Fifty-eight patients were enrolled in the study. Amorphous silicon EPIDs were calibrated for dose and used to acquire images of delivered fields. Measured EPID dose maps were back-projected using the planning computed tomographic (CT) images to calculate dose at prespecified points within the patient and compared with treatment planning system dose offline using point dose difference and point γ analysis. The deviation of the results was used to inform future action levels. Two hundred twenty-five transit images were analyzed, composed of breast, prostate, and head and neck IMRT fields. Patient measurements demonstrated the potential of the dose verification protocol to model dose well under complex conditions: 83.8% of all delivered beams achieved the initial set tolerance level of ΔD of 0 ± 5 cGy or %ΔD of 0% ± 5%. Importantly, the protocol was also sensitive to anatomic changes and spotted that 3 patients from 20 measured prostate patients had undergone anatomic change in comparison with the planning CT. Patient data suggested an EPID-reconstructed versus treatment planning system dose difference action level of 0% ± 7% for breast fields. Asymmetric action levels were more appropriate for inversed IMRT fields, using absolute dose difference (-2 ± 5 cGy) or summed field percentage dose difference (-6% ± 7%). The in vivo dose verification method was easy to use and simple to implement, and it could detect patient anatomic changes that impacted dose delivery. The system required no extra dose to the patient or treatment time delay and so could be used throughout the course of treatment to identify and limit systematic and random errors in dose delivery for patient groups. Copyright © 2016 Elsevier Inc. All rights reserved.

Low-Dose Naltrexone Treatment of Familial Benign Pemphigus (Hailey-Hailey Disease).

PubMed

Ibrahim, Omer; Hogan, Sara R; Vij, Alok; Fernandez, Anthony P

2017-10-01

Familial benign pemphigus, or Hailey-Hailey disease (HHD), is a rare and debilitating genetic dermatosis characterized by chronic, recurrent vesicles, erosions, and maceration in flexural areas. Despite the reported therapeutic modalities, such as topical and systemic corticosteroids, systemic immunomodulators, topical and systemic retinoids, and laser, HHD can still be markedly difficult to control. To assess low-dose naltrexone hydrochloride in the treatment of recalcitrant HHD. In this case series, 3 patients with biopsy-proven recalcitrant HHD were evaluated in the outpatient dermatology clinic at the Cleveland Clinic. Each patient was treated with low-dose naltrexone hydrochloride at a dosage of 1.5 to 3.0 mg per day. No laboratory monitoring was necessary. Clinical response (healing of erosions, improvement in erythema, and alleviation of pain), adverse effects, and subjective quality of life were monitored throughout the treatment. The study dates were January 2016 to January 2017. Objective clinical response as assessed by the treating dermatologist, subjective quality of life as reported by the patient, and recorded adverse effects were monitored throughout the treatment at intervals of 2 to 3 months. The 3 patients included a woman in her 40s and 2 men in their 60s. Each patient exhibited at least an 80% improvement in extent of disease, with one patient demonstrating 90% clearance. All 3 patients had substantial improvement in quality of life, with one patient reporting improvement in his depression. No adverse effects were recorded. Low-dose naltrexone may represent a low-cost and low-risk alternative or adjunct in the treatment of HHD.

Technical Note: Initial characterization of the new EBT-XD Gafchromic film.

PubMed

Grams, Michael P; Gustafson, Jon M; Long, Kenneth M; de los Santos, Luis E Fong

2015-10-01

To assess the dosimetric accuracy and energy dependence of the new EBT-eXtended Dose (XD) Gafchromic film and to compare the lateral response artifact (LRA) between EBT-XD and EBT3 film. EBT3 and EBT-XD calibration curves were created by exposing films to known doses from 0 to 3000 cGy using a 6 MV beam. To assess the accuracy and dynamic range of EBT-XD, a 60° enhanced dynamic wedge (EDW) was used to deliver a dose range of approximately 200-2900 cGy. Comparison to treatment planning system (TPS) calculation was made using a gamma analysis with 2%/2 mm passing criteria. To assess and compare the LRA between EBT3 and EBT-XD, 21 × 21 cm(2) open fields delivered doses of 1000, 2000, and 3000 cGy to both types of film. Films were placed at the center of the scanner, and ratios of measured to TPS predicted doses were calculated at 50 and 80 mm lateral from the scanner center in order to quantitatively assess the LRA. To evaluate the energy dependence of EBT-XD film, seven known doses ranging from 400 to 3000 cGy were delivered using both 6 and 18 MV beams and the resulting optical densities (ODs) compared. The gamma passing rate was 99.1% for the 6 MV EDW delivery. EBT-XD film exhibited minimal LRA (<1%) up to 3000 cGy. In contrast, EBT3 demonstrated an under-response of 11.3% and 22.7% at lateral positions of 50 and 80 mm, respectively, for the 3000 cGy exposure. Differences between ODs of the EBT-XD films exposed to known doses from 6 to 18 MV beams were <0.8% suggesting minimal energy dependence throughout this energy range. The LRA of EBT-XD is greatly reduced when compared to EBT3. This in combination with its accuracy from 0 to 3000 cGy and minimal energy dependence from 6 to 18 MV makes EBT-XD film well suited for dosimetric measurements in high dose SRS/SBRT applications.

Assessing doses to interventional radiologists using a personal dosimeter worn over a protective apron.

PubMed

Stranden, E; Widmark, A; Sekse, T

2008-05-01

Interventional radiologists receive significant radiation doses, and it is important to have simple methods for routine monitoring of their exposure. To evaluate the usefulness of a dosimeter worn outside the protective apron for assessments of dose to interventional radiologists. Assessments of effective dose versus dose to dosimeters worn outside the protective apron were achieved by phantom measurements. Doses outside and under the apron were assessed by phantom measurements and measurements on eight radiologists wearing two routine dosimeters for a 2-month period during ordinary working conditions. Finger doses for the same radiologists were recorded using thermoluminescent dosimeters (TLD; DXT-RAD Extremity dosimeters). Typical values for the ratio between effective dose and dosimeter dose were found to be about 0.02 when the radiologist used a thyroid shield and about 0.03 without. The ratio between the dose to the dosimeter under and outside a protective apron was found to be less than 0.04. There was very good correlation between finger dose and dosimeter dose. A personal dosimeter worn outside a protective apron is a good screening device for dose to the eyes and fingers as well as for effective dose, even though the effective dose is grossly overestimated. Relatively high dose to the fingers and eyes remains undetected by a dosimeter worn under the apron.

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

NASA Astrophysics Data System (ADS)

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

1996-12-01

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

Radiometric assessment of natural radioactivity levels of agricultural soil samples collected in Dakahlia, Egypt.

PubMed

Issa, Shams A M

2013-01-01

Determination of the natural radioactivity has been carried out, by using a gamma-ray spectrometry [NaI (Tl) 3″ × 3″] system, in surface soil samples collected from various locations in Dakahlia governorate, Egypt. These locations form the agriculturally important regions of Egypt. The study area has many industries such as chemical, paper, organic fertilisers and construction materials, and the soils of the study region are used as a construction material. Therefore, it becomes necessary to study the natural radioactivity levels in soil to assess the dose for the population in order to know the health risks. The activity concentrations of (226)Ra, (232)Th and (40)K in the soil ranged from 5.7 ± 0.3 to 140 ± 7, from 9.0 ± 0.4 to 139 ± 7 and from 22 ± 1 to 319 ± 16 Bq kg(-1), respectively. The absorbed dose rate, annual effective dose rate, radium equivalent (Req), excess lifetime cancer risk, hazard indices (Hex and Hin) and annual gonadal dose equivalent, which resulted from the natural radionuclides in the soil were calculated.

Measurements of energetic particle radiation in transit to Mars on the Mars Science Laboratory.

PubMed

Zeitlin, C; Hassler, D M; Cucinotta, F A; Ehresmann, B; Wimmer-Schweingruber, R F; Brinza, D E; Kang, S; Weigle, G; Böttcher, S; Böhm, E; Burmeister, S; Guo, J; Köhler, J; Martin, C; Posner, A; Rafkin, S; Reitz, G

2013-05-31

The Mars Science Laboratory spacecraft, containing the Curiosity rover, was launched to Mars on 26 November 2011, and for most of the 253-day, 560-million-kilometer cruise to Mars, the Radiation Assessment Detector made detailed measurements of the energetic particle radiation environment inside the spacecraft. These data provide insights into the radiation hazards that would be associated with a human mission to Mars. We report measurements of the radiation dose, dose equivalent, and linear energy transfer spectra. The dose equivalent for even the shortest round-trip with current propulsion systems and comparable shielding is found to be 0.66 ± 0.12 sievert.

Criticality accident dosimetry with ESR spectroscopy.

PubMed

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

1996-01-01

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

Assessment of Ethylene Vinyl-Acetato Copolymer (EVA) Samples Bombarded by Gamma Radiation via Linearity Analyses

NASA Astrophysics Data System (ADS)

de Oliveira, L. N.; do Nascimento, E. O.; Schimidt, F.; Antonio, P. L.; Caldas, L. V. E.

2018-03-01

Materials with the potential to become dosimeters are of interest in radiation physics. In this research, the materials were analyzed and compared in relation to their linearity ranges. Samples of ethylene vinyl-acetate copolymer (EVA) were irradiated with doses from 10 Gy to 10 kGy using a 60Co Gamma-Cell system 220 and evaluated with the FTIR technique. The linearity analyses were applied through two methodologies, searching for linear regions in their response. The results show that both applied analyses indicate linear regions in defined dose interval. The radiation detectors EVA can be useful for radiation dosimetry in intermediate and high doses.

Characteristic image quality of a third generation dual-source MDCT scanner: Noise, resolution, and detectability

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

Solomon, Justin, E-mail: justin.solomon@duke.edu; Wilson, Joshua; Samei, Ehsan

2015-08-15

Purpose: The purpose of this work was to assess the inherent image quality characteristics of a new multidetector computed tomography system in terms of noise, resolution, and detectability index as a function of image acquisition and reconstruction for a range of clinically relevant settings. Methods: A multisized image quality phantom (37, 30, 23, 18.5, and 12 cm physical diameter) was imaged on a SOMATOM Force scanner (Siemens Medical Solutions) under variable dose, kVp, and tube current modulation settings. Images were reconstructed with filtered back projection (FBP) and with advanced modeled iterative reconstruction (ADMIRE) with iterative strengths of 3, 4, andmore » 5. Image quality was assessed in terms of the noise power spectrum (NPS), task transfer function (TTF), and detectability index for a range of detection tasks (contrasts of approximately 45, 90, 300, −900, and 1000 HU, and 2–20 mm diameter) based on a non-prewhitening matched filter model observer with eye filter. Results: Image noise magnitude decreased with decreasing phantom size, increasing dose, and increasing ADMIRE strength, offering up to 64% noise reduction relative to FBP. Noise texture in terms of the NPS was similar between FBP and ADMIRE (<5% shift in peak frequency). The resolution, based on the TTF, improved with increased ADMIRE strength by an average of 15% in the TTF 50% frequency for ADMIRE-5. The detectability index increased with increasing dose and ADMIRE strength by an average of 55%, 90%, and 163% for ADMIRE 3, 4, and 5, respectively. Assessing the impact of mA modulation for a fixed average dose over the length of the phantom, detectability was up to 49% lower in smaller phantom sections and up to 26% higher in larger phantom sections for the modulated scan compared to a fixed tube current scan. Overall, the detectability exhibited less variability with phantom size for modulated scans compared to fixed tube current scans. Conclusions: Image quality increased with increasing dose and decreasing phantom size. The CT system exhibited nonlinear noise and resolution properties, especially at very low-doses, large phantom sizes, and for low-contrast objects. Objective image quality metrics generally increased with increasing dose and ADMIRE strength, and with decreasing phantom size. The ADMIRE algorithm could offer comparable image quality at reduced doses or improved image quality at the same dose. The use of tube current modulation resulted in more consistent image quality with changing phantom size.« less

Dependence of Coronary 3-Dimensional Dose Maps on Coronary Topologies and Beam Set in Breast Radiation Therapy: A Study Based on CT Angiographies

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

Moignier, Alexandra, E-mail: alexandra.moignier@gmail.com; Broggio, David; Derreumaux, Sylvie

2014-05-01

Purpose: In left-side breast radiation therapy (RT), doses to the left main (LM) and left anterior descending (LAD) coronary arteries are usually assessed after delineation by prior anatomic knowledge on the treatment planning computed tomography (CT) scan. In this study, dose sensitivity due to interindividual coronary topology variation was assessed, and hot spots were located. Methods and Materials: Twenty-two detailed heart models, created from heart computed tomography angiographies, were fitted into a single representative female thorax. Two breast RT protocols were then simulated into a treatment planning system: the first protocol comprised tangential and tumoral bed beams (TGs{sub T}B) atmore » 50 + 16 Gy, the second protocol added internal mammary chain beams at 50 Gy to TGs{sub T}B (TGs{sub T}B{sub I}MC). For the heart, the LAD, and the LM, several dose indicators were calculated: dose-volume histograms, mean dose (D{sub mean}), minimal dose received by the most irradiated 2% of the volume (D{sub 2%}), and 3-dimensional (3D) dose maps. Variations of these indicators with anatomies were studied. Results: For the LM, the intermodel dispersion of D{sub mean} and D{sub 2%} was 10% and 11%, respectively, with TGs{sub T}B and 40% and 80%, respectively, with TGs{sub T}B{sub I}MC. For the LAD, these dispersions were 19% (D{sub mean}) and 49% (D{sub 2%}) with TGs{sub T}B and 35% (D{sub mean}) and 76% (D{sub 2%}) with TGs{sub T}B{sub I}MC. The 3D dose maps revealed that the internal mammary chain beams induced hot spots between 20 and 30 Gy on the LM and the proximal LAD for some coronary topologies. Without IMC beams, hot spots between 5 and 26 Gy are located on the middle and distal LAD. Conclusions: Coronary dose distributions with hot spot location and dose level can change significantly depending on coronary topology, as highlighted by 3D coronary dose maps. In clinical practice, coronary imaging may be required for a relevant coronary dose assessment, especially in cases of internal mammary chain irradiation.« less

EVALUATING QUANTITATIVE FORMULAS FOR DOSE-RESPONSE ASSESSMENT OF CHEMICAL MIXTURES

EPA Science Inventory

Risk assessment formulas are often distinguished from dose-response models by being rough but necessary. The evaluation of these rough formulas is described here, using the example of mixture risk assessment. Two conditions make the dose-response part of mixture risk assessment d...

Attenuation in rats of impairments of memory by scopolamine, a muscarinic receptor antagonist, by mecamylamine, a nicotinic receptor antagonist.

PubMed

Newman, L A; Gold, P E

2016-03-01

Scopolamine, a muscarinic antagonist, impairs learning and memory for many tasks, supporting an important role for the cholinergic system in these cognitive functions. The findings are most often interpreted to indicate that a decrease in postsynaptic muscarinic receptor activation mediates the memory impairments. However, scopolamine also results in increased release of acetylcholine in the brain as a result of blocking presynaptic muscarinic receptors. The present experiments assess whether scopolamine-induced increases in acetylcholine release may impair memory by overstimulating postsynaptic cholinergic nicotinic receptors, i.e., by reaching the high end of a nicotinic receptor activation inverted-U dose-response function. Rats tested in a spontaneous alternation task showed dose-dependent working memory deficits with systemic injections of mecamylamine and scopolamine. When an amnestic dose of scopolamine (0.15 mg/kg) was co-administered with a subamnestic dose of mecamylamine (0.25 mg/kg), this dose of mecamylamine significantly attenuated the scopolamine-induced memory impairments. We next assessed the levels of acetylcholine release in the hippocampus in the presence of scopolamine and mecamylamine. Mecamylamine injections resulted in decreased release of acetylcholine, while scopolamine administration caused a large increase in acetylcholine release. These findings indicate that a nicotinic antagonist can attenuate impairments in memory produced by a muscarinic antagonist. The nicotinic antagonist may block excessive activation of nicotinic receptors postsynaptically or attenuate increases in acetylcholine release presynaptically. Either effect of a nicotinic antagonist-to decrease scopolamine-induced increases in acetylcholine output or to decrease postsynaptic acetylcholine receptor activation-may mediate the negative effects on memory of muscarinic antagonists.

Transferring mixtures of chemicals from sediment to a bioassay using silicone-based passive sampling and dosing.

PubMed

Mustajärvi, Lukas; Eriksson-Wiklund, Ann-Kristin; Gorokhova, Elena; Jahnke, Annika; Sobek, Anna

2017-11-15

Environmental mixtures of chemicals consist of a countless number of compounds with unknown identity and quantity. Yet, chemical regulation is mainly built around the assessment of single chemicals. Existing frameworks for assessing the toxicity of mixtures require that both the chemical composition and quantity are known. Quantitative analyses of the chemical composition of environmental mixtures are however extremely challenging and resource-demanding. Bioassays may therefore serve as a useful approach for investigating the combined toxicity of environmental mixtures of chemicals in a cost-efficient and holistic manner. In this study, an unknown environmental mixture of bioavailable semi-hydrophobic to hydrophobic chemicals was sampled from a contaminated sediment in a coastal Baltic Sea area using silicone polydimethylsiloxane (PDMS) as an equilibrium passive sampler. The chemical mixture was transferred to a PDMS-based passive dosing system, and its applicability was demonstrated using green algae Tetraselmis suecica in a cell viability assay. The proportion of dead cells increased significantly with increasing exposure level and in a dose-response manner. At an ambient concentration, the proportion of dead cells in the population was nearly doubled compared to the control; however, the difference was non-significant due to high inter-replicate variability and a low number of replicates. The validation of the test system regarding equilibrium sampling, loading efficiency into the passive dosing polymer, stability of the mixture composition, and low algal mortality in control treatments demonstrates that combining equilibrium passive sampling and passive dosing is a promising tool for investigating the toxicity of bioavailable semi-hydrophobic and hydrophobic chemicals in complex environmental mixtures.

Biometrical evaluation of the performance of the revised OECD Test Guideline 402 for assessing acute dermal toxicity.

PubMed

Mielke, H; Strickland, J; Jacobs, M N; Mehta, J M

2017-10-01

A comprehensive biometrical assessment was conducted to compare the performance of multiple test designs for acute dermal systemic toxicity to support the animal welfare update to the original OECD Test Guideline (TG) 402 for acute dermal toxicity. The test designs evaluated included: (1) two, three, or five animals per dose group (2) evident toxicity or lethality endpoints and (3) absence or presence of a one-animal sighting study. The revision of TG 402 respected the 3R principles (replace, reduce, refine) of animal testing. The results demonstrate that the TG 402 test design can be optimised with reduced animal numbers per test group, such that a scenario of two animals per group following a sighting study at a starting dose of 200 mg/kg bw (unless further information is available to better define the starting dose) would provide a classification which in most cases is conservative, without compromising both the statistical ability of the study to assess dermal toxicity, or the relevant classification outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

A methodology for the assessment of inhalation exposure to aluminium from antiperspirant sprays.

PubMed

Schwarz, Katharina; Pappa, Gerlinde; Miertsch, Heike; Scheel, Julia; Koch, Wolfgang

2018-04-01

Inhalative exposure can occur accidentally when using cosmetic spray products. Usually, a tiered approach is applied for exposure assessment, starting with rather conservative, simplistic calculation models that may be improved with measured data and more refined modelling. Here we report on an advanced methodology to mimic in-use conditions for antiperspirant spray products to provide a more accurate estimate of the amount of aluminium possibly inhaled and taken up systemically, thus contributing to the overall body burden. Four typical products were sprayed onto a skin surrogate in defined rooms. For aluminium, size-related aerosol release fractions, i.e. inhalable, thoracic and respirable, were determined by a mass balance method taking droplet maturation into account. These data were included into a simple two-box exposure model, allowing calculation of the inhaled aluminium dose over 12 min. Systemic exposure doses were calculated for exposure of the deep lung and the upper respiratory tract using the Multiple Path Particle Deposition Model (MPPD) model. The total systemically available dose of aluminium was in all cases found to be less than 0.5 µg per application. With this study it could be demonstrated that refinement of the input data of the two-box exposure model with measured data of released airborne aluminium is a valuable approach to analyse the contribution of antiperspirant spray inhalation to total aluminium exposure as part of the overall risk assessment. We suggest the methodology which can also be applied to other exposure modelling approaches for spray products, and further is adapted to other similar use scenarios.

Methods for Probabilistic Radiological Dose Assessment at a High-Level Radioactive Waste Repository.

NASA Astrophysics Data System (ADS)

Maheras, Steven James

Methods were developed to assess and evaluate the uncertainty in offsite and onsite radiological dose at a high-level radioactive waste repository to show reasonable assurance that compliance with applicable regulatory requirements will be achieved. Uncertainty in offsite dose was assessed by employing a stochastic precode in conjunction with Monte Carlo simulation using an offsite radiological dose assessment code. Uncertainty in onsite dose was assessed by employing a discrete-event simulation model of repository operations in conjunction with an occupational radiological dose assessment model. Complementary cumulative distribution functions of offsite and onsite dose were used to illustrate reasonable assurance. Offsite dose analyses were performed for iodine -129, cesium-137, strontium-90, and plutonium-239. Complementary cumulative distribution functions of offsite dose were constructed; offsite dose was lognormally distributed with a two order of magnitude range. However, plutonium-239 results were not lognormally distributed and exhibited less than one order of magnitude range. Onsite dose analyses were performed for the preliminary inspection, receiving and handling, and the underground areas of the repository. Complementary cumulative distribution functions of onsite dose were constructed and exhibited less than one order of magnitude range. A preliminary sensitivity analysis of the receiving and handling areas was conducted using a regression metamodel. Sensitivity coefficients and partial correlation coefficients were used as measures of sensitivity. Model output was most sensitive to parameters related to cask handling operations. Model output showed little sensitivity to parameters related to cask inspections.

Monte Carlo simulation of the dose response of a novel 2D silicon diode array for use in hybrid MRI-LINAC systems.

PubMed

Gargett, Maegan; Oborn, Brad; Metcalfe, Peter; Rosenfeld, Anatoly

2015-02-01

MRI-guided radiation therapy systems (MRIgRT) are being developed to improve online imaging during treatment delivery. At present, the operation of single point dosimeters and an ionization chamber array have been characterized in such systems. This work investigates a novel 2D diode array, named "magic plate," for both single point calibration and 2D positional performance, the latter being a key element of modern radiotherapy techniques that will be delivered by these systems. geant4 Monte Carlo methods have been employed to study the dose response of a silicon diode array to 6 MV photon beams, in the presence of in-line and perpendicularly aligned uniform magnetic fields. The array consists of 121 silicon diodes (dimensions 1.5 × 1.5 × 0.38 mm(3)) embedded in kapton substrate with 1 cm pitch, spanning a 10 × 10 cm(2) area in total. A geometrically identical, water equivalent volume was simulated concurrently for comparison. The dose response of the silicon diode array was assessed for various photon beam field shapes and sizes, including an IMRT field, at 1 T. The dose response was further investigated at larger magnetic field strengths (1.5 and 3 T) for a 4 × 4 cm(2) photon field size. The magic plate diode array shows excellent correspondence (< ± 1%) to water dose in the in-line orientation, for all beam arrangements and magnetic field strengths investigated. The perpendicular orientation, however, exhibits a dose shift with respect to water at the high-dose-gradient beam edge of jaw-defined fields [maximum (4.3 ± 0.8)% over-response, maximum (1.8 ± 0.8)% under-response on opposing side for 1 T, uncertainty 1σ]. The trend is not evident in areas with in-field dose gradients typical of IMRT dose maps. A novel 121 pixel silicon diode array detector has been characterized by Monte Carlo simulation for its performance inside magnetic fields representative of current prototype and proposed MRI-linear accelerator systems. In the in-line orientation, the silicon dose is directly proportional to the water dose. In the perpendicular orientation, there is a shift in dose response relative to water in the highest dose gradient regions, at the edge of jaw-defined and single-segment MLC fields. The trend was not observed in-field for an IMRT beam. The array is expected to be a valuable tool in MRIgRT dosimetry.

Monte Carlo simulation of the dose response of a novel 2D silicon diode array for use in hybrid MRI–LINAC systems

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

Gargett, Maegan, E-mail: mg406@uowmail.edu.au; Rosenfeld, Anatoly; Oborn, Brad

2015-02-15

Purpose: MRI-guided radiation therapy systems (MRIgRT) are being developed to improve online imaging during treatment delivery. At present, the operation of single point dosimeters and an ionization chamber array have been characterized in such systems. This work investigates a novel 2D diode array, named “magic plate,” for both single point calibration and 2D positional performance, the latter being a key element of modern radiotherapy techniques that will be delivered by these systems. Methods: GEANT4 Monte Carlo methods have been employed to study the dose response of a silicon diode array to 6 MV photon beams, in the presence of in-linemore » and perpendicularly aligned uniform magnetic fields. The array consists of 121 silicon diodes (dimensions 1.5 × 1.5 × 0.38 mm{sup 3}) embedded in kapton substrate with 1 cm pitch, spanning a 10 × 10 cm{sup 2} area in total. A geometrically identical, water equivalent volume was simulated concurrently for comparison. The dose response of the silicon diode array was assessed for various photon beam field shapes and sizes, including an IMRT field, at 1 T. The dose response was further investigated at larger magnetic field strengths (1.5 and 3 T) for a 4 × 4 cm{sup 2} photon field size. Results: The magic plate diode array shows excellent correspondence (< ± 1%) to water dose in the in-line orientation, for all beam arrangements and magnetic field strengths investigated. The perpendicular orientation, however, exhibits a dose shift with respect to water at the high-dose-gradient beam edge of jaw-defined fields [maximum (4.3 ± 0.8)% over-response, maximum (1.8 ± 0.8)% under-response on opposing side for 1 T, uncertainty 1σ]. The trend is not evident in areas with in-field dose gradients typical of IMRT dose maps. Conclusions: A novel 121 pixel silicon diode array detector has been characterized by Monte Carlo simulation for its performance inside magnetic fields representative of current prototype and proposed MRI–linear accelerator systems. In the in-line orientation, the silicon dose is directly proportional to the water dose. In the perpendicular orientation, there is a shift in dose response relative to water in the highest dose gradient regions, at the edge of jaw-defined and single-segment MLC fields. The trend was not observed in-field for an IMRT beam. The array is expected to be a valuable tool in MRIgRT dosimetry.« less

Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos

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

Moreira, Estefania G.; Department of Physiological Sciences, State University of Londrina, Londrina, PR; Yu Xiaozhong

2010-06-15

Considering the wide variety of effects that have been reported to occur in the developmental neurotoxicity of chlorpyrifos (CP) and the lack of consensus on their dependence of brain acetylcholinesterase (AChE) activity inhibition, we applied microarray technology to explore dose-dependent alterations in transcriptional response in the fetal and maternal C57BL/6 mouse brain after daily gestational exposure (days 6 to 17) to CP (2, 4, 10, 12 or 15 mg/kg, sc). We identified significantly altered genes across doses and assessed for overrepresentation of Gene Ontology (GO) biological processes and KEGG pathways. We further clustered genes based on their expression profiles acrossmore » doses and repeated the GO/pathways analysis for each cluster. The dose-effect relationship of CP on gene expression, both at the gene and pathway levels was non-monotonic and not necessarily related to brain AChE inhibition. The largest impact was observed in the 10 mg/kg dose group which was also the LOAEL for brain AChE inhibition. In the maternal brain, lower doses (4 mg/kg) influenced GO categories and pathways such as cell adhesion, behavior, lipid metabolism, long-term potentiation, nervous system development, neurogenesis, synaptic transmission. In the fetal brain, lower doses (2 and/or 4 mg/kg) significantly altered cell division, translation, transmission of nerve impulse, chromatin modification, long-term potentiation. In addition, some genes involved in nervous system development and signaling were shown to be specifically influenced by these lower CP doses. Our approach was sensitive and reflected the diversity of responses known to be disrupted by CP and highlighted possible additional consequences of CP neurotoxicity, such as disturbance of the ubiquitin proteasome system.« less

Development of a Web-Based Clinical Decision Support System for Drug Prescription: Non-Interventional Naturalistic Description of the Antipsychotic Prescription Patterns in 4345 Outpatients and Future Applications.

PubMed

Berrouiguet, Sofian; Barrigón, Maria Luisa; Brandt, Sara A; Ovejero-García, Santiago; Álvarez-García, Raquel; Carballo, Juan Jose; Lenca, Philippe; Courtet, Philippe; Baca-García, Enrique

2016-01-01

The emergence of electronic prescribing devices with clinical decision support systems (CDSS) is able to significantly improve management pharmacological treatments. We developed a web application available on smartphones in order to help clinicians monitor prescription and further propose CDSS. A web application (www.MEmind.net) was developed to assess patients and collect data regarding gender, age, diagnosis and treatment. We analyzed antipsychotic prescriptions in 4345 patients attended in five Psychiatric Community Mental Health Centers from June 2014 to October 2014. The web-application reported average daily dose prescribed for antipsychotics, prescribed daily dose (PDD), and the PDD to defined daily dose (DDD) ratio. The MEmind web-application reported that antipsychotics were used in 1116 patients out of the total sample, mostly in 486 (44%) patients with schizophrenia related disorders but also in other diagnoses. Second generation antipsychotics (quetiapine, aripiprazole and long-acting paliperidone) were preferably employed. Low doses were more frequently used than high doses. Long acting paliperidone and ziprasidone however, were the only two antipsychotics used at excessive dosing. Antipsychotic polypharmacy was used in 287 (26%) patients with classic depot drugs, clotiapine, amisulpride and clozapine. In this study we describe the first step of the development of a web application that is able to make polypharmacy, high dose usage and off label usage of antipsychotics visible to clinicians. Current development of the MEmind web application may help to improve prescription security via momentary feedback of prescription and clinical decision support system.

Effect of Edge-Preserving Adaptive Image Filter on Low-Contrast Detectability in CT Systems: Application of ROC Analysis

PubMed Central

Okumura, Miwa; Ota, Takamasa; Kainuma, Kazuhisa; Sayre, James W.; McNitt-Gray, Michael; Katada, Kazuhiro

2008-01-01

Objective. For the multislice CT (MSCT) systems with a larger number of detector rows, it is essential to employ dose-reduction techniques. As reported in previous studies, edge-preserving adaptive image filters, which selectively eliminate only the noise elements that are increased when the radiation dose is reduced without affecting the sharpness of images, have been developed. In the present study, we employed receiver operating characteristic (ROC) analysis to assess the effects of the quantum denoising system (QDS), which is an edge-preserving adaptive filter that we have developed, on low-contrast resolution, and to evaluate to what degree the radiation dose can be reduced while maintaining acceptable low-contrast resolution. Materials and Methods. The low-contrast phantoms (Catphan 412) were scanned at various tube current settings, and ROC analysis was then performed for the groups of images obtained with/without the use of QDS at each tube current to determine whether or not a target could be identified. The tube current settings for which the area under the ROC curve (Az value) was approximately 0.7 were determined for both groups of images with/without the use of QDS. Then, the radiation dose reduction ratio when QDS was used was calculated by converting the determined tube current to the radiation dose. Results. The use of the QDS edge-preserving adaptive image filter allowed the radiation dose to be reduced by up to 38%. Conclusion. The QDS was found to be useful for reducing the radiation dose without affecting the low-contrast resolution in MSCT studies. PMID:19043565

Development of a Web-Based Clinical Decision Support System for Drug Prescription: Non-Interventional Naturalistic Description of the Antipsychotic Prescription Patterns in 4345 Outpatients and Future Applications

PubMed Central

Berrouiguet, Sofian; Barrigón, Maria Luisa; Brandt, Sara A.; Ovejero-García, Santiago; Álvarez-García, Raquel; Carballo, Juan Jose; Lenca, Philippe; Courtet, Philippe; Baca-García, Enrique

2016-01-01

Purpose The emergence of electronic prescribing devices with clinical decision support systems (CDSS) is able to significantly improve management pharmacological treatments. We developed a web application available on smartphones in order to help clinicians monitor prescription and further propose CDSS. Method A web application (www.MEmind.net) was developed to assess patients and collect data regarding gender, age, diagnosis and treatment. We analyzed antipsychotic prescriptions in 4345 patients attended in five Psychiatric Community Mental Health Centers from June 2014 to October 2014. The web-application reported average daily dose prescribed for antipsychotics, prescribed daily dose (PDD), and the PDD to defined daily dose (DDD) ratio. Results The MEmind web-application reported that antipsychotics were used in 1116 patients out of the total sample, mostly in 486 (44%) patients with schizophrenia related disorders but also in other diagnoses. Second generation antipsychotics (quetiapine, aripiprazole and long-acting paliperidone) were preferably employed. Low doses were more frequently used than high doses. Long acting paliperidone and ziprasidone however, were the only two antipsychotics used at excessive dosing. Antipsychotic polypharmacy was used in 287 (26%) patients with classic depot drugs, clotiapine, amisulpride and clozapine. Conclusions In this study we describe the first step of the development of a web application that is able to make polypharmacy, high dose usage and off label usage of antipsychotics visible to clinicians. Current development of the MEmind web application may help to improve prescription security via momentary feedback of prescription and clinical decision support system. PMID:27764107

Deployment of the DosiKit System Under Operational Conditions: Experience From a French Defense National Nuclear Exercise.

PubMed

Entine, F; Bensimon Etzol, J; Bettencourt, C; Dondey, M; Michel, X; Gagna, G; Gellie, G; Corre, Y; Ugolin, N; Chevillard, S; Amabile, J-C

2018-07-01

Estimation of the dose received by accidentally irradiated victims is based on a tripod: clinical, biological, and physical dosimetry. The DosiKit system is an operational and mobile biodosimetry device allowing the measurement of external irradiation directly on the site of a radiological accident. This tool is based on capillary blood sample and hair follicle collection. The aim is to obtain a whole-body and local-surface dose assessment. This paper is about the technical evaluation of the DosiKit; the analytical process and scientific validation are briefly described. The Toulon exercise scenario was based on a major accident involving the reactor of a nuclear attack submarine. The design of the scenario made it impossible for several players (firefighters, medical team) to leave the area for a long time, and they were potentially exposed to high dose rates. The DosiKit system was fully integrated into a deployable radiological emergency laboratory, and the response to operational needs was very satisfactory.

Calcium kinetics with microgram stable isotope doses and saliva sampling

NASA Technical Reports Server (NTRS)

Smith, S. M.; Wastney, M. E.; Nyquist, L. E.; Shih, C. Y.; Wiesmann, H.; Nillen, J. L.; Lane, H. W.

1996-01-01

Studies of calcium kinetics require administration of tracer doses of calcium and subsequent repeated sampling of biological fluids. This study was designed to develop techniques that would allow estimation of calcium kinetics by using small (micrograms) doses of isotopes instead of the more common large (mg) doses to minimize tracer perturbation of the system and reduce cost, and to explore the use of saliva sampling as an alternative to blood sampling. Subjects received an oral dose (133 micrograms) of 43Ca and an i.v. dose (7.7 micrograms) of 46Ca. Isotopic enrichment in blood, urine, saliva and feces was well above thermal ionization mass spectrometry measurement precision up to 170 h after dosing. Fractional calcium absorptions determined from isotopic ratios in blood, urine and saliva were similar. Compartmental modeling revealed that kinetic parameters determined from serum or saliva data were similar, decreasing the necessity for blood samples. It is concluded from these results that calcium kinetics can be assessed with micrograms doses of stable isotopes, thereby reducing tracer costs and with saliva samples, thereby reducing the amount of blood needed.

Assessment of Mean Glandular Dose in Mammography System with Different Anode-Filter Combinations Using MCNP Code.

PubMed

Gholamkar, Lida; Mowlavi, Ali Asghar; Sadeghi, Mahdi; Athari, Mitra

2016-10-01

X-ray mammography is one of the general methods for early detection of breast cancer. Since glandular tissue in the breast is sensitive to radiation and it increases the risk of cancer, the given dose to the patient is very important in mammography. The aim of this study was to determine the average absorbed dose of X-ray radiation in the glandular tissue of the breast during mammography examinations as well as investigating factors that influence the mean glandular dose (MGD). One of the precise methods for determination of MGD absorbed by the breast is Monte Carlo simulation method which is widely used to assess the dose. We studied some different X-ray sources and exposure factors that affect the MGD. "Midi-future" digital mammography system with amorphous-selenium detector was simulated using the Monte Carlo N-particle extended (MCNPX) code. Different anode/filter combinations such as tungsten/silver (W/Ag), tungsten/rhodium (W/Rh), and rhodium/aluminium (Rh/Al) were simulated in this study. The voltage of X-ray tube ranged from 24 kV to 32 kV with 2 kV intervals and the breast phantom thickness ranged from 3 to 8 cm, and glandular fraction g varied from 10% to 100%. MGD was measured for different anode/filter combinations and the effects of changing tube voltage, phantom thickness, combination and glandular breast tissue on MGD were studied. As glandular g and X-ray tube voltage increased, the breast dose increased too, and the increase of breast phantom thickness led to the decrease of MGD. The obtained results for MGD were consistent with the result of Boone et al. that was previously reported. By comparing the results, we saw that W/Rh anode/filter combination is the best choice in breast mammography imaging because of the lowest delivered dose in comparison with W/Ag and Rh/Al. Moreover, breast thickness and g value have significant effects on MGD.

IRIS Toxicological Review of Inorganic Arsenic (Cancer) ...

EPA Pesticide Factsheets

EPA's Science Advisory Board (SAB) conducted a review of the scientific basis supporting the human health cancer hazard and dose-response assessment of inorganic arsenic that will appear on the Integrated Risk Information System (IRIS) database. EPA revised the assessment and is now returning the assessment to the SAB and releasing the document to the public for a focused review of EPA's responses to the SAB recommendations. This draft IRIS health assessment addresses only cancer human health effects that may result from chronic exposure to this chemical.

Electron beam processed transdermal delivery system for administration of an anti-anginal agent

NASA Astrophysics Data System (ADS)

Kotiyan, P. N.; Vavia, P. R.; Bharadwaj, Y. K.; Sabarwal, S.; Majali, A. B.

2002-12-01

Electron beam irradiation was used to synthesize a matrix type transdermal system of isosorbide dinitrate, an effective anti-anginal agent. The drug was dissolved in two monomeric systems, 2-ethylhexyl acrylate (EHA) and 2-ethylhexyl acrylate : methyl methacrylate (9 : 1). The solutions were then directly irradiated on a backing membrane (Scotchpak ®1006) at different doses to get transdermal patches. The developed systems were evaluated for residual monomer content, equilibrium weight swelling ratio, weight uniformity, thickness uniformity, drug content, peel strength, in vitro release and skin permeation kinetics. They possessed excellent tack and adhesive properties. In the case of isosorbide dinitrate-EHA systems, an increase in the peel strength values with respect to the skin was observed with increasing radiation doses. The systems exhibited promising skin permeation kinetics favorable for transdermal drug delivery. The radiation stability of the drug in the pure solid state form was also assessed.

Development of low-dose photon-counting contrast-enhanced tomosynthesis with spectral imaging.

PubMed

Schmitzberger, Florian F; Fallenberg, Eva Maria; Lawaczeck, Rüdiger; Hemmendorff, Magnus; Moa, Elin; Danielsson, Mats; Bick, Ulrich; Diekmann, Susanne; Pöllinger, Alexander; Engelken, Florian J; Diekmann, Felix

2011-05-01

To demonstrate the feasibility of low-dose photon-counting tomosynthesis in combination with a contrast agent (contrast material-enhanced tomographic mammography) for the differentiation of breast cancer. All studies were approved by the institutional review board, and all patients provided written informed consent. A phantom model with wells of iodinated contrast material (3 mg of iodine per milliliter) 1, 2, 5, 10, and 15 mm in diameter was assessed. Nine patients with malignant lesions and one with a high-risk lesion (atypical papilloma) were included (all women; mean age, 60.7 years). A multislit photon-counting tomosynthesis system was utilized (spectral imaging) to produce both low- and high-energy tomographic data (below and above the k edge of iodine, respectively) in a single scan, which allowed for dual-energy visualization of iodine. Images were obtained prior to contrast material administration and 120 and 480 seconds after contrast material administration. Four readers independently assessed the images along with conventional mammograms, ultrasonographic images, and magnetic resonance images. Glandular dose was estimated. Contrast agent was visible in the phantom model with simulated spherical tumor diameters as small as 5 mm. The average glandular dose was measured as 0.42 mGy per complete spectral imaging tomosynthesis scan of one breast. Because there were three time points (prior to contrast medium administration and 120 and 480 seconds after contrast medium administration), this resulted in a total dose of 1.26 mGy for the whole procedure in the breast with the abnormality. Seven of 10 cases were categorized as Breast Imaging Reporting and Data System score of 4 or higher by all four readers when reviewing spectral images in combination with mammograms. One lesion near the chest wall was not captured on the spectral image because of a positioning problem. The use of contrast-enhanced tomographic mammography has been demonstrated successfully in patients with promising diagnostic benefit. Further studies are necessary to fully assess diagnostic sensitivity and specificity. RSNA, 2011

The effect of dose reduction on the detection of anatomical structures on panoramic radiographs.

PubMed

Kaeppler, G; Dietz, K; Reinert, S

2006-07-01

The aim was to evaluate the effect of dose reduction on diagnostic accuracy using different screen-film combinations and digital techniques for panoramic radiography. Five observers assessed 201 pairs of panoramic radiographs (a total of 402 panoramic radiographs) taken with the Orthophos Plus (Sirona, Bensheim, Germany), for visualization of 11 anatomical structures on each side, using a 3-point scale -1, 0 and 1. Two radiographs of each patient were taken at two different times (conventional setting and setting with decreased dose, done by increasing tube potential settings or halving tube current). To compare the dose at different tube potential settings dose-length product was measured at the secondary collimator. Films with medium and regular intensifying screens (high and low tube potential settings) and storage phosphor plates (low tube potential setting, tube current setting equivalent to regular intensifying screen and halved) were compared. The five observers made 27 610 assessments. Intrarater agreement was expressed by Cohen's kappa coefficient. The results demonstrated an equivalence of regular screens (low tube potential setting) and medium screens (high and low tube potential settings). A significant difference existed between medium screens (low tube potential setting, mean score 0.92) and the group of regular film-screen combinations at high tube potential settings (mean score 0.89) and between all film-screen combinations and the digital system irrespective of exposure (mean score below 0.82). There were no significant differences between medium and regular screens (mean score 0.88 to 0.92) for assessment of the periodontal ligament space, but there was a significant difference compared with the digital system (mean score below 0.76). The kappa coefficient for intrarater agreement was moderate (0.55). New regular intensifying screens can replace medium screens at low tube potential settings. Digital panoramic radiographs should be taken at low tube potential levels with an exposure equivalent at least to a regular intensifying screen.

IRIS Toxicological Review of Dichloromethane (Methylene Chloride) (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Dichloromethane that when finalized will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Tetrahydrofuran (THF) (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of tetrahydrofuran (THF) that when finalized will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Trichloroethylene (TCE) (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Trichloroethylene (TCE) that when finalized will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Cerium Oxide and Cerium Compounds (External Review Draft)

EPA Science Inventory

EPA conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of cerium oxide and cerium compounds that will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Urea (Final Report) | Science ...

EPA Pesticide Factsheets

EPA has finalized the Toxicological Review of Urea: in support of the Integrated Risk Information System (IRIS). Now final, this assessment may be used by EPA’s program and regional offices to inform decisions to protect human health. The draft Toxicological Review of Urea provides scientific support and rationale for the hazard and dose-response assessment pertaining to chronic exposure to Urea.

A clinical trial assessing the safety and efficacy of taranabant, a CB1R inverse agonist, in obese and overweight patients: a high-dose study.

PubMed

Aronne, L J; Tonstad, S; Moreno, M; Gantz, I; Erondu, N; Suryawanshi, S; Molony, C; Sieberts, S; Nayee, J; Meehan, A G; Shapiro, D; Heymsfield, S B; Kaufman, K D; Amatruda, J M

2010-05-01

To evaluate the efficacy, safety and tolerability of taranabant in obese and overweight patients. Double-blind, randomized, placebo-controlled study. Patients were >or=18 years old, with body mass index of 27-43 kg m(-2), and 51% with metabolic syndrome (MS) randomized to placebo (N=417) or taranabant 2 mg (N=414), 4 mg (N=415) or 6 mg (N=1256) for 104 weeks. Key efficacy measurements included body weight, waist circumference (WC), lipid and glycemic end points. On the basis of risk/benefit assessments, the 6-mg dose was discontinued during year 1 (patients on 6 mg were down-dosed to 2 mg or placebo) and the 4-mg dose was discontinued during year 2 (patients on 4 mg were down-dosed to 2 mg). Changes from baseline in body weight at week 52 (all-patients-treated population, last observation carried forward analysis) were -2.6, -6.6 and -8.1 kg, respectively, for placebo and taranabant 2 and 4 mg (both doses P<0.001 vs placebo). For patients who completed year 1, changes from baseline in body weight at week 104 were -1.4, -6.4 and -7.6 kg for placebo and taranabant 2 and 4 mg, respectively (both doses P<0.001 vs placebo). The proportions of patients at weeks 52 and 104 who lost at least 5 and 10% of their baseline body weight were significantly higher and the proportions of patients who met criteria for MS were significantly lower for taranabant 2 and 4 mg vs placebo. The incidence of adverse experiences classified in the gastrointestinal, nervous, psychiatric, cutaneous and vascular organ systems were generally observed to be dose related with taranabant vs placebo. Taranabant at the 2- and 4-mg dose was effective in achieving clinically significant weight loss over 2 years and was associated with dose-related increases in adverse experiences. On the basis of these and other data, an assessment was made that the overall safety and efficacy profile of taranabant did not support its further development for the treatment of obesity.

An F1-extended one-generation reproductive toxicity study in Crl:CD(SD) rats with 2,4-dichlorophenoxyacetic acid.

PubMed

Marty, Mary Sue; Neal, Barbara H; Zablotny, Carol L; Yano, Barry L; Andrus, Amanda K; Woolhiser, Michael R; Boverhof, Darrell R; Saghir, Shakil A; Perala, Adam W; Passage, Julie K; Lawson, Marie A; Bus, James S; Lamb, James C; Hammond, Larry

2013-12-01

2,4-Dichlorophenoxyacetic acid (2,4-D) was assessed for systemic toxicity, reproductive toxicity, developmental neurotoxicity (DNT), developmental immunotoxicity (DIT), and endocrine toxicity. CD rats (27/sex/dose) were exposed to 0, 100, 300, 600 (female), or 800 (male) ppm 2,4-D in diet. Nonlinear toxicokinetic behavior was shown at high doses; the renal clearance saturation threshold for 2,4-D was exceeded markedly in females and slightly exceeded in males. Exposure was 4 weeks premating, 7 weeks postmating for P1 males and through lactation for P1 females. F1 offspring were examined for survival and development, and at weaning, pups were divided in cohorts, by sex and dose, and by systemic toxicity (10), DNT (10), DIT (20), and reproductive toxicity (≥ 23). Remaining weanlings were evaluated for systemic toxicity and neuropathology (10-12). Body weight decreased during lactation in high-dose P1 females and in F1 pups. Kidney was the primary target organ, with slight degeneration of proximal convoluted tubules observed in high-dose P1 males and in high-dose F1 males and females. A slight intergenerational difference in kidney toxicity was attributed to increased intake of 2,4-D in F1 offspring. Decreased weanling testes weights and delayed preputial separation in F1 males were attributed to decreased body weights. Endocrine-related effects were limited to slight thyroid hormone changes and adaptive histopathology in high-dose GD 17 dams seen only at a nonlinear toxicokinetic dose. 2,4-D did not cause reproductive toxicity, DNT, or DIT. The "No Observed Adverse Effect Level" for systemic toxicity was 300 ppm in both males (16.6 mg/kg/day) and females (20.6 mg/kg/day), which is approximately 6700- to 93 000-fold higher than that reported for 2,4-D exposures in human biomonitoring studies.

An F1-Extended One-Generation Reproductive Toxicity Study in Crl:CD(SD) Rats With 2,4-Dichlorophenoxyacetic Acid

PubMed Central

Marty, Mary Sue

2013-01-01

2,4-Dichlorophenoxyacetic acid (2,4-D) was assessed for systemic toxicity, reproductive toxicity, developmental neurotoxicity (DNT), developmental immunotoxicity (DIT), and endocrine toxicity. CD rats (27/sex/dose) were exposed to 0, 100, 300, 600 (female), or 800 (male) ppm 2,4-D in diet. Nonlinear toxicokinetic behavior was shown at high doses; the renal clearance saturation threshold for 2,4-D was exceeded markedly in females and slightly exceeded in males. Exposure was 4 weeks premating, 7 weeks postmating for P1 males and through lactation for P1 females. F1 offspring were examined for survival and development, and at weaning, pups were divided in cohorts, by sex and dose, and by systemic toxicity (10), DNT (10), DIT (20), and reproductive toxicity (≥ 23). Remaining weanlings were evaluated for systemic toxicity and neuropathology (10–12). Body weight decreased during lactation in high-dose P1 females and in F1 pups. Kidney was the primary target organ, with slight degeneration of proximal convoluted tubules observed in high-dose P1 males and in high-dose F1 males and females. A slight intergenerational difference in kidney toxicity was attributed to increased intake of 2,4-D in F1 offspring. Decreased weanling testes weights and delayed preputial separation in F1 males were attributed to decreased body weights. Endocrine-related effects were limited to slight thyroid hormone changes and adaptive histopathology in high-dose GD 17 dams seen only at a nonlinear toxicokinetic dose. 2,4-D did not cause reproductive toxicity, DNT, or DIT. The “No Observed Adverse Effect Level” for systemic toxicity was 300 ppm in both males (16.6mg/kg/day) and females (20.6mg/kg/day), which is approximately 6700- to 93 000-fold higher than that reported for 2,4-D exposures in human biomonitoring studies. PMID:24072463

Preclinical toxicity profile of oral bilastine.

PubMed

Lucero, María Luisa; Arteche, Joseba K; Sommer, E W; Casadesus, Agustín

2012-06-01

As part of the bilastine development program, and as mandated by regulatory authorities, several studies were performed with oral bilastine in different animal species to evaluate its toxicity profile. Toxicokinetic analyses conducted in tandem to evaluate systemic exposure, gender differences, and dose proportionality in the different animal species indicated that animals were systemically exposed to bilastine during treatment. Repeated-dose toxicity studies in beagle dogs (52 weeks) and in rats and mice (13 weeks) showed that bilastine at doses up to 2,000 mg/kg/day was not associated with any mortality, ocular effects, or nodules/masses. Likewise, no bilastine-associated neoplastic lesions were observed in rats and mice after 104 weeks of treatment with bilastine at doses up to 2,000 mg/kg/day. In general, bilastine-related clinical signs, body-weight changes, food consumption, clinical chemistry, haematology, and macro- and microscopic findings were of low order and reversible, with effects present only at the highest doses administered. Bilastine (up to 1,000 mg/kg/day) was well tolerated in pregnant/lactating rats and in their offspring and subsequent generations. With respect to effects on embryofoetal development in rabbits, bilastine at 400 mg/kg/day (the highest dose evaluated) was assessed to be the no observed adverse effects level. Overall, bilastine demonstrated a favorable toxicity profile in all animal models investigated and at higher doses than the corresponding recommended daily human dosage.

Acute radiation risk models

NASA Astrophysics Data System (ADS)

Smirnova, Olga

Biologically motivated mathematical models, which describe the dynamics of the major hematopoietic lineages (the thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems) in acutely/chronically irradiated humans are developed. These models are implemented as systems of nonlinear differential equations, which variables and constant parameters have clear biological meaning. It is shown that the developed models are capable of reproducing clinical data on the dynamics of these systems in humans exposed to acute radiation in the result of incidents and accidents, as well as in humans exposed to low-level chronic radiation. Moreover, the averaged value of the "lethal" dose rates of chronic irradiation evaluated within models of these four major hematopoietic lineages coincides with the real minimal dose rate of lethal chronic irradiation. The demonstrated ability of the models of the human thrombocytopoietic, lymphocytopoietic, granulocytopoietic, and erythropoietic systems to predict the dynamical response of these systems to acute/chronic irradiation in wide ranges of doses and dose rates implies that these mathematical models form an universal tool for the investigation and prediction of the dynamics of the major human hematopoietic lineages for a vast pattern of irradiation scenarios. In particular, these models could be applied for the radiation risk assessment for health of astronauts exposed to space radiation during long-term space missions, such as voyages to Mars or Lunar colonies, as well as for health of people exposed to acute/chronic irradiation due to environmental radiological events.

High-throughput sample processing and sample management; the functional evolution of classical cytogenetic assay towards automation.

PubMed

Ramakumar, Adarsh; Subramanian, Uma; Prasanna, Pataje G S

2015-11-01

High-throughput individual diagnostic dose assessment is essential for medical management of radiation-exposed subjects after a mass casualty. Cytogenetic assays such as the Dicentric Chromosome Assay (DCA) are recognized as the gold standard by international regulatory authorities. DCA is a multi-step and multi-day bioassay. DCA, as described in the IAEA manual, can be used to assess dose up to 4-6 weeks post-exposure quite accurately but throughput is still a major issue and automation is very essential. The throughput is limited, both in terms of sample preparation as well as analysis of chromosome aberrations. Thus, there is a need to design and develop novel solutions that could utilize extensive laboratory automation for sample preparation, and bioinformatics approaches for chromosome-aberration analysis to overcome throughput issues. We have transitioned the bench-based cytogenetic DCA to a coherent process performing high-throughput automated biodosimetry for individual dose assessment ensuring quality control (QC) and quality assurance (QA) aspects in accordance with international harmonized protocols. A Laboratory Information Management System (LIMS) is designed, implemented and adapted to manage increased sample processing capacity, develop and maintain standard operating procedures (SOP) for robotic instruments, avoid data transcription errors during processing, and automate analysis of chromosome-aberrations using an image analysis platform. Our efforts described in this paper intend to bridge the current technological gaps and enhance the potential application of DCA for a dose-based stratification of subjects following a mass casualty. This paper describes one such potential integrated automated laboratory system and functional evolution of the classical DCA towards increasing critically needed throughput. Published by Elsevier B.V.

SU-F-T-440: The Feasibility Research of Checking Cervical Cancer IMRT Pre- Treatment Dose Verification by Automated Treatment Planning Verification System

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

Liu, X; Yin, Y; Lin, X

Purpose: To assess the preliminary feasibility of automated treatment planning verification system in cervical cancer IMRT pre-treatment dose verification. Methods: The study selected randomly clinical IMRT treatment planning data for twenty patients with cervical cancer, all IMRT plans were divided into 7 fields to meet the dosimetric goals using a commercial treatment planning system(PianncleVersion 9.2and the EclipseVersion 13.5). The plans were exported to the Mobius 3D (M3D)server percentage differences of volume of a region of interest (ROI) and dose calculation of target region and organ at risk were evaluated, in order to validate the accuracy automated treatment planning verification system.more » Results: The difference of volume for Pinnacle to M3D was less than results for Eclipse to M3D in ROI, the biggest difference was 0.22± 0.69%, 3.5±1.89% for Pinnacle and Eclipse respectively. M3D showed slightly better agreement in dose of target and organ at risk compared with TPS. But after recalculating plans by M3D, dose difference for Pinnacle was less than Eclipse on average, results were within 3%. Conclusion: The method of utilizing the automated treatment planning system to validate the accuracy of plans is convenientbut the scope of differences still need more clinical patient cases to determine. At present, it should be used as a secondary check tool to improve safety in the clinical treatment planning.« less

Pulmonary disease in cystic fibrosis: assessment with chest CT at chest radiography dose levels.

PubMed

Ernst, Caroline W; Basten, Ines A; Ilsen, Bart; Buls, Nico; Van Gompel, Gert; De Wachter, Elke; Nieboer, Koenraad H; Verhelle, Filip; Malfroot, Anne; Coomans, Danny; De Maeseneer, Michel; de Mey, Johan

2014-11-01

To investigate a computed tomographic (CT) protocol with iterative reconstruction at conventional radiography dose levels for the assessment of structural lung abnormalities in patients with cystic fibrosis ( CF cystic fibrosis ). In this institutional review board-approved study, 38 patients with CF cystic fibrosis (age range, 6-58 years; 21 patients <18 years and 17 patients >18 years) underwent investigative CT (at minimal exposure settings combined with iterative reconstruction) as a replacement of yearly follow-up posteroanterior chest radiography. Verbal informed consent was obtained from all patients or their parents. CT images were randomized and rated independently by two radiologists with use of the Bhalla scoring system. In addition, mosaic perfusion was evaluated. As reference, the previous available conventional chest CT scan was used. Differences in Bhalla scores were assessed with the χ(2) test and intraclass correlation coefficients ( ICC intraclass correlation coefficient s). Radiation doses for CT and radiography were assessed for adults (>18 years) and children (<18 years) separately by using technical dose descriptors and estimated effective dose. Differences in dose were assessed with the Mann-Whitney U test. The median effective dose for the investigative protocol was 0.04 mSv (95% confidence interval [ CI confidence interval ]: 0.034 mSv, 0.10 mSv) for children and 0.05 mSv (95% CI confidence interval : 0.04 mSv, 0.08 mSv) for adults. These doses were much lower than those with conventional CT (median: 0.52 mSv [95% CI confidence interval : 0.31 mSv, 3.90 mSv] for children and 1.12 mSv [95% CI confidence interval : 0.57 mSv, 3.15 mSv] for adults) and of the same order of magnitude as those for conventional radiography (median: 0.012 mSv [95% CI confidence interval : 0.006 mSv, 0.022 mSv] for children and 0.012 mSv [95% CI confidence interval : 0.005 mSv, 0.031 mSv] for adults). All images were rated at least as diagnostically acceptable. Very good agreement was found in overall Bhalla score ( ICC intraclass correlation coefficient , 0.96) with regard to the severity of bronchiectasis ( ICC intraclass correlation coefficient , 0.87) and sacculations and abscesses ( ICC intraclass correlation coefficient , 0.84). Interobserver agreement was excellent ( ICC intraclass correlation coefficient , 0.86-1). For patients with CF cystic fibrosis , a dedicated chest CT protocol can replace the two yearly follow-up chest radiographic examinations without major dose penalty and with similar diagnostic quality compared with conventional CT.

Risk Assessment in the 21st Century | Science Inventory | US ...

EPA Pesticide Factsheets

For the past ~50 years, risk assessment depended almost exclusively on animal testing for hazard identification and dose-response assessment. Originally sound and effective, with increasing dependence on chemical tools and the number of chemicals in commerce, this traditional approach is no longer adequate. This presentation provides an update on current progress in achieving the goals outlined in the NAS report on Toxicology Testing in the 21st Century, highlighting many of the advances lead by the EPA. Topics covered include the evolution of the mode of action framework into a chemically agnostic, adverse outcome pathway (AOP), a systems-based data framework that facilitates integration of modifiable factors (e.g., genetic variation, life stages), and an understanding of networks, and mixtures. Further, the EDSP pivot is used to illustrate how AOPs drive development of predictive models for risk assessment based on assembly of high throughput assays representing AOP key elements. The birth of computational exposure science, capable of large-scale predictive exposure models, is reviewed. Although still in its infancy, development of non-targeted analysis to begin addressing exposome also is presented. Finally, the systems-based AEP is described that integrates exposure, toxicokinetics and AOPs into a comprehensive framework. For the past ~50 years, risk assessment depended almost exclusively on animal testing for hazard identification and dose-response as

The Pollution Hazard Assessment System: Documentation and Users Manual

DTIC Science & Technology

1989-10-01

term f(Ki,Si) is a measure of the ability of a pollutant to be transmitted from soil to the ingested item (if the item ingested is soil itself, this...limiting dose for cattle based on extrapolation from either: 43 o The long term human no observed effect dose level (NOEL) o A mammalian lifetime NOEL o A...101) * PANV(101) 11360 ANSWER-NOEL*100:RTURN 11400 INPUT I Enter Mammalian Lifetime NOEL in mg/kg-day: ",NOEL 11410 ANSWER-NOEL/lORETUW 11450 INPUT

Assessment of Risk Reduction for Lymphedema Following Sentinel Lymph Noded Guided Surgery for Primary Breast Cancer

DTIC Science & Technology

2006-10-01

patients with breast cancer underwent scanning with a hybrid camera which combined a dual-head SPECT camera and a low-dose, single slice CT scanner , (GE...investigated a novel approach which combines the output of a dual-head SPECT camera and a low-dose, single slice CT scanner , (GE Hawkeye®). This... scanner , (Hawkeye®, GE Medical system) is attempted in this study. This device is widely available in cardiology community and has the potential to

[The effect of bemetil on the production of DNA antibodies in patients with systemic lupus erythematosus].

PubMed

Lisitsyna, T A; Durnev, A D; Ivanova, M M; Speranskiĭ, A I; Seredenin, S B; Nasonova, V A

1999-01-01

The levels of autoantibodies against DNA in blood serum and severity of the disease were evaluated prior to, during, and after 8-week treatment of patients suffering from lupus erythematosus systemicus (LES) with prednisolonum (daily dose of 5-60 mg/kg, 15 patient) and with prednisolonum in combination with cyclophosphane (CP) (a total dose of 2-4 mg/kg per os. 15 patients), or bemithyl doses of 500-750 mg/day per os (15 patients) or bemithyl in combination with CP (the same doses, 16 patients). It was shown that introduction of bemithyl into LES treatment schedule significantly lowered the level of autoantibodies against DNA evaluated in immunoassay and reduced LES severity assessed using standard SLEDAI-1 and ECLAM scales.

A dose homogeneity and conformity evaluation between ViewRay and pinnacle-based linear accelerator IMRT treatment plans

PubMed Central

Saenz, Daniel L.; Paliwal, Bhudatt R.; Bayouth, John E.

2014-01-01

ViewRay, a novel technology providing soft-tissue imaging during radiotherapy is investigated for treatment planning capabilities assessing treatment plan dose homogeneity and conformity compared with linear accelerator plans. ViewRay offers both adaptive radiotherapy and image guidance. The combination of cobalt-60 (Co-60) with 0.35 Tesla magnetic resonance imaging (MRI) allows for magnetic resonance (MR)-guided intensity-modulated radiation therapy (IMRT) delivery with multiple beams. This study investigated head and neck, lung, and prostate treatment plans to understand what is possible on ViewRay to narrow focus toward sites with optimal dosimetry. The goal is not to provide a rigorous assessment of planning capabilities, but rather a first order demonstration of ViewRay planning abilities. Images, structure sets, points, and dose from treatment plans created in Pinnacle for patients in our clinic were imported into ViewRay. The same objectives were used to assess plan quality and all critical structures were treated as similarly as possible. Homogeneity index (HI), conformity index (CI), and volume receiving <20% of prescription dose (DRx) were calculated to assess the plans. The 95% confidence intervals were recorded for all measurements and presented with the associated bars in graphs. The homogeneity index (D5/D95) had a 1-5% inhomogeneity increase for head and neck, 3-8% for lung, and 4-16% for prostate. CI revealed a modest conformity increase for lung. The volume receiving 20% of the prescription dose increased 2-8% for head and neck and up to 4% for lung and prostate. Overall, for head and neck Co-60 ViewRay treatments planned with its Monte Carlo treatment planning software were comparable with 6 MV plans computed with convolution superposition algorithm on Pinnacle treatment planning system. PMID:24872603

A dose homogeneity and conformity evaluation between ViewRay and pinnacle-based linear accelerator IMRT treatment plans.

PubMed

Saenz, Daniel L; Paliwal, Bhudatt R; Bayouth, John E

2014-04-01

ViewRay, a novel technology providing soft-tissue imaging during radiotherapy is investigated for treatment planning capabilities assessing treatment plan dose homogeneity and conformity compared with linear accelerator plans. ViewRay offers both adaptive radiotherapy and image guidance. The combination of cobalt-60 (Co-60) with 0.35 Tesla magnetic resonance imaging (MRI) allows for magnetic resonance (MR)-guided intensity-modulated radiation therapy (IMRT) delivery with multiple beams. This study investigated head and neck, lung, and prostate treatment plans to understand what is possible on ViewRay to narrow focus toward sites with optimal dosimetry. The goal is not to provide a rigorous assessment of planning capabilities, but rather a first order demonstration of ViewRay planning abilities. Images, structure sets, points, and dose from treatment plans created in Pinnacle for patients in our clinic were imported into ViewRay. The same objectives were used to assess plan quality and all critical structures were treated as similarly as possible. Homogeneity index (HI), conformity index (CI), and volume receiving <20% of prescription dose (DRx) were calculated to assess the plans. The 95% confidence intervals were recorded for all measurements and presented with the associated bars in graphs. The homogeneity index (D5/D95) had a 1-5% inhomogeneity increase for head and neck, 3-8% for lung, and 4-16% for prostate. CI revealed a modest conformity increase for lung. The volume receiving 20% of the prescription dose increased 2-8% for head and neck and up to 4% for lung and prostate. Overall, for head and neck Co-60 ViewRay treatments planned with its Monte Carlo treatment planning software were comparable with 6 MV plans computed with convolution superposition algorithm on Pinnacle treatment planning system.

Systemic effects of ionizing radiation at the proteome and metabolome levels in the blood of cancer patients treated with radiotherapy: the influence of inflammation and radiation toxicity.

PubMed

Jelonek, Karol; Pietrowska, Monika; Widlak, Piotr

2017-07-01

Blood is the most common replacement tissue used to study systemic responses of organisms to different types of pathological conditions and environmental insults. Local irradiation during cancer radiotherapy induces whole body responses that can be observed at the blood proteome and metabolome levels. Hence, comparative blood proteomics and metabolomics are emerging approaches used in the discovery of radiation biomarkers. These techniques enable the simultaneous measurement of hundreds of molecules and the identification of sets of components that can discriminate different physiological states of the human body. Radiation-induced changes are affected by the dose and volume of irradiated tissues; hence, the molecular composition of blood is a hypothetical source of biomarkers for dose assessment and the prediction and monitoring of systemic responses to radiation. This review aims to provide a comprehensive overview on the available evidence regarding molecular responses to ionizing radiation detected at the level of the human blood proteome and metabolome. It focuses on patients exposed to radiation during cancer radiotherapy and emphasizes effects related to radiation-induced toxicity and inflammation. Systemic responses to radiation detected at the blood proteome and metabolome levels are primarily related to the intensity of radiation-induced toxicity, including inflammatory responses. Thus, several inflammation-associated molecules can be used to monitor or even predict radiation-induced toxicity. However, these abundant molecular features have a rather limited applicability as universal biomarkers for dose assessment, reflecting the individual predisposition of the immune system and tissue-specific mechanisms involved in radiation-induced damage.

Performance evaluation of an improved optical computed tomography polymer gel dosimeter system for 3D dose verification of static and dynamic phantom deliveries

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

Lopatiuk-Tirpak, O.; Langen, K. M.; Meeks, S. L.

2008-09-15

The performance of a next-generation optical computed tomography scanner (OCTOPUS-5X) is characterized in the context of three-dimensional gel dosimetry. Large-volume (2.2 L), muscle-equivalent, radiation-sensitive polymer gel dosimeters (BANG-3) were used. Improvements in scanner design leading to shorter acquisition times are discussed. The spatial resolution, detectable absorbance range, and reproducibility are assessed. An efficient method for calibrating gel dosimeters using the depth-dose relationship is applied, with photon- and electron-based deliveries yielding equivalent results. A procedure involving a preirradiation scan was used to reduce the edge artifacts in reconstructed images, thereby increasing the useful cross-sectional area of the dosimeter by nearly amore » factor of 2. Dose distributions derived from optical density measurements using the calibration coefficient show good agreement with the treatment planning system simulations and radiographic film measurements. The feasibility of use for motion (four-dimensional) dosimetry is demonstrated on an example comparing dose distributions from static and dynamic delivery of a single-field photon plan. The capability to visualize three-dimensional dose distributions is also illustrated.« less

SU-F-J-104: Weekly MRI for Dose Assessment of Organs at Risk During Treatment of HN Cancer of the Oropharynx

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

Ludwig, K; Li, J; Venigalla, P

2016-06-15

Purpose: Investigate the feasibility of using weekly MRI to assess dose to organs at risk utilizing deformable image registration. Methods: Sixteen H&N patients with oropharyngeal cancer were imaged on a 3T MR scanner using T2W and mDIXON sequence. Patients were imaged on a weekly basis in treatment position. Parotids (LP & RP), submandibular glands (LS, RS), and oral cavity (OC) were delineated on the weekly MR and reviewed by a board certified radiation oncologist. The original planning CT (pCT), RT-Dose, and RT-Structures were deformed and registered to each weekly MRIs. The deformed CTs and RT-Structures were imported to the treatmentmore » planning system (TPS) and rigidly registered to the pCT. Forward dose calculation of the original RT-Plan was used to estimate the delivered dose on the deformed CT. The dose volume histograms (DVH) statistics were performed to compare planned dose, deformed dose, and forward calculated dose. In addition, Dice similarity metric (DSM) was used to compare deformed and reference structures. Results: The average (min,max) DSM between deformed and reference structures was 0.71 (0.69,0.93); 0.70 (0.64,0.89); 0.65 (0.48,0.86); 0.63 (0.37,0.89); and 0.63 (0.58,0.87); for LP, RP, LS, RS, and OC respectively. The respective average relative structures volumes changed at a weekly rate of −4.99%; −4.40%; +3.45%; +1.46%; −1.39%, respectively. The percentage difference %(min,max) between estimated delivered dose and planned dose was +3.94 (−51.3,+30.5); +6.33 (−58.6,+82.7); +2.46 (−38.9,+37.6,); +2.38(−49.0,+28.9); +3.55(−17.0,+43.1). Conclusion: The recalculated dose based on weekly MRI deviated from planned dose for all OARs. Meanwhile, the deformed dose did not reflect the subtle changes in OARs as compared to the recalculated dose. This study demonstrates the feasibility of using weekly MRI to monitor volumetric changes which has important implications on actual delivered dose.« less

SU-F-J-14: Kilovoltage Cone-Beam CT Dose Estimation of Varian On-Board Imager Using GMctdospp Monte Carlo Framework

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

Kim, S; Rangaraj, D

2016-06-15

Purpose: Although cone-beam CT (CBCT) imaging became popular in radiation oncology, its imaging dose estimation is still challenging. The goal of this study is to assess the kilovoltage CBCT doses using GMctdospp - an EGSnrc based Monte Carlo (MC) framework. Methods: Two Varian OBI x-ray tube models were implemented in the GMctpdospp framework of EGSnrc MC System. The x-ray spectrum of 125 kVp CBCT beam was acquired from an EGSnrc/BEAMnrc simulation and validated with IPEM report 78. Then, the spectrum was utilized as an input spectrum in GMctdospp dose calculations. Both full and half bowtie pre-filters of the OBI systemmore » were created by using egs-prism module. The x-ray tube MC models were verified by comparing calculated dosimetric profiles (lateral and depth) to ion chamber measurements for a static x-ray beam irradiation to a cuboid water phantom. An abdominal CBCT imaging doses was simulated in GMctdospp framework using a 5-year-old anthropomorphic phantom. The organ doses and effective dose (ED) from the framework were assessed and compared to the MOSFET measurements and convolution/superposition dose calculations. Results: The lateral and depth dose profiles in the water cuboid phantom were well matched within 6% except a few areas - left shoulder of the half bowtie lateral profile and surface of water phantom. The organ doses and ED from the MC framework were found to be closer to MOSFET measurements and CS calculations within 2 cGy and 5 mSv respectively. Conclusion: This study implemented and validated the Varian OBI x-ray tube models in the GMctdospp MC framework using a cuboid water phantom and CBCT imaging doses were also evaluated in a 5-year-old anthropomorphic phantom. In future study, various CBCT imaging protocols will be implemented and validated and consequently patient CT images will be used to estimate the CBCT imaging doses in patients.« less

Poster — Thur Eve — 26: Evaluation of lens dose from anterior electron beams: comparison of Pinnacle and Gafchromic EBT3 film

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

Sanier, M; Wronski, M; Yeboah, C

The purpose of this work is twofold: 1) to measure dose profiles under lead shielding at the level of the lens for a range of clinical electron energies via film dosimetry; and, 2) to assess the validity of the Pinnacle treatment planning system (TPS) in calculating the penumbral doses under lead shielding with the heterogeneous electron algorithm. First, a film calibration curve that spanned the electron energies of interest, 6–18MeV, was created. Next, EBT3 film and lead shielding were incorporated into a solid water phantom with the film positioned 7mm below the lead and a variable thickness of bolus onmore » top. This geometry was reproduced in the Pinnacle TPS and used to calculate dose profiles using the heterogeneous electron algorithm. The measured vs. calculated dose profiles were normalized to d{sub max} in a homogeneous phantom with no lead shielding and compared. Pinnacle consistently overestimated the dose distal to the lead shielding with significant discrepancies occurring near the edge of the lead shield reaching 25% at the edge and 35% in the open field region. The film measurements showed that a minimum lead margin of 5mm extending beyond the diameter of the lens is required to adequately shield the lens to ≤10% of the dose at d{sub max}. These measurements allow for a reasonable estimate of the dose to the lens from anterior electron beams. They also allow for clinicians to assess the extent of the lead margin required to reduce the lens dose to an acceptable amount prior to radiotherapy treatment.« less

SU-E-J-101: Retroactive Calculation of TLD and Film Dose in Anthropomorphic Phantom as Assessment of Updated TPS Performance

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

Alkhatib, H; Oves, S

Purpose: To demonstrate a quick and comprehensive method verifying the accuracy of the updated dose model by recalculating dose distribution in an anthropomorphic phantom with a new version of the TPS and comparing the results to measured values. Methods: CT images and IMRT plan of an RPC anthropomorphic head phantom, previously calculated by Pinnacle 9.0, was re-computed using Pinnacle 9.2 and 9.6. The dosimeters within the phantom include four TLD capsules representing a primary PTV, two TLD capsules representing a secondary PTV, and two TLD capsules representing an organ at risk. Also included were three sheets of Gafchromic film. Performancemore » of the updated TPS version was assessed by recalculating point doses and dose profiles corresponding to TLD and film position respectively and then comparing the results to reported values by the RPC. Results: Comparing calculated doses to reported measured doses from the RPC yielded an average disagreement of 1.48%, 2.04% and 2.10% for versions 9.0, 9.2, 9.6 respectively. Computed doses points all meet the RPC's passing criteria with the exception of the point representing the superior organ at risk in version 9.6. However, qualitative analysis of the recalculated dose profiles showed improved agreement with those of the RPC, especially in the penumbra region. Conclusion: This work has demonstrated the calculation results of Pinnacle 9.2 and 9.6 vs 9.0 version. Additionally, this study illustrates a method for the user to gain confidence upgrade to a newer version of the treatment planning system.« less

IRIS Toxicological Review of Methanol (External Review Draft, 2013)

EPA Science Inventory

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of methanol (non-cancer) that when finalized will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Urea (External Review Draft)

EPA Science Inventory

EPA conducted a peer review and public comment of the scientific basis of a draft report supporting the human health hazard and dose-response assessment of Urea that when finalized will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Trichloroacetic Acid (TCA) (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Trichloroacetic acid (TCA) that when finalized will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of 1,1,2,2-Tetrachloroethane (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of 1,1,2,2-tetrachloroethane that will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Cis-& Trans-1,2-Dichloroethylene (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of cis- and trans-1,2-dichloroethylene that will appear in the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Beryllium and Compounds (2008 External Review Draft)

EPA Science Inventory

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of Beryllium that when finalized will appear on the Integrated Risk Information System (IRIS) database.

Evaluation of the Carcinogenicity of Ethylene Oxide (2006 External Review Draft)

EPA Science Inventory

EPA conducted a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of ethylene oxide (cancer) that when finalized will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Ethylene Glycol Mono-Butyl Ether (Egbe) (External Review Draft)

EPA Science Inventory

EPA has conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of ethylene glycol monobutyl ether that will appear on the Integrated Risk Information System (IRIS) database.

[Effectiveness of a quality control program in mammography for the Brazilian National Health System].

PubMed

Corrêa, Rosangela da Silveira; Freitas-Junior, Ruffo; Peixoto, João Emílio; Rodrigues, Danielle Cristina Netto; Lemos, Maria Eugênia Fonseca; Dias, Cíntia Melazo; Ferreira, Rubemar de Souza; Rahal, Rosemar Macedo Souza

2012-10-01

To assess the effectiveness of a quality control program in mammography services of the Brazilian National Health System (SUS). A prospective study using temporal analysis of a health surveillance action was conducted. A total of 35 service providers that had mammography equipment in operation and regularly performed exams between 2007 and 2009 in the state of Goiás, Central-Western Brazil, participated in this study. Services were assessed during three site visits by performance testing of mammography equipment, film processors, and other materials, and image quality and entrance surface dose in a phantom were also assessed. Each service was scored according to the percentage of tests that conformed to standards. The mean percentage for compliance among the participating service providers were 64.1% (± 13.3%) in the first visit, 68.4% (± 15.9%) in the second, and 77.1% (± 13.3%) in the third (p < 0.001). The main improvements resulted from adjustments to the breast compression force, the automatic exposure control system, and the alignment of the compression paddle. The doses measured were within the conformity range in 80% of the services assessed. The implementation of this program in the mammography services was effective at improving the operational parameters of the mammography machines, although 40% of the services did not reach the acceptable level of 70%. This result indicates the need to continue this health surveillance action.

Self-directed arm therapy at home after stroke with a sensor-based virtual reality training system.

PubMed

Wittmann, Frieder; Held, Jeremia P; Lambercy, Olivier; Starkey, Michelle L; Curt, Armin; Höver, Raphael; Gassert, Roger; Luft, Andreas R; Gonzenbach, Roman R

2016-08-11

The effect of rehabilitative training after stroke is dose-dependent. Out-patient rehabilitation training is often limited by transport logistics, financial resources and a lack of motivation/compliance. We studied the feasibility of an unsupervised arm therapy for self-directed rehabilitation therapy in patients' homes. An open-label, single group study involving eleven patients with hemiparesis due to stroke (27 ± 31.5 months post-stroke) was conducted. The patients trained with an inertial measurement unit (IMU)-based virtual reality system (ArmeoSenso) in their homes for six weeks. The self-selected dose of training with ArmeoSenso was the principal outcome measure whereas the Fugl-Meyer Assessment of the upper extremity (FMA-UE), the Wolf Motor Function Test (WMFT) and IMU-derived kinematic metrics were used to assess arm function, training intensity and trunk movement. Repeated measures one-way ANOVAs were used to assess differences in training duration and clinical scores over time. All subjects were able to use the system independently in their homes and no safety issues were reported. Patients trained on 26.5 ± 11.5 days out of 42 days for a duration of 137 ± 120 min per week. The weekly training duration did not change over the course of six weeks (p = 0.146). The arm function of these patients improved significantly by 4.1 points (p = 0.003) in the FMA-UE. Changes in the WMFT were not significant (p = 0.552). ArmeoSenso based metrics showed an improvement in arm function, a high number of reaching movements (387 per session), and minimal compensatory movements of the trunk while training. Self-directed home therapy with an IMU-based home therapy system is safe and can provide a high dose of rehabilitative therapy. The assessments integrated into the system allow daily therapy monitoring, difficulty adaptation and detection of maladaptive motor patterns such as trunk movements during reaching. Unique identifier: NCT02098135 .

Toward a real-time in vivo dosimetry system using plastic scintillation detectors

PubMed Central

Archambault, Louis; Briere, Tina M.; Pönisch, Falk; Beaulieu, Luc; Kuban, Deborah A.; Lee, Andrew; Beddar, Sam

2010-01-01

Purpose In this work, we present and validate a plastic scintillation detector (PSD) system designed for real-time multi-probe in vivo measurements. Methods and Materials The PSDs were built with a dose-sensitive volume of 0.4 mm3. PSDs were assembled into modular detector patches, each containing 5 closely packed PSDs. Continuous dose readings were performed every 150 ms, with a gap between consecutive readings of less than 0.3 ms. We first studied the effect of electron multiplication. We then assessed system performance in acrylic and anthropomorphic pelvic phantoms. Results The PSDs are compatible with clinical rectal balloons and are easily inserted into the anthropomorphic phantom. With an electron multiplication average gain factor of 40, a twofold increase in the signal-to-noise ratio was observed, making near real-time dosimetry feasible. Under calibration conditions, the PSDs agreed with ion chamber measurements to 0.08%. Precision, evaluated as a function of the total dose delivered, ranged from 2.3% at 2 cGy to 0.4% at 200 cGy. Conclusion Real-time PSD measurements are highly accurate and precise. These PSDs can be mounted onto rectal balloons, transforming these clinical devices into in vivo dose detectors without modifying current clinical practice. Real-time monitoring of the dose delivered near the rectum during prostate radiation therapy should help radiation oncologists protect this sensitive normal structure. PMID:20231074

Hydroxychloroquine Blood Levels in SLE: Clarifying dosing controversies and improving adherence

PubMed Central

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

2015-01-01

OBJECTIVES Hydroxychloroquine is used for its effect on systemic lupus erythematosus (SLE) disease activity and long-term 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 dosing controversy; rheumatologists recommend weight-based, while ophthalmologists advocate height-based ‘ideal body weight’ dosing. METHODS Patients were prescribed hydroxychloroquine not to exceed 6.5mg/kg (max400mg/day). In hemodialysis, the dose was 200mg after each session, in renal insufficiency it was 200mg/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 impact of measurement and counseling on adherence, we compared the proportion of patients with a level of 500ng/ml or higher based on how many prior assessments the patient had. RESULTS The proportion of patients with hydroxychloroquine levels in the therapeutic range differed significantly by age, gender 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, sub-therapeutic and therapeutic levels, disease activity decreased (SLEDAI 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). CONCLUSION There was a trend towards higher disease activity with lower hydroxychloroquine levels. Renal failure dosing led to sub-optimum levels. We show that weight-based dosing (max 400mg daily) is appropriate and that height does not appear to influence levels. Measurement, counseling and repeated testing can increase adherences rates. PMID:26428205

A phase I dose-escalation study to a predefined dose of a transforming growth factor-β1 monoclonal antibody (TβM1) in patients with metastatic cancer

PubMed Central

COHN, ALLEN; LAHN, MICHAEL M.; WILLIAMS, KRISTEN E.; CLEVERLY, ANN L.; PITOU, CELINE; KADAM, SUNIL K.; FARMEN, MARK W.; DESAIAH, DURISALA; RAJU, ROBERT; CONKLING, PAUL; RICHARDS, DONALD

2014-01-01

Transforming growth factor β (TGF-β) plays an important role in cancer. Monoclonal antibodies (mAb) designed to specifically block the TGF-β ligands, are expected to inhibit tumor progression in patients with metastatic cancer. TβM1 is a humanized mAb optimized for neutralizing activity against TGF-β1. The objective of this clinical trial was to assess the safety and tolerability of TβM1 in patients with metastatic cancer. In this phase I, uncontrolled, non-randomized, dose-escalation study, 18 eligible adult patients who had measurable disease per RECIST and a performance status of ≤2 on the ECOG scale were administered TβM1 intravenously over 10 min at doses of 20, 60, 120 and 240 mg on day 1 of each 28-day cycle. Safety was assessed by adverse events (as defined by CTCAE version 3.0) and possible relationship to study drug, dose-limiting toxicities and laboratory changes. Systemic drug exposure and pharmacodynamic (PD) parameters were assessed. TβM1 was safe when administered once monthly. The pharmacokinetic (PK) profile was consistent with a mAb with a mean elimination half-life approximately 9 days. Although anticipated changes in PD markers such as serum VEGF, bFGF and mRNA expression of SMAD7 were observed in whole-blood, suggesting activity of TβM1 on the targeted pathway, these changes were not consistent to represent a PD effect. Additionally, despite the presence of an activated TGF-β1 expression signature in patients’ whole blood, the short dosing duration did not translate into significant antitumor effect in the small number of patients investigated in this study PMID:25270361

Reduction of severe visual loss and complications following intra-arterial chemotherapy (IAC) for refractory retinoblastoma.

PubMed

Reddy, M Ashwin; Naeem, Zishan; Duncan, Catriona; Robertson, Fergus; Herod, Jane; Rennie, Adam; Liasis, Alki; Thompson, Dorothy Ann; Sagoo, Mandeep

2017-12-01

Intra-arterial chemotherapy (IAC) for retinoblastoma has been documented as causing visual loss and ocular motility problems. A lack of safety data has precluded its acceptance in all centres. Retrospective cohort study of patients with retinoblastoma from 2013 to 2015 who had a healthy foveola and relapsed following systemic chemotherapy. All required IAC. The correlation of complications with doses of melphalan +/- topotecan used and putative catheterisation complications was assessed. Ocular complications were determined using vision, macular (including pattern visual evoked potentials (PVEPs)), retinal electroretinograms (ERGs) and ocular motility functions. Efficacy (tumour control) was also assessed. All eyes had age appropriate doses of melphalan with five having additional doses of topotecan. Severe physiological reactions requiring adrenaline were seen in six patients during the catheterisation procedure. Difficulty was documented in accessing the ophthalmic artery in 7/27 catheterisations. The median/mean number of courses of chemotherapy was three. No child had severe visual loss as assessed by age appropriate tests (median follow-up 20.9 months, range 3.7-35.2 months). One child had nasal choroidal ischaemia and a sixth nerve palsy. Post-IAC PVEPs were performed in eight and reported as normal. All post-IAC ERGs were normal apart from one (total dose 20 mg melphalan 0.8 mg topotecan). Tumour control was achieved in six of nine cases. The proportion of visual and ocular motility complications may be reduced by providing age-adjusted doses of melphalan. Dose rather than complications from catheterisation is the most important risk factor for ocular injury. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Metabolism, distribution and elimination of lisdexamfetamine dimesylate: open-label, single-centre, phase I study in healthy adult volunteers.

PubMed

Krishnan, Suma M; Pennick, Michael; Stark, Jeffrey G

2008-01-01

Attention-deficit/hyperactivity disorder (ADHD) in children often persists into adulthood and is potentially associated with significant social and occupational impairments. It is important to understand the effects of pharmacological treatments of ADHD in adults. This study aimed to assess the absorption, metabolism and elimination of lisdexamfetamine dimesylate in normal, healthy adult subjects following a single oral dose. A secondary objective was to assess the safety and tolerability of treatment. In an open-label, single-centre study, six healthy adult volunteers aged 22-52 years received a single oral 70 mg dose of (14)C-radiolabelled lisdexamfetamine dimesylate in solution following a 10-hour fast. Blood samples drawn pre-dose and at time points up to 120 hours post-dose were used for plasma pharmacokinetic analysis of the active d-amphetamine and the intact parent compound lisdexamfetamine dimesylate. Recovery of radioactivity was determined by liquid scintillation counting of blood samples (whole blood and plasma), urine samples and faecal samples collected pre-dose and at designated time points up to 120 hours post-dose. Urine samples were also analysed for the presence of amphetamine-derived metabolites. Safety was assessed by adverse event reporting, changes in physical findings, vital sign measurements, ECG measurements, and clinical laboratory test results. For intact lisdexamfetamine dimesylate, the median time to reach maximum plasma drug concentration (t(max)) was 1.00 hour, and the mean maximum plasma drug concentration (C(max)) was 58.2 +/- 28.1 ng/mL. Intact lisdexamfetamine dimesylate exhibited modest systemic exposure (area under the drug concentration-time curve from time 0 to infinity [AUC(infinity)] 67.04 +/- 18.94 ng . h/mL), and rapid elimination (mean apparent terminal elimination half-life [t((1/2)beta)] 0.47 hours). For d-amphetamine, the median t(max) was 3.00 hours, and the mean C(max) was 80.3 +/- 11.8 ng/mL. The AUC(infinity) of d-amphetamine was 1342 +/- 216.9 ng . h/mL, and elimination occurred as a first-order process. The t((1/2)beta) of d-amphetamine was 10.39 hours. Peaks consistent with amphetamine and hippuric acid were identified in urine samples by high-performance liquid chromatography radioactive profiling. Relative to dose administered, 41.5% was recovered in urine as d-amphetamine, 24.8% as hippuric acid and 2.2% as intact lisdexamfetamine dimesylate. Less than 0.3% of the administered dose was recovered in the faeces. During the 0- to 48-hour urine samples, no unexpected adverse events or clinically significant laboratory, ECG or physical examination findings related to the study medication were observed. Following a single 70 mg oral dose, lisdexamfetamine dimesylate was quickly absorbed, extensively metabolized to d-amphetamine and its derivatives, and rapidly eliminated. Systemic exposure to d-amphetamine was approximately 20-fold higher than systemic exposure to intact lisdexamfetamine dimesylate in healthy adults. Lisdexamfetamine dimesylate, administered as a single 70 mg dose, was generally well tolerated in this study.

SU-G-TeP4-02: A Method for Evaluating the Direct Impact of Failed IMRT QAs On Patient Dose

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

Geneser, S; Butkus, M

Purpose: We developed a method to calculate patient doses corresponding to IMRT QA measurements in order to determine and assess the actual dose delivered for plans with failed (or borderline) IMRT QA. This work demonstrates the feasibility of automatically computing delivered patient dose from portal dosimetry measurements in the Varian TPS system, which would provide a valuable and clinically viable IMRT QA tool for physicists and physicians. Methods: IMRT QA fluences were measured using portal dosimetry, processed using in-house matlab software, and imported back into Eclipse to calculate dose on the planning CT. To validate the proposed workflow, the Eclipsemore » calculated portal dose for a 5-field sliding window prostate boost plan was processed as described above. The resulting dose was compared to the planned dose and found to be within 0.5 Gy. Two IMRT QA results for the prostate boost plan (one that failed and one that passed) were processed and the resulting patient doses were evaluated. Results: The max dose difference between IMRT QA #1 and the original planned and approved dose is 4.5 Gy, while the difference between the planned and IMRT QA #2 dose is 4.0 Gy. The inferior portion of the PTV is slightly underdosed in both plans, and the superior portion is slightly overdosed. The patient dose resulting from IMRT QA #1 and #2 differs by only 0.5 Gy. With this new information, it may be argued that the evaluated plan alteration to obtain passing gamma analysis produced clinically irrelevant differences. Conclusion: Evaluation of the delivered QA dose on the planning CT provides valuable information about the clinical relevance of failed or borderline IMRT QAs. This particular workflow demonstrates the feasibility of pushing the measured IMRT QA portal dosimetry results directly back onto the patient planning CT within the Varian system.« less

Gafchromic EBT-XD film: Dosimetry characterization in high-dose, volumetric-modulated arc therapy.

PubMed

Miura, Hideharu; Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

2016-11-08

Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT-XD films have been designed for optimal performance in the 40-4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose-response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high-dose volumetric-modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0-4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter-free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose-rate dependence. For clinical examinations, we compared the dose distribu-tion measured with EBT-XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT-XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ~ 3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ~ 1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ~ 1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film- measured and treatment planning system (TPS)-calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. © 2016 The Authors.

Susceptibility of various areas of the nervous system of hens to TOCP-induced delayed neuropathy.

PubMed

Classen, W; Gretener, P; Rauch, M; Weber, E; Krinke, G J

1996-01-01

Sensitivity of in-life parameters, biochemical endpoints, and susceptibility of various areas of the chicken nervous system to delayed neuropathy induced by tri-orthocresyl phosphate (TOCP) was assessed. Groups of hens were exposed to a single oral dose of TOCP of 0, 50, 200 or 500 mg/kg and the animals observed for 21 days. Perfusion fixed, paraffin embedded tissue sections were stained with Bodian's silver and Luxol blue and semi-thin epoxy sections with toluidine blue. Sciatic and tibial nerves, lumbosacral, midthoracic, and upper cervical spinal cord, medulla oblongata and cerebellum were examined using a semiquantitative scoring system. In pair-dosed hens inhibition of brain and spinal cord neurotoxic esterase (NTE) and cholinesterase and of plasma and erythrocyte cholinesterases was determined 24 hr and 48 hr after administration. At all dose levels NTE in brain and spinal cord and plasma cholinesterase was inhibited markedly. Quantitative inhibition of NTE was seen also in absence of neuropathy. Ataxia and body weight loss occurred in high-dose animals only, while dose-related neuropathy was seen in the distal tibial nerve, medulla oblongata and cerebellum. Ataxia was correlated best with neuropathy in peripheral nerves while degeneration of nerve fibers in the cerebellum, seen best in mid-longitudinal sections, was the most sensitive histological indicator of TOCP-induced delayed neuropathy. The particular susceptibility of spinocerebellar neurons was recognized long ago, but often has been neglected in delayed neurotoxicity studies and respective guidelines. Optimal sensitivity of toxicity tests is a prerequisite for risk assessment, can be cost efficient, and nowadays should be a main interest of animal welfare in order to reduce animals' suffering. Based on these data, determination of NTE inhibition together with histopathological examination of longitudinal sections of distal tibial nerves, mid-longitudinal sections of rostral cerebellum and cross sections of upper cervical spinal cord represents an optimally sensitive and cost efficient test requirement.

Assessing Inhalation Exposures Associated with Contamination Events in Water Distribution Systems

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

Davis, Michael J.; Janke, Robert; Taxon, Thomas N.

When a water distribution system (WDS) is contaminated, short-term inhalation exposures to airborne contaminants could occur as the result of domestic water use. The most important domestic sources of such exposures are likely to be showering and the use of aerosol-producing humidifiers, i.e., ultrasonic and impeller (cool-mist) units. A framework is presented for assessing the potential effects of short-term, system-wide inhalation exposures that could result from such activities during a contamination event. This framework utilizes available statistical models for showering frequency and duration, available exposure models for showering and humidifier use, and experimental results on both aerosol generation and themore » volatilization of chemicals during showering. New models for the times when showering occurs are developed using time-use data for the United States. Given a lack of similar models for how humidifiers are used, or the information needed to develop them, an analysis of the sensitivity of results to assumptions concerning humidifier use is presented. The framework is applied using network models for three actual WDSs. Simple models are developed for estimating upper bounds on the potential effects of system-wide inhalation exposures associated with showering and humidifier use. From a system-wide, population perspective, showering could result in significant inhalation doses of volatile chemical contaminants, and humidifier use could result in significant inhalation doses of microbial contaminants during a contamination event. From a system-wide perspective, showering is unlikely to be associated with significant doses of microbial contaminants. In conclusion, given the potential importance of humidifiers as a source of airborne contaminants during a contamination event, an improved understanding of the nature of humidifier use is warranted.« less

Assessing Inhalation Exposures Associated with Contamination Events in Water Distribution Systems

DOE PAGES

Davis, Michael J.; Janke, Robert; Taxon, Thomas N.

2016-12-08

When a water distribution system (WDS) is contaminated, short-term inhalation exposures to airborne contaminants could occur as the result of domestic water use. The most important domestic sources of such exposures are likely to be showering and the use of aerosol-producing humidifiers, i.e., ultrasonic and impeller (cool-mist) units. A framework is presented for assessing the potential effects of short-term, system-wide inhalation exposures that could result from such activities during a contamination event. This framework utilizes available statistical models for showering frequency and duration, available exposure models for showering and humidifier use, and experimental results on both aerosol generation and themore » volatilization of chemicals during showering. New models for the times when showering occurs are developed using time-use data for the United States. Given a lack of similar models for how humidifiers are used, or the information needed to develop them, an analysis of the sensitivity of results to assumptions concerning humidifier use is presented. The framework is applied using network models for three actual WDSs. Simple models are developed for estimating upper bounds on the potential effects of system-wide inhalation exposures associated with showering and humidifier use. From a system-wide, population perspective, showering could result in significant inhalation doses of volatile chemical contaminants, and humidifier use could result in significant inhalation doses of microbial contaminants during a contamination event. From a system-wide perspective, showering is unlikely to be associated with significant doses of microbial contaminants. In conclusion, given the potential importance of humidifiers as a source of airborne contaminants during a contamination event, an improved understanding of the nature of humidifier use is warranted.« less

Assessing Inhalation Exposures Associated with Contamination Events in Water Distribution Systems

PubMed Central

Davis, Michael J.; Janke, Robert; Taxon, Thomas N.

2016-01-01

When a water distribution system (WDS) is contaminated, short-term inhalation exposures to airborne contaminants could occur as the result of domestic water use. The most important domestic sources of such exposures are likely to be showering and the use of aerosol-producing humidifiers, i.e., ultrasonic and impeller (cool-mist) units. A framework is presented for assessing the potential effects of short-term, system-wide inhalation exposures that could result from such activities during a contamination event. This framework utilizes available statistical models for showering frequency and duration, available exposure models for showering and humidifier use, and experimental results on both aerosol generation and the volatilization of chemicals during showering. New models for the times when showering occurs are developed using time-use data for the United States. Given a lack of similar models for how humidifiers are used, or the information needed to develop them, an analysis of the sensitivity of results to assumptions concerning humidifier use is presented. The framework is applied using network models for three actual WDSs. Simple models are developed for estimating upper bounds on the potential effects of system-wide inhalation exposures associated with showering and humidifier use. From a system-wide, population perspective, showering could result in significant inhalation doses of volatile chemical contaminants, and humidifier use could result in significant inhalation doses of microbial contaminants during a contamination event. From a system-wide perspective, showering is unlikely to be associated with significant doses of microbial contaminants. Given the potential importance of humidifiers as a source of airborne contaminants during a contamination event, an improved understanding of the nature of humidifier use is warranted. PMID:27930709

A test-based method for the assessment of pre-crash warning and braking systems.

PubMed

Bálint, András; Fagerlind, Helen; Kullgren, Anders

2013-10-01

In this paper, a test-based assessment method for pre-crash warning and braking systems is presented where the effectiveness of a system is measured by its ability to reduce the number of injuries of a given type or severity in car-to-car rear-end collisions. Injuries with whiplash symptoms lasting longer than 1 month and MAIS2+ injuries in both vehicles involved in the crash are considered in the assessment. The injury reduction resulting from the impact speed reduction due to a pre-crash system is estimated using a method which has its roots in the dose-response model. Human-machine interaction is also taken into account in the assessment. The results reflect the self-protection as well as the partner-protection performance of a pre-crash system in the striking vehicle in rear-end collisions and enable a comparison between two or more systems. It is also shown how the method may be used to assess the importance of warning as part of a pre-crash system. Copyright © 2013 Elsevier Ltd. All rights reserved.

Fully automated bone mineral density assessment from low-dose chest CT

NASA Astrophysics Data System (ADS)

Liu, Shuang; Gonzalez, Jessica; Zulueta, Javier; de-Torres, Juan P.; Yankelevitz, David F.; Henschke, Claudia I.; Reeves, Anthony P.

2018-02-01

A fully automated system is presented for bone mineral density (BMD) assessment from low-dose chest CT (LDCT). BMD assessment is central in the diagnosis and follow-up therapy monitoring of osteoporosis, which is characterized by low bone density and is estimated to affect 12.3 million US population aged 50 years or older, creating tremendous social and economic burdens. BMD assessment from DXA scans (BMDDXA) is currently the most widely used and gold standard technique for the diagnosis of osteoporosis and bone fracture risk estimation. With the recent large-scale implementation of annual lung cancer screening using LDCT, great potential emerges for the concurrent opportunistic osteoporosis screening. In the presented BMDCT assessment system, each vertebral body is first segmented and labeled with its anatomical name. Various 3D region of interest (ROI) inside the vertebral body are then explored for BMDCT measurements at different vertebral levels. The system was validated using 76 pairs of DXA and LDCT scans of the same subject. Average BMDDXA of L1-L4 was used as the reference standard. Statistically significant (p-value < 0.001) strong correlation is obtained between BMDDXA and BMDCT at all vertebral levels (T1 - L2). A Pearson correlation of 0.857 was achieved between BMDDXA and average BMDCT of T9-T11 by using a 3D ROI taking into account of both trabecular and cortical bone tissue. These encouraging results demonstrate the feasibility of fully automated quantitative BMD assessment and the potential of opportunistic osteoporosis screening with concurrent lung cancer screening using LDCT.

Design and implementation of a system for treating paediatric patients with stereotactically-guided conformal radiotherapy.

PubMed

Adams, E J; Suter, B L; Warrington, A P; Black, P; Saran, F; Brada, M

2001-09-01

Stereotactically-guided conformal radiotherapy (SCRT) allows the delivery of highly conformal dose distributions to localised brain tumours. This is of particular importance for children, whose often excellent long-term prognosis should be accompanied by low toxicity. The commercial immobilisation system in use at our hospital for adults was felt to be too heavy for children, and precluded the use of anaesthesia, which is sometimes required for paediatric patients. This paper therefore describes the design and implementation of a system for treating children with SCRT. This system needed to be well tolerated by patients, with good access for treating typical childhood malignancies. A lightweight frame was developed for immobilisation, with a shell-based alternative for patients requiring general anaesthetic. Procedures were set up to introduce the patients to the frame system in order to maximise patient co-operation and comfort. Film measurements were made to assess the impact of the frame on transmission and surface dose. The reproducibility of the systems was assessed using electronic portal images. Both frame and shell systems are in clinical use. The frame weighs 0.6 kg and is well tolerated. It has a transmission of 92-96%, and fields which pass through it deliver surface doses of 58-82% of the dose at d(max), compared to 18% when no frame is present. However, the frame is constructed to maximise the availability of unobstructed beam directions. Reproducibility measurements for the frame showed a mean random error of 1.0+/-0.2mm in two dimensions (2D) and 1.4+/-0.7 mm in 3D. The mean systematic error in 3D was 2.2mm, and 90% of all overall 3D errors were less than 3.4mm. For the shell system, the mean 2D random error was 1.5+/-0.2mm. Two well-tolerated immobilisation devices have been developed for fractionated SCRT treatment of paediatric patients. A lightweight frame system gives a wide range of possible unobstructed beam directions, although beams that intersect the frame are not precluded, provided that output corrections are applied. A shell system allows the use of general anaesthesia. Both systems give reproducible immobilisation to complement the high-precision treatment delivery.

Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera).

PubMed

Maze, Ian S; Wright, Geraldine A; Mustard, Julie A

2006-01-01

Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses led to hemolymph ethanol levels of approximately 40-100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 h post-ingestion for low doses and at 24-48 h for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior.

Steady-state pharmacokinetics of fluvastatin in healthy subjects following a new extended release fluvastatin tablet, Lescol XL.

PubMed

Barilla, Denise; Prasad, Pratapa; Hubert, Martine; Gumbhir-Shah, Kavita

2004-03-01

This was an open-label, randomized, three-period, three-treatment, multiple dose, crossover study in 12 healthy male and female subjects. This study evaluated single dose and steady-state pharmacokinetics of fluvastatin following single and multiple dose administrations of a new extended release fluvastatin 8 h matrix tablet, Lescol XL 80 mg and 160 mg doses once a day. The study also included a twice a day administration of an immediate release (IR) form of fluvastatin capsule, Lescol, for comparative purposes. All doses were administered for 7 days. The safety and tolerability were also assessed. The pharmacokinetics of fluvastatin were evaluated on days 1 and 7 following each treatment. Fluvastatin systemic exposure was 50% less when administered as Lescol XL 80 mg qd compared with Lescol IR 40 mg bid. Conversely, fluvastatin systemic exposure was 22% higher when administered as Lescol XL 160 mg qd compared with Lescol IR 40 mg bid. Single doses of Lescol XL 80 mg and 160 mg were dose proportional but, deviation (30%) from dose proportionality was observed for the Lescol XL 160 mg at steady-state. There appeared to be moderate (20%-40%) accumulation of serum fluvastatin maximal concentrations and exposure after multiple doses of Lescol XL tablets. Both Lescol XL 80 mg and 160 mg showed delayed absorption and longer apparent elimination half-life compared with fluvastatin IR capsule. Single and multiple doses of fluvastatin were generally well tolerated in this healthy volunteer population. Adverse event profiles were consistent with the published safety profile of the marketed formulations. Aside from one incidence of creatine phosphokinase (CPK) elevation (following Lescol XL 160 mg qd treatment), there were no safety concerns with any of the treatments when administered acutely (7 days). Copyright 2004 John Wiley & Sons, Ltd.

The Effect of Route, Vehicle, and Divided Doses on the Pharmacokinetics of Chlorpyrifos and its Metabolite Trichloropyridinol in Neonatal Sprague-Dawley Rats

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

Marty, M. S.; Domoradzki, J. Y.; Hansen, S. C.

2007-12-01

There is a paucity of data on neonatal systemic exposure using different dosing paradigms. Male CD (Sprague-Dawley derived) rats at postnatal day (PND) 5 were dosed with chlorpyrifos (CPF, 1 mg/kg) using different routes of exposure, vehicles, and single vs. divided doses. Blood concentrations of CPF and its primary metabolite, trichloropyridinol (TCP), were measured at multiple times through 24 h. Groups included: single gavage bolus vs. divided gavage doses in corn oil (1 vs 3 times in 24 h), single gavage bolus vs. divided gavage doses in rat milk, and subcutaneous administration in DMSO. These data were compared with lactationalmore » exposure of PND 5 pups from dams exposed to CPF in the diet at 5 mg/kg/day for four weeks or published data from dams exposed to daily gavage with CPF at 5 mg/kg/day. Maternal blood CPF levels were an order of magnitude lower from dietary exposure than gavage (1.1 vs 14.8 ng/g), and blood CPF levels in PND 5 pups that nursed dietary-exposed or gavage-exposed dams were below the limit of detection. Single gavage doses of 1 mg/kg CPF in corn oil vehicle in pups resulted in CPF blood levels of 49 ng/g, and in milk vehicle about 9 ng/g. Divided doses led to lower peak CPF levels. A bolus dose of 1 mg/kg CPF in DMSO administered sc appeared to have substantially altered pharmacokinetics from orally administered chlorpyrifos. To be meaningful for risk assessment, neonatal studies require attention to the exposure scenario, since route, vehicle, dose and frequency of administration result in different systemic exposure to the test chemical and its metabolites.« less

PROPOSAL FOR A SIMPLE AND EFFICIENT MONTHLY QUALITY MANAGEMENT PROGRAM ASSESSING THE CONSISTENCY OF ROBOTIC IMAGE-GUIDED SMALL ANIMAL RADIATION SYSTEMS

PubMed Central

Brodin, N. Patrik; Guha, Chandan; Tomé, Wolfgang A.

2015-01-01

Modern pre-clinical radiation therapy (RT) research requires high precision and accurate dosimetry to facilitate the translation of research findings into clinical practice. Several systems are available that provide precise delivery and on-board imaging capabilities, highlighting the need for a quality management program (QMP) to ensure consistent and accurate radiation dose delivery. An ongoing, simple, and efficient QMP for image-guided robotic small animal irradiators used in pre-clinical RT research is described. Protocols were developed and implemented to assess the dose output constancy (based on the AAPM TG-61 protocol), cone-beam computed tomography (CBCT) image quality and object representation accuracy (using a custom-designed imaging phantom), CBCT-guided target localization accuracy and consistency of the CBCT-based dose calculation. To facilitate an efficient read-out and limit the user dependence of the QMP data analysis, a semi-automatic image analysis and data representation program was developed using the technical computing software MATLAB. The results of the first six months experience using the suggested QMP for a Small Animal Radiation Research Platform (SARRP) are presented, with data collected on a bi-monthly basis. The dosimetric output constancy was established to be within ±1 %, the consistency of the image resolution was within ±0.2 mm, the accuracy of CBCT-guided target localization was within ±0.5 mm, and dose calculation consistency was within ±2 s (± 3 %) per treatment beam. Based on these results, this simple quality assurance program allows for the detection of inconsistencies in dosimetric or imaging parameters that are beyond the acceptable variability for a reliable and accurate pre-clinical RT system, on a monthly or bi-monthly basis. PMID:26425981

Development of a dose-controlled multiculture cell exposure chamber for efficient delivery of airborne and engineered nanoparticles

NASA Astrophysics Data System (ADS)

Asimakopoulou, Akrivi; Daskalos, Emmanouil; Lewinski, Nastassja; Riediker, Michael; Papaioannou, Eleni; Konstandopoulos, Athanasios G.

2013-04-01

In order to study the various health influencing parameters related to engineered nanoparticles as well as to soot emitted by Diesel engines, there is an urgent need for appropriate sampling devices and methods for cell exposure studies that simulate the respiratory system and facilitate associated biological and toxicological tests. The objective of the present work was the further advancement of a Multiculture Exposure Chamber (MEC) into a dose-controlled system for efficient delivery of nanoparticles to cells. It was validated with various types of nanoparticles (Diesel engine soot aggregates, engineered nanoparticles for various applications) and with state-of-the-art nanoparticle measurement instrumentation to assess the local deposition of nanoparticles on the cell cultures. The dose of nanoparticles to which cell cultures are being exposed was evaluated in the normal operation of the in vitro cell culture exposure chamber based on measurements of the size specific nanoparticle collection efficiency of a cell free device. The average efficiency in delivering nanoparticles in the MEC was approximately 82%. The nanoparticle deposition was demonstrated by Transmission Electron Microscopy (TEM). Analysis and design of the MEC employs Computational Fluid Dynamics (CFD) and true to geometry representations of nanoparticles with the aim to assess the uniformity of nanoparticle deposition among the culture wells. Final testing of the dose-controlled cell exposure system was performed by exposing A549 lung cell cultures to fluorescently labeled nanoparticles. Delivery of aerosolized nanoparticles was demonstrated by visualization of the nanoparticle fluorescence in the cell cultures following exposure. Also monitored was the potential of the aerosolized nanoparticles to generate reactive oxygen species (ROS) (e.g. free radicals and peroxides generation), thus expressing the oxidative stress of the cells which can cause extensive cellular damage or damage on DNA.

Proposal for a Simple and Efficient Monthly Quality Management Program Assessing the Consistency of Robotic Image-Guided Small Animal Radiation Systems.

PubMed

Brodin, N Patrik; Guha, Chandan; Tomé, Wolfgang A

2015-11-01

Modern pre-clinical radiation therapy (RT) research requires high precision and accurate dosimetry to facilitate the translation of research findings into clinical practice. Several systems are available that provide precise delivery and on-board imaging capabilities, highlighting the need for a quality management program (QMP) to ensure consistent and accurate radiation dose delivery. An ongoing, simple, and efficient QMP for image-guided robotic small animal irradiators used in pre-clinical RT research is described. Protocols were developed and implemented to assess the dose output constancy (based on the AAPM TG-61 protocol), cone-beam computed tomography (CBCT) image quality and object representation accuracy (using a custom-designed imaging phantom), CBCT-guided target localization accuracy and consistency of the CBCT-based dose calculation. To facilitate an efficient read-out and limit the user dependence of the QMP data analysis, a semi-automatic image analysis and data representation program was developed using the technical computing software MATLAB. The results of the first 6-mo experience using the suggested QMP for a Small Animal Radiation Research Platform (SARRP) are presented, with data collected on a bi-monthly basis. The dosimetric output constancy was established to be within ±1 %, the consistency of the image resolution was within ±0.2 mm, the accuracy of CBCT-guided target localization was within ±0.5 mm, and dose calculation consistency was within ±2 s (±3%) per treatment beam. Based on these results, this simple quality assurance program allows for the detection of inconsistencies in dosimetric or imaging parameters that are beyond the acceptable variability for a reliable and accurate pre-clinical RT system, on a monthly or bi-monthly basis.

Development of QSAR models using artificial neural network analysis for risk assessment of repeated-dose, reproductive, and developmental toxicities of cosmetic ingredients.

PubMed

Hisaki, Tomoka; Aiba Née Kaneko, Maki; Yamaguchi, Masahiko; Sasa, Hitoshi; Kouzuki, Hirokazu

2015-04-01

Use of laboratory animals for systemic toxicity testing is subject to strong ethical and regulatory constraints, but few alternatives are yet available. One possible approach to predict systemic toxicity of chemicals in the absence of experimental data is quantitative structure-activity relationship (QSAR) analysis. Here, we present QSAR models for prediction of maximum "no observed effect level" (NOEL) for repeated-dose, developmental and reproductive toxicities. NOEL values of 421 chemicals for repeated-dose toxicity, 315 for reproductive toxicity, and 156 for developmental toxicity were collected from Japan Existing Chemical Data Base (JECDB). Descriptors to predict toxicity were selected based on molecular orbital (MO) calculations, and QSAR models employing multiple independent descriptors as the input layer of an artificial neural network (ANN) were constructed to predict NOEL values. Robustness of the models was indicated by the root-mean-square (RMS) errors after 10-fold cross-validation (0.529 for repeated-dose, 0.508 for reproductive, and 0.558 for developmental toxicity). Evaluation of the models in terms of the percentages of predicted NOELs falling within factors of 2, 5 and 10 of the in-vivo-determined NOELs suggested that the model is applicable to both general chemicals and the subset of chemicals listed in International Nomenclature of Cosmetic Ingredients (INCI). Our results indicate that ANN models using in silico parameters have useful predictive performance, and should contribute to integrated risk assessment of systemic toxicity using a weight-of-evidence approach. Availability of predicted NOELs will allow calculation of the margin of safety, as recommended by the Scientific Committee on Consumer Safety (SCCS).

In vivo skin dose measurement in breast conformal radiotherapy.

PubMed

Soleymanifard, Shokouhozaman; Aledavood, Seyed Amir; Noghreiyan, Atefeh Vejdani; Ghorbani, Mahdi; Jamali, Farideh; Davenport, David

2016-01-01

Accurate skin dose assessment is necessary during breast radiotherapy to assure that the skin dose is below the tolerance level and is sufficient to prevent tumour recurrence. The aim of the current study is to measure the skin dose and to evaluate the geometrical/anatomical parameters that affect it. Forty patients were simulated by TIGRT treatment planning system and treated with two tangential fields of 6 MV photon beam. Wedge filters were used to homogenise dose distribution for 11 patients. Skin dose was measured by thermoluminescent dosimeters (TLD-100) and the effects of beam incident angle, thickness of irradiated region, and beam entry separation on the skin dose were analysed. Average skin dose in treatment course of 50 Gy to the clinical target volume (CTV) was 36.65 Gy. The corresponding dose values for patients who were treated with and without wedge filter were 35.65 and 37.20 Gy, respectively. It was determined that the beam angle affected the average skin dose while the thickness of the irradiated region and the beam entry separation did not affect dose. Since the skin dose measured in this study was lower than the amount required to prevent tumour recurrence, application of bolus material in part of the treatment course is suggested for post-mastectomy advanced breast radiotherapy. It is more important when wedge filters are applied to homogenize dose distribution.

TRIAGE DOSE ASSESSMENT FOR PARTIAL-BODY EXPOSURE: DICENTRIC ANALYSIS

PubMed Central

Moroni, Maria; Pellmar, Terry C.

2009-01-01

Partial-body biodosimetry is likely to be required after a radiological or nuclear exposure. Clinical signs and symptoms, distribution of dicentrics in circulating blood cells, organ-specific biomarkers, physical signals in teeth and nails all can provide indications of non-homogeneous exposures. Organ specific biomarkers may provide early warning regarding physiological systems at risk after radiation injury. Use of a combination of markers and symptoms will be needed for clinical insights for therapeutic approaches. Analysis of dicentrics, a marker specific for radiation injury, is the “Gold standard” of biodosimetry and can reveal partial-body exposures. Automation of sample processing for dicentric analysis can increase throughput with customization of off-the-shelf technologies for cytogenetic sample processing and information management. Automated analysis of the metaphase spreads is currently limited but improvements are in development. Our efforts bridge the technological gaps to allow the use of dicentric chromosome assay (DCA) for risk-based stratification of mass casualties. This article summarizes current knowledge on partial-body cytogenetic dose assessment synthesizing information leading to the proposal of an approach to triage dose prediction in radiation mass casualties, based on equivalent whole-body doses under partial-body exposure conditions and assesses the validity of using this model. An initial screening using only 20 metaphase spreads per subject can confirm irradiation above 2-Gy. A subsequent increase to 50 metaphases improves dose determination to allow risk stratification for clinical triage. Metaphases evaluated for inhomogeneous distribution of dicentrics can reveal partial-body exposures. We tested the validity of this approach in an in vitro model that simulates partial-body irradiation by mixing irradiated and un-irradiated lymphocytes in various proportions. Our preliminary results support the notion that this approach will be effective under a range of conditions including some partial-body exposures, but may have limitations with low doses or small proportions of irradiated body. Our studies address an important problem in the diagnosis of partial-body irradiation and dose assessment in mass casualties and propose a solution. However, additional work is needed to fully develop and validate the application of DCA to partial-body exposures. PMID:20065689

SU-F-T-267: A Clarkson-Based Independent Dose Verification for the Helical Tomotherapy

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

Nagata, H; Juntendo University, Hongo, Tokyo; Hongo, H

2016-06-15

Purpose: There have been few reports for independent dose verification for Tomotherapy. We evaluated the accuracy and the effectiveness of an independent dose verification system for the Tomotherapy. Methods: Simple MU Analysis (SMU, Triangle Product, Ishikawa, Japan) was used as the independent verification system and the system implemented a Clarkson-based dose calculation algorithm using CT image dataset. For dose calculation in the SMU, the Tomotherapy machine-specific dosimetric parameters (TMR, Scp, OAR and MLC transmission factor) were registered as the machine beam data. Dose calculation was performed after Tomotherapy sinogram from DICOM-RT plan information was converted to the information for MUmore » and MLC location at more segmented control points. The performance of the SMU was assessed by a point dose measurement in non-IMRT and IMRT plans (simple target and mock prostate plans). Subsequently, 30 patients’ treatment plans for prostate were compared. Results: From the comparison, dose differences between the SMU and the measurement were within 3% for all cases in non-IMRT plans. In the IMRT plan for the simple target, the differences (Average±1SD) were −0.70±1.10% (SMU vs. TPS), −0.40±0.10% (measurement vs. TPS) and −1.20±1.00% (measurement vs. SMU), respectively. For the mock prostate, the differences were −0.40±0.60% (SMU vs. TPS), −0.50±0.90% (measurement vs. TPS) and −0.90±0.60% (measurement vs. SMU), respectively. For patients’ plans, the difference was −0.50±2.10% (SMU vs. TPS). Conclusion: A Clarkson-based independent dose verification for the Tomotherapy can be clinically available as a secondary check with the similar tolerance level of AAPM Task group 114. This research is partially supported by Japan Agency for Medical Research and Development (AMED)« less

Measured Neutron Spectra and Dose Equivalents From a Mevion Single-Room, Passively Scattered Proton System Used for Craniospinal Irradiation.

PubMed

Howell, Rebecca M; Burgett, Eric A; Isaacs, Daniel; Price Hedrick, Samantha G; Reilly, Michael P; Rankine, Leith J; Grantham, Kevin K; Perkins, Stephanie; Klein, Eric E

2016-05-01

To measure, in the setting of typical passively scattered proton craniospinal irradiation (CSI) treatment, the secondary neutron spectra, and use these spectra to calculate dose equivalents for both internal and external neutrons delivered via a Mevion single-room compact proton system. Secondary neutron spectra were measured using extended-range Bonner spheres for whole brain, upper spine, and lower spine proton fields. The detector used can discriminate neutrons over the entire range of the energy spectrum encountered in proton therapy. To separately assess internally and externally generated neutrons, each of the fields was delivered with and without a phantom. Average neutron energy, total neutron fluence, and ambient dose equivalent [H* (10)] were calculated for each spectrum. Neutron dose equivalents as a function of depth were estimated by applying published neutron depth-dose data to in-air H* (10) values. For CSI fields, neutron spectra were similar, with a high-energy direct neutron peak, an evaporation peak, a thermal peak, and an intermediate continuum between the evaporation and thermal peaks. Neutrons in the evaporation peak made the largest contribution to dose equivalent. Internal neutrons had a very low to negligible contribution to dose equivalent compared with external neutrons, largely attributed to the measurement location being far outside the primary proton beam. Average energies ranged from 8.6 to 14.5 MeV, whereas fluences ranged from 6.91 × 10(6) to 1.04 × 10(7) n/cm(2)/Gy, and H* (10) ranged from 2.27 to 3.92 mSv/Gy. For CSI treatments delivered with a Mevion single-gantry proton therapy system, we found measured neutron dose was consistent with dose equivalents reported for CSI with other proton beamlines. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Evaluation of the accuracy of mono-energetic electron and beta-emitting isotope dose-point kernels using particle and heavy ion transport code system: PHITS.

PubMed

Shiiba, Takuro; Kuga, Naoya; Kuroiwa, Yasuyoshi; Sato, Tatsuhiko

2017-10-01

We assessed the accuracy of mono-energetic electron and beta-emitting isotope dose-point kernels (DPKs) calculated using the particle and heavy ion transport code system (PHITS) for patient-specific dosimetry in targeted radionuclide treatment (TRT) and compared our data with published data. All mono-energetic and beta-emitting isotope DPKs calculated using PHITS, both in water and compact bone, were in good agreement with those in literature using other MC codes. PHITS provided reliable mono-energetic electron and beta-emitting isotope scaled DPKs for patient-specific dosimetry. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Pharmacological correction of central nervous system function in exposure to Coriolis acceleration].

PubMed

Karkishchenko, N N; Dimitriadi, N A; Molchanovskiĭ, V V

1986-01-01

Healthy volunteers with a low vestibular tolerance were exposed to Coriolis acceleration. Potassium orotate, pyracetame and riboxine were used as prophylactic measures against disorders in the function of the vestibular apparatus and higher compartments of the higher nervous system. The central nervous function was assessed with respect to the spectral power of electroencephalograms, short-term memory and mental performance. Potassium orotate given at a dose of 40 mg/kg body weight/day during 12-14 days as well as pyracetame given at a dose of 30 mg/kg body weight/day during 3 or 7 days increased significantly statokinetic tolerance and produced a protective effect on the central nervous function against Coriolis acceleration.

Effects of high energy radiation on the mechanical properties of epoxy/graphite fiber reinforced composites

NASA Technical Reports Server (NTRS)

Fornes, R. E.; Gilbert, R. D.; Memory, J. D.

1986-01-01

The epoxy resin system formed by tetraglycidyl 4,4'-diamino diphenyl methane (TGDDM) and 4,4'-diamino diphenyl sulfone (DDS) was characterized by dynamic mechanical analysis and differential scanning calorimetry. Dynamic mechanical properties of graphite fiber epoxy composite specimens formulated with two different adhesive systems (NARMCO 5208, NARMCO 5209) were determined. The specimens were exposed to varying dose levels of ionizing radiation (0.5 MeV electrons) with a maximum absorbed dose of 10,000 Mrads. Following irradiation, property measurements were made to assess the influence of radiation on the epoxy and composite specimens. The results established that ionizing radiation has a limited effect on the properties of epoxy and composite specimens.

Nuclear magnetic resonance spectroscopy reveals metabolic changes in living cardiomyocytes after low doses of ionizing radiation.

PubMed

Gramatyka, Michalina; Skorupa, Agnieszka; Sokół, Maria

2018-01-01

Several lines of evidence indicate that exposure of heart to ionizing radiation increases the risk of cardiotoxicity manifested by heart dysfunction and cardiovascular diseases. It was initially believed that the heart is an organ relatively resistant to radiation. Currently, however, it is suspected that even low doses of radiation (< 2 Gy) may have a negative impact on the cardiovascular system. Cardiotoxicity of ionizing radiation is associated with metabolic changes observed in cardiac cells injured by radiation. In this study, we used human cardiomyocytes as a model system, and studied their metabolic response to radiation using high-resolution magic angle spinning nuclear magnetic resonance techniques (HR-MAS NMR). Human cardiomyocytes cultured in vitro were exposed to ionizing radiation and their survival was assessed by clonogenic assay. Changes in apoptosis intensity and cell cycle distribution after the irradiation were measured as well. NMR spectra of cardiomyocytes were acquired using Bruker Avance 400 MHz spectrometer at a spinning rate of 3200 Hz. Survival of cardiomyocytes after NMR experiments was assessed by the Trypan blue exclusion assay. Exposure of cardiomyocytes to small doses of ionizing radiation had no effect on cell proliferation potential and intensity of cell death. However, analysis of metabolic profiles revealed changes in lipids, threonine, glycine, glycerophosphocholine, choline, valine, isoleucine, glutamate, reduced glutathione and taurine metabolism. The results of this study showed that ionizing radiation affects metabolic profiles of cardiomyocytes even at low doses, which potentially have no effect on cell viability.

External dose reconstruction for the former village of Metlino (Techa River, Russia) based on environmental surveys, luminescence measurements, and radiation transport modelling.

PubMed

Hiller, M M; Woda, C; Bougrov, N G; Degteva, M O; Ivanov, O; Ulanovsky, A; Romanov, S

2017-05-01

In the first years of its operation, the Mayak Production Association, a facility part of the Soviet nuclear weapons program in the Southern Urals, Russia, discharged large amounts of radioactively contaminated effluent into the nearby Techa River, thus exposing the people living at this river to external and internal radiations. The Techa River Cohort is a cohort intensely studied in epidemiology to investigate the correlation between low-dose radiation and health effects on humans. For the individuals in the cohort, the Techa River Dosimetry System describes the accumulated dose in human organs and tissues. In particular, organ doses from external exposure are derived from estimates of dose rate in air on the Techa River banks which were estimated from measurements and Monte Carlo modelling. Individual doses are calculated in accordance with historical records of individuals' residence histories, observational data of typical lifestyles for different age groups, and age-dependent conversion factors from air kerma to organ dose. The work here describes an experimentally independent assessment of the key input parameter of the dosimetry system, the integral air kerma, for the former village of Metlino, upper Techa River region. The aim of this work was thus to validate the Techa River Dosimetry System for the location of Metlino in an independent approach. Dose reconstruction based on dose measurements in bricks from a church tower and Monte Carlo calculations was used to model the historic air kerma accumulated in the time from 1949 to 1956 at the shoreline of the Techa River in Metlino. Main issues are caused by a change in the landscape after the evacuation of the village in 1956. Based on measurements and published information and data, two separate models for the historic pre-evacuation geometry and for the current geometry of Metlino were created. Using both models, a value for the air kerma was reconstructed, which agrees with that obtained in the Techa River Dosimetry System within a factor of two.

SU-E-T-87: Comparison Study of Dose Reconstruction From Cylindrical Diode Array Measurements, with TLD Measurements and Treatment Planning System Calculations in Anthropomorphic Head and Neck and Lung Phantoms

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

Benhabib, S; Cardan, R; Huang, M

Purpose: To assess dose calculated by the 3DVH software (Sun Nuclear Systems, Melbourne, FL) against TLD measurements and treatment planning system calculations in anthropomorphic phantoms. Methods: The IROC Houston (RPC) head and neck (HN) and lung phantoms were scanned and plans were generated using Eclipse (Varian Medical Systems, Milpitas, CA) following IROC Houston procedures. For the H and N phantom, 6 MV VMAT and 9-field dynamic MLC (DMLC) plans were created. For the lung phantom 6 MV VMAT and 15 MV 9-field dynamic MLC (DMLC) plans were created. The plans were delivered to the phantoms and to an ArcCHECK (Sunmore » Nuclear Systems, Melbourne, FL). The head and neck phantom contained 8 TLDs located at PTV1 (4), PTV2 (2), and OAR Cord (2). The lung phantom contained 4 TLDs, 2 in the PTV, 1 in the cord, and 1 in the heart. Daily outputs were recorded before each measurement for correction. 3DVH dose reconstruction software was used to project the calculated dose to patient anatomy. Results: For the HN phantom, the maximum difference between 3DVH and TLDs was -3.4% and between 3DVH and Eclipse was 1.2%. For the lung plan the maximum difference between 3DVH and TLDs was 4.3%, except for the spinal cord for which 3DVH overestimated the TLD dose by 12%. The maximum difference between 3DVH and Eclipse was 0.3%. 3DVH agreed well with Eclipse because the dose reconstruction algorithm uses the diode measurements to perturb the dose calculated by the treatment planning system; therefore, if there is a problem in the modeling or heterogeneity correction, it will be carried through to 3DVH. Conclusion: 3DVH agreed well with Eclipse and TLD measurements. Comparison of 3DVH with film measurements is ongoing. Work supported by PHS grant CA10953 and CA81647 (NCI, DHHS)« less

IRIS Toxicological Review of 1,4-Dioxane (External Review Draft, 2009)

EPA Science Inventory

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of 1,4-dioxane that when finalized will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of Methanol (Non-Cancer) (External Review Draft; April 2011)

EPA Science Inventory

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of methanol (non-cancer) that when finalized will appear on the Integrated Risk Information System (IRIS) database.

Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide (Revised August 2014 External Review Draft) (SAB Review Draft)

EPA Science Inventory

EPA is seeking peer review of the scientific basis supporting the human health hazard and dose-response assessment of ethylene oxide (cancer) that will appear in the Integrated Risk Information System (IRIS) database.

Radiological environmental dose assessment methods and compliance dose results for 2015 operations at the Savannah River Site

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

Jannik, G. T.; Dixon, K. L.

This report presents the environmental dose assessment methods and the estimated potential doses to the offsite public from 2015 Savannah River Site (SRS) atmospheric and liquid radioactive releases. Also documented are potential doses from special-case exposure scenarios - such as the consumption of deer meat, fish, and goat milk.

In vivo measurements for high dose rate brachytherapy with optically stimulated luminescent dosimeters

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

Sharma, Renu; Jursinic, Paul A.

2013-07-15

Purpose: To show the feasibility of clinical implementation of OSLDs for high dose-rate (HDR) in vivo dosimetry for gynecological and breast patients. To discuss how the OSLDs were characterized for an Ir-192 source, taking into account low gamma energy and high dose gradients. To describe differences caused by the dose calculation formalism of treatment planning systems.Methods: OSLD irradiations were made using the GammaMedplus iX Ir-192 HDR, Varian Medical Systems, Milpitas, CA. BrachyVision versions 8.9 and 10.0, Varian Medical Systems, Milpitas, CA, were used for calculations. Version 8.9 used the TG-43 algorithm and version 10.0 used the Acuros algorithm. The OSLDsmore » (InLight Nanodots) were characterized for Ir-192. Various phantoms were created to assess calculated and measured doses and the angular dependence and self-absorption of the Nanodots. Following successful phantom measurements, patient measurements for gynecological patients and breast cancer patients were made and compared to calculated doses.Results: The OSLD sensitivity to Ir-192 compared to 6 MV is between 1.10 and 1.25, is unique to each detector, and changes with accumulated dose. The measured doses were compared to those predicted by the treatment planning system and found to be in agreement for the gynecological patients to within measurement uncertainty. The range of differences between the measured and Acuros calculated doses was -10%-14%. For the breast patients, there was a discrepancy of -4.4% to +6.5% between the measured and calculated doses at the skin surface when the Acuros algorithm was used. These differences were within experimental uncertainty due to (random) error in the location of the detector with respect to the treatment catheter.Conclusions: OSLDs can be successfully used for HDR in vivo dosimetry. However, for the measurements to be meaningful one must account for the angular dependence, volume-averaging, and the greater sensitivity to Ir-192 gamma rays than to 6 MV x-rays if 6 MV x-rays were used for OSLD calibration. The limitations of the treatment planning algorithm must be understood, especially for surface dose measurements. Use of in vivo dosimetry for HDR brachytherapy treatments is feasible and has the potential to detect and prevent gross errors. In vivo HDR brachytherapy should be included as part of the QA for a HDR brachytherapy program.« less

SU-F-T-168: Development and Implementation of An Anthropomorphic Head & Neck Phantom for the Assessment of Proton Therapy Treatment Procedures

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

Branco, D; Taylor, P; Frank, S

2016-06-15

Purpose: To design a Head and Neck (H&N) anthropomorphic QA phantom that the Imaging and Radiation Oncology Core Houston (IROC-H) can use to verify the quality of intensity modulated proton therapy (IMPT) H&N treatments for institutions participating in NCI clinical trials. Methods: The phantom was created to serve as a remote auditing tool for IROC-H to evaluate an institution’s IMPT planning and delivery abilities. The design was based on the composition, size, and geometry of a generalized oropharyngeal tumor and contains critical structures (parotids and spinal cord). Radiochromic film in the axial and sagittal planes and thermoluminescent dosimeters (TLD)-100 capsulesmore » were embedded in the phantom and used to perform the dose delivery evaluation. A CT simulation was used to create a passive scatter and a spot scanning treatment plan with typical clinical constraints for H&N cancer. The IMPT plan was approved by a radiation oncologist and the phantom was irradiated multiple times. The measured dose distribution using a 7%/4mm gamma analysis (85% of pixels passing) and point doses were compared with the treatment planning system calculations. Results: The designed phantom could not achieve the target dose prescription and organ at risk dose constraints with the passive scatter treatment plan. The target prescription dose could be met but not the parotid dose constraint. The average TLD point dose ratio in the target was 0.975, well within the 5% acceptance criterion. The dose distribution analysis using various acceptance criteria, 5%/4mm, 5%/3mm, 7%/4mm and 7%/5mm, had average pixel passing rates of 85.9%, 81.8%, 89.6% and 91.6%, and respectively. Conclusion: An anthropomorphic IMPT H&N phantom was designed that can assess the dose delivery of proton sites wishing to participate in clinical trials using a 5% TLD dose and 7%/4mm gamma analysis acceptance criteria.« less

A phase I study to assess the single and multiple dose pharmacokinetics of THC/CBD oromucosal spray.

PubMed

Stott, C G; White, L; Wright, S; Wilbraham, D; Guy, G W

2013-05-01

A Phase I study to assess the single and multipledose pharmacokinetics (PKs) and safety and tolerability of oromucosally administered Δ(9)-tetrahydrocannabinol (THC)/cannabidiol (CBD) spray, an endocannabinoid system modulator, in healthy male subjects. Subjects received either single doses of THC/CBD spray as multiple sprays [2 (5.4 mg THC and 5.0 mg CBD), 4 (10.8 mg THC and 10.0 mg CBD) or 8 (21.6 mg THC and 20.0 mg CBD) daily sprays] or multiple doses of THC/CBD spray (2, 4 or 8 sprays once daily) for nine consecutive days, following fasting for a minimum of 10 h overnight prior to each dosing. Plasma samples were analyzed by gas chromatography-mass spectrometry for CBD, THC, and its primary metabolite 11-hydroxy-THC, and various PK parameters were investigated. Δ(9)-Tetrahydrocannabinol and CBD were rapidly absorbed following single-dose administration. With increasing single and multiple doses of THC/CBD spray, the mean peak plasma concentration (Cmax) increased for all analytes. There was evidence of dose-proportionality in the single but not the multiple dosing data sets. The bioavailability of THC was greater than CBD at single and multiple doses, and there was no evidence of accumulation for any analyte with multiple dosing. Inter-subject variability ranged from moderate to high for all PK parameters in this study. The time to peak plasma concentration (Tmax) was longest for all analytes in the eight spray group, but was similar in the two and four spray groups. THC/CBD spray was well-tolerated in this study and no serious adverse events were reported. The mean Cmax values (<12 ng/mL) recorded in this study were well below those reported in patients who smoked/inhaled cannabis, which is reassuring since elevated Cmax values are linked to significant psychoactivity. There was also no evidence of accumulation on repeated dosing.

Assessing dose rate distributions in VMAT plans

NASA Astrophysics Data System (ADS)

Mackeprang, P.-H.; Volken, W.; Terribilini, D.; Frauchiger, D.; Zaugg, K.; Aebersold, D. M.; Fix, M. K.; Manser, P.

2016-04-01

Dose rate is an essential factor in radiobiology. As modern radiotherapy delivery techniques such as volumetric modulated arc therapy (VMAT) introduce dynamic modulation of the dose rate, it is important to assess the changes in dose rate. Both the rate of monitor units per minute (MU rate) and collimation are varied over the course of a fraction, leading to different dose rates in every voxel of the calculation volume at any point in time during dose delivery. Given the radiotherapy plan and machine specific limitations, a VMAT treatment plan can be split into arc sectors between Digital Imaging and Communications in Medicine control points (CPs) of constant and known MU rate. By calculating dose distributions in each of these arc sectors independently and multiplying them with the MU rate, the dose rate in every single voxel at every time point during the fraction can be calculated. Independently calculated and then summed dose distributions per arc sector were compared to the whole arc dose calculation for validation. Dose measurements and video analysis were performed to validate the calculated datasets. A clinical head and neck, cranial and liver case were analyzed using the tool developed. Measurement validation of synthetic test cases showed linac agreement to precalculated arc sector times within  ±0.4 s and doses  ±0.1 MU (one standard deviation). Two methods for the visualization of dose rate datasets were developed: the first method plots a two-dimensional (2D) histogram of the number of voxels receiving a given dose rate over the course of the arc treatment delivery. In similarity to treatment planning system display of dose, the second method displays the dose rate as color wash on top of the corresponding computed tomography image, allowing the user to scroll through the variation over time. Examining clinical cases showed dose rates spread over a continuous spectrum, with mean dose rates hardly exceeding 100 cGy min-1 for conventional fractionation. A tool to analyze dose rate distributions in VMAT plans with sub-second accuracy was successfully developed and validated. Dose rates encountered in clinical VMAT test cases show a continuous spectrum with a mean less than or near 100 cGy min-1 for conventional fractionation.

Dosimetric quality control of Eclipse treatment planning system using pelvic digital test object

NASA Astrophysics Data System (ADS)

Benhdech, Yassine; Beaumont, Stéphane; Guédon, Jeanpierre; Crespin, Sylvain

2011-03-01

Last year, we demonstrated the feasibility of a new method to perform dosimetric quality control of Treatment Planning Systems in radiotherapy, this method is based on Monte-Carlo simulations and uses anatomical Digital Test Objects (DTOs). The pelvic DTO was used in order to assess this new method on an ECLIPSE VARIAN Treatment Planning System. Large dose variations were observed particularly in air and bone equivalent material. In this current work, we discuss the results of the previous paper and provide an explanation for observed dose differences, the VARIAN Eclipse (Anisotropic Analytical) algorithm was investigated. Monte Carlo simulations (MC) were performed with a PENELOPE code version 2003. To increase efficiency of MC simulations, we have used our parallelized version based on the standard MPI (Message Passing Interface). The parallel code has been run on a 32- processor SGI cluster. The study was carried out using pelvic DTOs and was performed for low- and high-energy photon beams (6 and 18MV) on 2100CD VARIAN linear accelerator. A square field (10x10 cm2) was used. Assuming the MC data as reference, χ index analyze was carried out. For this study, a distance to agreement (DTA) was set to 7mm while the dose difference was set to 5% as recommended in the TRS-430 and TG-53 (on the beam axis in 3-D inhomogeneities). When using Monte Carlo PENELOPE, the absorbed dose is computed to the medium, however the TPS computes dose to water. We have used the method described by Siebers et al. based on Bragg-Gray cavity theory to convert MC simulated dose to medium to dose to water. Results show a strong consistency between ECLIPSE and MC calculations on the beam axis.

Controlled circumferential renal sympathetic denervation with preservation of the renal arterial wall using intraluminal ultrasound: a next-generation approach for treating sympathetic overactivity.

PubMed

Sakakura, Kenichi; Roth, Austin; Ladich, Elena; Shen, Kai; Coleman, Leslie; Joner, Michael; Virmani, Renu

2015-02-01

The Paradise Ultrasound Renal Denervation System is a next-generation catheter-based device which was used to investigate whether the target ablation area can be controlled by changing ultrasound energy and duration to optimise nerve injury while preventing damage to the arterial wall. Five ultrasound doses were tested in a thermal gel model. Catheter-based ultrasound denervation was performed in 15 swine (29 renal arteries) to evaluate five different doses in vivo, and animals were euthanised at seven days for histopathologic assessment. In the gel model, the peak temperature was highest in the low power-long duration (LP-LD) dose, followed by the mid-low power-mid duration (MLP-MD) dose and the mid-high power-short duration (MHP-SD) dose, and lowest in the mid power-short duration (MP-SD) dose and the high power-ultra short duration (HP-USD) dose. In the animal study, total ablation area was significantly greater in the LP-LD group, followed by the MLP-MD group, and it was least in the HP-USD, MP-SD and MHP-SD groups (p=0.02). Maximum distance was significantly greater in the LP-LD group, followed by the MLP-MD group, the MHP-SD group, and the HP-USD group, and shortest in the MP-SD group (p=0.007). The short spare distance was not different among the five groups (p=0.38). Renal artery damage was minimal, while preserving significant nerve damage in all groups. The Paradise Ultrasound Renal Denervation System is a controllable system where total ablation area and depth of ablation can be optimised by changing ultrasound power and duration while sparing renal arterial tissue damage but allowing sufficient peri-arterial nerve damage.

SU-E-P-05: Is Routine Treatment Planning System Quality Assurance Necessary?

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

Alaei, P

Purpose: To evaluate the variation of dose calculations using a treatment planning system (TPS) over a two year period and assessment of the need for TPS QA on regular intervals. Methods: Two phantoms containing solid water and lung- and bone-equivalent heterogeneities were constructed in two different institutions for the same brand treatment planning system. Multiple plans, consisting of photons and electron beams, including IMRT and VMAT ones, were created and calculated on the phantoms. The accuracy of dose computation in the phantoms was evaluated at the onset by dose measurements within the phantoms. The dose values at up to 24more » points of interest (POI) within the solid water, lung, and bone slabs, as well as mean doses to several regions of interest (ROI), were re-calculated over a two-year period which included two software upgrades. The variations in POI and ROI dose values were analyzed and evaluated. Results: The computed doses vary slightly month-over-month. There are noticeable variations at the times of software upgrade, if the upgrade involves remodeling and/or re-commissioning of the beams. The variations are larger in certain points within the phantom, usually in the buildup region or near interfaces, and are almost non-existent for electron beams. Conclusion: Routine TPS QA is recommended by AAPM and other professional societies, and is often required by accreditation organizations. The frequency and type of QA, though, is subject to debate. The results presented here demonstrate that the frequency of these tests could be at longer intervals than monthly. However, it is essential to perform TPS QA at the time of commissioning and after each software upgrade.« less

Memory-enhancing effect of aspirin is mediated through opioid system modulation in an AlCl3-induced neurotoxicity mouse model

PubMed Central

RIZWAN, SAIMA; IDREES, AYESHA; ASHRAF, MUHAMMAD; AHMED, TOUQEER

2016-01-01

Neurodegenerative disorders such as Alzheimers disease (AD) are multifaceted and there are currently a limited number of therapeutic strategies available to treat them. Aspirin is known to act on multiple therapeutic targets and is a successful anti-inflammatory agent in various tissues. The present study aimed to ascertain the performance of aspirin when employed as a therapeutic agent to treat neurodegeneration on novel targets, including opioid system genes, in an AlCl3-induced neurotoxicity mouse model. The effects of two doses of aspirin (5 and 20 mg/kg aspirin for 12 days) were investigated in an AlCl3-induced neurotoxicity mouse model (150 mg/kg AlCl3 for 12 days). Neurological improvements were assessed through different behavioral tests and the effects of aspirin on opioid system gene expression levels were assessed by reverse transcription-polymerase chain reaction. Both doses resulted in improvements in cognitive behavior. A 5 mg/kg dose of aspirin was revealed to be effective for spatial memory improvement (7.14±0.84 sec), whilst a 20 mg/kg dose was superior for improving extinction learning (7.63±4.04%). Aspirin (5 mg/kg) also significantly improved contextual memory (48.05±10.6%) when compared with the AlCl3-treated group (1.49±0.62%; P<0.001). Aspirin was also observed to significantly decrease δ-opioid receptor expression in the cortex (1.09±0.08 and 1.27±0.08, respectively) at both doses (5 and 20 mg/kg) when compared with the AlCl3-treated group (3.69±1.43; P<0.05). Furthermore, aspirin at 5 mg/kg significantly reduced expression of prodynorphin in the cortex (0.57±0.20) when compared with the AlCl3-treated group (1.95±0.84; P<0.05). Notably, the effect of aspirin was significant in the cortex but not in the hippocampus. In summary, aspirin was effective in ameliorating the AD-like symptoms via the modulation of opioid systems. However, additional studies are required to determine the long term effects of aspirin on such conditions. PMID:27168835

Variable thickness transient ground-water flow model. Volume 3. Program listings

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

Reisenauer, A.E.

1979-12-01

The Assessment of Effectiveness of Geologic Isolation Systems (AEGIS) Program is developing and applying the methodology for assessing the far-field, long-term post-closure safety of deep geologic nuclear waste repositories. AEGIS is being performed by Pacific Northwest Laboratory (PNL) under contract with the Office of Nuclear Waste Isolation (OWNI) for the Department of Energy (DOE). One task within AEGIS is the development of methodology for analysis of the consequences (water pathway) from loss of repository containment as defined by various release scenarios. Analysis of the long-term, far-field consequences of release scenarios requires the application of numerical codes which simulate the hydrologicmore » systems, model the transport of released radionuclides through the hydrologic systems to the biosphere, and, where applicable, assess the radiological dose to humans. Hydrologic and transport models are available at several levels of complexity or sophistication. Model selection and use are determined by the quantity and quality of input data. Model development under AEGIS and related programs provides three levels of hydrologic models, two levels of transport models, and one level of dose models (with several separate models). This is the third of 3 volumes of the description of the VTT (Variable Thickness Transient) Groundwater Hydrologic Model - second level (intermediate complexity) two-dimensional saturated groundwater flow.« less

Attenuation in rats of impairments of memory by scopolamine, a muscarinic receptor antagonist, by mecamylamine, a nicotinic receptor antagonist

PubMed Central

Newman, L. A.

2015-01-01

Rationale Scopolamine, a muscarinic antagonist, impairs learning and memory for many tasks, supporting an important role for the cholinergic system in these cognitive functions. The findings are most often interpreted to indicate that a decrease in postsynaptic muscarinic receptor activation mediates the memory impairments. However, scopolamine also results in increased release of acetylcholine in the brain as a result of blocking presynaptic muscarinic receptors. Objectives The present experiments assess whether scopolamine-induced increases in acetylcholine release may impair memory by overstimulating postsynaptic cholinergic nicotinic receptors, i.e., by reaching the high end of a nicotinic receptor activation inverted-U dose-response function. Results Rats tested in a spontaneous alternation task showed dose-dependent working memory deficits with systemic injections of mecamylamine and scopolamine. When an amnestic dose of scopolamine (0.15 mg/kg) was co-administered with a subamnestic dose of mecamylamine (0.25 mg/kg), this dose of mecamylamine significantly attenuated the scopolamine-induced memory impairments. We next assessed the levels of acetylcholine release in the hippocampus in the presence of scopolamine and mecamylamine. Mecamylamine injections resulted in decreased release of acetylcholine, while scopolamine administration caused a large increase in acetylcholine release. Conclusions These findings indicate that a nicotinic antagonist can attenuate impairments in memory produced by a muscarinic antagonist. The nicotinic antagonist may block excessive activation of nicotinic receptors postsynaptically or attenuate increases in acetylcholine release presynaptically. Either effect of a nicotinic antagonist—to decrease scopolamine-induced increases in acetylcholine output or to decrease post-synaptic acetylcholine receptor activation—may mediate the negative effects on memory of muscarinic antagonists. PMID:26660295

A pharmacokinetic/pharmacodynamic investigation: assessment of edivoxetine and atomoxetine on systemic and central 3,4-dihydroxyphenylglycol, a biochemical marker for norepinephrine transporter inhibition.

PubMed

Kielbasa, William; Pan, Alan; Pereira, Alvaro

2015-03-01

Inhibition of norepinephrine (NE) reuptake into noradrenergic nerves is a common therapeutic target in the central nervous system (CNS). In noradrenergic nerves, NE is oxidized by monoamine oxidase to 3,4-dihydroxyphenylglycol (DHPG). In this study, 40 healthy male subjects received the NE transporter (NET) inhibitor edivoxetine (EDX) or atomoxetine (ATX), or placebo. The pharmacokinetic and pharmacodynamic profile of these drugs in plasma and cerebrospinal fluid (CSF) was assessed. In Part A, subjects received EDX once daily (QD) for 14 or 15 days at targeted doses of 6mg or 9mg. In Part B, subjects received 80mg ATX QD for 14 or 15 days. Each subject received a lumbar puncture before receiving drug and after 14 or 15 days of dosing. Plasma and urine were collected at baseline and after 14 days of dosing. Edivoxetine plasma and CSF concentrations increased dose dependently. The time to maximum plasma concentration of EDX was 2h, and the half-life was 9h. At the highest EDX dose of 9mg, DHPG concentrations were reduced from baseline by 51% at 8h postdose in CSF, and steady-state plasma and urine DHPG concentrations decreased by 38% and 26%, respectively. For 80mg ATX, the decrease of plasma, CSF, or urine DHPG was similar to EDX. Herein we provide clinical evidence that EDX and ATX decrease DHPG concentrations in the periphery and CNS, presumably via NET inhibition. EDX and ATX concentrations measured in the CSF confirmed the availability of those drugs in the CNS. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Safety and immunogenicity of the killed bivalent (O1 and O139) whole-cell cholera vaccine in the Philippines.

PubMed

Capeding, Maria Rosario Z; Gonzales, Maria Liza Antoinette M; Dhingra, Mandeep Singh; D'Cor, Naveena Aloysia; Midde, Venkat Jayanth; Patnaik, Badri Narayan; Thollot, Yaël; Desauziers, Eric

2017-10-03

The killed bivalent (O1 and O139) whole cell oral cholera vaccine (OCV) (Shanchol™) was first licensed in India in 2009 and World Health Organization pre-qualified in 2011. We assessed the safety and immunogenicity of this OCV in the Philippines. This was a phase IV, single-arm, descriptive, open-label study. We recruited 336 participants from 2 centers: 112 participants in each age group (1-4, 5-14 and ≥ 15 years). Participants received 2 OCV doses 14 d apart. Safety was monitored throughout the trial. Blood samples were collected at baseline (pre-vaccination) and 14 d after each dose. Serum vibriocidal antibody titers to V. cholerae O1 (El Tor Inaba and El Tor Ogawa) and O139 strains were assessed, with seroconversion defined as ≥ 4-fold increase from baseline in titers. No immediate unsolicited systemic adverse events/reactions were observed. Unsolicited systemic adverse events were mostly grade 1 intensity. One serious adverse event occurred after the first dose, but was unrelated to vaccination. High seroconversion rates (range 69-92%) were achieved against the O1 serotypes with a trend toward higher rates in the 1-4 y (86-92%) and 5-14 y (86-88%) age groups than the ≥ 15 y age group (69-83%). Lower seroconversion rates were achieved against the O139 serotype (35-70%), particularly in those aged ≥ 15 y (35-42%). The 2-dose regimen of the killed bivalent whole cell OCV was well-tolerated in this study conducted in the Philippines, a cholera-endemic country. Robust immune responses were observed even after a single-dose.

Sustained neuroprotection from a single intravitreal injection of PGJ₂ in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy.

PubMed

Miller, Neil R; Johnson, Mary A; Nolan, Theresa; Guo, Yan; Bernstein, Alexander M; Bernstein, Steven L

2014-10-08

Prostaglandin J₂ (PGJ₂) is neuroprotective in a murine model of nonarteritic anterior ischemic optic neuropathy (NAION). After assessing for potential toxicity, we evaluated the efficacy of a single intravitreal (IVT) injection of PGJ₂ in a nonhuman primate model of NAION (pNAION). We assessed PGJ₂ toxicity by administering it as a single high-dose intravenous (IV) injection, consecutive daily high-dose IV injections, or a single IVT injection in one eye of five adult rhesus monkeys. To assess efficacy, we induced pNAION in one eye of five adult male rhesus monkeys using a laser-activated rose bengal induction method. We then injected the eye with either PGJ₂ or phosphate-buffered saline (PBS) intravitreally immediately or 5 hours post induction. We performed a clinical assessment, optical coherence tomography, electrophysiological testing, fundus photography, and fluorescein angiography in all animals prior to induction and at 1 day, 1 week, 2 weeks, and 4 weeks after induction. Following analysis of the first eye, we induced pNAION in the contralateral eye and then injected either PGJ₂ or PBS. We euthanized all animals 5 weeks after final assessment of the fellow eye and performed both immunohistochemical and light and electron microscopic analyses of the retina and optic nerves. PGJ₂ caused no permanent systemic toxicity regardless of the amount injected or route of delivery, and there was no evidence of any ocular toxicity with the dose of PGJ₂ used in efficacy studies. Transient reduction in the amplitudes of the visual evoked potentials and the N95 component of the pattern electroretinogram (PERG) occurred after both IV and IVT administration of high doses of PGJ₂; however, the amplitudes returned to normal in all animals within 1 week. In all eyes, a single IVT dose of PGJ₂ administered immediately or shortly after induction of pNAION resulted in a significant reduction of clinical, electrophysiological, and histological damage compared with vehicle-injected eyes (P = 0.03 for both VEP and PERG; P = 0.05 for axon counts). In nonhuman primates, PGJ₂ administered either intravenously or intravitreally produces no permanent toxicity at even four times the dose given for neuroprotection. Additionally, a single IVT dose of PGJ₂ is neuroprotective when administered up to 5 hours after induction of pNAION. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

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

Kruger, R.

The US National Lung Screening Trial (NLST) was a multi-center randomized, controlled trial comparing a low-dose CT (LDCT) to posterior-anterior (PA) chest x-ray (CXR) in screening older, current and former heavy smokers for early detection of lung cancer. Recruitment was launched in September 2002 and ended in April 2004 when 53,454 participants had been randomized at 33 screening sites in equal proportions. Funded by the National Cancer Institute this trial demonstrated that LDCT screening reduced lung cancer mortality. The US Preventive Services Task Force (USPSTF) cited NLST findings and conclusions in its deliberations and analysis of lung cancer screening. Undermore » the 2010 Patient Protection and Affordable Care Act, the USPSTF favorable recommendation regarding lung cancer CT screening assisted in obtaining third-party payers coverage for screening. The objective of this session is to provide an introduction to the NLST and the trial findings, in addition to a comprehensive review of the dosimetry investigations and assessments completed using individual NLST participant CT and CXR examinations. Session presentations will review and discuss the findings of two independent assessments, a CXR assessment and the findings of a CT investigation calculating individual organ dosimetry values. The CXR assessment reviewed a total of 73,733 chest x-ray exams that were performed on 92 chest imaging systems of which 66,157 participant examinations were used. The CT organ dosimetry investigation collected scan parameters from 23,773 CT examinations; a subset of the 75,133 CT examinations performed using 97 multi-detector CT scanners. Organ dose conversion coefficients were calculated using a Monte Carlo code. An experimentally-validated CT scanner simulation was coupled with 193 adult hybrid computational phantoms representing the height and weight of the current U.S. population. The dose to selected organs was calculated using the organ dose library and the abstracted scan parameters. This session will review the results and summarize the individualized doses to major organs and the mean effective dose and CTDIvol estimate for 66,157 PA chest and 23,773 CT examinations respectively, using size-dependent computational phantoms coupled with Monte Carlo calculations. Learning Objectives: Review and summarize relevant NLST findings and conclusions. Understand the scope and scale of the NLST specific to participant dosimetry. Provide a comprehensive review of NLST participant dosimetry assessments. Summarize the results of an investigation providing individualized organ dose estimates for NLST participant cohorts.« less

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

Fakir, H.; Gaede, S.; Mulligan, M.

Purpose: To design a versatile, nonhomogeneous insert for the dose verification phantom ArcCHECK{sup Trade-Mark-Sign} (Sun Nuclear Corp., FL) and to demonstrate its usefulness for the verification of dose distributions in inhomogeneous media. As an example, we demonstrate it can be used clinically for routine quality assurance of two volumetric modulated arc therapy (VMAT) systems for lung stereotactic body radiation therapy (SBRT): SmartArc{sup Registered-Sign} (Pinnacle{sup 3}, Philips Radiation Oncology Systems, Fitchburg, WI) and RapidArc{sup Registered-Sign} (Eclipse{sup Trade-Mark-Sign }, Varian Medical Systems, Palo Alto, CA). Methods: The cylindrical detector array ArcCHECK{sup Trade-Mark-Sign} has a retractable homogeneous acrylic insert. In this work, wemore » designed and manufactured a customized heterogeneous insert with densities that simulate soft tissue, lung, bone, and air. The insert offers several possible heterogeneity configurations and multiple locations for point dose measurements. SmartArc{sup Registered-Sign} and RapidArc{sup Registered-Sign} plans for lung SBRT were generated and copied to ArcCHECK{sup Trade-Mark-Sign} for each inhomogeneity configuration. Dose delivery was done on a Varian 2100 ix linac. The evaluation of dose distributions was based on gamma analysis of the diode measurements and point doses measurements at different positions near the inhomogeneities. Results: The insert was successfully manufactured and tested with different measurements of VMAT plans. Dose distributions measured with the homogeneous insert showed gamma passing rates similar to our clinical results ({approx}99%) for both treatment-planning systems. Using nonhomogeneous inserts decreased the passing rates by up to 3.6% in the examples studied. Overall, SmartArc{sup Registered-Sign} plans showed better gamma passing rates for nonhomogeneous measurements. The discrepancy between calculated and measured point doses was increased up to 6.5% for the nonhomogeneous insert depending on the inhomogeneity configuration and measurement location. SmartArc{sup Registered-Sign} and RapidArc{sup Registered-Sign} plans had similar plan quality but RapidArc{sup Registered-Sign} plans had significantly higher monitor units (up to 70%). Conclusions: A versatile, nonhomogeneous insert was developed for ArcCHECK{sup Trade-Mark-Sign} for an easy and quick evaluation of dose calculations with nonhomogeneous media and for comparison of different treatment planning systems. The device was tested for SmartArc{sup Registered-Sign} and RapidArc{sup Registered-Sign} plans for lung SBRT, showing the uncertainties of dose calculations with inhomogeneities. The new insert combines the convenience of the ArcCHECK{sup Trade-Mark-Sign} and the possibility of assessing dose distributions in inhomogeneous media.« less

Development of complex-shaped liver multicellular spheroids as a human-based model for nanoparticle toxicity assessment in vitro

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

Dubiak-Szepietowska, Monika, E-mail: Monika.Dubiak-Szepietowska@fh-jena.de; Karczmarczyk, Aleksandra; Jönsson-Niedziółka, Martin

The emergence of human-based models is incontestably required for the study of complex physiological pathways and validation of reliable in vitro methods as alternative for in vivo studies in experimental animals for toxicity assessment. With this objective, we have developed and tested three dimensional environments for cells using different types of hydrogels including transglutaminase-cross-linked gelatin, collagen type I, and growth-factor depleted Matrigel. Cells grown in Matrigel exhibited the greatest cell proliferation and spheroid diameter. Moreover, analysis of urea and albumin biosynthesis revealed that the created system allowed the immortalized liver cell line HepG2 to re-establish normal hepatocyte-like properties which weremore » not observed under the conditions of conventional cell cultures. This study presents a scalable technology for production of complex-shaped liver multicellular spheroids as a system which improves the predictive value of cell-based assays for safety and risk assessment. The time- and dose-dependent toxicity of nanoparticles demonstrates a higher cytotoxic effect when HepG2 cells grown as monolayer than embedded in hydrogels. The experimental setup provided evidence that the cell environment has significant influence on cell sensitivity and that liver spheroid is a useful and novel tool to examine nanoparticle dosing effect even at the level of in vitro studies. Therefore, this system can be applied to a wide variety of potentially hostile compounds in basic screening to provide initial warning of adverse effects and trigger subsequent analysis and remedial actions. - Highlights: • Comparison of HepG2 cells growth in Matrigel, Collagen I gel and gelatin gel. • Examination of nanoparticles (NP) dosing effect at the level of in vitro studies. • Influence of the cell culture media composition on the cytotoxic effect of NP.« less

Evaluation of lens dose from anterior electron beams: comparison of Pinnacle and Gafchromic EBT3 film

PubMed Central

Wronski, Matt; Yeboah, Collins

2015-01-01

Lens dose is a concern during the treatment of facial lesions with anterior electron beams. Lead shielding is routinely employed to reduce lens dose and minimize late complications. The purpose of this work is twofold: 1) to measure dose profiles under large‐area lead shielding at the lens depth for clinical electron energies via film dosimetry; and 2) to assess the accuracy of the Pinnacle treatment planning system in calculating doses under lead shields. First, to simulate the clinical geometry, EBT3 film and 4 cm wide lead shields were incorporated into a Solid Water phantom. With the lead shield inside the phantom, the film was positioned at a depth of 0.7 cm below the lead, while a variable thickness of solid water, simulating bolus, was placed on top. This geometry was reproduced in Pinnacle to calculate dose profiles using the pencil beam electron algorithm. The measured and calculated dose profiles were normalized to the central‐axis dose maximum in a homogeneous phantom with no lead shielding. The resulting measured profiles, functions of bolus thickness and incident electron energy, can be used to estimate the lens dose under various clinical scenarios. These profiles showed a minimum lead margin of 0.5 cm beyond the lens boundary is required to shield the lens to ≤10% of the dose maximum. Comparisons with Pinnacle showed a consistent overestimation of dose under the lead shield with discrepancies of ∼25% occurring near the shield edge. This discrepancy was found to increase with electron energy and bolus thickness and decrease with distance from the lead edge. Thus, the Pinnacle electron algorithm is not recommended for estimating lens dose in this situation. The film measurements, however, allow for a reasonable estimate of lens dose from electron beams and for clinicians to assess the lead margin required to reduce the lens dose to an acceptable level. PACS number(s): 87.53.Bn, 87.53.Kn, 87.55.‐x, 87.55.D‐ PMID:27074448

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

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

Olch, A

2015-06-15

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

Standard-, Reduced-, and No-Dose Thin-Section Radiologic Examinations: Comparison of Capability for Nodule Detection and Nodule Type Assessment in Patients Suspected of Having Pulmonary Nodules.

PubMed

Ohno, Yoshiharu; Koyama, Hisanobu; Yoshikawa, Takeshi; Kishida, Yuji; Seki, Shinichiro; Takenaka, Daisuke; Yui, Masao; Miyazaki, Mitsue; Sugimura, Kazuro

2017-08-01

Purpose To compare the capability of pulmonary thin-section magnetic resonance (MR) imaging with ultrashort echo time (UTE) with that of standard- and reduced-dose thin-section computed tomography (CT) in nodule detection and evaluation of nodule type. Materials and Methods The institutional review board approved this study, and written informed consent was obtained from each patient. Standard- and reduced-dose chest CT (60 and 250 mA) and MR imaging with UTE were used to examine 52 patients; 29 were men (mean age, 66.4 years ± 7.3 [standard deviation]; age range, 48-79 years) and 23 were women (mean age, 64.8 years ± 10.1; age range, 42-83 years). Probability of nodule presence was assessed for all methods with a five-point visual scoring system. All nodules were then classified as missed, ground-glass, part-solid, or solid nodules. To compare nodule detection capability of the three methods, consensus for performances was rated by using jackknife free-response receiver operating characteristic analysis, and κ analysis was used to compare intermethod agreement for nodule type classification. Results There was no significant difference (F = 0.70, P = .59) in figure of merit between methods (standard-dose CT, 0.86; reduced-dose CT, 0.84; MR imaging with UTE, 0.86). There was no significant difference in sensitivity between methods (standard-dose CT vs reduced-dose CT, P = .50; standard-dose CT vs MR imaging with UTE, P = .50; reduced-dose CT vs MR imaging with UTE, P >.99). Intermethod agreement was excellent (standard-dose CT vs reduced-dose CT, κ = 0.98, P < .001; standard-dose CT vs MR imaging with UTE, κ = 0.98, P < .001; reduced-dose CT vs MR imaging with UTE, κ = 0.99, P < .001). Conclusion Pulmonary thin-section MR imaging with UTE was useful in nodule detection and evaluation of nodule type, and it is considered at least as efficacious as standard- or reduced-dose thin-section CT. © RSNA, 2017 Online supplemental material is available for this article.

Dose assessment of digital tomosynthesis in pediatric imaging

NASA Astrophysics Data System (ADS)

Gislason, Amber; Elbakri, Idris A.; Reed, Martin

2009-02-01

We investigated the potential for digital tomosynthesis (DT) to reduce pediatric x-ray dose while maintaining image quality. We utilized the DT feature (VolumeRadTM) on the GE DefiniumTM 8000 flat panel system installed in the Winnipeg Children's Hospital. Facial bones, cervical spine, thoracic spine, and knee of children aged 5, 10, and 15 years were represented by acrylic phantoms for DT dose measurements. Effective dose was estimated for DT and for corresponding digital radiography (DR) and computed tomography (CT) patient image sets. Anthropomorphic phantoms of selected body parts were imaged by DR, DT, and CT. Pediatric radiologists rated visualization of selected anatomic features in these images. Dose and image quality comparisons between DR, DT, and CT determined the usefulness of tomosynthesis for pediatric imaging. CT effective dose was highest; total DR effective dose was not always lowest - depending how many projections were in the DR image set. For the cervical spine, DT dose was close to and occasionally lower than DR dose. Expert radiologists rated visibility of the central facial complex in a skull phantom as better than DR and comparable to CT. Digital tomosynthesis has a significantly lower dose than CT. This study has demonstrated DT shows promise to replace CT for some facial bones and spinal diagnoses. Other clinical applications will be evaluated in the future.

Phase I Trial of Simultaneous In-Field Boost With Helical Tomotherapy for Patients With One to Three Brain Metastases

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

Rodrigues, George, E-mail: george.rodrigues@lhsc.on.ca; Yartsev, Slav; Yaremko, Brian

2011-07-15

Purpose: Stereotactic radiosurgery is an alternative to surgical resection for selected intracranial lesions. Integrated image-guided intensity-modulated-capable radiotherapy platforms such as helical tomotherapy (HT) could potentially replace traditional radiosurgery apparatus. The present study's objective was to determine the maximally tolerated dose of a simultaneous in-field boost integrated with whole brain radiotherapy for palliative treatment of patients with one to three brain metastases using HT. Methods and Materials: The inclusion/exclusion criteria and endpoints were consistent with the Radiation Therapy Oncology Group 9508 radiosurgery trial. The cohorts were constructed with a 3 + 3 design; however, additional patients were enrolled in the lowermore » dose tolerable cohorts during the toxicity assessment periods. Whole brain radiotherapy (30 Gy in 10 fractions) was delivered with a 5-30-Gy (total lesion dose of 35-60 Gy in 10 fractions) simultaneous in-field boost delivered to the brain metastases. The maximally tolerated dose was determined by the frequency of neurologic Grade 3-5 National Cancer Institute Common Toxicity Criteria, version 3.0, dose-limiting toxicity events within each Phase I cohort. Results: A total of 48 patients received treatment in the 35-Gy (n = 3), 40-Gy (n = 16), 50-Gy (n = 15), 55-Gy (n = 8), and 60-Gy (n = 6) cohorts. No patients experienced dose-limiting toxicity events in any of the trial cohorts. The 3-month RECIST assessments available for 32 of the 48 patients demonstrated a complete response in 2, a partial response in 16, stable disease in 6, and progressive disease in 8 patients. Conclusion: The delivery of 60 Gy in 10 fractions to one to three brain metastases synchronously with 30 Gy whole brain radiotherapy was achieved without dose-limiting central nervous system toxicity as assessed 3 months after treatment. This approach is being tested in a Phase II efficacy trial.« less

Mercury study report to Congress. Volume 5. Health effects of mercury and mercury compounds

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

Hassett-Sipple, B.; Swartout, J.; Schoeny, R.

1997-12-01

This volume summarizes the available information on human health effects and animal data for hazard identification and dose-response assessment for three forms of mercury: elemental mercury, mercury chloride (inorganic mercury), and methylmercury (organic mercury). Effects are summarized by endpoint. The risk assessment evaluates carcinogenicity, mutagenicity, developmental toxicity and general systemic toxicity of these chemical species of mercury. Toxicokinetics (absorption, distribution, metabolism and excretion) are described for each of the three mercury species. Reference doses are calculated for inorganic and methylmercury; a reference concentrations for inhaled elemental mercury is provided. A quantitative analysis of factors contributing to variability and uncertainty inmore » the methylmercury RfD is provided in an appendix. Interactions and sensitive populations are described. the draft volume assesses ongoing research and research needs to reduce uncertainty surrounding adverse human health consequences of methylmercury exposure.« less

Mercury study report to Congress. Volume 4. Health effects of mercury and mercury compounds. Sab review draft

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

Schoeny, R.

1996-06-01

This volume of the draft Mercury Study Report to Congress summarizes the available information on human health effects and animal data for hazard identification and dose-response assessment for three forms of mercury: elemental mercury, mercury chloride (inorganic mercury), and methylmercury (organic mercury). Effects are summarized by endpoint. The risk assessment evaluates carcinogenicity, mutagenicity, developmental toxicity and general systemic toxicity of these chemical species of mercury. Toxicokinetics (absorption, distribution, metabolism and excretion) are described for each of the three mercury species. PBPK models are described, but not applied in risk assessment. Reference doses are calculated for inorganic and methylmercury; a referencemore » concentration for inhaled elemental mercury is provided. A quantitiative analysis of factors contributing to variability and uncertainty in the methylmercury RfD is provided in an appendix. Interations and sensitive populations are described.« less

Formation of nitrosodimethylamine (NDMA) during chlorine disinfection of wastewater effluents prior to use in irrigation systems.

PubMed

Pehlivanoglu-Mantas, Elif; Hawley, Elisabeth L; Deeb, Rula A; Sedlak, David L

2006-01-01

The probable human carcinogen nitrosodimethylamine (NDMA) is produced when wastewater effluent is disinfected with chlorine. In systems where wastewater effluent is used for landscape or crop irrigation, relatively high chlorine doses (i.e., up to 2,000,mg-min/L) are often used to ensure adequate disinfection and to minimize biofouling in the irrigation system. To assess the formation of NDMA in such systems, samples were collected from several locations in full-scale wastewater treatment systems and their associated irrigation systems. Up to 460 ng/L of NDMA was produced in full-scale systems in which chloramines were formed when wastewater effluent was disinfected with chlorine in the presence of ammonia. Less than 20 ng/L of NDMA was produced in systems that used free chlorine (i.e., HOCl/OCl(-)) for disinfection in the absence of ammonia. The production of NDMA in ammonia-containing systems was correlated with the concentration of NDMA precursors in the wastewater effluent and the overall dose of chlorine applied. Much of the NDMA formation occurred in chlorine contact basins or in storage basins where water that contained chloramines was held after disinfection. When landscape or crop irrigation is practiced with ammonia-containing wastewater effluent, NDMA production can be controlled by use of lower chlorine doses or by application of alternative disinfectants.

Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis

PubMed Central

Watanabe, Tomoya; Mlakar, Logan; Heywood, Jonathan; Malaab, Maya; Hoffman, Stanley

2017-01-01

The murine bleomycin (BLM)-induced fibrosis model is the most widely used in systemic sclerosis (SSc) studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness. Dermal thickness and the level of collagen in skin treated with high-dose BLM was significantly higher than in skin treated with low dose BLM or vehicle. A reduction in the thickness of the adipose layer was noted in both high and low dose groups at earlier time points suggesting that the loss of the fat layer precedes the onset of fibrosis. High-dose BLM also induced dermal fibrosis and increased expression of fibrosis-associated genes ex vivo in human skin, thus confirming and extending the in vivo findings, and demonstrating that a human organ culture model can be used to assess the effect of BLM on skin. In summary, our findings suggest that the BLM pump model is an attractive model to analyze the underlying mechanisms of fibrosis and test the efficacy of potential therapies. However, the choice of mouse strain, duration of BLM administration and dose must be carefully considered when using this model. PMID:28651005

Optimization of a murine and human tissue model to recapitulate dermal and pulmonary features of systemic sclerosis.

PubMed

Watanabe, Tomoya; Nishimoto, Tetsuya; Mlakar, Logan; Heywood, Jonathan; Malaab, Maya; Hoffman, Stanley; Feghali-Bostwick, Carol

2017-01-01

The murine bleomycin (BLM)-induced fibrosis model is the most widely used in systemic sclerosis (SSc) studies. It has been reported that systemic delivery of BLM via continuous diffusion from subcutaneously implanted osmotic minipumps can cause fibrosis of the skin, lungs, and other internal organs. However, the mouse strain, dosage of BLM, administration period, and additional important features differ from one report to the next. In this study, by employing the pump model in C57BL/6J mice, we show a dose-dependent increase in lung fibrosis by day 28 and a transient increase in dermal thickness. Dermal thickness and the level of collagen in skin treated with high-dose BLM was significantly higher than in skin treated with low dose BLM or vehicle. A reduction in the thickness of the adipose layer was noted in both high and low dose groups at earlier time points suggesting that the loss of the fat layer precedes the onset of fibrosis. High-dose BLM also induced dermal fibrosis and increased expression of fibrosis-associated genes ex vivo in human skin, thus confirming and extending the in vivo findings, and demonstrating that a human organ culture model can be used to assess the effect of BLM on skin. In summary, our findings suggest that the BLM pump model is an attractive model to analyze the underlying mechanisms of fibrosis and test the efficacy of potential therapies. However, the choice of mouse strain, duration of BLM administration and dose must be carefully considered when using this model.

SU-E-I-43: Pediatric CT Dose and Image Quality Optimization

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

Stevens, G; Singh, R

2014-06-01

Purpose: To design an approach to optimize radiation dose and image quality for pediatric CT imaging, and to evaluate expected performance. Methods: A methodology was designed to quantify relative image quality as a function of CT image acquisition parameters. Image contrast and image noise were used to indicate expected conspicuity of objects, and a wide-cone system was used to minimize scan time for motion avoidance. A decision framework was designed to select acquisition parameters as a weighted combination of image quality and dose. Phantom tests were used to acquire images at multiple techniques to demonstrate expected contrast, noise and dose.more » Anthropomorphic phantoms with contrast inserts were imaged on a 160mm CT system with tube voltage capabilities as low as 70kVp. Previously acquired clinical images were used in conjunction with simulation tools to emulate images at different tube voltages and currents to assess human observer preferences. Results: Examination of image contrast, noise, dose and tube/generator capabilities indicates a clinical task and object-size dependent optimization. Phantom experiments confirm that system modeling can be used to achieve the desired image quality and noise performance. Observer studies indicate that clinical utilization of this optimization requires a modified approach to achieve the desired performance. Conclusion: This work indicates the potential to optimize radiation dose and image quality for pediatric CT imaging. In addition, the methodology can be used in an automated parameter selection feature that can suggest techniques given a limited number of user inputs. G Stevens and R Singh are employees of GE Healthcare.« less

The selective glycine uptake inhibitor org 25935 as an adjunctive treatment to atypical antipsychotics in predominant persistent negative symptoms of schizophrenia: results from the GIANT trial.

PubMed

Schoemaker, Joep H; Jansen, Wim T; Schipper, Jacques; Szegedi, Armin

2014-04-01

Using a selective glycine uptake inhibitor as adjunctive to second-generation antipsychotic (SGA) was hypothesized to ameliorate negative and/or cognitive symptoms in subjects with schizophrenia. Subjects with predominant persistent negative symptoms (previously stabilized ≥3 months on an SGA) were enrolled in a randomized, placebo-controlled trial to investigate adjunctive treatment with Org 25935, a selective inhibitor of type 1 glycine transporter, over 12 weeks in a flexible dose design. Org 25935 was tested at 4 to 8 mg twice daily and 12 to 16 mg twice daily versus placebo. Primary efficacy outcome was mean change from baseline in Scale for Assessment of Negative Symptoms composite score. Secondary efficacy end points were Positive and Negative Syndrome Scale total and subscale scores, depressive symptoms (Calgary Depression Scale for Schizophrenia), global functioning (Global Assessment of Functioning scale), and cognitive measures using a computerized battery (Central Nervous System Vital Signs). Responder rates were assessed post hoc. A total of 215 subjects were randomized, of which 187 (87%) completed the trial. Both dose groups of Org 25935 did not differ significantly from placebo on Scale for Assessment of Negative Symptoms, Positive and Negative Syndrome Scale (total or subscale scores), Global Assessment of Functioning, or the majority of tested cognitive domains. Org 25935 was generally well tolerated within the tested dose range, with no meaningful effects on extrapyramidal symptoms and some reports of reversible visual adverse effects. Org 25935 did not differ significantly from placebo in reducing negative symptoms or improving cognitive functioning when administered as adjunctive treatment to SGA. In our study population, Org 25935 appeared to be well tolerated in the tested dose ranges.

Calculation of out-of-field dose distribution in carbon-ion radiotherapy by Monte Carlo simulation.

PubMed

Yonai, Shunsuke; Matsufuji, Naruhiro; Namba, Masao

2012-08-01

Recent radiotherapy technologies including carbon-ion radiotherapy can improve the dose concentration in the target volume, thereby not only reducing side effects in organs at risk but also the secondary cancer risk within or near the irradiation field. However, secondary cancer risk in the low-dose region is considered to be non-negligible, especially for younger patients. To achieve a dose estimation of the whole body of each patient receiving carbon-ion radiotherapy, which is essential for risk assessment and epidemiological studies, Monte Carlo simulation plays an important role because the treatment planning system can provide dose distribution only in∕near the irradiation field and the measured data are limited. However, validation of Monte Carlo simulations is necessary. The primary purpose of this study was to establish a calculation method using the Monte Carlo code to estimate the dose and quality factor in the body and to validate the proposed method by comparison with experimental data. Furthermore, we show the distributions of dose equivalent in a phantom and identify the partial contribution of each radiation type. We proposed a calculation method based on a Monte Carlo simulation using the PHITS code to estimate absorbed dose, dose equivalent, and dose-averaged quality factor by using the Q(L)-L relationship based on the ICRP 60 recommendation. The values obtained by this method in modeling the passive beam line at the Heavy-Ion Medical Accelerator in Chiba were compared with our previously measured data. It was shown that our calculation model can estimate the measured value within a factor of 2, which included not only the uncertainty of this calculation method but also those regarding the assumptions of the geometrical modeling and the PHITS code. Also, we showed the differences in the doses and the partial contributions of each radiation type between passive and active carbon-ion beams using this calculation method. These results indicated that it is essentially important to include the dose by secondary neutrons in the assessment of the secondary cancer risk of patients receiving carbon-ion radiotherapy with active as well as passive beams. We established a calculation method with a Monte Carlo simulation to estimate the distribution of dose equivalent in the body as a first step toward routine risk assessment and an epidemiological study of carbon-ion radiotherapy at NIRS. This method has the advantage of being verifiable by the measurement.

Establishment of postal audit system in intensity-modulated radiotherapy by radiophotoluminescent glass dosimeters and a radiochromic film.

PubMed

Okamoto, Hiroyuki; Minemura, Toshiyuki; Nakamura, Mitsuhiro; Mizuno, Hideyuki; Tohyama, Naoki; Nishio, Teiji; Wakita, Akihisa; Nakamura, Satoshi; Nishioka, Shie; Iijima, Kotaro; Fujiyama, Daisuke; Itami, Jun; Nishimura, Yasumasa

2018-04-01

We developed an efficient postal audit system to independently assess the delivered dose using radiophotoluminescent glass dosimeters (RPLDs) and the positional differences of fields using EBT3 film at the axial plane for intensity-modulated radiotherapy (IMRT). The audit phantom had a C-shaped target structure as a planning target volume (PTV) with four measurement points for the RPLDs and a cylindrical structure as the organ at risk (OAR) for one measurement point. The phantoms were sent to 24 institutions. Point dose measurements with a 0.6 cm 3 PTW farmer chamber were also performed to justify glass dosimetry in IMRT. The measured dose with the RPLDs was compared to the calculated dose in the institution's treatment planning system (TPS). The mean ± 1.96σ of the ratio of the measured dose with the RPLDs to the farmer chamber was 0.997 ± 0.024 with no significant difference (p = .175). The investigations demonstrated that glass dosimetry was reliable with a high measurement accuracy comparable to the chamber. The mean ± 1.96σ for the dose differences with a reference of the TPS dose for the PTV and the OAR was 0.1 ± 2.5% and -2.1 ± 17.8%, respectively. The mean ± 1.96σ for the right-left and the anterior-posterior direction was -0.9 ± 2.8 and 0.5 ± 1.4 mm, respectively. This study is the first report to justify glass dosimetry for implementation in IMRT audit in Japan. We demonstrate that our postal audit system has high accuracy with a high-level criterion of 3%/3 mm. Copyright © 2018 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Pharmacological validation of individual animal locomotion, temperature and behavioural analysis in group-housed rats using a novel automated home cage analysis system: A comparison with the modified Irwin test.

PubMed

Tse, Karen; Sillito, Rowland; Keerie, Amy; Collier, Rachel; Grant, Claire; Karp, Natasha A; Vickers, Cathy; Chapman, Kathryn; Armstrong, J Douglas; Redfern, William S

2018-04-01

The ActualHCA™ system continuously monitors the activity, temperature and behavior of group-housed rats without invasive surgery. The system was validated to detect the contrasting effects of sedative and stimulant test agents (chlorpromazine, clonidine and amphetamine), and compared with the modified Irwin test (mIT) with rectal temperature measurements. Six male Han Wistar rats per group were used to assess each test agent and vehicle controls in separate ActualHCA™ recordings and mIT. The mIT was undertaken at 15, 30 mins, 1, 2, 4 and 24 h post-dose. ActualHCA™ recorded continuously for 24 h post-dose under 3 experimental conditions: dosed during light phase, dark phase, and light phase with a scheduled cage change at the time of peak effects determined by mIT. ActualHCA™ detected an increase stimulated activity from the cage change at 1-2 h post-dose which was obliterated by chlorpromazine and clonidine. Amphetamine increased activity up to 4 h post-dose in all conditions. Temperature from ActualHCA™ was affected by all test agents in all conditions. The mIT showed effects on all 3 test agents up to 4 h post-dose, with maximal effects at 1-2 h post-dose. The maximal effects on temperature from ActualHCA™ differed from mIT. Delayed effects on activity were detected by ActualHCA™, but not on mIT. Continuous monitoring has the advantage of capturing effects over time that may be missed with manual tests using pre-determined time points. This automated behavioural system does not replace the need for conventional methods but could be implemented simultaneously to improve our understanding of behavioural pharmacology. Copyright © 2018 Elsevier Inc. All rights reserved.

Evaluation of the peripheral dose to uterus in breast carcinoma radiotherapy.

PubMed

Martín Rincón, C; Jerez Sainz, I; Modolell Farré, I; España López, M L; López Franco, P; Muñiz, J L; Romero, A M; Rodríguez, R

2002-01-01

The absorbed dose outside of the direct fields of radiotherapy treatment (or peripheral dose, PD) is responsible for radiation exposure of the fetus in pregnant women. Because the radiological protection of the unborn child is of particular concern in the early period of the pregnancy, the aim of this study is to estimate the PD in order to assess the absorbed dose in the uterus in a pregnant patient irradiated for breast carcinoma therapy. The treatment was simulated on an Alderson-Rando anthropomorphic phantom, and the radiation dose to the fetus was measured using an ionisation chamber and thermoluminescence dosemeters. Two similar treatments plans with and without wedges were delivered, using a 6 MV photon beam with two isocentric opposite tangential fields with a total dose of 50 Gy, in accordance with common established procedures. Average field parameters for more than 300 patients were studied. Measurements showed the fetal dose to be slightly lower than 50 mGy, a level at which the risk to the fetus is uncertain, although several authors consider this value as the dose threshold for deterministic effects. The planning system (PS) underestimated PD values and no significant influence was found with the use of wedge filters.

Radiation protection recommendations as applied to the disposal of long-lived solid radioactive waste. A report of The International Commission on Radiological Protection.

PubMed

1998-01-01

(79) Waste, by definition, has no benefit. It should be viewed as one aspect of the beneficial practice that gave rise to it. Furthermore, radioactive waste management should be placed in the context of the management of society's waste in general. (80) A major issue in evaluating the acceptability of a disposal system for long-lived solid radioactive waste is that doses or risks may arise from exposures in the distant future. There is uncertainty surrounding any estimate of these doses or risks due to lack of knowledge about future conditions. Such exposures are treated as potential exposures as their magnitude depends on future processes and conditions that have probabilities associated with them. (81) Nevertheless, the Commission recognises a basic principle that individuals and populations in the future should be afforded at least the same level of protection from the action of disposing of radioactive waste today as is the current generation. This implies use of the current quantitative dose and risk criteria derived from considering associated health detriment. Therefore, protection of future generations should be achieved by applying these dose or risk criteria to the estimated future doses or risks in appropriately defined critical groups. These estimates should not be regarded as measures of health detriment beyond times of around several hundreds of years into the future. In the case of these longer time periods, they represent indicators of the protection afforded by the disposal system. (82 Constrained optimisation is the central approach to evaluating the radiological acceptability of a waste disposal system; dose or risk constraints are used rather than dose or risk limits. By this transition from limitation to optimisation, the needs of practical application of the radiological protection system to the disposal of long-lived solid waste disposal are met: determination of acceptability now for exposures that may occur in the distant future. Optimisation should be applied in an iterative manner during the disposal system development process and should particularly cover both site selection and repository design. (83) Two broad categories of exposure situations should be considered: natural processes and human intrusion. The latter only refers to intrusion that is inadvertent. The radiological implications of deliberate intrusion into a repository are the responsibility of the intruder. Assessed doses or risks arising from natural processes should be compared with a dose constraint of 0.3 mSv per year or its risk equivalent of around 10(-5) per year. With regard to human intrusion, the consequences from one or more plausible stylized scenarios should be considered in order to evaluate the resilience of the repository to such events. (84) The Commission considers that in circumstances where human intrusion could lead to doses to those living around the site sufficiently high that intervention on current criteria would almost always be justified, reasonable efforts should be made at the repository development stage to reduce the probability of human intrusion or to limit its consequences. In this respect, the Commission has previously advised that an existing annual dose of around 10 mSv per year may be used as a generic reference level below which intervention is not likely to be justifiable. Conversely, an existing annual dose of around 100 mSv per year may be used as a generic reference level above which intervention should be considered almost always justifiable. Similar considerations apply in situations where the thresholds for deterministic effects in relevant organs are exceeded. (85) Compliance with the constraints can be assessed by utilising either an aggregated risk-oriented approach, with a risk constraint, or a disaggregated dose/probability approach, with a dose constraint, or a combination of both. A similar level of protection can be achieved by any of these approaches; however, more information may

Mobile C-arm cone-beam CT for guidance of spine surgery: Image quality, radiation dose, and integration with interventional guidance

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

Schafer, S.; Nithiananthan, S.; Mirota, D. J.

Purpose: A flat-panel detector based mobile isocentric C-arm for cone-beam CT (CBCT) has been developed to allow intraoperative 3D imaging with sub-millimeter spatial resolution and soft-tissue visibility. Image quality and radiation dose were evaluated in spinal surgery, commonly relying on lower-performance image intensifier based mobile C-arms. Scan protocols were developed for task-specific imaging at minimum dose, in-room exposure was evaluated, and integration of the imaging system with a surgical guidance system was demonstrated in preclinical studies of minimally invasive spine surgery. Methods: Radiation dose was assessed as a function of kilovolt (peak) (80-120 kVp) and milliampere second using thoracic andmore » lumbar spine dosimetry phantoms. In-room radiation exposure was measured throughout the operating room for various CBCT scan protocols. Image quality was assessed using tissue-equivalent inserts in chest and abdomen phantoms to evaluate bone and soft-tissue contrast-to-noise ratio as a function of dose, and task-specific protocols (i.e., visualization of bone or soft-tissues) were defined. Results were applied in preclinical studies using a cadaveric torso simulating minimally invasive, transpedicular surgery. Results: Task-specific CBCT protocols identified include: thoracic bone visualization (100 kVp; 60 mAs; 1.8 mGy); lumbar bone visualization (100 kVp; 130 mAs; 3.2 mGy); thoracic soft-tissue visualization (100 kVp; 230 mAs; 4.3 mGy); and lumbar soft-tissue visualization (120 kVp; 460 mAs; 10.6 mGy) - each at (0.3 x 0.3 x 0.9 mm{sup 3}) voxel size. Alternative lower-dose, lower-resolution soft-tissue visualization protocols were identified (100 kVp; 230 mAs; 5.1 mGy) for the lumbar region at (0.3 x 0.3 x 1.5 mm{sup 3}) voxel size. Half-scan orbit of the C-arm (x-ray tube traversing under the table) was dosimetrically advantageous (prepatient attenuation) with a nonuniform dose distribution ({approx}2 x higher at the entrance side than at isocenter, and {approx}3-4 lower at the exit side). The in-room dose (microsievert) per unit scan dose (milligray) ranged from {approx}21 {mu}Sv/mGy on average at tableside to {approx}0.1 {mu}Sv/mGy at 2.0 m distance to isocenter. All protocols involve surgical staff stepping behind a shield wall for each CBCT scan, therefore imparting {approx}zero dose to staff. Protocol implementation in preclinical cadaveric studies demonstrate integration of the C-arm with a navigation system for spine surgery guidance-specifically, minimally invasive vertebroplasty in which the system provided accurate guidance and visualization of needle placement and bone cement distribution. Cumulative dose including multiple intraoperative scans was {approx}11.5 mGy for CBCT-guided thoracic vertebroplasty and {approx}23.2 mGy for lumbar vertebroplasty, with dose to staff at tableside reduced to {approx}1 min of fluoroscopy time ({approx}40-60 {mu}Sv), compared to 5-11 min for the conventional approach. Conclusions: Intraoperative CBCT using a high-performance mobile C-arm prototype demonstrates image quality suitable to guidance of spine surgery, with task-specific protocols providing an important basis for minimizing radiation dose, while maintaining image quality sufficient for surgical guidance. Images demonstrate a significant advance in spatial resolution and soft-tissue visibility, and CBCT guidance offers the potential to reduce fluoroscopy reliance, reducing cumulative dose to patient and staff. Integration with a surgical guidance system demonstrates precise tracking and visualization in up-to-date images (alleviating reliance on preoperative images only), including detection of errors or suboptimal surgical outcomes in the operating room.« less

Application of the Bulgarian emergency response system in case of nuclear accident in environmental assessment study

NASA Astrophysics Data System (ADS)

Syrakov, Dimiter; Veleva, Blagorodka; Georgievs, Emilia; Prodanova, Maria; Slavov, Kiril; Kolarova, Maria

2014-05-01

The development of the Bulgarian Emergency Response System (BERS) for short term forecast in case of accidental radioactive releases to the atmosphere has been started in the mid 1990's [1]. BERS comprises of two main parts - operational and accidental, for two regions 'Europe' and 'Northern Hemisphere'. The operational part runs automatically since 2001 using the 72 hours meteorological forecast from DWD Global model, resolution in space of 1.5o and in time - 12 hours. For specified Nuclear power plants (NPPs), 3 days trajectories are calculated and presented on NIMH's specialized Web-site (http://info.meteo.bg/ews/). The accidental part is applied when radioactive releases are reported or in case of emergency exercises. BERS is based on numerical weather forecast information and long-range dispersion model accounting for the transport, dispersion, and radioactive transformations of pollutants. The core of the accidental part of the system is the Eulerian 3D dispersion model EMAP calculating concentration and deposition fields [2]. The system is upgraded with a 'dose calculation module' for estimation of the prognostic dose fields of 31 important radioactive gaseous and aerosol pollutants. The prognostic doses significant for the early stage of a nuclear accident are calculated as follows: the effective doses from external irradiation (air submersion + ground shinning); effective dose from inhalation; summarized effective dose and absorbed thyroid dose [3]. The output is given as 12, 24, 36, 48, 60 and 72 hours prognostic dose fields according the updated meteorology. The BERS was upgraded to simulate the dispersion of nuclear materials from Fukushima NPP [4], and results were presented in NIMH web-site. In addition BERS took part in the respective ENSEMBLE exercises to model 131I and 137Cs in Fukushima source term. In case of governmental request for expertise BERS was applied for environmental impact assessment of hypothetical accidental transboundary radioactive pollution. The consequences were estimated based on the worst emission scenario for the existing basic reactor type, selection of real meteorological forecast conditions, favoring the direct transport of the contaminated air masses to the territory of the country in consideration. In the present work BERS is used to estimate the worst case accidental scenario impact from a possible new unit of Paks Nuclear Power Plant, Hungary over the territory of Bulgaria. 1. D.Syrakov, M.Prodanova, 1998, Atmospheric Environment, 32 (24), 4367-4375. 2. D. Syrakov, M. Prodanova, K. Slavov, Inernationsal J. Environment and Pollution, 20, 1-6 (2003) 286-296. 3. D. Syrakov, B. Veleva, M. Prodanova, T. Popova, M. Kolarova, Journal of Environmental Radioactivity 100 (2009) 151-156. 4. D.Syrakov, M Prodanova, J. Intern. Sci. Publ.: Ecology & Safety Vol. 6 Part 1 (2011) 94-102. www.scientific-publications.net.

Digital mammography--DQE versus optimized image quality in clinical environment: an on site study

NASA Astrophysics Data System (ADS)

Oberhofer, Nadia; Fracchetti, Alessandro; Springeth, Margareth; Moroder, Ehrenfried

2010-04-01

The intrinsic quality of the detection system of 7 different digital mammography units (5 direct radiography DR; 2 computed radiography CR), expressed by DQE, has been compared with their image quality/dose performances in clinical use. DQE measurements followed IEC 62220-1-2 using a tungsten test object for MTF determination. For image quality assessment two different methods have been applied: 1) measurement of contrast to noise ratio (CNR) according to the European guidelines and 2) contrast-detail (CD) evaluation. The latter was carried out with the phantom CDMAM ver. 3.4 and the commercial software CDMAM Analyser ver. 1.1 (both Artinis) for automated image analysis. The overall image quality index IQFinv proposed by the software has been validated. Correspondence between the two methods has been shown figuring out a linear correlation between CNR and IQFinv. All systems were optimized with respect to image quality and average glandular dose (AGD) within the constraints of automatic exposure control (AEC). For each equipment, a good image quality level was defined by means of CD analysis, and the corresponding CNR value considered as target value. The goal was to achieve for different PMMA-phantom thicknesses constant image quality, that means the CNR target value, at minimum dose. All DR systems exhibited higher DQE and significantly better image quality compared to CR systems. Generally switching, where available, to a target/filter combination with an x-ray spectrum of higher mean energy permitted dose savings at equal image quality. However, several systems did not allow to modify the AEC in order to apply optimal radiographic technique in clinical use. The best ratio image quality/dose was achieved by a unit with a-Se detector and W anode only recently available on the market.

Systemic and cerebral exposure to and pharmacokinetics of flavonols and terpene lactones after dosing standardized Ginkgo biloba leaf extracts to rats via different routes of administration.

PubMed

Chen, Feng; Li, Li; Xu, Fang; Sun, Yan; Du, Feifei; Ma, Xutao; Zhong, Chenchun; Li, Xiuxue; Wang, Fengqing; Zhang, Nating; Li, Chuan

2013-09-01

Flavonols and terpene lactones are putatively responsible for the properties of Ginkgo biloba leaf extracts that relate to prevention and treatment of cardiovascular disease and cerebral insufficiency. Here, we characterized rat systemic and cerebral exposure to these ginkgo compounds after dosing, as well as the compounds' pharmacokinetics. Rats received single or multiple doses of ShuXueNing injection (prepared from GBE50 for intravenous administration) or GBE50 (a standardized extract of G. biloba leaves for oral administration). Brain delivery of the ginkgo compounds was assessed with microdialysis. Various rat samples were analysed using liquid chromatography/mass spectrometry. Slow terminal elimination features of the flavonols counterbalanced the influence of poor oral bioavailability on their systemic exposure levels, which also resulted in significant accumulation of the compounds in plasma during the subchronic treatment with ShuXueNing injection and GBE50. Unlike the flavonols, the terpene lactones had poor enterohepatic circulation due to their rapid renal excretion and unknown metabolism. The flavonol glycosides occurred as major forms in plasma after dosing with ShuXueNing injection, while the flavonol aglycone conjugates were predominant in plasma after dosing with GBE50. Cerebral exposure was negligible for the flavonols and low for the terpene lactones. Unlike the significant systemic exposure levels, the levels of cerebral exposure to the flavonols and terpene lactones are low. The elimination kinetic differences between the two classes of ginkgo compounds influence their relative systemic exposure levels. The information gained is relevant to linking ginkgo administration to the medicinal effects. © 2013 The Authors. British Journal of Pharmacology published by John Wiley &. Sons Ltd on behalf of The British Pharmacological Society.

Systemic and cerebral exposure to and pharmacokinetics of flavonols and terpene lactones after dosing standardized Ginkgo biloba leaf extracts to rats via different routes of administration

PubMed Central

Chen, Feng; Li, Li; Xu, Fang; Sun, Yan; Du, Feifei; Ma, Xutao; Zhong, Chenchun; Li, Xiuxue; Wang, Fengqing; Zhang, Nating; Li, Chuan

2013-01-01

BACKGROUND AND PURPOSE Flavonols and terpene lactones are putatively responsible for the properties of Ginkgo biloba leaf extracts that relate to prevention and treatment of cardiovascular disease and cerebral insufficiency. Here, we characterized rat systemic and cerebral exposure to these ginkgo compounds after dosing, as well as the compounds’ pharmacokinetics. EXPERIMENTAL APPROACH Rats received single or multiple doses of ShuXueNing injection (prepared from GBE50 for intravenous administration) or GBE50 (a standardized extract of G. biloba leaves for oral administration). Brain delivery of the ginkgo compounds was assessed with microdialysis. Various rat samples were analysed using liquid chromatography/mass spectrometry. KEY RESULTS Slow terminal elimination features of the flavonols counterbalanced the influence of poor oral bioavailability on their systemic exposure levels, which also resulted in significant accumulation of the compounds in plasma during the subchronic treatment with ShuXueNing injection and GBE50. Unlike the flavonols, the terpene lactones had poor enterohepatic circulation due to their rapid renal excretion and unknown metabolism. The flavonol glycosides occurred as major forms in plasma after dosing with ShuXueNing injection, while the flavonol aglycone conjugates were predominant in plasma after dosing with GBE50. Cerebral exposure was negligible for the flavonols and low for the terpene lactones. CONCLUSION AND IMPLICATIONS Unlike the significant systemic exposure levels, the levels of cerebral exposure to the flavonols and terpene lactones are low. The elimination kinetic differences between the two classes of ginkgo compounds influence their relative systemic exposure levels. The information gained is relevant to linking ginkgo administration to the medicinal effects. PMID:23808355

Influence of dosemeter position for the assessment of eye lens dose during interventional cardiology.

PubMed

Principi, Sara; Ginjaume, Mercè; Duch, Maria Amor; Sánchez, Roberto M; Fernández, Jose M; Vano, Eliseo

2015-04-01

The equivalent dose limit for the eye lens for occupational exposure recommended by the ICRP has been reduced to 20 mSv y(-1) averaged over defined periods of 5 y, with no single year exceeding 50 mSv. The compliance with this new requirement could not be easy in some workplace such as interventional radiology and cardiology. The aim of this study is to evaluate different possible approaches in order to have a good estimate of the eye lens dose during interventional procedures. Measurements were performed with an X-ray system Philips Allura FD-10, using a PMMA phantom to simulate the patient scattered radiation and a Rando phantom to simulate the cardiologist. Thermoluminescence (TL) whole-body and TL eye lens dosemeters together with Philips DoseAware active dosemeters were located on different positions of the Rando phantom to estimate the eye lens dose in typical cardiology procedures. The results show that, for the studied conditions, any of the analysed dosemeter positions are suitable for eye lens dose assessment. However, the centre of the thyroid collar and the left ear position provide a better estimate. Furthermore, in practice, improper use of the ceiling-suspended screen can produce partial protection of some parts of the body, and thus large differences between the measured doses and the actual exposure of the eye could arise if the dosemeter is not situated close to the eye. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Influence of CT automatic tube current modulation on uncertainty in effective dose.

PubMed

Sookpeng, S; Martin, C J; Gentle, D J

2016-01-01

Computed tomography (CT) scanners are equipped with automatic tube current modulation (ATCM) systems that adjust the current to compensate for variations in patient attenuation. CT dosimetry variables are not defined for ATCM situations and, thus, only the averaged values are displayed and analysed. The patient effective dose (E), which is derived from a weighted sum of organ equivalent doses, will be modified by the ATCM. Values for E for chest-abdomen-pelvis CT scans have been calculated using the ImPACT spreadsheet for patients on five CT scanners. Values for E resulting from the z-axis modulation under ATCM have been compared with results assessed using the same effective mAs values with constant tube currents. Mean values for E under ATCM were within ±10 % of those for fixed tube currents for all scanners. Cumulative dose distributions under ATCM have been simulated for two patient scans using single-slice dose profiles measured in elliptical and cylindrical phantoms on one scanner. Contributions to the effective dose from organs in the upper thorax under ATCM are 30-35 % lower for superficial tissues (e.g. breast) and 15-20 % lower for deeper organs (e.g. lungs). The effect on doses to organs in the abdomen depends on body shape, and they can be 10-22 % higher for larger patients. Results indicate that scan dosimetry parameters, dose-length product and effective mAs averaged over the whole scan can provide an assessment in terms of E that is sufficiently accurate to quantify relative risk for routine patient exposures under ATCM. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dental flat panel conebeam CT in the evaluation of patients with inflammatory sinonasal disease: Diagnostic efficacy and radiation dose savings.

PubMed

Leiva-Salinas, C; Flors, L; Gras, P; Más-Estellés, F; Lemercier, P; Patrie, J T; Wintermark, M; Martí-Bonmatí, L

2014-01-01

CT is the imaging modality of choice to study the paranasal sinuses; unfortunately, it involves significant radiation dose. Our aim was to assess the diagnostic validity, image quality, and radiation-dose savings of dental conebeam CT in the evaluation of patients with suspected inflammatory disorders of the paranasal sinuses. We prospectively studied 40 patients with suspected inflammatory disorders of the sinuses with dental conebeam CT and standard CT. Two radiologists analyzed the images independently, blinded to clinical information. The image quality of both techniques and the diagnostic validity of dental conebeam CT compared with the reference standard CT were assessed by using 3 different scoring systems. Image noise, signal-to-noise ratio, and contrast-to-noise ratio were calculated for both techniques. The absorbed radiation dose to the lenses and thyroid and parotid glands was measured by using a phantom and dosimeter chips. The effective radiation dose for CT was calculated. All dental conebeam CT scans were judged of diagnostic quality. Compared with CT, the conebeam CT image noise was 37.3% higher (P < .001) and the SNR of the bone was 75% lower (P < .001). The effective dose of our conebeam CT protocol was 23 μSv. Compared with CT, the absorbed radiation dose to the lenses and parotid and thyroid glands with conebeam CT was 4%, 7.8%, and 7.3% of the dose delivered to the same organs by conventional CT (P < .001). Dental conebeam CT is a valid imaging procedure for the evaluation of patients with inflammatory sinonasal disorders. © 2014 by American Journal of Neuroradiology.

A comparison of the central nervous system effects of haloperidol, chlorpromazine and sulpiride in normal volunteers.

PubMed Central

McClelland, G R; Cooper, S M; Pilgrim, A J

1990-01-01

1. Twelve healthy male volunteers participated in four experimental occasions during each of which they were dosed with one of the following anti-psychotic drugs: chlorpromazine (50 mg), haloperidol (3 mg), sulpiride (400 mg) and placebo. Drugs were allocated to subjects in a double-blind, crossover fashion. 2. The subject's mood state, psychometric performance and electroencephalogram (EEG) were assessed pre-dose, and at 2, 4, 6, 8, 24 and 48 h post-dose. Mood states were assessed using 16 visual analogue scales and psychomotor performance was measured using the following tests: elapsed time estimation, tapping rate, choice reaction times, a rapid information processing task, flash fusion threshold, a manipulative motor task, digit span, body sway and tremor. 3. Chlorpromazine and haloperidol significantly reduced subjective ratings of 'alertness' and 'contentedness', and haloperidol significantly reduced feelings of 'calmness'. Sulpiride did not significantly affect any of the visual analogue scales. 4. All three anti-psychotic drugs had similar EEG effects with peak effect 2 to 4 h postdose. The profile was characterised by an increase in the proportion of slow wave activity (delta and theta) as well as decreased alpha (8-14 Hz) and faster (beta) wave activity. 5. Chlorpromazine reduced tapping rate and increased choice reaction movement times. Haloperidol reduced the flash fusion threshold frequency at 6 h post-dose. Sulpiride prolonged the duration of the manipulative motor task, particularly at 48 h post-dose. 6. All three anti-psychotic drugs impaired performance on the rapid information processing task. Chlorpromazine significantly reduced the number of correct letter pair identifications at 2, 4 and 6 h post-dose, haloperidol at 4, 6, 8, 24 and 48 h post-dose, and sulpiride at 24 h post-dose.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2288826

Intraoperative near infrared fluorescence guided identification of the ureters using low dose methylene blue: a first in human experience.

PubMed

Verbeek, Floris P R; van der Vorst, Joost R; Schaafsma, Boudewijn E; Swijnenburg, Rutger-Jan; Gaarenstroom, Katja N; Elzevier, Henk W; van de Velde, Cornelis J H; Frangioni, John V; Vahrmeijer, Alexander L

2013-08-01

Near infrared fluorescence imaging is a promising technique that offers real-time visual information during surgery. In this study we report the first clinical results to our knowledge of ureteral imaging using near infrared fluorescence after a simple peripheral infusion of methylene blue. Furthermore, we assessed the optimal timing and dose of methylene blue. A total of 12 patients who underwent lower abdominal surgery were included in this prospective feasibility study. Near infrared fluorescence imaging was performed using the Mini-FLARE™ imaging system. To determine optimal timing and dose, methylene blue was injected intravenously at doses of 0.25, 0.5 or 1 mg/kg after exposure of the ureters. Imaging was performed for up to 60 minutes after injection. In all patients both ureters could be clearly visualized within 10 minutes after infusion of methylene blue. The signal lasted at least up to 60 minutes after injection. The mean signal-to-background ratio of the ureter was 2.27 ± 1.22 (4), 2.61 ± 1.88 (4) and 3.58 ± 3.36 (4) for the 0.25, 0.5 and 1 mg/kg groups, respectively. A mixed model analysis was used to compare signal-to-background ratios among dose groups and times, and to assess the relationship between dose and time. A significant difference among time points (p <0.001) was found. However, no difference was observed among dose groups (p = 0.811). This study demonstrates the first successful use of near infrared fluorescence using low dose methylene blue for the identification of the ureters during lower abdominal surgery. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Application of Natural Language Processing and Network Analysis Techniques to Post-market Reports for the Evaluation of Dose-related Anti-Thymocyte Globulin Safety Patterns.

PubMed

Botsis, Taxiarchis; Foster, Matthew; Arya, Nina; Kreimeyer, Kory; Pandey, Abhishek; Arya, Deepa

2017-04-26

To evaluate the feasibility of automated dose and adverse event information retrieval in supporting the identification of safety patterns. We extracted all rabbit Anti-Thymocyte Globulin (rATG) reports submitted to the United States Food and Drug Administration Adverse Event Reporting System (FAERS) from the product's initial licensure in April 16, 1984 through February 8, 2016. We processed the narratives using the Medication Extraction (MedEx) and the Event-based Text-mining of Health Electronic Records (ETHER) systems and retrieved the appropriate medication, clinical, and temporal information. When necessary, the extracted information was manually curated. This process resulted in a high quality dataset that was analyzed with the Pattern-based and Advanced Network Analyzer for Clinical Evaluation and Assessment (PANACEA) to explore the association of rATG dosing with post-transplant lymphoproliferative disorder (PTLD). Although manual curation was necessary to improve the data quality, MedEx and ETHER supported the extraction of the appropriate information. We created a final dataset of 1,380 cases with complete information for rATG dosing and date of administration. Analysis in PANACEA found that PTLD was associated with cumulative doses of rATG >8 mg/kg, even in periods where most of the submissions to FAERS reported low doses of rATG. We demonstrated the feasibility of investigating a dose-related safety pattern for a particular product in FAERS using a set of automated tools.

Terbinafine in combination with other antifungal agents for treatment of resistant or refractory mycoses: investigating optimal dosing regimens using a physiologically based pharmacokinetic model.

PubMed

Dolton, Michael J; Perera, Vidya; Pont, Lisa G; McLachlan, Andrew J

2014-01-01

Terbinafine is increasingly used in combination with other antifungal agents to treat resistant or refractory mycoses due to synergistic in vitro antifungal activity; high doses are commonly used, but limited data are available on systemic exposure, and no assessment of pharmacodynamic target attainment has been made. Using a physiologically based pharmacokinetic (PBPK) model for terbinafine, this study aimed to predict total and unbound terbinafine concentrations in plasma with a range of high-dose regimens and also calculate predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine concentrations accumulated significantly during the first 28 days of treatment; the area under the concentration-time curve (AUC)/MIC ratios and AUC for the free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken every 12 h provided the highest systemic exposure; on day 7 of treatment, the predicted AUC, maximum concentration (Cmax), and minimum concentration (Cmin) were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard-dose regimen of 250 mg once daily. Close agreement was seen between the concentrations predicted by the PBPK model and the observed concentrations, indicating good predictive performance. This study provides the first report of predicted terbinafine exposure in plasma with a range of high-dose regimens.

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

Li Heng; Sahoo, Narayan; Poenisch, Falk

Purpose: The purpose of this work was to assess the monitor unit (MU) values and position accuracy of spot scanning proton beams as recorded by the daily treatment logs of the treatment control system, and furthermore establish the feasibility of using the delivered spot positions and MU values to calculate and evaluate delivered doses to patients. Methods: To validate the accuracy of the recorded spot positions, the authors generated and executed a test treatment plan containing nine spot positions, to which the authors delivered ten MU each. The spot positions were measured with radiographic films and Matrixx 2D ion-chambers arraymore » placed at the isocenter plane and compared for displacements from the planned and recorded positions. Treatment logs for 14 patients were then used to determine the spot MU values and position accuracy of the scanning proton beam delivery system. Univariate analysis was used to detect any systematic error or large variation between patients, treatment dates, proton energies, gantry angles, and planned spot positions. The recorded patient spot positions and MU values were then used to replace the spot positions and MU values in the plan, and the treatment planning system was used to calculate the delivered doses to patients. The results were compared with the treatment plan. Results: Within a treatment session, spot positions were reproducible within {+-}0.2 mm. The spot positions measured by film agreed with the planned positions within {+-}1 mm and with the recorded positions within {+-}0.5 mm. The maximum day-to-day variation for any given spot position was within {+-}1 mm. For all 14 patients, with {approx}1 500 000 spots recorded, the total MU accuracy was within 0.1% of the planned MU values, the mean (x, y) spot displacement from the planned value was (-0.03 mm, -0.01 mm), the maximum (x, y) displacement was (1.68 mm, 2.27 mm), and the (x, y) standard deviation was (0.26 mm, 0.42 mm). The maximum dose difference between calculated dose to the patient based on the plan and recorded data was within 2%. Conclusions: The authors have shown that the treatment log file in a spot scanning proton beam delivery system is precise enough to serve as a quality assurance tool to monitor variation in spot position and MU value, as well as the delivered dose uncertainty from the treatment delivery system. The analysis tool developed here could be useful for assessing spot position uncertainty and thus dose uncertainty for any patient receiving spot scanning proton beam therapy.« less

Key Performance Indicators for the Assessment of Pediatric Pharmacotherapeutic Guidance

PubMed Central

Barrett, Jeffrey S.; Patel, Dimple; Jayaraman, Bhuvana; Narayan, Mahesh; Zuppa, Athena

2008-01-01

Given the paucity of actual guidance provided for managing pediatric drug therapy, prescribing caregivers must be able to draw on the limited published information in pediatrics and/or guidance provided in adults with some account for expected pediatric response. Guidance for managing drug therapy in children is clearly desirable. Our objectives were to construct key performance indicators (KPIs) for pediatric pharmacotherapy guidance to identify drugs where pharmacotherapy guidance would be most beneficial. A pilot survey to assess variation in caregiver appreciation for pediatric dosing guidance has also been constructed to provide a complementary subjective assessment. Three KPI categories, drug utilization (based on hospital admission and billing data collected from 2001 through 2006), medical need, and guidance outcome value along with a KPI composite score have been proposed. Low scores are favored with respect to prioritization for pharmacotherapy guidance. The pilot survey consisted of 15 questions to assess 1) physician knowledge regarding dosing guidance, 2) attitudes toward dose modification and patient individualization, 3) the accessibility, ease of use and appropriateness of existing data stores, and 4) frequency of dosing modification, consultation of dosing compendiums and estimate of success rate in dosing guidance. Pilot results suggest that dosing guidance is generally viewed as important and that the existing resources are insufficient to guide recommendations for all drugs. While the majority of respondents check more than one resource less than 25% of the time, at least 25% of the respondents check more than one resource 25–50% of the time. The majority viewed the relevance of dosing guidance very important to the management of drug therapy. The questionnaire is being extended to the primary care centers, the Kids First Network and specialty care centers. Results will guide the development of decision support systems (DSS) that provide patient-specific pharmacotherapy guidance as part of our pediatric knowledgebase initiative. For the top 25 most utilized agents at our institution over the last 6 years, KPI score ranged from 35 (dexamethasone) to 77 (cefazolin and ampicillin) with an average score of 55. Prototype DSS for tacrolimus and methotrexate are strongly supported by the KPI scoring which ranks their selection in the top 5% of drugs on formulary. KPI metrics provide an objective means of ranking agents for which pediatric pharmacotherapeutic guidance is clearly needed. PMID:23055875

Key performance indicators for the assessment of pediatric pharmacotherapeutic guidance.

PubMed

Barrett, Jeffrey S; Patel, Dimple; Jayaraman, Bhuvana; Narayan, Mahesh; Zuppa, Athena

2008-07-01

Given the paucity of actual guidance provided for managing pediatric drug therapy, prescribing caregivers must be able to draw on the limited published information in pediatrics and/or guidance provided in adults with some account for expected pediatric response. Guidance for managing drug therapy in children is clearly desirable. Our objectives were to construct key performance indicators (KPIs) for pediatric pharmacotherapy guidance to identify drugs where pharmacotherapy guidance would be most beneficial. A pilot survey to assess variation in caregiver appreciation for pediatric dosing guidance has also been constructed to provide a complementary subjective assessment. Three KPI categories, drug utilization (based on hospital admission and billing data collected from 2001 through 2006), medical need, and guidance outcome value along with a KPI composite score have been proposed. Low scores are favored with respect to prioritization for pharmacotherapy guidance. The pilot survey consisted of 15 questions to assess 1) physician knowledge regarding dosing guidance, 2) attitudes toward dose modification and patient individualization, 3) the accessibility, ease of use and appropriateness of existing data stores, and 4) frequency of dosing modification, consultation of dosing compendiums and estimate of success rate in dosing guidance. Pilot results suggest that dosing guidance is generally viewed as important and that the existing resources are insufficient to guide recommendations for all drugs. While the majority of respondents check more than one resource less than 25% of the time, at least 25% of the respondents check more than one resource 25-50% of the time. The majority viewed the relevance of dosing guidance very important to the management of drug therapy. The questionnaire is being extended to the primary care centers, the Kids First Network and specialty care centers. Results will guide the development of decision support systems (DSS) that provide patient-specific pharmacotherapy guidance as part of our pediatric knowledgebase initiative. For the top 25 most utilized agents at our institution over the last 6 years, KPI score ranged from 35 (dexamethasone) to 77 (cefazolin and ampicillin) with an average score of 55. Prototype DSS for tacrolimus and methotrexate are strongly supported by the KPI scoring which ranks their selection in the top 5% of drugs on formulary. KPI metrics provide an objective means of ranking agents for which pediatric pharmacotherapeutic guidance is clearly needed.

Concepts for dose determination in flat-detector CT

NASA Astrophysics Data System (ADS)

Kyriakou, Yiannis; Deak, Paul; Langner, Oliver; Kalender, Willi A.

2008-07-01

Flat-detector computed tomography (FD-CT) scanners provide large irradiation fields of typically 200 mm in the cranio-caudal direction. In consequence, dose assessment according to the current definition of the computed tomography dose index CTDIL=100 mm, where L is the integration length, would demand larger ionization chambers and phantoms which do not appear practical. We investigated the usefulness of the CTDI concept and practical dosimetry approaches for FD-CT by measurements and Monte Carlo (MC) simulations. An MC simulation tool (ImpactMC, VAMP GmbH, Erlangen, Germany) was used to assess the dose characteristics and was calibrated with measurements of air kerma. For validation purposes measurements were performed on an Axiom Artis C-arm system (Siemens Medical Solutions, Forchheim, Germany) equipped with a flat detector of 40 cm × 30 cm. The dose was assessed for 70 kV and 125 kV in cylindrical PMMA phantoms of 160 mm and 320 mm diameter with a varying phantom length from 150 to 900 mm. MC simulation results were compared to the values obtained with a calibrated ionization chambers of 100 mm and 250 mm length and to thermoluminesence (TLD) dose profiles. The MCs simulations were used to calculate the efficiency of the CTDIL determination with respect to the desired CTDI∞. Both the MC simulation results and the dose distributions obtained by MC simulation were in very good agreement with the CTDI measurements and with the reference TLD profiles, respectively, to within 5%. Standard CTDI phantoms which have a z-extent of 150 mm underestimate the dose at the center by up to 55%, whereas a z-extent of >=600 mm appears to be sufficient for FD-CT; the baseline value of the respective profile was within 1% to the reference baseline. As expected, the measurements with ionization chambers of 100 mm and 250 mm offer a limited accuracy, whereas an increased integration length of >=600 mm appeared to be necessary to approximate CTDI∞ in within 1%. MC simulations appear to offer a practical and accurate way of assessing conversion factors for arbitrary dosimetry setups using a standard pencil chamber to provide estimates of CTDI∞. This would eliminate the need for extra-long phantoms and ionization chambers or excessive amounts of TLDs.

IRIS Toxicological Review of Ammonia Noncancer Inhalation ...

EPA Pesticide Factsheets

EPA has finalized the Integrated Risk Information System (IRIS) Assessment of Ammonia (Noncancer Inhalation). This assessment addresses the potential noncancer human health effects from long-term inhalation exposure to ammonia. Now final, this assessment will update the current toxicological information on ammonia posted in 1991. EPA’s program and regional offices may use this assessment to inform decisions to protect human health. EPA completed the Integrated Risk Information System (IRIS) health assessment for ammonia. IRIS is an EPA database containing Agency scientific positions on potential adverse human health effects that may result from chronic (or lifetime) exposure to chemicals in the environment. IRIS contains chemical-specific summaries of qualitative and quantitative health information in support of two steps of the risk assessment paradigm, i.e., hazard identification and dose-response evaluation. IRIS assessments are used in combination with specific situational exposure assessment information to evaluate potential public health risk associated with environmental contaminants.

IRIS Toxicological Review of Carbon Tetrachloride (External Review Draft)

EPA Science Inventory

EPA conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of carbon tetrachloride that will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that science is used credibly and...

IRIS Toxicological Review of Bromobenzene (External Review Draft)

EPA Science Inventory

EPA has conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of Bromobenzene that will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that science is used credibly and app...

IRIS Toxicological Review of Acrylamide (External Review Draft)

EPA Science Inventory

EPA has conducted a peer review by EPA’s Science Advisory Board (SAB) of the scientific basis supporting the human health hazard and dose-response assessment of acrylamide that once finalized will appear on the Integrated Risk Information System (IRIS) database. Peer review is m...

IRIS Toxicological Review of Tetrachloroethylene (Perchloroethylene) (External Review Draft)

EPA Science Inventory

EPA conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of tetrachloroethylene that will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that science is used credibly and ...

IRIS Toxicological Review of Nitrobenzene (External Review Draft)

EPA Science Inventory

EPA has conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessments of nitrobenzene, that will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that science is used credibly and a...

A radiological assessment of nuclear power and propulsion operations near Space Station Freedom

NASA Technical Reports Server (NTRS)

Bolch, Wesley E.; Thomas, J. Kelly; Peddicord, K. Lee; Nelson, Paul; Marshall, David T.; Busche, Donna M.

1990-01-01

Scenarios were identified which involve the use of nuclear power systems in the vicinity of Space Station Freedom (SSF) and their radiological impact on the SSF crew was quantified. Several of the developed scenarios relate to the use of SSF as an evolutionary transportation node for lunar and Mars missions. In particular, radiation doses delivered to SSF crew were calculated for both the launch and subsequent return of a Nuclear Electric Propulsion (NEP) cargo vehicle and a Nuclear Thermal Rocket (NTR) personnel vehicle to low earth orbit. The use of nuclear power on co-orbiting platforms and the storage and handling issues associated with radioisotope power systems were also explored as they relate to SSF. A central philosophy in these analyses was the utilization of a radiation dose budget, defined as the difference between recommended dose limits from all radiation sources and estimated doses received by crew members from natural space radiations. Consequently, for each scenario examined, the dose budget concept was used to identify and quantify constraints on operational parameters such as launch separation distances, returned vehicle parking distances, and reactor shutdown times prior to vehicle approach. The results indicate that realistic scenarios do not exist which would preclude the use of nuclear power sources in the vicinity of SSF. The radiation dose to the SSF crew can be maintained at safe levels solely by implementing proper and reasonable operating procedures.

A Multiple Parameters Biodosimetry Tool with Various Blood Cell Counts - the Hemodose Approach

NASA Technical Reports Server (NTRS)

Hu, Shaowen

2014-01-01

There continue to be important concerns about the possibility of the occurrence of acute radiation syndromes following nuclear and radiological terrorism or accidents that may result in mass casualties in densely populated areas. To guide medical personnel in their clinical decisions for effective medical management and treatment of the exposed individuals, biological markers are usually applied to examine radiation induced biological changes to assess the severity of radiation injury to sensitive organ systems. Among these the peripheral blood cell counts are widely used to assess the extent of radiation induced bone marrow injury. This is due to the fact that the hematopoietic system is the most vulnerable part of the human body to radiation damage. Particularly, the lymphocyte, granulocyte, and platelet cells are the most radiosensitive of the blood elements, and monitoring their changes after exposure is regarded as a practical and recommended laboratory test to estimate radiation dose and injury. Based upon years of physiological and pathophysiological investigation of mammalian hematopoietic systems, and rigorous coarse-grained bio-mathematical modeling and validation on species from mouse, to dog, monkey, and human, we have developed a set of software tools Hemodose, which can use single or serial granulocyte, lymphocyte, leukocyte, or platelet counts after exposure to estimate absorbed doses of adult victims very rapidly and accurately. Some patient data from historical accidents are utilized as examples to demonstrate the capabilities of these tools as a rapid point-of-care diagnostic or centralized high-throughput assay system in a large-scale radiological disaster scenario. Most significant to the improvement of national and local preparedness of a potential nuclear/radiological disaster, this HemoDose approach establishes robust correlations between the absorbed doses and victim's various types of blood cell counts not only in the early time window (1 or 2 days), but also in the very late phase (up to 4 weeks) after exposure.

Dose-dependent bioavailability indicators for curcumin and two of its novel derivatives.

PubMed

Abd el Aziz, Mohamed; El-Asmer, Mohamed; Rezq, Ameen; Al-Malki, Abdulrahman; Kumosani, Taha; Fouad, Hanan; Ahmed, Hanan; Taha, Fatma; Hassouna, Amira; Hafez, Hafez

2014-01-01

Novel water-soluble curcumin derivatives have been developed to overcome low in vivo bioavailability of curcumin. The aim of this work is to assess the potential utility of certain downstream targets as bioavailability indicators of systemic activity of pure curcumin and two novel water-soluble curcumin derivatives (NCD) by constructing dose-dependent response curves and to prove whether this novel curcumin derivatives retained, improved, or abolished biological activity of pure curcumin when applied in vivo. Pure curcumin (CUR), curcumin-carboxy derivative (NCD-1), and curcumin protein conjugate (NCD-2) were administered orally to rats at escalating doses: 37, 74, 148, and 296 μM/kg body weight, respectively. Plasma levels of GST activity, cavernous tissue levels of cGMP, and enzymatic activity of both HO-1 and GST were assessed one and half and 24 hours after oral administration of curcumin formulae. This study showed that there was a progressive elevation of cavernous tissue levels of cGMP and enzymatic activity of both HO-1 and GST in a dose-dependent manner that was maintained for 24 h with CUR, NCD-1, and NCD-2. Plasma GST activity was decreased by the lowest doses on the curve. The three dose-dependent bioavailability indicators as surrogates of curcumin and two of its novel derivatives are valid in the studied range of concentration and extended time. The novel curcumin derivatives still conserve with improvement the biological activity of natural curcumin when applied in vivo. © 2013 International Union of Biochemistry and Molecular Biology.

The Acute Gastrointestinal Syndrome in High-Dose Irradiated Mice

PubMed Central

Booth, Catherine; Tudor, Gregory; Tudor, Julie; Katz, Barry P; MacVittie, Thomas

2012-01-01

The most detailed reports of the response of the gastrointestinal system to high dose acute radiation have focused mainly on understanding the histopathology. However, to enable medical countermeasure assessment under the animal rule criteria, it is necessary to have a robust model in which the relationship between radiation dose and intestinal radiation syndrome incidence, timing and severity are established and correlated with histopathology. Although many mortality studies have been published, they have used a variety of mouse strains, ages, radiation sources and husbandry conditions, all of which influence the dose response. Further, it is clear that the level of bone marrow irradiation and supportive care can influence endpoints. In order to create robust baseline data we have generated dose response data in adult male mice, maintained under identical conditions, and exposed to either total or partial-body irradiation. Partial-body irradiation includes both extensive (40%) and minimal (5%) bone marrow sparing models, the latter designed to correlate with an established primate model and allow assessment of effects of any medical countermeasure on all three major radiation syndromes (intestinal, bone marrow and lung) in the surviving mice. Lethal dose (LD30, LD50 and LD70) data are described in the various models, along with the impact of enteric flora and response to supportive care. Correlation with diarrhea severity and histopathology are also described. This data can be used to aid the design of good laboratory practice (GLP) compliant Animal Rule studies that are reflective of the conditions following accidental radiation exposure. PMID:23091876

Assessing health risks of synthetic vitreous fibers: an integrative approach.

PubMed

McClellan, R O

1994-12-01

This paper reviews a tiered approach to acquiring information from multiple experimental systems to understand and assess the potential human health risks of exposure to airborne synthetic fibers. The approach is grounded in the now widely accepted research-risk assessment-risk management paradigm. It involves the acquisition of information that will provide mechanistic linkages within the exposure-dose-response paradigm. It advocates the use of the inhalation route of exposure for developing relevant information for assessing human health risks and calls attention to serious problems encountered using nonphysiologic routes of administration to assess human health risks.

Relationship between Individual External Doses, Ambient Dose Rates and Individuals' Activity-Patterns in Affected Areas in Fukushima following the Fukushima Daiichi Nuclear Power Plant Accident.

PubMed

Naito, Wataru; Uesaka, Motoki; Yamada, Chie; Kurosawa, Tadahiro; Yasutaka, Tetsuo; Ishii, Hideki

2016-01-01

The accident at Fukushima Daiichi Nuclear Power Plant on March 11, 2011, released radioactive material into the atmosphere and contaminated the land in Fukushima and several neighboring prefectures. Five years after the nuclear disaster, the radiation levels have greatly decreased due to physical decay, weathering, and decontamination operations in Fukushima. The populations of 12 communities were forced to evacuate after the accident; as of March 2016, the evacuation order has been lifted in only a limited area, and permanent habitation is still prohibited in most of the areas. In order for the government to lift the evacuation order and for individuals to return to their original residential areas, it is important to assess current and future realistic individual external doses. Here, we used personal dosimeters along with the Global Positioning System and Geographic Information System to understand realistic individual external doses and to relate individual external doses, ambient doses, and activity-patterns of individuals in the affected areas in Fukushima. The results showed that the additional individual external doses were well correlated to the additional ambient doses based on the airborne monitoring survey. The results of linear regression analysis suggested that the additional individual external doses were on average about one-fifth that of the additional ambient doses. The reduction factors, which are defined as the ratios of the additional individual external doses to the additional ambient doses, were calculated to be on average 0.14 and 0.32 for time spent at home and outdoors, respectively. Analysis of the contribution of various activity patterns to the total individual external dose demonstrated good agreement with the average fraction of time spent daily in each activity, but the contribution due to being outdoors varied widely. These results are a valuable contribution to understanding realistic individual external doses and the corresponding airborne monitoring-based ambient doses and time-activity patterns of individuals. Moreover, the results provide important information for predicting future cumulative doses after the return of residents to evacuation order areas in Fukushima.

Relationship between Individual External Doses, Ambient Dose Rates and Individuals’ Activity-Patterns in Affected Areas in Fukushima following the Fukushima Daiichi Nuclear Power Plant Accident

PubMed Central

Kurosawa, Tadahiro; Yasutaka, Tetsuo; Ishii, Hideki

2016-01-01

The accident at Fukushima Daiichi Nuclear Power Plant on March 11, 2011, released radioactive material into the atmosphere and contaminated the land in Fukushima and several neighboring prefectures. Five years after the nuclear disaster, the radiation levels have greatly decreased due to physical decay, weathering, and decontamination operations in Fukushima. The populations of 12 communities were forced to evacuate after the accident; as of March 2016, the evacuation order has been lifted in only a limited area, and permanent habitation is still prohibited in most of the areas. In order for the government to lift the evacuation order and for individuals to return to their original residential areas, it is important to assess current and future realistic individual external doses. Here, we used personal dosimeters along with the Global Positioning System and Geographic Information System to understand realistic individual external doses and to relate individual external doses, ambient doses, and activity-patterns of individuals in the affected areas in Fukushima. The results showed that the additional individual external doses were well correlated to the additional ambient doses based on the airborne monitoring survey. The results of linear regression analysis suggested that the additional individual external doses were on average about one-fifth that of the additional ambient doses. The reduction factors, which are defined as the ratios of the additional individual external doses to the additional ambient doses, were calculated to be on average 0.14 and 0.32 for time spent at home and outdoors, respectively. Analysis of the contribution of various activity patterns to the total individual external dose demonstrated good agreement with the average fraction of time spent daily in each activity, but the contribution due to being outdoors varied widely. These results are a valuable contribution to understanding realistic individual external doses and the corresponding airborne monitoring-based ambient doses and time-activity patterns of individuals. Moreover, the results provide important information for predicting future cumulative doses after the return of residents to evacuation order areas in Fukushima. PMID:27494021

Transcriptomic Dose-Response Analysis for Mode of Action ...

EPA Pesticide Factsheets

Microarray and RNA-seq technologies can play an important role in assessing the health risks associated with environmental exposures. The utility of gene expression data to predict hazard has been well documented. Early toxicogenomics studies used relatively high, single doses with minimal replication. Thus, they were not useful in understanding health risks at environmentally-relevant doses. Until the past decade, application of toxicogenomics in dose response assessment and determination of chemical mode of action has been limited. New transcriptomic biomarkers have evolved to detect chemical hazards in multiple tissues together with pathway methods to study biological effects across the full dose response range and critical time course. Comprehensive low dose datasets are now available and with the use of transcriptomic benchmark dose estimation techniques within a mode of action framework, the ability to incorporate informative genomic data into human health risk assessment has substantially improved. The key advantage to applying transcriptomic technology to risk assessment is both the sensitivity and comprehensive examination of direct and indirect molecular changes that lead to adverse outcomes. Book Chapter with topic on future application of toxicogenomics technologies for MoA and risk assessment

SU-E-T-317: The Development of a DIBH Technique for Left Sided Breast Patients Undergoing Radiation Therapy Utilizing Varians RPM System in a Community Hospital

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

Hasson, B; Young, M; Workie, D

2014-06-01

Purpose: To develop and implement a Deep Inhalation Breath Hold program (DIBH) for treatment of patients with Left-sided breast cancer in a community hospital. Methods: All patients with left sided breast cancer underwent a screening free breathing CT. Evaluation of the conventional tangent treatment fields and the heart was conducted. If the heart would not be excluded using tangents, the patient then received DIBH breathe coaching. The patients returned for a 4D CT simulation. The patients breathing cycle was monitored using the Varian Real-Time position ManagementTM (RPM) system to assess duration of DIBH, amplitude, phase and recovery time to normalmore » breathing. Then a DIBH CT was obtained at the desired amplitude. Duplicate plans were developed for both free breathing and DIBH on the Eclipse planning system and comparison DVH's were created. The plan that provided the prescribed treatment coverage and the least doses to the OAR (heart, Lt. Lung) was determined. Those patients selected to receive treatment with DIBH were set up for treatment, and breathing was monitored using the RPM system. Practice trials were used to confirm that the amplitude, phase and recovery were consistent with findings from simulation. Results: 10 patients have been treated using the DIBH procedure in our clinic. The DIBH patients had an average increase of 80% lung volume on DIBH, decreased lung volume receiving 50% of the dose, and decreases in the V20 dose. Significant reduction in the maximum and mean dose to the heart, as well as the dose to 1CC of the volume for the DIBH plans. Conclusion: Using the RPM system already available in the clinic, staff training, and patient coaching a simple DIBH program was setup. The use of DIBH has shown promise in reducing doses to the critical organs while maintaining PTV coverage for left sided breast treatments.« less

Gafchromic EBT‐XD film: Dosimetry characterization in high‐dose, volumetric‐modulated arc therapy

PubMed Central

Ozawa, Shuichi; Hosono, Fumika; Sumida, Naoki; Okazue, Toshiya; Yamada, Kiyoshi; Nagata, Yasushi

2016-01-01

Radiochromic films are important tools for assessing complex dose distributions. Gafchromic EBT‐XD films have been designed for optimal performance in the 40–4,000 cGy dose range. We investigated the dosimetric characteristics of these films, including their dose‐response, postexposure density growth, and dependence on scanner orientation, beam energy, and dose rate with applications to high‐dose volumetric‐modulated arc therapy (VMAT) verification. A 10 MV beam from a TrueBeam STx linear accelerator was used to irradiate the films with doses in the 0–4,000 cGy range. Postexposure coloration was analyzed at postirradiation times ranging from several minutes to 48 h. The films were also irradiated with 6 MV (dose rate (DR): 600 MU/min), 6 MV flattening filter‐free (FFF) (DR: 1,400 MU/ min), and 10 MV FFF (DR: 2,400 MU/min) beams to determine the energy and dose‐rate dependence. For clinical examinations, we compared the dose distribution measured with EBT‐XD films and calculated by the planning system for four VMAT cases. The red channel of the EBT‐XD film exhibited a wider dynamic range than the green and blue channels. Scanner orientation yielded a variation of ∼3% in the net optical density (OD). The difference between the film front and back scan orientations was negligible, with variation of ∼1.3% in the net OD. The net OD increased sharply within the first 6 hrs after irradiation and gradually afterwards. No significant difference was observed for the beam energy and dose rate, with a variation of ∼1.5% in the net OD. The gamma passing rates (at 3%, 3 mm) between the film‐ measured and treatment planning system (TPS)‐calculated dose distributions under a high dose VMAT plan in the absolute dose mode were more than 98.9%. PACS number(s): 87.56 Fc PMID:27929504

An assessment of a 3D EPID-based dosimetry system using conventional two- and three-dimensional detectors for VMAT.

PubMed

Stevens, S; Dvorak, P; Spevacek, V; Pilarova, K; Bray-Parry, M; Gesner, J; Richmond, A

2018-01-01

To provide a 3D dosimetric evaluation of a commercial portal dosimetry system using 2D/3D detectors under ideal conditions using VMAT. A 2D ion chamber array, radiochromic film and gel dosimeter were utilised to provide a dosimetric evaluation of transit phantom and pre-treatment 'fluence' EPID back-projected dose distributions for a standard VMAT plan. In-house 2D and 3D gamma methods compared pass statistics relative to each dosimeter and TPS dose distributions. Fluence mode and transit EPID dose distributions back-projected onto phantom geometry produced 2D gamma pass rates in excess of 97% relative to other tested detectors and exported TPS dose planes when a 3%, 3 mm global gamma criterion was applied. Use of a gel dosimeter within a glass vial allowed comparison of measured 3D dose distributions versus EPID 3D dose and TPS calculated distributions. 3D gamma comparisons between modalities at 3%, 3 mm gave pass rates in excess of 92%. Use of fluence mode was indicative of transit results under ideal conditions with slightly reduced dose definition. 3D EPID back projected dose distributions were validated against detectors in both 2D and 3D. Cross validation of transit dose delivered to a patient is limited due to reasons of practicality and the tests presented are recommended as a guideline for 3D EPID dosimetry commissioning; allowing direct comparison between detector, TPS, fluence and transit modes. The results indicate achievable gamma scores for a complex VMAT plan in a homogenous phantom geometry and contributes to growing experience of 3D EPID dosimetry. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Spot scanning proton therapy plan assessment: design and development of a dose verification application for use in routine clinical practice

NASA Astrophysics Data System (ADS)

Augustine, Kurt E.; Walsh, Timothy J.; Beltran, Chris J.; Stoker, Joshua B.; Mundy, Daniel W.; Parry, Mark D.; Bues, Martin; Fatyga, Mirek

2016-04-01

The use of radiation therapy for the treatment of cancer has been carried out clinically since the late 1800's. Early on however, it was discovered that a radiation dose sufficient to destroy cancer cells can also cause severe injury to surrounding healthy tissue. Radiation oncologists continually strive to find the perfect balance between a dose high enough to destroy the cancer and one that avoids damage to healthy organs. Spot scanning or "pencil beam" proton radiotherapy offers another option to improve on this. Unlike traditional photon therapy, proton beams stop in the target tissue, thus better sparing all organs beyond the targeted tumor. In addition, the beams are far narrower and thus can be more precisely "painted" onto the tumor, avoiding exposure to surrounding healthy tissue. To safely treat patients with proton beam radiotherapy, dose verification should be carried out for each plan prior to treatment. Proton dose verification systems are not currently commercially available so the Department of Radiation Oncology at the Mayo Clinic developed its own, called DOSeCHECK, which offers two distinct dose simulation methods: GPU-based Monte Carlo and CPU-based analytical. The three major components of the system include the web-based user interface, the Linux-based dose verification simulation engines, and the supporting services and components. The architecture integrates multiple applications, libraries, platforms, programming languages, and communication protocols and was successfully deployed in time for Mayo Clinic's first proton beam therapy patient. Having a simple, efficient application for dose verification greatly reduces staff workload and provides additional quality assurance, ultimately improving patient safety.

Calculation of Organ Doses for a Large Number of Patients Undergoing CT Examinations.

PubMed

Bahadori, Amir; Miglioretti, Diana; Kruger, Randell; Flynn, Michael; Weinmann, Sheila; Smith-Bindman, Rebecca; Lee, Choonsik

2015-10-01

The objective of our study was to develop an automated calculation method to provide organ dose assessment for a large cohort of pediatric and adult patients undergoing CT examinations. We adopted two dose libraries that were previously published: the volume CT dose index-normalized organ dose library and the tube current-exposure time product (100 mAs)-normalized weighted CT dose index library. We developed an algorithm to calculate organ doses using the two dose libraries and the CT parameters available from DICOM data. We calculated organ doses for pediatric (n = 2499) and adult (n = 2043) CT examinations randomly selected from four health care systems in the United States and compared the adult organ doses with the values calculated from the ImPACT calculator. The median brain dose was 20 mGy (pediatric) and 24 mGy (adult), and the brain dose was greater than 40 mGy for 11% (pediatric) and 18% (adult) of the head CT studies. Both the National Cancer Institute (NCI) and ImPACT methods provided similar organ doses (median discrepancy < 20%) for all organs except the organs located close to the scanning boundaries. The visual comparisons of scanning coverage and phantom anatomies revealed that the NCI method, which is based on realistic computational phantoms, provides more accurate organ doses than the ImPACT method. The automated organ dose calculation method developed in this study reduces the time needed to calculate doses for a large number of patients. We have successfully used this method for a variety of CT-related studies including retrospective epidemiologic studies and CT dose trend analysis studies.

Compliance assessed by the Medication Event Monitoring System.

PubMed Central

Olivieri, N F; Matsui, D; Hermann, C; Koren, G

1991-01-01

The accurate assessment of patient compliance is especially crucial in evaluating the efficacy of a new treatment. Because of the problems associated with parenteral desferrioxamine, the development of a safe, effective, and convenient iron chelator is of high priority. The high morbidity and mortality associated with iron overload requires careful evaluation of the ability of any new agent to promote long term effective iron chelation. Patients' compliance with an orally available chelating agent, 1,2,-dimethyl-3-hydroxypyrid-4-one (L1), that has been demonstrated to induce in vivo iron excretion equivalent to that of desferrioxamine during supervised short term administration, was examined. Compliance was assessed in seven patients by patient interview, by daily diaries reviewed monthly with each patient, and with the use of the Medication Event Monitoring System (MEMS) standard pill bottles with microprocessors in the cap that record the timing and frequency of bottle openings. L1 was dispensed in MEMS containers to the patients, who, unaware of their significance, recorded compliance using a daily diary. Overall compliance rate (% of prescribed doses taken) measured by MEMS was 88.7 +/- 6.8%. When 'doubling of doses' was accounted for, significantly poorer compliance with L1 was noted by MEMS (91.7 +/- 7.4%) than by patients' diaries (95.7 +/- 5.2%). There was no significant difference in patient compliance recorded between the first and last 30 day period of drug administration. MEMS can eliminate the confounding variable of erratic patient compliance in the evaluation of a new drug's efficacy. As MEMS cannot distinguish a missed dose from one doubled at the next bottle opening, the use of patient diaries is a useful adjunct to the accurate assessment of compliance and should be combined with the use of MEMS. PMID:1776885

The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 1. The Russell-Muller debate

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

Calabrese, Edward J., E-mail: edwardc@schoolph.uma

This paper assesses the discovery of the dose-rate effect in radiation genetics and how it challenged fundamental tenets of the linear non-threshold (LNT) dose response model, including the assumptions that all mutational damage is cumulative and irreversible and that the dose-response is linear at low doses. Newly uncovered historical information also describes how a key 1964 report by the International Commission for Radiological Protection (ICRP) addressed the effects of dose rate in the assessment of genetic risk. This unique story involves assessments by two leading radiation geneticists, Hermann J. Muller and William L. Russell, who independently argued that the report'smore » Genetic Summary Section on dose rate was incorrect while simultaneously offering vastly different views as to what the report's summary should have contained. This paper reveals occurrences of scientific disagreements, how conflicts were resolved, which view(s) prevailed and why. During this process the Nobel Laureate, Muller, provided incorrect information to the ICRP in what appears to have been an attempt to manipulate the decision-making process and to prevent the dose-rate concept from being adopted into risk assessment practices. - Highlights: • The discovery of radiation dose rate challenged the scientific basis of LNT. • Radiation dose rate occurred in males and females. • The dose rate concept supported a threshold dose-response for radiation.« less

Assessment of the dose reduction potential of a model-based iterative reconstruction algorithm using a task-based performance metrology

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

Samei, Ehsan, E-mail: samei@duke.edu; Richard, Samuel

2015-01-15

Purpose: Different computed tomography (CT) reconstruction techniques offer different image quality attributes of resolution and noise, challenging the ability to compare their dose reduction potential against each other. The purpose of this study was to evaluate and compare the task-based imaging performance of CT systems to enable the assessment of the dose performance of a model-based iterative reconstruction (MBIR) to that of an adaptive statistical iterative reconstruction (ASIR) and a filtered back projection (FBP) technique. Methods: The ACR CT phantom (model 464) was imaged across a wide range of mA setting on a 64-slice CT scanner (GE Discovery CT750 HD,more » Waukesha, WI). Based on previous work, the resolution was evaluated in terms of a task-based modulation transfer function (MTF) using a circular-edge technique and images from the contrast inserts located in the ACR phantom. Noise performance was assessed in terms of the noise-power spectrum (NPS) measured from the uniform section of the phantom. The task-based MTF and NPS were combined with a task function to yield a task-based estimate of imaging performance, the detectability index (d′). The detectability index was computed as a function of dose for two imaging tasks corresponding to the detection of a relatively small and a relatively large feature (1.5 and 25 mm, respectively). The performance of MBIR in terms of the d′ was compared with that of ASIR and FBP to assess its dose reduction potential. Results: Results indicated that MBIR exhibits a variability spatial resolution with respect to object contrast and noise while significantly reducing image noise. The NPS measurements for MBIR indicated a noise texture with a low-pass quality compared to the typical midpass noise found in FBP-based CT images. At comparable dose, the d′ for MBIR was higher than those of FBP and ASIR by at least 61% and 19% for the small feature and the large feature tasks, respectively. Compared to FBP and ASIR, MBIR indicated a 46%–84% dose reduction potential, depending on task, without compromising the modeled detection performance. Conclusions: The presented methodology based on ACR phantom measurements extends current possibilities for the assessment of CT image quality under the complex resolution and noise characteristics exhibited with statistical and iterative reconstruction algorithms. The findings further suggest that MBIR can potentially make better use of the projections data to reduce CT dose by approximately a factor of 2. Alternatively, if the dose held unchanged, it can improve image quality by different levels for different tasks.« less

Comparative Iron Oxide Nanoparticle Cellular Dosimetry and Response in Mice by the Inhalation and Liquid Cell Culture Exposure Routes

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

Teeguarden, Justin G.; Mikheev, Vladimir B.; Minard, Kevin R.

testing the rapidly growing number of nanomaterials requires large scale use of in vitro systems under the presumption that these systems are sufficiently predictive or descriptive of responses in in vivo systems for effective use in hazard ranking. We hypothesized that improved relationships between in vitro and in vivo models of experimental toxicology for nanomaterials would result from placing response data in vitro and in vivo on the same dose scale, the amount of material associated with cells (target cell dose). Methods: Balb/c mice were exposed nose-only to an aerosol of 12.8 nm (68.6 nm CMD, 19.9 mg/m3, 4 hours)more » super paramagnetic iron oxide particles, target cell doses were calculated and biomarkers of response anchored with histological evidence were identified by global transcriptomics. Representative murine epithelial and macrophage cell types were exposed in vitro to the same material in liquid suspension for four hours and levels nanoparticle regulated cytokine transcripts identified in vivo were quantified as a function of measured nanoparticle cellular dose. Results. Target tissue doses of 0.009-0.4 μg SPIO/cm2 lung led to an inflammatory response in the alveolar region characterized by interstitial inflammation and macrophage infiltration. In vitro, higher target tissue doses of ~1.2-4 μg SPIO/ cm2 of cells were required to induce transcriptional regulation of markers of inflammation, CXCL2 CCL3, in C10 lung epithelial cells. Estimated in vivo macrophage SPIO nanoparticle doses ranged from 1-100 pg/cell, and induction of inflammatory markers was observed in vitro in macrophages at doses of 8-35 pg/cell. Conclusions: Application of target tissue dosimetry revealed good correspondence between target cell doses triggering inflammatory processes in vitro and in vivo in the alveolar macrophage population, but not in the epithelial cells of the alveolar region. These findings demonstrate the potential for target tissue dosimetry to enable the more quantitative comparison of in vitro and in vivo systems advance their use for hazard assessment and extrapolation to humans. The mildly inflammogentic cellular doses experienced by mice were similar those calculated for humans exposed to the same at the existing permissible exposure limit of 10 mg/m3 iron oxide (as Fe).« less

Heart Rate Variability (HRV) modifications in adult hemiplegic patients after botulinum toxin type A (nt-201) injection.

PubMed

Invernizzi, M; Carda, S; Molinari, C; Stagno, D; Cisari, C; Baricich, A

2015-08-01

The most important adverse effect of BoNT-A is the systemic diffusion of the toxin. There is some evidence that the administration of high doses can increase the risk of systemic diffusion and the development of clinically evident adverse effects, however an international consensus does not exist about its maximum dose. The aim of this study was to evaluate changes in autonomic heart drive induced by high doses (higher than 600 units) of incobotulinumtoxinA injection in spastic stroke patients. Moreover, the treatment safety by monitoring adverse events occurrence was assessed. Case control study. Eleven stroke survivors with spastic hemiplegia. Patients were treated with intramuscular focal injections of IncobotulinumtoxinA (NT 201; Xeomin®, Merz Pharmaceuticals GmbH, Frankfurt, Germany). Doses were below 12 units/Kg. Each patient underwent an ECG recording before injection and 10 days after treatment. Linear and non-linear Heart Rate variability (HRV) measures were derived from ECGs with a dedicated software. None of the variable considered showed statistically significant changes after BoNT-A injection. The use of incobotulinumtoxinA in adult patients at doses up to 12 units/kg seems to be safe regarding autonomic heart drive. The use of IncobotulinumtoxinA up to 600 units could be a safe therapeutic option in spastic hemiplegic stroke survivors.

10 CFR 20.1003 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... assessment of dose equivalent by the use of devices designed to be worn by an individual; (2) The assessment... equipment) means devices designed to be worn by a single individual for the assessment of dose equivalent... radionuclide in a year by the reference man that would result in a committed effective dose equivalent of 5...

10 CFR 20.1003 - Definitions.

Code of Federal Regulations, 2012 CFR

2012-01-01

... assessment of dose equivalent by the use of devices designed to be worn by an individual; (2) The assessment... equipment) means devices designed to be worn by a single individual for the assessment of dose equivalent... radionuclide in a year by the reference man that would result in a committed effective dose equivalent of 5...

10 CFR 20.1003 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-01-01

... assessment of dose equivalent by the use of devices designed to be worn by an individual; (2) The assessment... equipment) means devices designed to be worn by a single individual for the assessment of dose equivalent... radionuclide in a year by the reference man that would result in a committed effective dose equivalent of 5...

10 CFR 20.1003 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... assessment of dose equivalent by the use of devices designed to be worn by an individual; (2) The assessment... equipment) means devices designed to be worn by a single individual for the assessment of dose equivalent... radionuclide in a year by the reference man that would result in a committed effective dose equivalent of 5...

10 CFR 20.1003 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-01-01

... assessment of dose equivalent by the use of devices designed to be worn by an individual; (2) The assessment... equipment) means devices designed to be worn by a single individual for the assessment of dose equivalent... radionuclide in a year by the reference man that would result in a committed effective dose equivalent of 5...

Image quality improvement in megavoltage cone beam CT using an imaging beam line and a sintered pixelated array system

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

Breitbach, Elizabeth K.; Maltz, Jonathan S.; Gangadharan, Bijumon

2011-11-15

Purpose: To quantify the improvement in megavoltage cone beam computed tomography (MVCBCT) image quality enabled by the combination of a 4.2 MV imaging beam line (IBL) with a carbon electron target and a detector system equipped with a novel sintered pixelated array (SPA) of translucent Gd{sub 2}O{sub 2}S ceramic scintillator. Clinical MVCBCT images are traditionally acquired with the same 6 MV treatment beam line (TBL) that is used for cancer treatment, a standard amorphous Si (a-Si) flat panel imager, and the Kodak Lanex Fast-B (LFB) scintillator. The IBL produces a greater fluence of keV-range photons than the TBL, to whichmore » the detector response is more optimal, and the SPA is a more efficient scintillator than the LFB. Methods: A prototype IBL + SPA system was installed on a Siemens Oncor linear accelerator equipped with the MVision{sup TM} image guided radiation therapy (IGRT) system. A SPA strip consisting of four neighboring tiles and measuring 40 cm by 10.96 cm in the crossplane and inplane directions, respectively, was installed in the flat panel imager. Head- and pelvis-sized phantom images were acquired at doses ranging from 3 to 60 cGy with three MVCBCT configurations: TBL + LFB, IBL + LFB, and IBL + SPA. Phantom image quality at each dose was quantified using the contrast-to-noise ratio (CNR) and modulation transfer function (MTF) metrics. Head and neck, thoracic, and pelvic (prostate) cancer patients were imaged with the three imaging system configurations at multiple doses ranging from 3 to 15 cGy. The systems were assessed qualitatively from the patient image data. Results: For head and neck and pelvis-sized phantom images, imaging doses of 3 cGy or greater, and relative electron densities of 1.09 and 1.48, the CNR average improvement factors for imaging system change of TBL + LFB to IBL + LFB, IBL + LFB to IBL + SPA, and TBL + LFB to IBL + SPA were 1.63 (p < 10{sup -8}), 1.64 (p < 10{sup -13}), 2.66 (p < 10{sup -9}), respectively. For all imaging doses, soft tissue contrast was more easily differentiated on IBL + SPA head and neck and pelvic images than TBL + LFB and IBL + LFB. IBL + SPA thoracic images were comparable to IBL + LFB images, but less noisy than TBL + LFB images at all imaging doses considered. The mean MTFs over all imaging doses were comparable, at within 3%, for all imaging system configurations for both the head- and pelvis-sized phantoms. Conclusions: Since CNR scales with the square root of imaging dose, changing from TBL + LFB to IBL + LFB and IBL + LFB to IBL + SPA reduces the imaging dose required to obtain a given CNR by factors of 0.38 and 0.37, respectively. MTFs were comparable between imaging system configurations. IBL + SPA patient image quality was always better than that of the TBL + LFB system and as good as or better than that of the IBL + LFB system, for a given dose.« less

Practical applications of internal dose calculations

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

Carbaugh, E.H.

1994-06-01

Accurate estimates of intake magnitude and internal dose are the goal for any assessment of an actual intake of radioactivity. When only one datum is available on which to base estimates, the choices for internal dose assessment become straight-forward: apply the appropriate retention or excretion function, calculate the intake, and calculate the dose. The difficulty comes when multiple data and different types of data become available. Then practical decisions must be made on how to interpret conflicting data, or how to adjust the assumptions and techniques underlying internal dose assessments to give results consistent with the data. This article describesmore » nine types of adjustments which can be incorporated into calculations of intake and internal dose, and then offers several practical insights to dealing with some real-world internal dose puzzles.« less

Sensitivity and specificity of dosing alerts for dosing errors among hospitalized pediatric patients

PubMed Central

Stultz, Jeremy S; Porter, Kyle; Nahata, Milap C

2014-01-01

Objectives To determine the sensitivity and specificity of a dosing alert system for dosing errors and to compare the sensitivity of a proprietary system with and without institutional customization at a pediatric hospital. Methods A retrospective analysis of medication orders, orders causing dosing alerts, reported adverse drug events, and dosing errors during July, 2011 was conducted. Dosing errors with and without alerts were identified and the sensitivity of the system with and without customization was compared. Results There were 47 181 inpatient pediatric orders during the studied period; 257 dosing errors were identified (0.54%). The sensitivity of the system for identifying dosing errors was 54.1% (95% CI 47.8% to 60.3%) if customization had not occurred and increased to 60.3% (CI 54.0% to 66.3%) with customization (p=0.02). The sensitivity of the system for underdoses was 49.6% without customization and 60.3% with customization (p=0.01). Specificity of the customized system for dosing errors was 96.2% (CI 96.0% to 96.3%) with a positive predictive value of 8.0% (CI 6.8% to 9.3). All dosing errors had an alert over-ridden by the prescriber and 40.6% of dosing errors with alerts were administered to the patient. The lack of indication-specific dose ranges was the most common reason why an alert did not occur for a dosing error. Discussion Advances in dosing alert systems should aim to improve the sensitivity and positive predictive value of the system for dosing errors. Conclusions The dosing alert system had a low sensitivity and positive predictive value for dosing errors, but might have prevented dosing errors from reaching patients. Customization increased the sensitivity of the system for dosing errors. PMID:24496386

BIOACCUMULATION OF POPS IN FISH AND ESTIMATION OF HUMAN DIETARY EXPOSURE AND DOSE

EPA Science Inventory

The risk assessment process is fundamental in understanding and controlling environmental health risks. Risk assessment includes four steps: hazard identification, dose-response assessment, exposure assessment, and risk characterization. Exposure assessments seek to characteriz...

IRIS Toxicological Review of 1,4-Dioxane (with Inhalation Update) (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of 1,4-Dioxane (with inhalation update) that when finalized will appear on the Integrated Risk Information System (IRIS) database.

IRIS Toxicological Review of 2-Hexanone (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review of the scientific basis supporting the human health hazard and dose-response assessment of 2-hexanone that will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that science is used credibly and appro...

DOSE RESPONSE DEETERMINATION OF NMDA ANTAGONISTS AND GABA AGONIST ON SUSTAINED ATTENTION.

EPA Science Inventory

We have shown that acute inhalation of toluene impairs sustained attention as assessed with a visual signal detection task (SDT). In vitro studies indicate that the NMDA and GABA systems are primary targets of anesthetic agents and organic solvents such as toluene. Pharmacologica...

IRIS Toxicological Review of Ethyl Tertiary Butyl Ether (ETBE) (External Review Draft, 2009)

EPA Science Inventory

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of ethyl tertiary butyl ether (ETBE) that when finalized will appear on the Integrated Risk Information System (IRIS) database.

MO-FG-CAMPUS-TeP1-01: An Efficient Method of 3D Patient Dose Reconstruction Based On EPID Measurements for Pre-Treatment Patient Specific QA

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

David, R; Lee, C; Calvary Mater Newcastle, Newcastle

Purpose: To demonstrate an efficient and clinically relevant patient specific QA method by reconstructing 3D patient dose from 2D EPID images for IMRT plans. Also to determine the usefulness of 2D QA metrics when assessing 3D patient dose deviations. Methods: Using the method developed by King et al (Med Phys 39(5),2839–2847), EPID images of IMRT fields were acquired in air and converted to dose at 10 cm depth (SAD setup) in a flat virtual water phantom. Each EPID measured dose map was then divided by the corresponding treatment planning system (TPS) dose map calculated with an identical setup, to derivemore » a 2D “error matrix”. For each field, the error matrix was used to adjust the doses along the respective ray lines in the original patient 3D dose. All field doses were combined to derive a reconstructed 3D patient dose for quantitative analysis. A software tool was developed to efficiently implement the entire process and was tested with a variety of IMRT plans for 2D (virtual flat phantom) and 3D (in-patient) QA analysis. Results: The method was tested on 60 IMRT plans. The mean (± standard deviation) 2D gamma (2%,2mm) pass rate (2D-GPR) was 97.4±3.0% and the mean 2D gamma index (2D-GI) was 0.35±0.06. The 3D PTV mean dose deviation was 1.8±0.8%. The analysis showed very weak correlations between both the 2D-GPR and 2D-GI when compared with PTV mean dose deviations (R2=0.3561 and 0.3632 respectively). Conclusion: Our method efficiently calculates 3D patient dose from 2D EPID images, utilising all of the advantages of an EPID-based dosimetry system. In this study, the 2D QA metrics did not predict the 3D patient dose deviation. This tool allows reporting of the 3D volumetric dose parameters thus providing more clinically relevant patient specific QA.« less

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

Individualized texting for adherence building (iTAB): improving antiretroviral dose timing among HIV-infected persons with co-occurring bipolar disorder.

PubMed

Moore, David J; Poquette, Amelia; Casaletto, Kaitlin B; Gouaux, Ben; Montoya, Jessica L; Posada, Carolina; Rooney, Alexandra S; Badiee, Jayraan; Deutsch, Reena; Letendre, Scott L; Depp, Colin A; Grant, Igor; Atkinson, J Hampton

2015-03-01

HIV+ persons with co-occurring bipolar disorder (HIV+/BD+) have elevated rates of medication nonadherence. We conducted a 30-day randomized controlled trial of a two-way, text messaging system, iTAB (n = 25), compared to an active comparison (CTRL) (n = 25) to improve antiretroviral (ARV) and psychotropic (PSY) adherence and dose timing. Both groups received medication adherence psychoeducation and daily texts assessing mood. The iTAB group additionally received personalized medication reminder texts. Participants responded to over 90 % of the mood and adherence text messages. Mean adherence, as assessed via electronic monitoring caps, was high and comparable between groups for both ARV (iTAB 86.2 % vs. CTRL 84.8 %; p = 0.95, Cliff's d = 0.01) and PSY (iTAB 78.9 % vs. CTRL 77.3 %; p = 0.43, Cliff's d = -0.13) medications. However, iTAB participants took ARVs significantly closer to their intended dosing time than CTRL participants (iTAB: 27.8 vs. CTRL: 77.0 min from target time; p = 0.02, Cliff's d = 0.37). There was no group difference on PSY dose timing. Text messaging interventions may represent a low-burden approach to improving timeliness of medication-taking behaviors among difficult-to-treat populations. The benefits of improved dose timing for long-term medication adherence require additional investigation.

Individualized Texting for Adherence Building (iTAB): Improving Antiretroviral Dose Timing Among HIV-Infected Persons with Co-occurring Bipolar Disorder

PubMed Central

Poquette, Amelia; Casaletto, Kaitlin B.; Gouaux, Ben; Montoya, Jessica L.; Posada, Carolina; Rooney, Alexandra S.; Badiee, Jayraan; Deutsch, Reena; Letendre, Scott L.; Depp, Colin A.; Grant, Igor; Atkinson, J. Hampton

2015-01-01

HIV+ persons with co-occurring bipolar disorder (HIV+/BD+) have elevated rates of medication nonadherence. We conducted a 30-day randomized controlled trial of a two-way, text messaging system, iTAB (n = 25), compared to an active comparison (CTRL) (n = 25) to improve antiretroviral (ARV) and psychotropic (PSY) adherence and dose timing. Both groups received medication adherence psychoeducation and daily texts assessing mood. The iTAB group additionally received personalized medication reminder texts. Participants responded to over 90 % of the mood and adherence text messages. Mean adherence, as assessed via electronic monitoring caps, was high and comparable between groups for both ARV (iTAB 86.2 % vs. CTRL 84.8 %; p = 0.95, Cliff’s d = 0.01) and PSY (iTAB 78.9 % vs. CTRL 77.3 %; p = 0.43, Cliff’s d = −0.13) medications. However, iTAB participants took ARVs significantly closer to their intended dosing time than CTRL participants (iTAB: 27.8 vs. CTRL: 77.0 min from target time; p = 0.02, Cliff’s d = 0.37). There was no group difference on PSY dose timing. Text messaging interventions may represent a low-burden approach to improving timeliness of medication-taking behaviors among difficult-to-treat populations. The benefits of improved dose timing for long-term medication adherence require additional investigation. PMID:25504449

Development of Safety Assessment Code for Decommissioning of Nuclear Facilities

NASA Astrophysics Data System (ADS)

Shimada, Taro; Ohshima, Soichiro; Sukegawa, Takenori

A safety assessment code, DecDose, for decommissioning of nuclear facilities has been developed, based on the experiences of the decommissioning project of Japan Power Demonstration Reactor (JPDR) at Japan Atomic Energy Research Institute (currently JAEA). DecDose evaluates the annual exposure dose of the public and workers according to the progress of decommissioning, and also evaluates the public dose at accidental situations including fire and explosion. As for the public, both the internal and the external doses are calculated by considering inhalation, ingestion, direct radiation from radioactive aerosols and radioactive depositions, and skyshine radiation from waste containers. For external dose for workers, the dose rate from contaminated components and structures to be dismantled is calculated. Internal dose for workers is calculated by considering dismantling conditions, e.g. cutting speed, cutting length of the components and exhaust velocity. Estimation models for dose rate and staying time were verified by comparison with the actual external dose of workers which were acquired during JPDR decommissioning project. DecDose code is expected to contribute the safety assessment for decommissioning of nuclear facilities.

Statistical model based iterative reconstruction (MBIR) in clinical CT systems. Part II. Experimental assessment of spatial resolution performance.

PubMed

Li, Ke; Garrett, John; Ge, Yongshuai; Chen, Guang-Hong

2014-07-01

Statistical model based iterative reconstruction (MBIR) methods have been introduced to clinical CT systems and are being used in some clinical diagnostic applications. The purpose of this paper is to experimentally assess the unique spatial resolution characteristics of this nonlinear reconstruction method and identify its potential impact on the detectabilities and the associated radiation dose levels for specific imaging tasks. The thoracic section of a pediatric phantom was repeatedly scanned 50 or 100 times using a 64-slice clinical CT scanner at four different dose levels [CTDIvol =4, 8, 12, 16 (mGy)]. Both filtered backprojection (FBP) and MBIR (Veo(®), GE Healthcare, Waukesha, WI) were used for image reconstruction and results were compared with one another. Eight test objects in the phantom with contrast levels ranging from 13 to 1710 HU were used to assess spatial resolution. The axial spatial resolution was quantified with the point spread function (PSF), while the z resolution was quantified with the slice sensitivity profile. Both were measured locally on the test objects and in the image domain. The dependence of spatial resolution on contrast and dose levels was studied. The study also features a systematic investigation of the potential trade-off between spatial resolution and locally defined noise and their joint impact on the overall image quality, which was quantified by the image domain-based channelized Hotelling observer (CHO) detectability index d'. (1) The axial spatial resolution of MBIR depends on both radiation dose level and image contrast level, whereas it is supposedly independent of these two factors in FBP. The axial spatial resolution of MBIR always improved with an increasing radiation dose level and/or contrast level. (2) The axial spatial resolution of MBIR became equivalent to that of FBP at some transitional contrast level, above which MBIR demonstrated superior spatial resolution than FBP (and vice versa); the value of this transitional contrast highly depended on the dose level. (3) The PSFs of MBIR could be approximated as Gaussian functions with reasonably good accuracy. (4) Thez resolution of MBIR showed similar contrast and dose dependence. (5) Noise standard deviation assessed on the edges of objects demonstrated a trade-off with spatial resolution in MBIR. (5) When both spatial resolution and image noise were considered using the CHO analysis, MBIR led to significant improvement in the overall CT image quality for both high and low contrast detection tasks at both standard and low dose levels. Due to the intrinsic nonlinearity of the MBIR method, many well-known CT spatial resolution and noise properties have been modified. In particular, dose dependence and contrast dependence have been introduced to the spatial resolution of CT images by MBIR. The method has also introduced some novel noise-resolution trade-off not seen in traditional CT images. While the benefits of MBIR regarding the overall image quality, as demonstrated in this work, are significant, the optimal use of this method in clinical practice demands a thorough understanding of its unique physical characteristics.

Assessment of Mean Glandular Dose in Mammography System with Different Anode-Filter Combinations Using MCNP Code

PubMed Central

Gholamkar, Lida; Mowlavi, Ali Asghar; Sadeghi, Mahdi; Athari, Mitra

2016-01-01

Background X-ray mammography is one of the general methods for early detection of breast cancer. Since glandular tissue in the breast is sensitive to radiation and it increases the risk of cancer, the given dose to the patient is very important in mammography. Objectives The aim of this study was to determine the average absorbed dose of X-ray radiation in the glandular tissue of the breast during mammography examinations as well as investigating factors that influence the mean glandular dose (MGD). One of the precise methods for determination of MGD absorbed by the breast is Monte Carlo simulation method which is widely used to assess the dose. Materials and Methods We studied some different X-ray sources and exposure factors that affect the MGD. “Midi-future” digital mammography system with amorphous-selenium detector was simulated using the Monte Carlo N-particle extended (MCNPX) code. Different anode/filter combinations such as tungsten/silver (W/Ag), tungsten/rhodium (W/Rh), and rhodium/aluminium (Rh/Al) were simulated in this study. The voltage of X-ray tube ranged from 24 kV to 32 kV with 2 kV intervals and the breast phantom thickness ranged from 3 to 8 cm, and glandular fraction g varied from 10% to 100%. Results MGD was measured for different anode/filter combinations and the effects of changing tube voltage, phantom thickness, combination and glandular breast tissue on MGD were studied. As glandular g and X-ray tube voltage increased, the breast dose increased too, and the increase of breast phantom thickness led to the decrease of MGD. The obtained results for MGD were consistent with the result of Boone et al. that was previously reported. Conclusion By comparing the results, we saw that W/Rh anode/filter combination is the best choice in breast mammography imaging because of the lowest delivered dose in comparison with W/Ag and Rh/Al. Moreover, breast thickness and g value have significant effects on MGD. PMID:27895876

Pharmacodynamic and pharmacokinetic effects of the intravenous CB1 receptor agonist Org 26828 in healthy male volunteers.

PubMed

Zuurman, Lineke; Passier, Paul C C M; de Kam, Marieke L; Kleijn, Huub J; Cohen, Adam F; van Gerven, Joop M A

2010-11-01

An ideal drug for outpatient treatments under conscious sedation would have both sedative and analgesic properties. CB1/CB2 agonists are expected to have sedative, amnestic, analgesic and anti-emetic properties. The main objective of this first study in humans was to assess the sedative properties of intravenous Org 26828. In addition, pharmacokinetics, amnestic properties, postural stability, and behavioural and cardiovascular effects were studied. Midazolam intravenous 0.1 mg/kg and placebo were used as controls. The pharmacokinetic parameters (Cmax and AUC0-inf) of the main metabolite Org 26761 were proportional to dose. No effects were observed after doses up to 0.3 μg/kg of Org 26828. Dose-related effects were observed at higher doses. Although subjects reported subjective sedation after administration of Org 26828 at 3 and 6 μg/kg, the observed sedation was considerably less than after midazolam. Doses higher than the maximum tolerated dose of 1 μg/kg of Org 26828 caused unpleasant central nervous system effects (anxiety, paranoia, hallucinations). Therefore, Org 26828 is not suitable for providing sedation for outpatient surgical procedures.

Implementing Toxicity Testing in the 21st Century (TT21C): Making safety decisions using toxicity pathways, and progress in a prototype risk assessment.

PubMed

Adeleye, Yeyejide; Andersen, Melvin; Clewell, Rebecca; Davies, Michael; Dent, Matthew; Edwards, Sue; Fowler, Paul; Malcomber, Sophie; Nicol, Beate; Scott, Andrew; Scott, Sharon; Sun, Bin; Westmoreland, Carl; White, Andrew; Zhang, Qiang; Carmichael, Paul L

2015-06-05

Risk assessment methodologies in toxicology have remained largely unchanged for decades. The default approach uses high dose animal studies, together with human exposure estimates, and conservative assessment (uncertainty) factors or linear extrapolations to determine whether a specific chemical exposure is 'safe' or 'unsafe'. Although some incremental changes have appeared over the years, results from all new approaches are still judged against this process of extrapolating high-dose effects in animals to low-dose exposures in humans. The US National Research Council blueprint for change, entitled Toxicity Testing in the 21st Century: A Vision and Strategy called for a transformation of toxicity testing from a system based on high-dose studies in laboratory animals to one founded primarily on in vitro methods that evaluate changes in normal cellular signalling pathways using human-relevant cells or tissues. More recently, this concept of pathways-based approaches to risk assessment has been expanded by the description of 'Adverse Outcome Pathways' (AOPs). The question, however, has been how to translate this AOP/TT21C vision into the practical tools that will be useful to those expected to make safety decisions. We have sought to provide a practical example of how the TT21C vision can be implemented to facilitate a safety assessment for a commercial chemical without the use of animal testing. To this end, the key elements of the TT21C vision have been broken down to a set of actions that can be brought together to achieve such a safety assessment. Such components of a pathways-based risk assessment have been widely discussed, however to-date, no worked examples of the entire risk assessment process exist. In order to begin to test the process, we have taken the approach of examining a prototype toxicity pathway (DNA damage responses mediated by the p53 network) and constructing a strategy for the development of a pathway based risk assessment for a specific chemical in a case study mode. This contribution represents a 'work-in-progress' and is meant to both highlight concepts that are well-developed and identify aspects of the overall process which require additional development. To guide our understanding of what a pathways-based risk assessment could look like in practice, we chose to work on a case study chemical (quercetin) with a defined human exposure and to bring a multidisciplinary team of chemists, biologists, modellers and risk assessors to work together towards a safety assessment. Our goal was to see if the in vitro dose response for quercetin could be sufficiently understood to construct a TT21C risk assessment without recourse to rodent carcinogenicity study data. The data presented include high throughput pathway biomarkers (p-H2AX, p-ATM, p-ATR, p-Chk2, p53, p-p53, MDM2 and Wip1) and markers of cell-cycle, apoptosis and micronuclei formation, plus gene transcription in HT1080 cells. Eighteen point dose response curves were generated using flow cytometry and imaging to determine the concentrations that resulted in significant perturbation. NOELs and BMDs were compared to the output from biokinetic modelling and the potential for in vitro to in vivo extrapolation explored. A first tier risk assessment was performed comparing the total quercetin concentration in the in vitro systems with the predicted total quercetin concentration in plasma and tissues. The shortcomings of this approach and recommendations for improvement are described. This paper therefore describes the current progress in an ongoing research effort aimed at providing a pathways-based, proof-of-concept in vitro-only safety assessment for a consumer use product. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

MO-C-18A-01: Advances in Model-Based 3D Image Reconstruction

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

Chen, G; Pan, X; Stayman, J

2014-06-15

Recent years have seen the emergence of CT image reconstruction techniques that exploit physical models of the imaging system, photon statistics, and even the patient to achieve improved 3D image quality and/or reduction of radiation dose. With numerous advantages in comparison to conventional 3D filtered backprojection, such techniques bring a variety of challenges as well, including: a demanding computational load associated with sophisticated forward models and iterative optimization methods; nonlinearity and nonstationarity in image quality characteristics; a complex dependency on multiple free parameters; and the need to understand how best to incorporate prior information (including patient-specific prior images) within themore » reconstruction process. The advantages, however, are even greater – for example: improved image quality; reduced dose; robustness to noise and artifacts; task-specific reconstruction protocols; suitability to novel CT imaging platforms and noncircular orbits; and incorporation of known characteristics of the imager and patient that are conventionally discarded. This symposium features experts in 3D image reconstruction, image quality assessment, and the translation of such methods to emerging clinical applications. Dr. Chen will address novel methods for the incorporation of prior information in 3D and 4D CT reconstruction techniques. Dr. Pan will show recent advances in optimization-based reconstruction that enable potential reduction of dose and sampling requirements. Dr. Stayman will describe a “task-based imaging” approach that leverages models of the imaging system and patient in combination with a specification of the imaging task to optimize both the acquisition and reconstruction process. Dr. Samei will describe the development of methods for image quality assessment in such nonlinear reconstruction techniques and the use of these methods to characterize and optimize image quality and dose in a spectrum of clinical applications. Learning Objectives: Learn the general methodologies associated with model-based 3D image reconstruction. Learn the potential advantages in image quality and dose associated with model-based image reconstruction. Learn the challenges associated with computational load and image quality assessment for such reconstruction methods. Learn how imaging task can be incorporated as a means to drive optimal image acquisition and reconstruction techniques. Learn how model-based reconstruction methods can incorporate prior information to improve image quality, ease sampling requirements, and reduce dose.« less

Do fungi need to be included within environmental radiation protection assessment models?

PubMed

Guillén, J; Baeza, A; Beresford, N A; Wood, M D

2017-09-01

Fungi are used as biomonitors of forest ecosystems, having comparatively high uptakes of anthropogenic and naturally occurring radionuclides. However, whilst they are known to accumulate radionuclides they are not typically considered in radiological assessment tools for environmental (non-human biota) assessment. In this paper the total dose rate to fungi is estimated using the ERICA Tool, assuming different fruiting body geometries, a single ellipsoid and more complex geometries considering the different components of the fruit body and their differing radionuclide contents based upon measurement data. Anthropogenic and naturally occurring radionuclide concentrations from the Mediterranean ecosystem (Spain) were used in this assessment. The total estimated weighted dose rate was in the range 0.31-3.4 μGy/h (5 th -95 th percentile), similar to natural exposure rates reported for other wild groups. The total estimated dose was dominated by internal exposure, especially from 226 Ra and 210 Po. Differences in dose rate between complex geometries and a simple ellipsoid model were negligible. Therefore, the simple ellipsoid model is recommended to assess dose rates to fungal fruiting bodies. Fungal mycelium was also modelled assuming a long filament. Using these geometries, assessments for fungal fruiting bodies and mycelium under different scenarios (post-accident, planned release and existing exposure) were conducted, each being based on available monitoring data. The estimated total dose rate in each case was below the ERICA screening benchmark dose, except for the example post-accident existing exposure scenario (the Chernobyl Exclusion Zone) for which a dose rate in excess of 35 μGy/h was estimated for the fruiting body. Estimated mycelium dose rate in this post-accident existing exposure scenario was close to the 400 μGy/h benchmark for plants, although fungi are generally considered to be less radiosensitive than plants. Further research on appropriate mycelium geometries and their radionuclide content is required. Based on the assessments presented in this paper, there is no need to recommend that fungi should be added to the existing assessment tools and frameworks; if required some tools allow a geometry representing fungi to be created and used within a dose assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

Effect of Admission Oral Diuretic Dose on Response to Continuous versus Bolus Intravenous Diuretics in Acute Heart Failure: An Analysis from DOSE-AHF

PubMed Central

Shah, Ravi V.; McNulty, Steven; O'Connor, Christopher M.; Felker, G. Michael; Braunwald, Eugene; Givertz, Michael M.

2014-01-01

Background Results from the Diuretic Optimization Strategies in Acute Heart Failure (DOSE-AHF) study suggest that an initial continuous infusion of loop diuretics is not superior to bolus dosing with regard to clinical endpoints in AHF. We hypothesized that outpatient furosemide dose was associated with congestion and poorer renal function, and explored the hypothesis that a continuous infusion may be more effective in patients on higher outpatient diuretic doses. Methods DOSE-AHF randomized 308 patients within 24 hours of admission to high vs. low initial intravenous diuretic dose given as either a continuous infusion or bolus. We compared baseline characteristics and assessed associations between mode of administration (bolus vs. continuous) and outcomes in patients receiving high-dose (≥120 mg furosemide equivalent, n=177) versus low-dose (<120 mg furosemide equivalent, n=131) outpatient diuretics. Results Patients on higher doses of furosemide were less frequently on renin-angiotensin system inhibitors (P=.01), and had worse renal function and more advanced symptoms. There was a significant interaction between outpatient dose and mode of therapy (P=0.01) with respect to net fluid loss at 72 hours after adjusting for creatinine and intensification strategy. Admission diuretic dose was associated with an increased risk of death or rehospitalization at 60 days (adjusted HR=1.08 per 20-mg increment in dose, 95% CI 1.01–1.16, P=.03). Conclusions In acute HF, patients on higher diuretic doses have greater disease severity, and may benefit from an initial bolus strategy. PMID:23194486

Acute ethanol ingestion produces dose-dependent effects on motor behavior in the honey bee (Apis mellifera)

PubMed Central

Maze, Ian S.; Wright, Geraldine A.; Mustard, Julie A.

2006-01-01

Ethanol consumption produces characteristic behavioral states in animals that include sedation, disorientation, and disruption of motor function. Using individual honey bees, we assessed the effects of ethanol ingestion on motor function via continuous observations of their behavior. Consumption of 1 M sucrose solutions containing a range of ethanol doses lead to hemolymph ethanol levels of approximately 40 to 100 mM. Using ethanol doses in this range, we observed time and dose-dependent effects of ethanol on the percent of time our subjects spent walking, stopped, or upside down, and on the duration and frequency of bouts of behavior. The effects on grooming and flying behavior were more complex. Behavioral recovery from ethanol treatment was both time and ethanol dose dependent, occurring between 12 and 24 hr post-ingestion for low doses and at 24 to 48 hours for higher doses. Furthermore, the amount of ethanol measured in honey bee hemolymph appeared to correlate with recovery. We predict that the honey bee will prove to be an excellent model system for studying the influence of ethanol on the neural mechanisms underlying behavior. PMID:17070538

Digital radiography: optimization of image quality and dose using multi-frequency software.

PubMed

Precht, H; Gerke, O; Rosendahl, K; Tingberg, A; Waaler, D

2012-09-01

New developments in processing of digital radiographs (DR), including multi-frequency processing (MFP), allow optimization of image quality and radiation dose. This is particularly promising in children as they are believed to be more sensitive to ionizing radiation than adults. To examine whether the use of MFP software reduces the radiation dose without compromising quality at DR of the femur in 5-year-old-equivalent anthropomorphic and technical phantoms. A total of 110 images of an anthropomorphic phantom were imaged on a DR system (Canon DR with CXDI-50 C detector and MLT[S] software) and analyzed by three pediatric radiologists using Visual Grading Analysis. In addition, 3,500 images taken of a technical contrast-detail phantom (CDRAD 2.0) provide an objective image-quality assessment. Optimal image-quality was maintained at a dose reduction of 61% with MLT(S) optimized images. Even for images of diagnostic quality, MLT(S) provided a dose reduction of 88% as compared to the reference image. Software impact on image quality was found significant for dose (mAs), dynamic range dark region and frequency band. By optimizing image processing parameters, a significant dose reduction is possible without significant loss of image quality.

Investigation of the practical aspects of an additional 0.1 mm copper x-ray spectral filter for cine acquisition mode imaging in a clinical care setting.

PubMed

Fetterly, Kenneth A

2010-11-01

Minimizing the x-ray radiation dose is an important aspect of patient safety during interventional fluoroscopy procedures. This work investigates the practical aspects of an additional 0.1 mm Cu x-ray beam spectral filter applied to cine acquisition mode imaging on patient dose and image quality. Measurements were acquired using clinical interventional imaging systems. Acquisition images of Solid Water phantoms (15-40 cm) were acquired using x-ray beams with the x-ray tube inherent filtration and using an additional 0.1 mm Cu x-ray beam spectral filter. The skin entrance air kerma (dose) rate was measured and the signal difference to noise ratio (SDNR) of an iodine target embedded into the phantom was calculated to assess image quality. X-ray beam parameters were recorded and analyzed and a primary x-ray beam simulation was performed to assess additional x-ray tube burden attributable to the Cu filter. For all phantom thicknesses, the 0.1 mm Cu filter resulted in a 40% reduction in the entrance air kerma rate to the phantoms and a 9% reduction in the SDNR of the iodine phantom. The expected additional tube load required by the 0.1 mm Cu filter ranged from 11% for a 120 kVp x-ray beam to 43% for a 60 kVp beam. For these clinical systems, use of the 0.1 mm Cu filter resulted in a favorable compromise between reduced skin dose rate and image quality and increased x-ray tube burden.

Bulgarian experience in the establishment of reference dose levels and implementation of a quality control system in diagnostic radiology.

PubMed

Vassileva, J; Dimov, A; Slavchev, A; Karadjov, A

2005-01-01

Results from a Bulgarian patient dose survey in diagnostic radiology are presented. Reference levels for entrance surface dose (ESD) were 0.9 mGy for chest radiography (PA), 30 mGy for lumbar spine (Lat), 10 mGy for pelvis, 5 mGy for skull (AP), 3 mGy for skull (Lat) and 13 mGy for mammography. Quality control (QC) programmes were proposed for various areas of diagnostic radiology. Film processing QC warranted special attention. Proposed QC programmes included parameters to be tested, level of expertise needed and two action levels: remedial and suspension. Programmes were tested under clinical conditions to assess initial results and draw conclusions for further QC system development. On the basis of international experience, measurement protocols were developed for all parameters tested. QC equipment was provided as part of the PHARE project. A future problem for QC programme implementation may be the small number of medical physics experts in diagnostic radiology.

Dosimetric feasibility of real-time MRI-guided proton therapy

PubMed Central

Moteabbed, M.; Schuemann, J.; Paganetti, H.

2014-01-01

Purpose: Magnetic resonance imaging (MRI) is a prime candidate for image-guided radiotherapy. This study was designed to assess the feasibility of real-time MRI-guided proton therapy by quantifying the dosimetric effects induced by the magnetic field in patients’ plans and identifying the associated clinical consequences. Methods: Monte Carlo dose calculation was performed for nine patients of various treatment sites (lung, liver, prostate, brain, skull-base, and spine) and tissue homogeneities, in the presence of 0.5 and 1.5 T magnetic fields. Dose volume histogram (DVH) parameters such as D95, D5, and V20 as well as equivalent uniform dose were compared for the target and organs at risk, before and after applying the magnetic field. The authors further assessed whether the plans affected by clinically relevant dose distortions could be corrected independent of the planning system. Results: By comparing the resulting dose distributions and analyzing the respective DVHs, it was determined that despite the observed lateral beam deflection, for magnetic fields of up to 0.5 T, neither was the target coverage jeopardized nor was the dose to the nearby organs increased in all cases except for prostate. However, for a 1.5 T magnetic field, the dose distortions were more pronounced and of clinical concern in all cases except for spine. In such circumstances, the target was severely underdosed, as indicated by a decrease in D95 of up to 41% of the prescribed dose compared to the nominal situation (no magnetic field). Sites such as liver and spine were less affected due to higher tissue homogeneity, typically smaller beam range, and the choice of beam directions. Simulations revealed that small modifications to certain plan parameters such as beam isocenter (up to 19 mm) and gantry angle (up to 10°) are sufficient to compensate for the magnetic field-induced dose disturbances. The authors’ observations indicate that the degree of required corrections strongly depends on the beam range and direction relative to the magnetic field. This method was also applicable to more heterogeneous scenarios such as skull-base tumors. Conclusions: This study confirmed the dosimetric feasibility of real-time MRI-guided proton therapy and delivering a clinically acceptable dose to patients with various tumor locations within magnetic fields of up to 1.5 T. This work could serve as a guide and encouragement for further efforts toward clinical implementation of hybrid MRI–proton gantry systems. PMID:25370627

Dosimetric feasibility of real-time MRI-guided proton therapy

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

Moteabbed, M., E-mail: mmoteabbed@partners.org; Schuemann, J.; Paganetti, H.

2014-11-01

Purpose: Magnetic resonance imaging (MRI) is a prime candidate for image-guided radiotherapy. This study was designed to assess the feasibility of real-time MRI-guided proton therapy by quantifying the dosimetric effects induced by the magnetic field in patients’ plans and identifying the associated clinical consequences. Methods: Monte Carlo dose calculation was performed for nine patients of various treatment sites (lung, liver, prostate, brain, skull-base, and spine) and tissue homogeneities, in the presence of 0.5 and 1.5 T magnetic fields. Dose volume histogram (DVH) parameters such as D{sub 95}, D{sub 5}, and V{sub 20} as well as equivalent uniform dose were comparedmore » for the target and organs at risk, before and after applying the magnetic field. The authors further assessed whether the plans affected by clinically relevant dose distortions could be corrected independent of the planning system. Results: By comparing the resulting dose distributions and analyzing the respective DVHs, it was determined that despite the observed lateral beam deflection, for magnetic fields of up to 0.5 T, neither was the target coverage jeopardized nor was the dose to the nearby organs increased in all cases except for prostate. However, for a 1.5 T magnetic field, the dose distortions were more pronounced and of clinical concern in all cases except for spine. In such circumstances, the target was severely underdosed, as indicated by a decrease in D{sub 95} of up to 41% of the prescribed dose compared to the nominal situation (no magnetic field). Sites such as liver and spine were less affected due to higher tissue homogeneity, typically smaller beam range, and the choice of beam directions. Simulations revealed that small modifications to certain plan parameters such as beam isocenter (up to 19 mm) and gantry angle (up to 10°) are sufficient to compensate for the magnetic field-induced dose disturbances. The authors’ observations indicate that the degree of required corrections strongly depends on the beam range and direction relative to the magnetic field. This method was also applicable to more heterogeneous scenarios such as skull-base tumors. Conclusions: This study confirmed the dosimetric feasibility of real-time MRI-guided proton therapy and delivering a clinically acceptable dose to patients with various tumor locations within magnetic fields of up to 1.5 T. This work could serve as a guide and encouragement for further efforts toward clinical implementation of hybrid MRI–proton gantry systems.« less

IRIS Toxicological Review of Dibutyl Phthalate (DBP) (External Review Draft) 2006

EPA Science Inventory

The U.S. EPA has conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of dibutyl phthalate that will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that science is used cr...

Combining Toxicological and Chemical Characterization of Complex Mixtures to Understand the Impact of the Unknown Fraction

EPA Science Inventory

Toxicological assessment of adverse health outcomes associated with exposure to complex mixtures provides an integrated response of the organism (or in vitro test system) that accounts for additivity among the components (both dose and response) as well as any greater than or les...

UPDATE A COMPUTER MODEL, TITLED GENII-NESHAPS VERSION 2, FOR EVALUATING ATMOSPHERIC RELEASES OF RADIONUCLIDES.

EPA Science Inventory

The GENII System provides a state-of-the-art, fully documented set of programs for calculating radiation dose and risk from radionuclides released to the environment. The GENII-NESHAPs Edition can be utilized for assessing compliance with 40 CFR 61, Subparts H and I.

HARMONIZATION AND COMMUNICATION OF PBPK MODELS USING THE EXPOSURE RELATED DOSE ESTIMATION MODEL (ERDEM) SYSTEM: TRICHLOROETHYLENE

EPA Science Inventory

In support of the trichloroethylene (TCE) risk assessment for the Office of Air and Radiation, Office of Solid Waste and Emergency Response, and Office of Water, NERL and NCEA are developing an updated physiologically-based pharmacokinetic (PBPK) model. The PBPK modeling effort ...

HARMONIZATION AND COMMUNICATION OF PBPK MODELS USING THE EXPOSURE RELATED DOSE MODEL (ERDEM) SYSTEM: TRICHLOROETHYLENE

EPA Science Inventory

In support of the trichloroethylene (TCE) risk assessment for the Office of Air and Radiation, Office of Solid Waste and Emergency Response, and Office of Water, NERL and NCEA are developing an updated physiologically-based pharmacokinetic (PBPK) model. The PBPK modeling effor...

IRIS Toxicological Review of 1,2,3-Trichloropropane (External Review Draft)

EPA Science Inventory

EPA conducted a peer review of the scientific basis supporting the human health hazard and dose-response assessment of 1,2,3-trichloropropane (TCP) that once finalized will appear on the Integrated Risk Information System (IRIS) database. Peer review is meant to ensure that scie...

Development of a Relative Potency Factor (Rpf) Approach for Polycyclic Aromatic Hydrocarbon (PAH) Mixtures (External Review Draft)

EPA Science Inventory

EPA is conducting a peer review and public comment of the scientific basis supporting the human health hazard and dose-response assessment of polycyclic aromatic hydrocarbon (PAH) mixtures that when finalized will appear on the Integrated Risk Information System (IRIS) database. ...

QUANTIFYING ULTRAVIOLET RADIATION DOSE RELATIVE TO WETLAND HABITAT VARIABLES FOR THE ASSESSMENT OF RISK TO AMPHIBIANS

EPA Science Inventory

Ultraviolet B radiation (UV-B) has increased globally over the last several decades due to reduction of stratospheric ozone. UV-B may also increase when climate change alters cloud cover, rainfall, and distributions of vegetation. In aquatic systems, these factors can also intera...

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

EPA Science Inventory

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

Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide (Revised July 2013 External Review Draft) (Public Comment Draft)

EPA Science Inventory

EPA is initiating a public comment period prior to peer review of the scientific basis supporting the human health hazard and dose-response assessment of ethylene oxide (cancer) that will appear in the Integrated Risk Information System (IRIS) database.

Advances in In Vitro and In Silico Tools for Toxicokinetic Dose Modeling and Predictive Toxicology (WC10)

EPA Science Inventory

Recent advances in vitro assays, in silico tools, and systems biology approaches provide opportunities for refined mechanistic understanding for chemical safety assessment that will ultimately lead to reduced reliance on animal-based methods. With the U.S. commercial chemical lan...

Quality control in interstitial brachytherapy of the breast using pulsed dose rate: treatment planning and dose delivery with an Ir-192 afterloading system.

PubMed

Mangold, C A; Rijnders, A; Georg, D; Van Limbergen, E; Pötter, R; Huyskens, D

2001-01-01

In the Radiotherapy Department of Leuven, about 20% of all breast cancer patients treated with breast conserving surgery and external radiotherapy receive an additional boost with pulsed dose rate (PDR) Ir-192 brachytherapy. An investigation was performed to assess the accuracy of the delivered PDR brachytherapy treatment. Secondly, the feasibility of in vivo measurements during PDR dose delivery was investigated. Two phantoms are manufactured to mimic a breast, one for thermoluminescent dosimetry (TLD) measurements, and one for dosimetry using radiochromic films. The TLD phantom allows measurements at 34 dose points in three planes including the basal dose points. The film phantom is designed in such a way that films can be positioned in a plane parallel and orthogonal to the needles. The dose distributions calculated with the TPS are in good agreement with both TLD and radiochromic film measurements (average deviations of point doses <+/-5%). However, close to the interface tissue-air the dose is overestimated by the TPS since it neglects the finite size of a breast and the associated lack of backscatter (average deviations of point doses -14%). Most deviations between measured and calculated doses, are in the order of magnitude of the uncertainty associated with the source strength specification, except for the point doses measured close to the skin. In vivo dosimetry during PDR brachytherapy treatment was found to be a valuable procedure to detect large errors, e.g. errors caused by an incorrect data transfer.

Pharmacokinetics and pharmacodynamics of DSTA4637A: A novel THIOMAB™ antibody antibiotic conjugate against Staphylococcus aureus in mice

PubMed Central

Zhou, Chenguang; Lehar, Sophie; Gutierrez, Johnny; Rosenberger, Carrie M.; Ljumanovic, Nina; Dinoso, Jason; Koppada, Neelima; Hong, Kyu; Baruch, Amos; Saad, Ola; Mariathasan, Sanjeev; Kamath, Amrita V.

2016-01-01

ABSTRACT DSTA4637A, a novel THIOMAB™ antibody antibiotic conjugate (TAC) against Staphylococcus aureus (S. aureus), is currently being investigated as a potential therapy against S. aureus infections. Structurally, TAC is composed of an anti-S. aureus antibody linked to a potent antibiotic, dmDNA31. The goal of the current study was to characterize the pharmacokinetics (PK) of TAC in mice, assess the effect of S. aureus infection on its PK, and evaluate its pharmacodynamics (PD) by measuring the bacterial load in various organs at different timepoints following TAC treatment. Plasma concentrations of 3 analytes, total antibody (TAb), antibody-conjugated dmDNA31 (ac-dmDNA31), and unconjugated dmDNA31, were measured in these studies. In non-infected mice (target antigen absent), following intravenous (IV) administration of a single dose of TAC, systemic concentration-time profiles of both TAb and ac-dmDNA31 were bi-exponential and characterized by a short distribution phase and a long elimination phase as expected for a monoclonal antibody-based therapeutic. Systemic exposures of both TAb and ac-dmDNA31 were dose proportional over the dose range tested (5 to 50 mg/kg). In a mouse model of systemic S. aureus infection (target antigen present), a single IV dose of TAC demonstrated PK behavior similar to that in the non-infected mice, and substantially reduced bacterial load in the heart, kidney, and bones on 7 and 14 d post dosing. These findings have increased our understanding of the PK and PK/PD of this novel molecule, and have shown that at efficacious dose levels the presence of S. aureus infection had minimal effect on TAC PK. PMID:27653831

Assessment of hepatic function decline after stereotactic body radiation therapy for primary liver cancer.

PubMed

Toesca, Diego A S; Osmundson, Evan C; von Eyben, Rie; Shaffer, Jenny L; Koong, Albert C; Chang, Daniel T

This study aims to determine how the albumin-bilirubin (ALBI) score compares with the Child-Pugh (CP) score for assessing liver function following stereotactic body radiation therapy (SBRT). In total, 60 patients, 40 with hepatocellular carcinoma (HCC) and 20 with cholangiocarcinoma (CCA), were treated with SBRT. Liver function panels were obtained before and at 1, 3, 6, and 12 months after SBRT. Laboratory values were censored after locoregional recurrence, further liver-directed therapies, or liver transplant. A significant decline in hepatic function occurred after SBRT for HCC patients only (P = .001 by ALBI score; P < .0001 by CP score). By converting radiation doses to biologically equivalent doses by using a standard linear quadratic model using α/β of 10, the strongest dosimetric predictor of liver function decline for HCC was the volume of normal liver irradiated by a dose of 40 Gy when assessing liver function by the ALBI score (P = .07), and the volume of normal liver irradiated by a dose of 20 Gy by using the CP score (P= .0009). For CCA patients, the volume of normal liver irradiated by a dose of 40 Gy remained the strongest dosimetric predictor when using the ALBI score (P = .002), but no dosimetric predictor was significant using the CP score. Hepatic function decline correlated with worse overall survival for HCC (by ALBI, P = .0005; by CP, P < .0001) and for CCA (by ALBI, P = NS; by CP, P = .008). ALBI score was similarly able to predict hepatic function decline compared with CP score, and both systems correlated with survival. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

A novel adaptive needle insertion sequencing for robotic, single needle MR-guided high-dose-rate prostate brachytherapy

NASA Astrophysics Data System (ADS)

Borot de Battisti, M.; de Senneville, B. Denis; Hautvast, G.; Binnekamp, D.; Lagendijk, J. J. W.; Maenhout, M.; Moerland, M. A.

2017-05-01

MR-guided high-dose-rate (HDR) brachytherapy has gained increasing interest as a treatment for patients with localized prostate cancer because of the superior value of MRI for tumor and surrounding tissues localization. To enable needle insertion into the prostate with the patient in the MR bore, a single needle MR-compatible robotic system involving needle-by-needle dose delivery has been developed at our institution. Throughout the intervention, dose delivery may be impaired by: (1) sub-optimal needle positioning caused by e.g. needle bending, (2) intra-operative internal organ motion such as prostate rotations or swelling, or intra-procedural rectum or bladder filling. This may result in failure to reach clinical constraints. To assess the first aforementioned challenge, a recent study from our research group demonstrated that the deposited dose may be greatly improved by real-time adaptive planning with feedback on the actual needle positioning. However, the needle insertion sequence is left to the doctor and therefore, this may result in sub-optimal dose delivery. In this manuscript, a new method is proposed to determine and update automatically the needle insertion sequence. This strategy is based on the determination of the most sensitive needle track. The sensitivity of a needle track is defined as its impact on the dose distribution in case of sub-optimal positioning. A stochastic criterion is thus presented to determine each needle track sensitivity based on needle insertion simulations. To assess the proposed sequencing strategy, HDR prostate brachytherapy was simulated on 11 patients with varying number of needle insertions. Sub-optimal needle positioning was simulated at each insertion (modeled by typical random angulation errors). In 91% of the scenarios, the dose distribution improved when the needle was inserted into the most compared to the least sensitive needle track. The computation time for sequencing was less than 6 s per needle track. The proposed needle insertion sequencing can therefore assist in delivering an optimal dose in HDR prostate brachytherapy.

Treatment of Narcolepsy with Methamphetamine

PubMed Central

Miller, Merrill M.; Hajdukovic, Roza; Erman, Milton K.

2008-01-01

Summary Eight pairs of subjects (each consisting of a narcoleptic and a control matched on the basis of age, sex, educational background and job) were evaluated under the following double-blind, randomized treatment conditions: baseline, placebo, low dose and high dose methamphetamine. Subjects were drug-free for 2 weeks prior to beginning the protocol. Methamphetamine was the only drug taken during the protocol and was given in a single morning dose of 0, 20 or 40–60 mg to narcoleptics and 0, 5 or 10 mg to controls. The protocol was 28 days long, with each of the four treatment conditions lasting 4 days followed by 3 days of washout. Nighttime polysomnography and daytime testing were done during the last 24 hours of each treatment condition. Daytime sleep tendency was assessed with the multiple sleep latency test (MSLT). Daytime performance was assessed with performance tests including a simple, computer-based driving task. Narcoleptics’ mean MSLT sleep latency increased from 4.3 minutes on placebo to 9.3 minutes on high dose, compared with an increase from 10.4 to 17.1 minutes for controls. Narcoleptics’ error rate on the driving task decreased from 2.53% on placebo to 0.33% on high dose, compared with a decrease from 0.22% to 0.16% for controls. The effects of methamphetamine on nocturnal sleep were generally dose-dependent and affected sleep continuity and rapid eye movement (REM) sleep. Elimination half life was estimated to be between 15.9 and 22.0 hours. Mild side effects emerged in a dose-dependent fashion and most often involved the central nervous system and gastrointestinal tract. We concluded that methamphetamine caused a dose-dependent decrease in daytime sleep tendency and improvement in performance in both narcoleptics and controls. Methamphetamine at doses of 40–60 mg allowed narcoleptics to function at levels comparable to those of unmedicated controls. PMID:8341891

Extrapolation of systemic bioavailability assessing skin absorption and epidermal and hepatic metabolism of aromatic amine hair dyes in vitro

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

Manwaring, John, E-mail: manwaring.jd@pg.com; Rothe, Helga; Obringer, Cindy

Approaches to assess the role of absorption, metabolism and excretion of cosmetic ingredients that are based on the integration of different in vitro data are important for their safety assessment, specifically as it offers an opportunity to refine that safety assessment. In order to estimate systemic exposure (AUC) to aromatic amine hair dyes following typical product application conditions, skin penetration and epidermal and systemic metabolic conversion of the parent compound was assessed in human skin explants and human keratinocyte (HaCaT) and hepatocyte cultures. To estimate the amount of the aromatic amine that can reach the general circulation unchanged after passagemore » through the skin the following toxicokinetically relevant parameters were applied: a) Michaelis–Menten kinetics to quantify the epidermal metabolism; b) the estimated keratinocyte cell abundance in the viable epidermis; c) the skin penetration rate; d) the calculated Mean Residence Time in the viable epidermis; e) the viable epidermis thickness and f) the skin permeability coefficient. In a next step, in vitro hepatocyte K{sub m} and V{sub max} values and whole liver mass and cell abundance were used to calculate the scaled intrinsic clearance, which was combined with liver blood flow and fraction of compound unbound in the blood to give hepatic clearance. The systemic exposure in the general circulation (AUC) was extrapolated using internal dose and hepatic clearance, and C{sub max} was extrapolated (conservative overestimation) using internal dose and volume of distribution, indicating that appropriate toxicokinetic information can be generated based solely on in vitro data. For the hair dye, p-phenylenediamine, these data were found to be in the same order of magnitude as those published for human volunteers. - Highlights: • An entirely in silico/in vitro approach to predict in vivo exposure to dermally applied hair dyes • Skin penetration and epidermal conversion assessed in human skin explants and HaCaT • Systemic metabolism was modeled using hepatocyte cultures. • Toxicokinetically relevant parameters were applied to estimate systemic exposure. • There was a good agreement between in vitro and in vivo data.« less

Progress in Assessing Air Pollutant Risks from In Vitro Exposures: Matching Ozone Dose and Effect in Human Airway Cells

PubMed Central

Hatch, Gary E.; Duncan, Kelly E.; Diaz-Sanchez, David; Schmitt, Michael T.; Ghio, Andrew J.; Carraway, Martha Sue; McKee, John; Dailey, Lisa A.; Berntsen, Jon; Devlin, Robert B.

2014-01-01

In vitro exposures to air pollutants could, in theory, facilitate a rapid and detailed assessment of molecular mechanisms of toxicity. However, it is difficult to ensure that the dose of a gaseous pollutant to cells in tissue culture is similar to that of the same cells during in vivo exposure of a living person. The goal of the present study was to compare the dose and effect of O3 in airway cells of humans exposed in vivo to that of human cells exposed in vitro. Ten subjects breathed labeled O3 (18O3, 0.3 ppm, 2 h) while exercising intermittently. Bronchial brush biopsies and lung lavage fluids were collected 1 h post exposure for in vivo data whereas in vitro data were obtained from primary cultures of human bronchial epithelial cells exposed to 0.25–1.0 ppm 18O3 for 2 h. The O3 dose to the cells was defined as the level of 18O incorporation and the O3 effect as the fold increase in expression of inflammatory marker genes (IL-8 and COX-2). Dose and effect in cells removed from in vivo exposed subjects were lower than in cells exposed to the same 18O3 concentration in vitro suggesting upper airway O3 scrubbing in vivo. Cells collected by lavage as well as previous studies in monkeys show that cells deeper in the lung receive a higher O3 dose than cells in the bronchus. We conclude that the methods used herein show promise for replicating and comparing the in vivo dose and effect of O3 in an in vitro system. PMID:24928893

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

Evidence Theory Based Uncertainty Quantification in Radiological Risk due to Accidental Release of Radioactivity from a Nuclear Power Plant

NASA Astrophysics Data System (ADS)

Ingale, S. V.; Datta, D.

2010-10-01

Consequence of the accidental release of radioactivity from a nuclear power plant is assessed in terms of exposure or dose to the members of the public. Assessment of risk is routed through this dose computation. Dose computation basically depends on the basic dose assessment model and exposure pathways. One of the exposure pathways is the ingestion of contaminated food. The aim of the present paper is to compute the uncertainty associated with the risk to the members of the public due to the ingestion of contaminated food. The governing parameters of the ingestion dose assessment model being imprecise, we have approached evidence theory to compute the bound of the risk. The uncertainty is addressed by the belief and plausibility fuzzy measures.

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

Organ radiation exposure with EOS: GATE simulations versus TLD measurements

NASA Astrophysics Data System (ADS)

Clavel, A. H.; Thevenard-Berger, P.; Verdun, F. R.; Létang, J. M.; Darbon, A.

2016-03-01

EOS® is an innovative X-ray imaging system allowing the acquisition of two simultaneous images of a patient in the standing position, during the vertical scan of two orthogonal fan beams. This study aimed to compute organs radiation exposure to a patient, in the particular geometry of this system. Two different positions of the patient in the machine were studied, corresponding to postero-anterior plus left lateral projections (PA-LLAT) and antero-posterior plus right lateral projections (AP-RLAT). To achieve this goal, a Monte-Carlo simulation was developed based on a GATE environment. To model the physical properties of the patient, a computational phantom was produced based on computed tomography scan data of an anthropomorphic phantom. The simulations provided several organs doses, which were compared to previously published dose results measured with Thermo Luminescent Detectors (TLD) in the same conditions and with the same phantom. The simulation results showed a good agreement with measured doses at the TLD locations, for both AP-RLAT and PA-LLAT projections. This study also showed that the organ dose assessed only from a sample of locations, rather than considering the whole organ, introduced significant bias, depending on organs and projections.

Finite-element three-dimensional ground-water (FE3DGW) flow model - formulation, program listings and users' manual

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

Gupta, S.K.; Cole, C.R.; Bond, F.W.

1979-12-01

The Assessment of Effectiveness of Geologic Isolation Systems (AEGIS) Program is developing and applying the methodology for assessing the far-field, long-term post-closure safety of deep geologic nuclear waste repositories. AEGIS is being performed by Pacific Northwest Laboratory (PNL) under contract with the Office of Nuclear Waste Isolation (OWNI) for the Department of Energy (DOE). One task within AEGIS is the development of methodology for analysis of the consequences (water pathway) from loss of repository containment as defined by various release scenarios. Analysis of the long-term, far-field consequences of release scenarios requires the application of numerical codes which simulate the hydrologicmore » systems, model the transport of released radionuclides through the hydrologic systems to the biosphere, and, where applicable, assess the radiological dose to humans. Hydrologic and transport models are available at several levels of complexity or sophistication. Model selection and use are determined by the quantity and quality of input data. Model development under AEGIS and related programs provides three levels of hydrologic models, two levels of transport models, and one level of dose models (with several separate models). This document consists of the description of the FE3DGW (Finite Element, Three-Dimensional Groundwater) Hydrologic model third level (high complexity) three-dimensional, finite element approach (Galerkin formulation) for saturated groundwater flow.« less

Terbinafine in Combination with Other Antifungal Agents for Treatment of Resistant or Refractory Mycoses: Investigating Optimal Dosing Regimens Using a Physiologically Based Pharmacokinetic Model

PubMed Central

Dolton, Michael J.; Perera, Vidya; Pont, Lisa G.

2014-01-01

Terbinafine is increasingly used in combination with other antifungal agents to treat resistant or refractory mycoses due to synergistic in vitro antifungal activity; high doses are commonly used, but limited data are available on systemic exposure, and no assessment of pharmacodynamic target attainment has been made. Using a physiologically based pharmacokinetic (PBPK) model for terbinafine, this study aimed to predict total and unbound terbinafine concentrations in plasma with a range of high-dose regimens and also calculate predicted pharmacodynamic parameters for terbinafine. Predicted terbinafine concentrations accumulated significantly during the first 28 days of treatment; the area under the concentration-time curve (AUC)/MIC ratios and AUC for the free, unbound fraction (fAUC)/MIC ratios increased by 54 to 62% on day 7 of treatment and by 80 to 92% on day 28 compared to day 1, depending on the dose regimen. Of the high-dose regimens investigated, 500 mg of terbinafine taken every 12 h provided the highest systemic exposure; on day 7 of treatment, the predicted AUC, maximum concentration (Cmax), and minimum concentration (Cmin) were approximately 4-fold, 1.9-fold, and 4.4-fold higher than with a standard-dose regimen of 250 mg once daily. Close agreement was seen between the concentrations predicted by the PBPK model and the observed concentrations, indicating good predictive performance. This study provides the first report of predicted terbinafine exposure in plasma with a range of high-dose regimens. PMID:24126579

The interaction between hippocampal GABA-B and cannabinoid receptors upon spatial change and object novelty discrimination memory function.

PubMed

Nasehi, Mohammad; Alaghmandan-Motlagh, Niyousha; Ebrahimi-Ghiri, Mohaddeseh; Nami, Mohammad; Zarrindast, Mohammad-Reza

2017-10-01

Previous studies have postulated functional links between GABA and cannabinoid systems in the hippocampus. The aim of the present study was to investigate any possible interaction between these systems in spatial change and object novelty discrimination memory consolidation in the dorsal hippocampus (CA1 region) of NMRI mice. Assessment of the spatial change and object novelty discrimination memory function was carried out in a non-associative task. The experiment comprised mice exposure to an open field containing five objects followed by the examination of their reactivity to object displacement (spatial change) and object substitution (object novelty) after three sessions of habituation. Our results showed that the post-training intraperitoneal administration of the higher dose of ACPA (0.02 mg/kg) impaired both spatial change and novelty discrimination memory functions. Meanwhile, the higher dose of GABA-B receptor agonist, baclofen, impaired the spatial change memory by itself. Moreover, the post-training intra-CA1 microinjection of a subthreshold dose of baclofen increased the ACPA effect on spatial change and novelty discrimination memory at a lower and higher dose, respectively. On the other hand, the lower and higher but not mid-level doses of GABA-B receptor antagonist, phaclofen, could reverse memory deficits induced by ACPA. However, phaclofen at its mid-level dose impaired the novelty discrimination memory and whereas the higher dose impaired the spatial change memory. Based on our findings, GABA-B receptors in the CA1 region appear to modulate the ACPA-induced cannabinoid CB1 signaling upon spatial change and novelty discrimination memory functions.

Pharmacokinetics and safety of imiquimod 5% cream in the treatment of actinic keratoses of the face, scalp, or hands and arms.

PubMed

Harrison, Lester I; Skinner, Shari L; Marbury, Thomas C; Owens, Mary L; Kurup, Sarala; McKane, Scott; Greene, Robert J

2004-06-01

The safety and efficacy of imiquimod 5% cream is being evaluated for the treatment of dysplastic lesions of the epidermis (actinic keratoses, AK). The objective of this clinical study was to describe the pharmacokinetics and safety of topical imiquimod during multiple dosing of AK subjects. A total of 58 adult subjects with 5 to 20 AK lesions at the treatment site applied imiquimod cream three times per week for up to 16 weeks as follows: 12 males and 11 females applied 12.5 mg imiquimod to the face; 11 males applied 25 mg to the entire balding area of the scalp; and 12 males and 12 females applied 75 mg to both hands and forearms. Pharmacokinetics and safety were assessed after the first and last doses, as well as biweekly. Imiquimod and its metabolites were measured in the serum and urine using sensitive liquid chromatography/mass spectrometry methods. Less than 0.6% of the applied doses was recovered in the urine of all subjects. Serum imiquimod levels were low, reflecting minimal dermal absorption, and increased with dose, although not proportionally. Peak levels at the end of dosing were 0.1, 0.2, and 1.6 ng/ml for the face, scalp, and hands/arms groups, respectively. A two- to fourfold accumulation was seen at the end of dosing. Local application site reactions were the most common adverse event, reported by approximately 50% of the subjects in each treatment group. The small number of systemic adverse events, including 'flu-like symptoms, were mostly mild and did not show a dose response. Thus, minimal systemic absorption and good safety margins for topical imiquimod were seen in AK subjects with doses as high as 75 mg three times per week for 16 weeks.