Characterization of MOSFET dosimeters for low‐dose measurements in maxillofacial anthropomorphic phantoms

PubMed Central

Wolff, Jan E.; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

2015-01-01

The aims of this study were to characterize reinforced metal‐oxide‐semiconductor field‐effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low‐dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET dosimeter sensitivities for two dental photon energy ranges, dose dependency, dose rate dependency, and accumulated dose dependency. A further aim was to compare the performance of MOSFETs with those of TLDs in an anthropomorphic phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET dosimeter sensitivities were evaluated for two photon energy ranges (50–90 kVp) using a constant dose and polymethylmethacrylate backscatter material. MOSFET and TLD comparative point‐dose measurements were performed on an anthropomorphic phantom that was exposed with a clinical CBCT protocol. The MOSFET single exposure low dose limit (25% uncertainty, k=2) was 1.69 mGy. An averaging of eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low‐dose limit. The sensitivity was 3.09±0.13 mV/mGy independently of the photon energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated threshold voltages between 8300 mV and 17500 mV. The point doses in an anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was −8%. The MOSFET dosimeters presented statistically insignificant energy dependency. By averaging multiple exposures, the MOSFET dosimeters can achieve a TLD‐comparable low‐dose limit and constitute a feasible method for diagnostic dosimetry using anthropomorphic phantoms. However, for single in vivo measurements (<1.7 mGy) the sensitivity is too low. PACS number: 87.50.wj PMID:26219008

Radionuclides in bats using a contaminated pond on the Nevada National Security Site, USA

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

Warren, Ronald W.; Hall, Derek B.; Greger, Paul D.

In this study, perched groundwater percolating through radionuclide contamination in the E Tunnel Complex on the Nevada National Security Site, formerly the Nevada Test Site, emerges and is stored in a series of ponds making it available to wildlife, including bats. Since many bat species using the ponds are considered sensitive or protected/regulated and little information is available on dose to bats from radioactive water sources, bats were sampled to determine if the dose they were receiving exceeded the United States Department of Energy dose limit of 1.0E-3 Gy/day. Radionuclide concentrations in water, sediment, and flying insects were also measuredmore » as input parameters to the dose rate model and to examine trophic level relationships. The RESRAD-Biota model was used to calculate dose rates to bats using different screening levels. Efficacy of RESRAD-Biota and suggested improvements are discussed. Finally, dose to bats foraging and drinking at these ponds is well below the dose limit set to protect terrestrial biota populations.« less

Radionuclides in bats using a contaminated pond on the Nevada National Security Site, USA

DOE PAGES

Warren, Ronald W.; Hall, Derek B.; Greger, Paul D.

2014-01-03

In this study, perched groundwater percolating through radionuclide contamination in the E Tunnel Complex on the Nevada National Security Site, formerly the Nevada Test Site, emerges and is stored in a series of ponds making it available to wildlife, including bats. Since many bat species using the ponds are considered sensitive or protected/regulated and little information is available on dose to bats from radioactive water sources, bats were sampled to determine if the dose they were receiving exceeded the United States Department of Energy dose limit of 1.0E-3 Gy/day. Radionuclide concentrations in water, sediment, and flying insects were also measuredmore » as input parameters to the dose rate model and to examine trophic level relationships. The RESRAD-Biota model was used to calculate dose rates to bats using different screening levels. Efficacy of RESRAD-Biota and suggested improvements are discussed. Finally, dose to bats foraging and drinking at these ponds is well below the dose limit set to protect terrestrial biota populations.« less

Using RADFET for the real-time measurement of gamma radiation dose rate

NASA Astrophysics Data System (ADS)

Andjelković, Marko S.; Ristić, Goran S.; Jakšić, Aleksandar B.

2015-02-01

RADFETs (RADiation sensitive Field Effect Transistors) are integrating ionizing radiation dosimeters operating on the principle of conversion of radiation-induced threshold voltage shift into absorbed dose. However, one of the major drawbacks of RADFETs is the inability to provide the information on the dose rate in real-time using the conventional absorbed dose measurement technique. The real-time monitoring of dose rate and absorbed dose can be achieved with the current mode dosimeters such as PN and PIN diodes/photodiodes, but these dosimeters have some limitations as absorbed dose meters and hence they are often not a suitable replacement for RADFETs. In that sense, this paper investigates the possibility of using the RADFET as a real-time dose rate meter so that it could be applied for simultaneous online measurement of the dose rate and absorbed dose. A RADFET sample, manufactured by Tyndall National Institute, Cork, Ireland, was tested as a dose rate meter under gamma irradiation from a Co-60 source. The RADFET was configured as a PN junction, such that the drain, gate and source terminals were grounded, while the radiation-induced current was measured at the bulk terminal, whereby the bulk was successively biased with 0 , 10 , 20  and 30 V. In zero-bias mode the radiation-induced current was unstable, but in the biased mode the current response was stable for the investigated dose rates from 0.65  to 32.1 Gy h-1 and up to the total absorbed dose of 25 Gy. The current increased with the dose rate in accordance with the power law, whereas the sensitivity of the current read-out was linear with respect to the applied bias voltage. Comparison with previously analyzed PIN photodiodes has shown that the investigated RADFET is competitive with PIN photodiodes as a gamma radiation dose rate meter and therefore has the potential to be employed for the real-time monitoring of the dose rate and absorbed dose.

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.

Conditioning of the 4 Curies Radium-226 Sealed Radiation Source in Thailand

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

Punnachaiya, M.; Sawangsri, T.; Wanabongse, P.

This paper describes the conditioning of the 4 curies Radium-226 (Ra-226) sealed radiation source using as a teletherapy unit for cancer treatment in Thailand. The conditioning was under the International Atomic Energy Agency (IAEA) supervision and budgetary supports, comprised of 6 operational steps: the surface dose rate and actual dimension of radium unit measurements, the appropriate lead shielding design with IAEA approval, confirmation of radioactive contamination before conditioning (smear test and radon gas leakage test), transfer of radium source unit into the designed shielding, confirmation of radioactive contamination and dose rate measurement after conditioning, and transportation of Ra-226 conditioning wastemore » package to OAP interim waste storage. The Ra-226 unit was taken out of OAP temporary waste storage for the surface dose rate and the actual dimension measurements behind the 12 inches thick heavy concrete shielding. The maximum measured surface dose rate was 70 R/hr. The special lead container was designed according to its surface dose rate along the source unit which the maximum permissible dose limit for surface dose rate of waste package after conditioning at 2 mSv/hr was applied. The IAEA approved container had total weight of 2.4 ton. After the confirmation of radioactive contamination, Ra-226 source unit was transferred and loaded in the designed lead shielding within 2 minutes. The results of smear test before and after conditioning including radon gas leakage test revealed that there was no radioactive contamination. After conditioning, the surface dose rate measured on the top, bottom were 15,10 mR/hr and varied from 6 - 50 mR/hr around lead container. The Ra-226 conditioning waste package was safely transported to store in OAP interim waste storage. Total working time including the time consumed for radon gas leakage test was 3.5 hours. The total radiation dose received by 16 operators, were ranged from 1 - 69.84 {mu}Sv and the operational team completed the conditioning safely within the effective dose limit for occupational exposure of 50 mSv/year (200 {mu}Sv/day). (authors)« less

Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.

PubMed

Mancuso, Mariateresa; Pasquali, Emanuela; Braga-Tanaka, Ignacia; Tanaka, Satoshi; Pannicelli, Alessandro; Giardullo, Paola; Pazzaglia, Simonetta; Tapio, Soile; Atkinson, Michael J; Saran, Anna

2015-10-13

There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/- mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE-/- females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response.

Experimental Platform for Ultra-high Dose Rate FLASH Irradiation of Small Animals Using a Clinical Linear Accelerator

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

Schüler, Emil; Trovati, Stefania; King, Gregory

Purpose: A key factor limiting the effectiveness of radiation therapy is normal tissue toxicity, and recent preclinical data have shown that ultra-high dose rate irradiation (>50 Gy/s, “FLASH”) potentially mitigates this effect. However, research in this field has been strongly limited by the availability of FLASH irradiators suitable for small animal experiments. We present a simple methodologic approach for FLASH electron small animal irradiation with a clinically available linear accelerator (LINAC). Methods and Materials: We investigated the FLASH irradiation potential of a Varian Clinac 21EX in both clinical mode and after tuning of the LINAC. We performed detailed FLUKA Monte Carlomore » and experimental dosimetric characterization at multiple experimental locations within the LINAC head. Results: Average dose rates of ≤74 Gy/s were achieved in clinical mode, and the dose rate after tuning exceeded 900 Gy/s. We obtained 220 Gy/s at 1-cm depth for a >4-cm field size with 90% homogeneity throughout a 2-cm-thick volume. Conclusions: We present an approach for using a clinical LINAC for FLASH irradiation. We obtained dose rates exceeding 200 Gy/s after simple tuning of the LINAC, with excellent dosimetric properties for small animal experiments. This will allow for increased availability of FLASH irradiation to the general research community.« less

Effects of dose scaling on delivery quality assurance in tomotherapy

PubMed Central

Nalichowski, Adrian; Burmeister, Jay

2012-01-01

Delivery quality assurance (DQA) of tomotherapy plans is routinely performed with silver halide film which has a limited range due to the effects of saturation. DQA plans with dose values exceeding this limit require the dose of the entire plan to be scaled downward if film is used, to evaluate the dose distribution in two dimensions. The potential loss of fidelity between scaled and unscaled DQA plans as a function of dose scaling is investigated. Three treatment plans for 12 Gy fractions designed for SBRT of the lung were used to create DQA procedures that were scaled between 100% and 10%. The dose was measured with an ionization chamber array and compared to values from the tomotherapy treatment planning system. Film and cylindrical ion chamber measurements were also made for one patient for scaling factors of 50% to 10% to compare with the ionization chamber array measurements. The array results show the average gamma pass rate is ≥99% from 100% to 30% scaling. The average gamma pass rate falls to 93.6% and 51.1% at 20% and 10% scaling, respectively. Film analysis yields similar pass rates. Cylindrical ion chambers did not exhibit significant variation with dose scaling, but only represent points in the low gradient region of the dose distribution. Scaling the dose changes the mechanics of the radiation delivery, as well as the signal‐to‐noise ratio. Treatment plans which exhibit parameters that differ significantly from those common to DQA plans studied in this paper may exhibit different behavior. Dose scaling should be limited to the smallest degree possible. Planar information, such as that from film or a detector array, is required. The results show that it is not necessary to perform both a scaled and unscaled DQA plan for the treatment plans considered here. PACS numbers: 87.55.km, 87.55.Qr PMID:22231213

PACKAGING CERTIFICATION PROGRAM METHODOLOGY FOR DETERMINING DOSE RATES FOR SMALL GRAM QUANTITIES IN SHIPPING PACKAGINGS

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

Nathan, S.; Loftin, B.; Abramczyk, G.

The Small Gram Quantity (SGQ) concept is based on the understanding that small amounts of hazardous materials, in this case radioactive materials (RAM), are significantly less hazardous than large amounts of the same materials. This paper describes a methodology designed to estimate an SGQ for several neutron and gamma emitting isotopes that can be shipped in a package compliant with 10 CFR Part 71 external radiation level limits regulations. These regulations require packaging for the shipment of radioactive materials, under both normal and accident conditions, to perform the essential functions of material containment, subcriticality, and maintain external radiation levels withinmore » the specified limits. By placing the contents in a helium leak-tight containment vessel, and limiting the mass to ensure subcriticality, the first two essential functions are readily met. Some isotopes emit sufficiently strong photon radiation that small amounts of material can yield a large dose rate outside the package. Quantifying the dose rate for a proposed content is a challenging issue for the SGQ approach. It is essential to quantify external radiation levels from several common gamma and neutron sources that can be safely placed in a specific packaging, to ensure compliance with federal regulations. The Packaging Certification Program (PCP) Methodology for Determining Dose Rate for Small Gram Quantities in Shipping Packagings provides bounding shielding calculations that define mass limits compliant with 10 CFR 71.47 for a set of proposed SGQ isotopes. The approach is based on energy superposition with dose response calculated for a set of spectral groups for a baseline physical packaging configuration. The methodology includes using the MCNP radiation transport code to evaluate a family of neutron and photon spectral groups using the 9977 shipping package and its associated shielded containers as the base case. This results in a set of multipliers for 'dose per particle' for each spectral group. For a given isotope, the source spectrum is folded with the response for each group. The summed contribution from all isotopes determines the total dose from the RAM in the container.« less

Thermal limits on MV x-ray production by bremsstrahlung targets in the context of novel linear accelerators.

PubMed

Wang, Jinghui; Trovati, Stefania; Borchard, Philipp M; Loo, Billy W; Maxim, Peter G; Fahrig, Rebecca

2017-12-01

To study the impact of target geometrical and linac operational parameters, such as target material and thickness, electron beam size, repetition rate, and mean current on the ability of the radiotherapy treatment head to deliver high-dose-rate x-ray irradiation in the context of novel linear accelerators capable of higher repetition rates/duty cycle than conventional clinical linacs. The depth dose in a water phantom without a flattening filter and heat deposition in an x-ray target by 10 MeV pulsed electron beams were calculated using the Monte-Carlo code MCNPX, and the transient temperature behavior of the target was simulated by ANSYS. Several parameters that affect both the dose distribution and temperature behavior were investigated. The target was tungsten with a thickness ranging from 0 to 3 mm and a copper heat remover layer. An electron beam with full width at half maximum (FWHM) between 0 and3 mm and mean current of 0.05-2 mA was used as the primary beam at repetition rates of 100, 200, 400, and 800 Hz. For a 10 MeV electron beam with FWHM of 1 mm, pulse length of 5 μs, by using a thin tungsten target with thickness of 0.2 mm instead of 1 mm, and by employing a high repetition rate of 800 Hz instead of 100 Hz, the maximum dose rate delivered can increase two times from 0.57 to 1.16 Gy/s. In this simple model, the limiting factor on dose rate is the copper heat remover's softening temperature, which was considered to be 500°C in our study. A high dose rate can be obtained by employing thin targets together with high repetition rate electron beams enabled by novel linac designs, whereas the benefit of thin targets is marginal at conventional repetition rates. Next generation linacs used to increase dose rate need different target designs compared to conventional linacs. © 2017 American Association of Physicists in Medicine.

Evaluation of the Environmental Gamma-ray Dose Rate by Skyshine Analysis During the Maintenance of an Activated TFC in ITER

NASA Astrophysics Data System (ADS)

Sato, S.; Takatsu, H.; Maki, K.; Yamada, K.; Mori, S.; Iida, H.; Santoro, R. T.

1997-09-01

Gamma-ray exposure dose rates at the ITER site boundary were estimated for the cases of removal of a failed activated Toroidal Field (TF) coil from the torus and removal of a failed activated TF coil together with a sector of the activated Vacuum Vessel (VV). Skyshine analyses were performed using the two-dimensional SN radiation transport code, DOT3.5. The exposure gamma-ray dose rates on the ground at the site boundary (presently assumed to be 1 km from the ITER building), were calculated to be 1.1 and 84 μSv/year for removal of the TF coil without and with a VV sector, respectively. The dose rate level for the latter case is close to the tentative radiation limit of 100 μSv/year so an additional ˜14 cm of concrete is required in the ITER building roof to satisfy the criterion for a safety factor often for the site boundary dose rate.

Effects of gamma irradiation dose-rate on sterile male Aedesaegypti

NASA Astrophysics Data System (ADS)

Ernawan, Beni; Tambunan, Usman Sumo Friend; Sugoro, Irawan; Sasmita, Hadian Iman

2017-06-01

Aedesaegypti is the most important vector for dengue, yellow fever and Zika viruses. Considering its medical importance, vector population control program utilizing radiation-based sterile insect technique (SIT) is one of the potential methods for preventing and limiting the dispersal of these viruses. The present study was undertaken to evaluate the dose-rates effects of γ-sterilization on quality parameters of sterile males. Males Ae.aegypti at the pupal stage were sterilized by applying 70 Gyγ-rays in varies dose-rates, i.e. 0 (control), 300, 600, 900, 1200 and 1500Gy/h utilizing panoramic irradiator. Adult males that emerged from the pupal stage were assessed for their quality parameters, which are the percentage of emergence, longevity, sterility and mating competitiveness. The results herein indicate that there was no major effect of dose-rate on the percentage of emergence, the data showedthat there were no differences between irradiated males compared with control. Generally, the longevity of irradiated males was lower compared to control. The data also demonstrated that longevity was significantly increased at the dose-rate from 300 to 900Gy/h, then decreased at the dose-rate 900 to 1500 Gy/h. Sterility of irradiated maleswas significantly different compared to control, while there was no significantly different at dose rate 300 to 1500 Gy/h. Mating competitiveness of irradiated males was increased at the dose rate from 300 to 1200 Gy/h, then the value was decreased significantly at the dose rate 1500 Gy/h. The dose-rate effects of γ-sterilization were discussed in the context genetic vector control, in particular, the SIT. The results give information and contribute to better understanding towards γ-sterilization optimization and quality parameters of sterile male Ae. aegypti on SIT methods.

Classification of radiation effects for dose limitation purposes: history, current situation and future prospects

PubMed Central

Hamada, Nobuyuki; Fujimichi, Yuki

2014-01-01

Radiation exposure causes cancer and non-cancer health effects, each of which differs greatly in the shape of the dose–response curve, latency, persistency, recurrence, curability, fatality and impact on quality of life. In recent decades, for dose limitation purposes, the International Commission on Radiological Protection has divided such diverse effects into tissue reactions (formerly termed non-stochastic and deterministic effects) and stochastic effects. On the one hand, effective dose limits aim to reduce the risks of stochastic effects (cancer/heritable effects) and are based on the detriment-adjusted nominal risk coefficients, assuming a linear-non-threshold dose response and a dose and dose rate effectiveness factor of 2. On the other hand, equivalent dose limits aim to avoid tissue reactions (vision-impairing cataracts and cosmetically unacceptable non-cancer skin changes) and are based on a threshold dose. However, the boundary between these two categories is becoming vague. Thus, we review the changes in radiation effect classification, dose limitation concepts, and the definition of detriment and threshold. Then, the current situation is overviewed focusing on (i) stochastic effects with a threshold, (ii) tissue reactions without a threshold, (iii) target organs/tissues for circulatory disease, (iv) dose levels for limitation of cancer risks vs prevention of non-life-threatening tissue reactions vs prevention of life-threatening tissue reactions, (v) mortality or incidence of thyroid cancer, and (vi) the detriment for tissue reactions. For future discussion, one approach is suggested that classifies radiation effects according to whether effects are life threatening, and radiobiological research needs are also briefly discussed. PMID:24794798

Assessment of natural radionuclides and its radiological hazards from tiles made in Nigeria

NASA Astrophysics Data System (ADS)

Joel, E. S.; Maxwell, O.; Adewoyin, O. O.; Ehi-Eromosele, C. O.; Embong, Z.; Saeed, M. A.

2018-03-01

Activity concentration of 10 different brands of tiles made in Nigeria were analyzed using High purity Germanium gamma detector and its hazard indices such as absorbed dose rate, radium equivalent activity, external Hazard Index (Hex), internal Hazard Index (Hin), Annual Effective Dose (mSv/y), Gamma activity Index (Iγ) and Alpha Index (Iα) were determined. The result showed that the average activity concentrations of radionuclides (226Ra, 232Th and 40K) content are within the recommended limit. The average radium equivalent is within the recommended limit of 370 Bq/kg. The result obtained further showed that the mean values for the absorbed dose rate (D), external and internal hazard index, the annual effective dose (AEDR) equivalent, gamma activity index and Alpha Index were: 169.22 nGyh-1, 0.95 and 1.14, 1.59 mSv/y, 1.00 Sv yr-1 and 0.34 respectively. The result established that radiological hazards such as absorbed dose rate, internal hazard, annual effective dose rate, gamma activity index and Alpha Index for some samples are found to be slightly close or above international recommended values. The result for the present study was compared with tiles sample from others countries, it was observed that the concentration of tiles made in Nigeria and other countries are closer, however recommends proper radiation monitoring for some tiles made in Nigeria before usage due to the long term health effect.

Dose-rate-dependent damage of cerium dioxide in the scanning transmission electron microscope.

PubMed

Johnston-Peck, Aaron C; DuChene, Joseph S; Roberts, Alan D; Wei, Wei David; Herzing, Andrew A

2016-11-01

Beam damage caused by energetic electrons in the transmission electron microscope is a fundamental constraint limiting the collection of artifact-free information. Through understanding the influence of the electron beam, experimental routines may be adjusted to improve the data collection process. Investigations of CeO 2 indicate that there is not a critical dose required for the accumulation of electron beam damage. Instead, measurements using annular dark field scanning transmission electron microscopy and electron energy loss spectroscopy demonstrate that the onset of measurable damage occurs when a critical dose rate is exceeded. The mechanism behind this phenomenon is that oxygen vacancies created by exposure to a 300keV electron beam are actively annihilated as the sample re-oxidizes in the microscope environment. As a result, only when the rate of vacancy creation exceeds the recovery rate will beam damage begin to accumulate. This observation suggests that dose-intensive experiments can be accomplished without disrupting the native structure of the sample when executed using dose rates below the appropriate threshold. Furthermore, the presence of an encapsulating carbonaceous layer inhibits processes that cause beam damage, markedly increasing the dose rate threshold for the accumulation of damage. Published by Elsevier B.V.

Dose-rate-dependent damage of cerium dioxide in the scanning transmission electron microscope

PubMed Central

Johnston-Peck, Aaron C.; DuChene, Joseph S.; Roberts, Alan D.; Wei, Wei David; Herzing, Andrew A.

2016-01-01

Beam damage caused by energetic electrons in the transmission electron microscope is a fundamental constraint limiting the collection of artifact-free information. Through understanding the influence of the electron beam, experimental routines may be adjusted to improve the data collection process. Investigations of CeO2 indicate that there is not a critical dose required for the accumulation of electron beam damage. Instead, measurements using annular dark field scanning transmission electron microscopy and electron energy loss spectroscopy demonstrate that the onset of measurable damage occurs when a critical dose rate is exceeded. The mechanism behind this phenomenon is that oxygen vacancies created by exposure to a 300 keV electron beam are actively annihilated as the sample re-oxidizes in the microscope environment. As a result, only when the rate of vacancy creation exceeds the recovery rate will beam damage begin to accumulate. This observation suggests that dose-intensive experiments can be accomplished without disrupting the native structure of the sample when executed using dose rates below the appropriate threshold. Furthermore, the presence of an encapsulating carbonaceous layer inhibits processes that cause beam damage, markedly increasing the dose rate threshold for the accumulation of damage. PMID:27469265

A Commentary on: "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008".

PubMed

Brooks, Antone L

2015-04-01

This commentary provides a very brief overview of the book "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008" ( http://lowdose.energy.gov ). The book summarizes and evaluates the research progress, publications and impact of the U.S. Department of Energy Low Dose Radiation Research Program over its first 10 years. The purpose of this book was to summarize the impact of the program's research on the current thinking and low-dose paradigms associated with the radiation biology field and to help stimulate research on the potential adverse and/or protective health effects of low doses of ionizing radiation. In addition, this book provides a summary of the data generated in the low dose program and a scientific background for anyone interested in conducting future research on the effects of low-dose or low-dose-rate radiation exposure. This book's exhaustive list of publications coupled with discussions of major observations should provide a significant resource for future research in the low-dose and dose-rate region. However, because of space limitations, only a limited number of critical references are mentioned. Finally, this history book provides a list of major advancements that were accomplished by the program in the field of radiation biology, and these bulleted highlights can be found in last part of chapters 4-10.

Dose rate constants for the quantity Hp(3) for frequently used radionuclides in nuclear medicine.

PubMed

Szermerski, Bastian; Bruchmann, Iris; Behrens, Rolf; Geworski, Lilli

2016-12-01

According to recent studies, the human eye lens is more sensitive to ionising radiation than previously assumed. Therefore, the dose limit for personnel occupationally exposed to ionising radiation will be lowered from currently 150 mSv to 20 mSv per year. Currently, no data base for a reliable estimation of the dose to the lens of the eye is available for nuclear medicine. Furthermore, the dose is usually not monitored. The aim of this work was to determine dose rate constants for the quantity H p (3), which is supposed to estimate the dose to the lens of the eye. For this, H p (3)-dosemeters were fixed to an Alderson Phantom at different positions. The dosemeters were exposed to radiation from nuclides typically used in nuclear medicine in their geometries analog to their application in nuclear medicine, e.g. syringe or vial. The results show that the handling of high-energy beta (i.e. electron or positron) emitters may lead to a relevant dose to the lens of the eye. For low-energy beta emitters and gamma emitters, an exceeding of the lowered dose limit seems to be unlikely. Copyright © 2015. Published by Elsevier GmbH.

Impact of the Revised 10 CFR 835 on the Neutron Dose Rates at LLNL

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

Radev, R

2009-01-13

In June 2007, 10 CFR 835 [1] was revised to include new radiation weighting factors for neutrons, updated dosimetric models, and dose terms consistent with the newer ICRP recommendations. A significant aspect of the revised 10 CFR 835 is the adoption of the recommendations outlined in ICRP-60 [2]. The recommended new quantities demand a review of much of the basic data used in protection against exposure to sources of ionizing radiation. The International Commission on Radiation Units and Measurements has defined a number of quantities for use in personnel and area monitoring [3,4,5] including the ambient dose equivalent H*(d) tomore » be used for area monitoring and instrument calibrations. These quantities are used in ICRP-60 and ICRP-74. This report deals only with the changes in the ambient dose equivalent and ambient dose rate equivalent for neutrons as a result of the implementation of the revised 10 CFR 835. In the report, the terms neutron dose and neutron dose rate will be used for convenience for ambient neutron dose and ambient neutron dose rate unless otherwise stated. This report provides a qualitative and quantitative estimate of how much the neutron dose rates at LLNL will change with the implementation of the revised 10 CFR 835. Neutron spectra and dose rates from selected locations at the LLNL were measured with a high resolution spectroscopic neutron dose rate system (ROSPEC) as well as with a standard neutron rem meter (a.k.a., a remball). The spectra obtained at these locations compare well with the spectra from the Radiation Calibration Laboratory's (RCL) bare californium source that is currently used to calibrate neutron dose rate instruments. The measurements obtained from the high resolution neutron spectrometer and dose meter ROSPEC and the NRD dose meter compare within the range of {+-}25%. When the new radiation weighting factors are adopted with the implementation of the revised 10 CFR 835, the measured dose rates will increase by up to 22%. The health physicists should consider this increase for any areas that have dose rates near a posting limit, such as near the 100 mrem/hr for a high radiation area, as this increase in measured dose rate may result in some changes to postings and consequent radiological controls.« less

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

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

Ahmed, S; Ahmed, S; Ahmed, F

2016-06-15

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

A Detailed Dosimetric Analysis of Spinal Cord Tolerance in High-Dose Spine Radiosurgery.

PubMed

Katsoulakis, Evangelia; Jackson, Andrew; Cox, Brett; Lovelock, Michael; Yamada, Yoshiya

2017-11-01

Dose-volume tolerance of the spinal cord (SC) in spinal stereotactic radiosurgery (SRS) is difficult to define because radiation myelitis rates are low, and published reports document cases of myelopathy but do not account for the total number of patients treated at given dose-volume combinations who do not have myelitis. This study reports SC toxicity from single-fraction spinal SRS and presents a comprehensive atlas of the incidence of adverse events to examine dose-volume predictors. A prospective database of all patients undergoing single-fraction spinal SRS at our institution between 2004 and 2011 was reviewed. SC toxicity was defined by clinical myelitis with accompanying magnetic resonance imaging (MRI) signal changes that were not attributable to tumor progression. Dose-volume histogram (DVH) atlases were created for these endpoints. Rates of adverse events with 95% confidence limits and probabilities that rates of adverse events were <2% and <5% for myelitis were determined as functions of dose and absolute volume. Information about DVH and myelitis was available for 228 patients treated at 259 sites. The median follow-up time was 14.6 months (range, 0.1-138.3 months). The median prescribed dose to the planning treatment volume was 24 Gy (range, 18-24 Gy). There were 2 cases of radiation myelitis (rate r=0.7%) with accompanying MRI signal changes. Myelitis occurred in 2 patients, with Dmax >13.33 Gy, and minimum doses to the hottest 0.1, 0.2, 0.5, and 1 cc were >10.66, 10.9, and 8 Gy, respectively; however, both myelitis cases occurred below the 34th percentile for Dmax and there were 194 DVHs in total with Dmax >13.33 Gy. A median SC Dmax of 13.85 Gy is safe and supports that a Dmax limit of 14 Gy carries a low <1% rate of myelopathy. No dose-volume thresholds or relationships between SC dose and myelitis were apparent. This is the largest study examining dosimetric data and radiation-induced myelitis in de novo spine SRS. Copyright © 2017 Elsevier Inc. All rights reserved.

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

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

Ben-Josef, Edgar, E-mail: edgar.ben-josef@uphs.upenn.edu; Schipper, Mathew; Francis, Isaac R.

2012-12-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of {>=}1500/mm{sup 3}, platelets {>=}100,000/mm{sup 3}, creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase {<=}2.5 Multiplication-Sign upper limit of normal. FDR-G (1000 mg/m{sup 2}/100 min intravenously) wasmore » given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) {>=}3, neutropenic fever, or deterioration in performance status to {>=}3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.« less

Estimation of low-level neutron dose-equivalent rate by using extrapolation method for a curie level Am-Be neutron source.

PubMed

Li, Gang; Xu, Jiayun; Zhang, Jie

2015-01-01

Neutron radiation protection is an important research area because of the strong radiation biological effect of neutron field. The radiation dose of neutron is closely related to the neutron energy, and the connected relationship is a complex function of energy. For the low-level neutron radiation field (e.g. the Am-Be source), the commonly used commercial neutron dosimeter cannot always reflect the low-level dose rate, which is restricted by its own sensitivity limit and measuring range. In this paper, the intensity distribution of neutron field caused by a curie level Am-Be neutron source was investigated by measuring the count rates obtained through a 3 He proportional counter at different locations around the source. The results indicate that the count rates outside of the source room are negligible compared with the count rates measured in the source room. In the source room, 3 He proportional counter and neutron dosimeter were used to measure the count rates and dose rates respectively at different distances to the source. The results indicate that both the count rates and dose rates decrease exponentially with the increasing distance, and the dose rates measured by a commercial dosimeter are in good agreement with the results calculated by the Geant4 simulation within the inherent errors recommended by ICRP and IEC. Further studies presented in this paper indicate that the low-level neutron dose equivalent rates in the source room increase exponentially with the increasing low-energy neutron count rates when the source is lifted from the shield with different radiation intensities. Based on this relationship as well as the count rates measured at larger distance to the source, the dose rates can be calculated approximately by the extrapolation method. This principle can be used to estimate the low level neutron dose values in the source room which cannot be measured directly by a commercial dosimeter. Copyright © 2014 Elsevier Ltd. All rights reserved.

PCP METHODOLOGY FOR DETERMINING DOSE RATES FOR SMALL GRAM QUANTITIES IN SHIPPING PACKAGINGS

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

Nathan, S.

The Small Gram Quantity (SGQ) concept is based on the understanding that small amounts of hazardous materials, in this case radioactive materials, are significantly less hazardous than large amounts of the same materials. This study describes a methodology designed to estimate an SGQ for several neutron and gamma emitting isotopes that can be shipped in a package compliant with 10 CFR Part 71 external radiation level limits regulations. These regulations require packaging for the shipment of radioactive materials perform, under both normal and accident conditions, the essential functions of material containment, subcriticality, and maintain external radiation levels within regulatory limits.more » 10 CFR 71.33(b)(1)(2)&(3) state radioactive and fissile materials must be identified and their maximum quantity, chemical and physical forms be included in an application. Furthermore, the U.S. Federal Regulations require application contain an evaluation demonstrating the package (i.e., the packaging and its contents) satisfies the external radiation standards for all packages (10 CFR 71.31(2), 71.35(a), & 71.47). By placing the contents in a He leak-tight containment vessel, and limiting the mass to ensure subcriticality, the first two essential functions are readily met. Some isotopes emit sufficiently strong photon radiation that small amounts of material can yield a large external dose rate. Quantifying of the dose rate for a proposed content is a challenging issue for the SGQ approach. It is essential to quantify external radiation levels from several common gamma and neutron sources that can be safely placed in a specific packaging, to ensure compliance with federal regulations. The Packaging Certification Program (PCP) Methodology for Determining Dose Rate for Small Gram Quantities in Shipping Packagings described in this report provides bounding mass limits for a set of proposed SGQ isotopes. Methodology calculations were performed to estimate external radiation levels for the 9977 shipping package using the MCNP radiation transport code to develop a set of response multipliers (Green's functions) for 'dose per particle' for each neutron and photon spectral group. The source spectrum for each isotope generated using the ORIGEN-S and RASTA computer codes was folded with the response multipliers to generate the dose rate per gram of each isotope in the 9977 shipping package and its associated shielded containers. The maximum amount of a single isotope that could be shipped within the regulatory limits contained in 10 CFR 71.47 for dose rate at the surface of the package is determined. If a package contains a mixture of isotopes, the acceptability for shipment can be determined by a sum of fractions approach. Furthermore, the results of this analysis can be easily extended to additional radioisotopes by simply evaluating the neutron and/or photon spectra of those isotopes and folding the spectral data with the Green's functions provided.« less

Potential Treatment of Inflammatory and Proliferative Diseases by Ultra-Low Doses of Ionizing Radiations

PubMed Central

Sanders, Charles L.

2012-01-01

Ultra-low doses and dose- rates of ionizing radiation are effective in preventing disease which suggests that they also may be effective in treating disease. Limited experimental and anecdotal evidence indicates that low radiation doses from radon in mines and spas, thorium-bearing monazite sands and enhanced radioactive uranium ore obtained from a natural geological reactor may be useful in treating many inflammatory conditions and proliferative disorders, including cancer. Optimal therapeutic applications were identified via a literature survey as dose-rates ranging from 7 to 11μGy/hr or 28 to 44 times world average background rates. Rocks from an abandoned uranium mine in Utah were considered for therapeutic application and were examined by γ-ray and laser-induced breakdown fluorescence spectroscopy. The rocks showed the presence of transuranics and fission products with a γ-ray energy profile similar to aged spent uranium nuclear fuel (93% dose due to β particles and 7% due to γ rays). Mud packs of pulverized uranium ore rock dust in sealed plastic bags delivering bag surface β,γ dose-rates of 10–450 μGy/h were used with apparent success to treat several inflammatory and proliferative conditions in humans. PMID:23304108

Ionizing radiation sensitivity of the ocular lens and its dose rate dependence.

PubMed

Hamada, Nobuyuki

2017-10-01

In 2011, the International Commission on Radiological Protection reduced the threshold for the lens effects of low linear energy transfer (LET) radiation. On one hand, the revised threshold of 0.5 Gy is much lower than previously recommended thresholds, but mechanisms behind high radiosensitivity remain incompletely understood. On the other hand, such a threshold is independent of dose rate, in contrast to previously recommended separate thresholds each for single and fractionated/protracted exposures. Such a change was made predicated on epidemiological evidence suggesting that a threshold for fractionated/protracted exposures is not higher than an acute threshold, and that a chronic threshold is uncertain. Thus, the dose rate dependence is still unclear. This paper therefore reviews the current knowledge on the radiosensitivity of the lens and the dose rate dependence of radiation cataractogenesis, and discusses its mechanisms. Mounting biological evidence indicates that the lens cells are not necessarily radiosensitive to cell killing, and the high radiosensitivity of the lens thus appears to be attributable to other mechanisms (e.g., excessive proliferation, abnormal differentiation, a slow repair of DNA double-strand breaks, telomere, senescence, crystallin changes, non-targeted effects and inflammation). Both biological and epidemiological evidence generally supports the lack of dose rate effects. However, there is also biological evidence for the tissue sparing dose rate (or fractionation) effect of low-LET radiation and an enhancing inverse dose fractionation effect of high-LET radiation at a limited range of LET. Emerging epidemiological evidence in chronically exposed individuals implies the inverse dose rate effect. Further biological and epidemiological studies are warranted to gain deeper knowledge on the radiosensitivity of the lens and dose rate dependence of radiation cataractogenesis.

Limited Margin Radiation Therapy for Children and Young Adults With Ewing Sarcoma Achieves High Rates of Local Tumor Control

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

Talleur, Aimee C.; Navid, Fariba; Spunt, Sheri L.

Purpose: To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors ≥8 cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS). Methods and Materials: Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8 cm at diagnosis, received a standard dose of 55.8 Gy and tumors ≥8 cm, an escalated dose to 64.8 Gy. Patients with microscopic residual disease after resectionmore » received adjuvant RT to 50.4 Gy. Adjuvant brachytherapy was permitted in selected patients. Results: Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0 years (2.9-24.7 years), 9.0 cm (2.4-17.0 cm), and 54.5 months (1.9-122.2 months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1 Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failures included 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4% ± 3.1%, with no statistical difference seen between RT treatment groups and no local failures in the escalated-dose RT treatment group. Conclusions: Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS.« less

Low and high dose rate heavy ion radiation-induced intestinal and colonic tumorigenesis in APC1638N/+ mice

NASA Astrophysics Data System (ADS)

Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun; Fornace, Albert J.; Datta, Kamal

2017-05-01

Ionizing radiation (IR) is a recognized risk factor for colorectal cancer (CRC) and astronauts undertaking long duration space missions are expected to receive IR doses in excess of permissible limits with implications for colorectal carcinogenesis. Exposure to IR in outer space occurs at low doses and dose rates, and energetic heavy ions due to their high linear energy transfer (high-LET) characteristics remain a major concern for CRC risk in astronauts. Previously, we have demonstrated that intestinal tumorigenesis in a mouse model (APC1638N/+) of human colorectal cancer was significantly higher after exposure to high dose rate energetic heavy ions relative to low-LET γ radiation. The purpose of the current study was to compare intestinal tumorigenesis in APC1638N/+ mice after exposure to energetic heavy ions at high (50 cGy/min) and relatively low (0.33 cGy/min) dose rate. Male and female mice (6-8 weeks old) were exposed to either 10 or 50 cGy of 28Si (energy: 300 MeV/n; LET: 70 keV/μm) or 56Fe (energy: 1000 MeV/n; LET: 148 keV/μm) ions at NASA Space Radiation Laboratory in Brookhaven National Laboratory. Mice (n = 20 mice/group) were euthanized and intestinal and colon tumor frequency and size were counted 150 days after radiation exposure. Intestinal tumorigenesis in male mice exposed to 56Fe was similar for high and low dose rate exposures. Although male mice showed a decreasing trend at low dose rate relative to high dose rate exposures, the differences in tumor frequency between the two types of exposures were not statistically significant after 28Si radiation. In female mice, intestinal tumor frequency was similar for both radiation type and dose rates tested. In both male and female mice intestinal tumor size was not different after high and low dose rate radiation exposures. Colon tumor frequency in male and female mice after high and low dose rate energetic heavy ions was also not significantly different. In conclusion, intestinal and colonic tumor frequency and size was similar irrespective of energetic heavy ion radiation dose rate suggesting that carcinogenic potential of energetic heavy ions is independent of dose rate.

Radiation Protection Considerations

NASA Astrophysics Data System (ADS)

Adorisio, C.; Roesler, S.; Urscheler, C.; Vincke, H.

This chapter summarizes the legal Radiation Protection (RP) framework to be considered in the design of HiLumi LHC. It details design limits and constraints, dose objectives and explains how the As Low As Reasonably Achievable (ALARA) approach is formalized at CERN. Furthermore, features of the FLUKA Monte Carlo code are summarized that are of relevance for RP studies. Results of FLUKA simulations for residual dose rates during Long Shutdown 1 (LS1) are compared to measurements demonstrating good agreement and providing proof for the accuracy of FLUKA predictions for future shutdowns. Finally, an outlook for the residual dose rate evolution until LS3 is given.

Mumps Postexposure Prophylaxis with a Third Dose of Measles-Mumps-Rubella Vaccine, Orange County, New York, USA

PubMed Central

Lawler, Jacqueline; Curns, Aaron T.; Brandeburg, Christina; Wallace, Gregory S.

2013-01-01

Although the measles-mumps-rubella (MMR) vaccine is not recommended for mumps postexposure prophylaxis (PEP), data on its effectiveness are limited. During the 2009–2010 mumps outbreak in the northeastern United States, we assessed effectiveness of PEP with a third dose of MMR vaccine among contacts in Orthodox Jewish households who were given a third dose within 5 days of mumps onset in the household’s index patient. We compared mumps attack rates between persons who received a third MMR dose during the first incubation period after onset in the index patient and 2-dose vaccinated persons who had not. Twenty-eight (11.7%) of 239 eligible household members received a third MMR dose as PEP. Mumps attack rates were 0% among third-dose recipients versus 5.2% among 2-dose recipients without PEP (p = 0.57). Although a third MMR dose administered as PEP did not have a significant effect, it may offer some benefits in specific outbreak contexts. PMID:23965729

Preliminary Shielding Analysis for HCCB TBM Transport

NASA Astrophysics Data System (ADS)

Miao, Peng; Zhao, Fengchao; Cao, Qixiang; Zhang, Guoshu; Feng, Kaiming

2015-09-01

A preliminary shielding analysis on the transport of the Chinese helium cooled ceramic breeder test blanket module (HCCB TBM) from France back to China after being irradiated in ITER is presented in this contribution. Emphasis was placed on irradiation safety during transport. The dose rate calculated by MCNP/4C for the conceptual package design satisfies the relevant dose limits from IAEA that the dose rate 3 m away from the surface of the package containing low specific activity III materials should be less than 10 mSv/h. The change with location and the time evolution of dose rates after shutdown have also been studied. This will be helpful for devising the detailed transport plan of HCCB TBM back to China in the near future. supported by the Major State Basic Research Development Program of China (973 Program) (No. 2013GB108000)

Characterization of a commercial multileaf collimator used for intensity modulated radiation therapy.

PubMed

Low, D A; Sohn, J W; Klein, E E; Markman, J; Mutic, S; Dempsey, J F

2001-05-01

The characteristics of a commercial multileaf collimator (MLC) to deliver static and dynamic multileaf collimation (SMLC and DMLC, respectively) were investigated to determine their influence on intensity modulated radiation therapy (IMRT) treatment planning and quality assurance. The influence of MLC leaf positioning accuracy on sequentially abutted SMLC fields was measured by creating abutting fields with selected gaps and overlaps. These data were also used to measure static leaf positioning precision. The characteristics of high leaf-velocity DMLC delivery were measured with constant velocity leaf sequences starting with an open field and closing a single leaf bank. A range of 1-72 monitor units (MU) was used providing a range of leaf velocities. The field abutment measurements yielded dose errors (as a percentage of the open field max dose) of 16.7+/-0.7% mm(-1) and 12.8+/-0.7% mm(-1) for 6 MV and 18 MV photon beams, respectively. The MLC leaf positioning precision was 0.080+/-0.018 mm (single standard deviation) highlighting the excellent delivery hardware tolerances for the tested beam delivery geometry. The high leaf-velocity DMLC measurements showed delivery artifacts when the leaf sequence and selected monitor units caused the linear accelerator to move the leaves at their maximum velocity while modulating the accelerator dose rate to deliver the desired leaf and MU sequence (termed leaf-velocity limited delivery). According to the vendor, a unique feature to their linear accelerator and MLC is that the dose rate is reduced to provide the correct cm MU(-1) leaf velocity when the delivery is leaf-velocity limited. However, it was found that the system delivered roughly 1 MU per pulse when the delivery was leaf-velocity limited causing dose profiles to exhibit discrete steps rather than a smooth dose gradient. The root mean square difference between the steps and desired linear gradient was less than 3% when more than 4 MU were used. The average dose per MU was greater and less than desired for closing and opening leaf patterns, respectively, when the delivery was leaf-velocity limited. The results indicated that the dose delivery artifacts should be minor for most clinical cases, but limit the assumption of dose linearity when significantly reducing the delivered dose for dosimeter characterization studies or QA measurements.

Long-Segment Fusion for Adult Spinal Deformity Correction Using Low-Dose Recombinant Human Bone Morphogenetic Protein-2: A Retrospective Review of Fusion Rates.

PubMed

Schmitt, Paul J; Kelleher, John P; Ailon, Tamir; Heller, Joshua E; Kasliwal, Manish K; Shaffrey, Christopher I; Smith, Justin S

2016-08-01

Although use of very high-dose recombinant human bone morphogenetic protein-2 (rhBMP-2) has been reported to markedly improve fusion rates in adult spinal deformity (ASD) surgery, most centers use much lower doses due to cost constraints. How effective these lower doses are for fusion enhancement remains unclear. To assess fusion rates using relatively low-dose rhBMP-2 for ASD surgery. This was a retrospective review of consecutive ASD patients that underwent thoracic to sacral fusion. Patients that achieved 2-year follow-up were analyzed. Impact of patient and surgical factors on fusion rate was assessed, and fusion rates were compared with historical cohorts. Of 219 patients, 172 (78.5%) achieved 2-year follow-up and were analyzed. Using an average rhBMP-2 dose of 3.1 mg/level (average total dose = 35.9 mg/case), the 2-year fusion rate was 73.8%. Cancellous allograft, local autograft, and very limited iliac crest bone graft (<20 mL, obtained during iliac bolt placement) were also used. On multivariate analysis, female sex was associated with a higher fusion rate, whereas age, comorbidity score, deformity type, and 3-column osteotomy were not. There were no complications directly attributable to rhBMP-2. Fusion rates for ASD using low-dose rhBMP-2 were comparable to those reported for iliac crest bone graft but lower than for high-dose rhBMP-2. Importantly, there were substantial differences between patients in the present series and those in the historical comparison groups that could not be fully adjusted for based on available data. Prospective evaluation of rhBMP-2 dosing for ASD surgery is warranted to define the most appropriate dose that balances benefits, risks, and costs. ASD, adult spinal deformityICBG, iliac crest bone graftOR, odds ratiorhBMP-2, recombinant human bone morphogenetic protein-2RR, risk ratioTCO, 3-column osteotomy.

Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions.

PubMed

Canonica, Giorgio Walter; Arp, Jan; Keegstra, Johan René; Chrystyn, Henry

2015-10-01

Spiromax(®) is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide-formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. Mean values for both budesonide and formoterol were within 85%-115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min. The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min. DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment.

The New Radiobiology: Returning to Our Roots

PubMed Central

Ulsh, Brant A.

2012-01-01

In 2005, two expert advisory bodies examined the evidence on the effects of low doses of ionizing radiation. The U.S. National Research Council concluded that current scientific evidence is consistent with the linear no-threshold dose-response relationship (NRCNA 2005) while the French National Academies of Science and Medicine concluded the opposite (Aurengo et al. 2005). These contradictory conclusions may stem in part from an emphasis on epidemiological data (a “top down” approach) versus an emphasis on biological mechanisms (a “bottom up” approach). In this paper, the strengths and limitations of the top down and bottom up approaches are discussed, and proposals for strengthening and reconciling them are suggested. The past seven years since these two reports were published have yielded increasing evidence of nonlinear responses of biological systems to low radiation doses delivered at low dose-rates. This growing body of evidence is casting ever more doubt on the extrapolation of risks observed at high doses and dose-rates to estimate risks associated with typical environmental and occupational exposures. This paper compares current evidence on low dose, low dose-rate effects against objective criteria of causation. Finally, some questions for a post-LNT world are posed. PMID:23304107

Phase I/II trial of single-fraction high-dose-rate brachytherapy-boosted hypofractionated intensity-modulated radiation therapy for localized adenocarcinoma of the prostate.

PubMed

Myers, Michael A; Hagan, Michael P; Todor, Dorin; Gilbert, Lynn; Mukhopadhyay, Nitai; Randolf, Jessica; Heimiller, Jeffrey; Anscher, Mitchell S

2012-01-01

A Phase I/II protocol was conducted to examine the toxicity and efficacy of the combination of intensity-modulated radiation therapy (IMRT) with a single-fraction high-dose-rate (HDR) brachytherapy implant. From 2001 through 2006, 26 consecutive patients were treated on the trial. The primary objective was to demonstrate a high rate of completion without experiencing a treatment-limiting toxicity. Eligibility was limited to patients with T stage ≤2b, prostate-specific antigen (PSA) ≤20, and Gleason score ≤7. Treatment began with a single HDR fraction of 6Gy to the entire prostate and 9Gy to the peripheral zone, followed by IMRT optimized to deliver in 28 fractions with a normalized total dose of 70Gy. Patients received 50.4Gy to the pelvic lymph node. The prostate dose (IMRT and HDR) resulted in an average biologic equivalent dose >128Gy (α/β=3). Patients whose pretreatment PSA was ≥10ng/mL, Gleason score 7, or stage ≥T2b received short-term androgen ablation. Median followup was 53 months (9-68 months). There were no biochemical failures by either the American Society of Therapeutic Radiology and Oncology or the Phoenix definitions. The median nadir PSA was 0.32ng/mL. All the 26 patients completed the treatment as prescribed. The rate of Grade 3 late genitourinary toxicity was 3.8% consisting of a urethral stricture. There was no other Grade 3 or 4 genitourinary or gastrointestinal toxicities. Single-fraction HDR-boosted IMRT is a safe effective method of dose escalation for localized prostate cancer. Copyright © 2012 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Fieldable computer system for determining gamma-ray pulse-height distributions, flux spectra, and dose rates from Little Boy

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

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

1984-01-01

Our system consists of a LeCroy 3500 data acquisition system with a built-in CAMAC crate and eight bismuth-germanate detectors 7.62 cm in diameter and 7.62 cm long. Gamma-ray pulse-height distributions are acquired simultaneously for up to eight positions. The system was very carefully calibrated and characterized from 0.1 to 8.3 MeV using gamma-ray spectra from a variety of radioactive sources. By fitting the pulse-height distributions from the sources with a function containing 17 parameters, we determined theoretical repsonse functions. We use these response functions to unfold the distributions to obtain flux spectra. A flux-to-dose-rate conversion curve based on the workmore » of Dimbylow and Francis is then used to obtain dose rates. Direct use of measured spectra and flux-to-dose-rate curves to obtain dose rates avoids the errors that can arise from spectrum dependence in simple gamma-ray dosimeter instruments. We present some gamma-ray doses for the Little Boy assembly operated at low power. These results can be used to determine the exposures of the Hiroshima survivors and thus aid in the establishment of radation exposure limits for the nuclear industry.« less

Microfluidic Thrombosis under Multiple Shear Rates and Antiplatelet Therapy Doses

PubMed Central

Ku, David N.; Forest, Craig R.

2014-01-01

The mainstay of treatment for thrombosis, the formation of occlusive platelet aggregates that often lead to heart attack and stroke, is antiplatelet therapy. Antiplatelet therapy dosing and resistance are poorly understood, leading to potential incorrect and ineffective dosing. Shear rate is also suspected to play a major role in thrombosis, but instrumentation to measure its influence has been limited by flow conditions, agonist use, and non-systematic and/or non-quantitative studies. In this work we measured occlusion times and thrombus detachment for a range of initial shear rates (500, 1500, 4000, and 10000 s−1) and therapy concentrations (0–2.4 µM for eptifibatide, 0–2 mM for acetyl-salicylic acid (ASA), 3.5–40 Units/L for heparin) using a microfluidic device. We also measured complete blood counts (CBC) and platelet activity using whole blood impedance aggregometry. Effects of shear rate and dose were analyzed using general linear models, logistic regressions, and Cox proportional hazards models. Shear rates have significant effects on thrombosis/dose-response curves for all tested therapies. ASA has little effect on high shear occlusion times, even at very high doses (up to 20 times the recommended dose). Under ASA therapy, thrombi formed at high shear rates were 4 times more prone to detachment compared to those formed under control conditions. Eptifibatide reduced occlusion when controlling for shear rate and its efficacy increased with dose concentration. In contrast, the hazard of occlusion from ASA was several orders of magnitude higher than that of eptifibatide. Our results show similar dose efficacy to our low shear measurements using whole blood aggregometry. This quantitative and statistically validated study of the effects of a wide range of shear rate and antiplatelet therapy doses on occlusive thrombosis contributes to more accurate understanding of thrombosis and to models for optimizing patient treatment. PMID:24404131

Dating Middle Pleistocene loess using IRSL luminescence

NASA Astrophysics Data System (ADS)

Michel, L.

2008-12-01

Loess is a unique palaeoclimate proxy that has a relatively global distribution. A major issue in loess studies is their age, as most terrestrial sediments are outside the realm of isotopic dating methods. Luminescence dating of loess has been attempted with limited success as Optically Stimulated Luminescence (OSL) from the two common dosimeters used in luminescence, quartz and feldspar minerals, both yielded age underestimates. Quartz is limited by dose saturation and feldspar suffers from anomalous fading. Over the last decade, we have developed methods to deal with anomalous fading and hence correct Infrared Stimulated Luminescence (IRSL) ages from feldspar dominated samples. A method known as Dose Rate Correction (DRC) has been successfully applied to loess from the Western European Belt, for ages as old as the Middle Pleistocene. Ages using the same method have been obtained for loess in Alaska and the technique is now being extended to loess from Illinois and China. IRSL can also be used as a reliable telecorrelation tool as luminescence properties of loess are broadly similar, whatever the geological provenance. DRC corrected IRSL extends the applicability of luminescence to dating loess up to at least 500 ka. The limiting factor in the specific case of loess is dose saturation due to relatively high dose rate compared to the average terrestrial sediment radioactivity.

The relationship between infecting dose and severity of disease in reported outbreaks of Salmonella infections.

PubMed Central

Glynn, J. R.; Bradley, D. J.

1992-01-01

The relationship between size of the infecting dose and severity of the resulting disease has been investigated for salmonella infections by reanalysis of data within epidemics for 32 outbreaks, and comparing data between outbreaks for 68 typhoid epidemics and 49 food-poisoning outbreaks due to salmonellas. Attack rate, incubation period, amount of infected food consumed and type of vehicle are used as proxy measures of infecting dose, while case fatality rates for typhoid and case hospitalization rates for food poisoning salmonellas were used to assess severity. Limitations of the data are discussed. Both unweighted and logit analysis models are used. There is no evidence for a dose-severity relationship for Salmonella typhi, but evidence of a correlation between dose and severity is available from within-epidemic or between-epidemic analysis, or both, for Salmonella typhimurium, S. enteritidis, S. infantis, S. newport, and S. thompson. The presence of such a relationship affects the way in which control interventions should be assessed. PMID:1468522

Status of NCRP Scientific Committee 1-23 Commentary on Guidance on Radiation Dose Limits for the Lens of the Eye.

PubMed

Dauer, Lawrence T; Ainsbury, Elizabeth A; Dynlacht, Joseph; Hoel, David; Klein, Barbara E K; Mayer, Don; Prescott, Christina R; Thornton, Raymond H; Vano, Eliseo; Woloschak, Gayle E; Flannery, Cynthia M; Goldstein, Lee E; Hamada, Nobuyuki; Tran, Phung K; Grissom, Michael P; Blakely, Eleanor A

2016-02-01

Previous National Council on Radiation Protection and Measurements (NCRP) publications have addressed the issues of risk and dose limitation in radiation protection and included guidance on specific organs and the lens of the eye. NCRP decided to prepare an updated commentary intended to enhance the previous recommendations provided in earlier reports. The NCRP Scientific Committee 1-23 (SC 1-23) is charged with preparing a commentary that will evaluate recent studies on the radiation dose response for the development of cataracts and also consider the type and severity of the cataracts as well as the dose rate; provide guidance on whether existing dose limits to the lens of the eye should be changed in the United States; and suggest research needs regarding radiation effects on and dose limits to the lens of the eye. A status of the ongoing work of SC 1-23 was presented at the Annual Meeting, "Changing Regulations and Radiation Guidance: What Does the Future Hold?" The following represents a synopsis of a few main points in the current draft commentary. It is likely that several changes will be forthcoming as SC 1-23 responds to subject matter expert review and develops a final document, expected by mid 2016.

The Study of External Dose Rate and Retained Body Activity of Patients Receiving 131I Therapy for Differentiated Thyroid Carcinoma

PubMed Central

Zhang, Haiying; Jiao, Ling; Cui, Songye; Wang, Liang; Tan, Jian; Zhang, Guizhi; He, Yajing; Ruan, Shuzhou; Fan, Saijun; Zhang, Wenyi

2014-01-01

Radiation safety is an integral part of targeted radionuclide therapy. The aim of this work was to study the external dose rate and retained body activity as functions of time in differentiated thyroid carcinoma patients receiving 131I therapy. Seventy patients were stratified into two groups: the ablation group (A) and the follow-up group (FU). The patients’ external dose rate was measured, and simultaneously, their retained body radiation activity was monitored at various time points. The equations of the external dose rate and the retained body activity, described as a function of hours post administration, were fitted. Additionally, the release time for patients was calculated. The reduction in activity in the group receiving a second or subsequent treatment was more rapid than the group receiving only the initial treatment. Most important, an expeditious method was established to indirectly evaluate the retained body activity of patients by measuring the external dose rate with a portable radiation survey meter. By this method, the calculated external dose rate limits are 19.2, 8.85, 5.08 and 2.32 μSv·h−1 at 1, 1.5, 2 and 3 m, respectively, according to a patient’s released threshold level of retained body activity <400 MBq. This study is beneficial for radiation safety decision-making. PMID:25337944

Radiation exposure of the radiologist's eye lens during CT-guided interventions.

PubMed

Heusch, Philipp; Kröpil, Patric; Buchbender, Christian; Aissa, Joel; Lanzman, Rotem S; Heusner, Till A; Ewen, Klaus; Antoch, Gerald; Fürst, Günther

2014-02-01

In the past decade the number of computed tomography (CT)-guided procedures performed by interventional radiologists have increased, leading to a significantly higher radiation exposure of the interventionalist's eye lens. Because of growing concern that there is a stochastic effect for the development of lens opacification, eye lens dose reduction for operators and patients should be of maximal interest. To determine the interventionalist's equivalent eye lens dose during CT-guided interventions and to relate the results to the maximum of the recommended equivalent dose limit. During 89 CT-guided interventions (e.g. biopsies, drainage procedures, etc.) measurements of eye lens' radiation doses were obtained from a dedicated dosimeter system for scattered radiation. The sensor of the personal dosimeter system was clipped onto the side of the lead glasses which was located nearest to the CT gantry. After the procedure, radiation dose (µSv), dose rate (µSv/min) and the total exposure time (s) were recorded. For all 89 interventions, the median total exposure lens dose was 3.3 µSv (range, 0.03-218.9 µSv) for a median exposure time of 26.2 s (range, 1.1-94.0 s). The median dose rate was 13.9 µSv/min (range, 1.1-335.5 µSv/min). Estimating 50-200 CT-guided interventions per year performed by one interventionalist, the median dose of the eye lens of the interventional radiologist does not exceed the maximum of the ICRP-recommended equivalent eye lens dose limit of 20 mSv per year.

Radionuclide production and dose rate estimation during the commissioning of the W-Ta spallation target

NASA Astrophysics Data System (ADS)

Yu, Q. Z.; Liang, T. J.

2018-06-01

China Spallation Neutron Source (CSNS) is intended to begin operation in 2018. CSNS is an accelerator-base multidisciplinary user facility. The pulsed neutrons are produced by a 1.6GeV short-pulsed proton beam impinging on a W-Ta spallation target, at a beam power of100 kW and a repetition rate of 25 Hz. 20 neutron beam lines are extracted for the neutron scattering and neutron irradiation research. During the commissioning and maintenance scenarios, the gamma rays induced from the W-Ta target can cause the dose threat to the personal and the environment. In this paper, the gamma dose rate distributions for the W-Ta spallation are calculated, based on the engineering model of the target-moderator-reflector system. The shipping cask is analyzed to satisfy the dose rate limit that less than 2 mSv/h at the surface of the shipping cask. All calculations are performed by the Monte carlo code MCNPX2.5 and the activation code CINDER’90.

Light dose versus rate of delivery: implications for macroalgal productivity.

PubMed

Desmond, Matthew J; Pritchard, Daniel W; Hepburn, Christopher D

2017-06-01

The role of how light is delivered over time is an area of macroalgal photosynthesis that has been overlooked but may play a significant role in controlling rates of productivity and the structure and persistence of communities. Here we present data that quantify the relative influence of total quantum dose and delivery rate on the photosynthetic productivity of five ecologically important Phaeophyceae species from southern New Zealand. Results suggested that greater net oxygen production occurs when light is delivered at a lower photon flux density (PFD) over a longer period compared to a greater PFD over a shorter period, given the same total dose. This was due to greater efficiency (α) at a lower PFD which, for some species, meant a compensatory effect can occur. This resulted in equal or greater productivity even when the total quantum dose of the lower PFD was significantly reduced. It was also shown that light limitation at Huriawa Peninsula, where macroaglae were sourced, may be restricting the acclimation potential of species at greater depths, and that even at shallow depth periods of significant light limitation are likely to occur. This research is of particular interest as the variability of light delivery to coastal reef systems increases as a result of anthropogenic disturbances, and as the value of in situ community primary productivity estimates is recognised.

Optimizing bevacizumab dosing in glioblastoma: less is more.

PubMed

Ajlan, Abdulrazag; Thomas, Piia; Albakr, Abdulrahman; Nagpal, Seema; Recht, Lawrence

2017-10-01

Compared to traditional chemotherapies, where dose limiting toxicities represent the maximum possible dose, monoclonal antibody therapies are used at doses well below maximum tolerated dose. However, there has been little effort to ascertain whether there is a submaximal dose at which the efficacy/complication ratio is maximized. Thus, despite the general practice of using Bevacizumab (BEV) at dosages of 10 mg/kg every other week for glioma patients, there has not been much prior work examining whether the relatively high complication rates reported with this agent can be decreased by lowering the dose without impairing efficacy. We assessed charts from 80 patients who received BEV for glioblastoma to survey the incidence of complications relative to BEV dose. All patients were treated with standard upfront chemoradiation. The toxicity was graded based on the NCI CTCAE, version 4.03. The rate of BEV serious related adverse events was 12.5% (n = 10/80). There were no serious adverse events (≥grade 3) when the administered dose was (<3 mg/kg/week), compared to a 21% incidence in those who received higher doses (≥3 mg/kg/week) (P < 0.01). Importantly, the three patient deaths attributable to BEV administration occurred in patients receiving higher doses. Patients who received lower doses also had a better survival rate, although this did not reach statistical significance [median OS 39 for low dose group vs. 17.3 for high dose group (P = 0.07)]. Lower rates of serious BEV related toxicities are noted when lower dosages are used without diminishing positive clinical impact. Further work aimed at optimizing BEV dosage is justified.

Randomized Trial of 2 Versus 1 Dose of Measles Vaccine: Effect on Hospital Admission of Children After 9 Months of Age.

PubMed

Brønd, Marie; Martins, Cesario L; Byberg, Stine; Benn, Christine S; Whittle, Hilton; Garly, May-Lill; Aaby, Peter; Fisker, Ane B

2017-06-15

Two doses of measles vaccine (MV) might reduce the nonmeasles mortality rate more than 1 dose of MV does. The effect of 2 versus 1 dose on morbidity has not been examined. Within a randomized trial of the effect of 2 doses versus 1 dose of MV on mortality in Guinea-Bissau, we investigated the effect on hospital admissions. Children were randomly assigned 1:2 to receive MV at 4.5 and 9 months of age or the currently recommended dose at 9 months. We compared hospital admission rates among children between 9 and 18 months of age in a Cox regression model with age as the underlying time scale. Half of the children had received neonatal vitamin A supplementation (NVAS) in another trial. The beneficial effect of MV at 4.5 and 9 months on mortality was limited to children who had not received NVAS; therefore, we investigated the interaction of MV with NVAS on admission rates. Among 5626 children (2 doses of MV, 1960 children; 1 dose of MV, 3666), we identified 311 hospital admissions of children between 9 and 18 months of age. Overall, compared to 1 dose of MV, 2 doses reduced the risk of hospital admission for children who had not received NVAS (hazard ratio [HR], 0.66 [95% confidence interval (CI), 0.47-0.93]), but we found no effect among NVAS recipients (HR, 1.16 [95% CI, 0.82-1.63]) (P = .02 for interaction). The benefit of 2 doses of MV was limited to children who had not received NVAS. NVAS is not generally recommended; hence, an early 2-dose measles vaccination policy might reduce hospital admissions more than the current policy of providing the first MV at 9 months of age. ClinicalTrials.gov identifier NCT00168558. © The Author 2017. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Experimental and theoretical studies of nuclear generation of ozone from oxygen and oxygen-sulfur hexafluoride mixtures

NASA Astrophysics Data System (ADS)

Elsayed-Ali, H. E.; Miley, G. H.

1986-08-01

A series of experimental measurements of the yield of O3 in nuclear-induced O2 and O2-SF6 discharges are reported. The discharges were created by bombardment with energetic particles from the 10B(n,α)7Li reaction. Continuous irradiation at dose rates of 1015-1017 eV cm-3 s-1 and pulsed irradiation (˜10 ms FWHM) at a peak dose rate of ˜1020 eV cm-3 s-1 were conducted. At the lower dose rates, the addition of SF6 generally increased the ozone yield due to the slowing of ozone destruction by negative oxygen and ozone ions. In contrast, at the high dose rates, the ozone concentration decreased due to SF6 suppression of atomic oxygen formation by ion-ion recombination. A numerical model was developed and tested against experimental conditions. This model indicates that the steady-state ozone concentration was limited by the reaction O-3+O3→2O2+O-2 with a rate coefficient of ˜1×10-12 cm3 s-1. In addition to dose rate effects, pressure and temperature effects on ozone production are discussed and methods for increasing the ozone yield are suggested.

Measurement of radon/thoron exhalation rates and gamma-ray dose rate in granite areas in Japan.

PubMed

Prasad, G; Ishikawa, T; Hosoda, M; Sahoo, S K; Kavasi, N; Sorimachi, A; Tokonami, S; Uchida, S

2012-11-01

Radon and thoron exhalation rates and gamma-ray dose rate in different places in Hiroshima Prefecture were measured. Exhalation rates were measured using an accumulation chamber method. The radon exhalation rate was found to vary from 3 to 37 mBq m(-2) s(-1), while the thoron exhalation rate ranged from 40 to 3330 mBq m(-2) s(-1). The highest radon exhalation rate (37 mBq m(-2) s(-1)) and gamma-ray dose rate (92 nGy h(-1)) were found in the same city (Kure City). In Kure City, indoor radon and thoron concentrations were previously measured at nine selected houses using a radon-thoron discriminative detector (Raduet). The indoor radon concentrations varied from 16 to 78 Bq m(-3), which was higher than the average value in Japan (15.5 Bq m(-3)). The indoor thoron concentration ranged from ND (not detected: below a detection limit of approximately 10 Bq m(-3)) to 314 Bq m(-3). The results suggest that radon exhalation rate from the ground is an influential factor for indoor radon concentration.

Interpretation of Gamma Index for Quality Assurance of Simultaneously Integrated Boost (SIB) IMRT Plans for Head and Neck Carcinoma

NASA Astrophysics Data System (ADS)

Atiq, Maria; Atiq, Atia; Iqbal, Khalid; Shamsi, Quratul ain; Andleeb, Farah; Buzdar, Saeed Ahmad

2017-12-01

Objective: The Gamma Index is prerequisite to estimate point-by-point difference between measured and calculated dose distribution in terms of both Distance to Agreement (DTA) and Dose Difference (DD). This study aims to inquire what percentage of pixels passing a certain criteria assure a good quality plan and suggest gamma index as efficient mechanism for dose verification of Simultaneous Integrated Boost Intensity Modulated Radiotherapy plans. Method: In this study, dose was calculated for 14 head and neck patients and IMRT Quality Assurance was performed with portal dosimetry using the Eclipse treatment planning system. Eclipse software has a Gamma analysis function to compare measured and calculated dose distribution. Plans of this study were deemed acceptable when passing rate was 95% using tolerance for Distance to agreement (DTA) as 3mm and Dose Difference (DD) as 5%. Result and Conclusion: Thirteen cases pass tolerance criteria of 95% set by our institution. Confidence Limit for DD is 9.3% and for gamma criteria our local CL came out to be 2.0% (i.e., 98.0% passing). Lack of correlation was found between DD and γ passing rate with R2 of 0.0509. Our findings underline the importance of gamma analysis method to predict the quality of dose calculation. Passing rate of 95% is achieved in 93% of cases which is adequate level of accuracy for analyzed plans thus assuring the robustness of SIB IMRT treatment technique. This study can be extended to investigate gamma criteria of 5%/3mm for different tumor localities and to explore confidence limit on target volumes of small extent and simple geometry.

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

NASA Astrophysics Data System (ADS)

Hajdas, Wojtek; Mrigakshi, Alankrita; Xiao, Hualin

2017-04-01

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

Optimal Dosing of Botulinum Toxin for Treatment of Chronic Anal Fissure: A Systematic Review and Meta-Analysis.

PubMed

Lin, Jin Xin; Krishna, Sanjeev; Su'a, Bruce; Hill, Andrew G

2016-09-01

Chronic anal fissures are associated with significant morbidity and reduced quality of life. Studies have investigated the efficacy of botulinum toxin with variable results; thus, there is currently no consensus on botulinum toxin dose or injection sites. This study aimed to systematically analyze trials studying the efficacy of botulinum toxin for treatment of chronic anal fissure to identify an optimum dosage and injection regimen. A comprehensive review of the literature was conducted according to PRISMA guidelines. PubMed/Medline, Embase, Scopus, and the Cochrane Library were searched from inception to June 2015. All clinical trials that investigated the efficacy of botulinum toxin for chronic anal fissure were selected according to specific criteria. The interventions used were various doses of botulinum toxin. Clinical outcomes, dosage, and injection site data were evaluated with weighted pooled results for each dosage and 95% confidence intervals. There were 1158 patients, with 661 in botulinum toxin treatment arms, from 18 clinical trials included in this review. The outcomes of interest were 3-month healing, incontinence, and recurrence rates. Meta-regression analysis demonstrated a small decrease in healing rate (0.34%; 95% CI, 0-0.68; p = 0.048) with each increase in dosage, a small increase in incontinence rate (1.02 times; 95% CI, 1.0002-1.049; p = 0.048) with each increase in dosage and a small increase in recurrence rate (1.037 times; 95% CI, 1.018-1.057; p = 0.0002) with each increase in dosage. The optimum injection site could not be determined. This study was limited by weaknesses in the underlying evidence, such as variable quality, short follow-up, and a limited range of doses represented. Fissure healing with lower doses of botulinum toxin is as effective as with high doses. Lower doses also reduce the risk of incontinence and recurrence in the long term.

Assessing doses to terrestrial wildlife at a radioactive waste disposal site: inter-comparison of modelling approaches.

PubMed

Johansen, M P; Barnett, C L; Beresford, N A; Brown, J E; Černe, M; Howard, B J; Kamboj, S; Keum, D-K; Smodiš, B; Twining, J R; Vandenhove, H; Vives i Batlle, J; Wood, M D; Yu, C

2012-06-15

Radiological doses to terrestrial wildlife were examined in this model inter-comparison study that emphasised factors causing variability in dose estimation. The study participants used varying modelling approaches and information sources to estimate dose rates and tissue concentrations for a range of biota types exposed to soil contamination at a shallow radionuclide waste burial site in Australia. Results indicated that the dominant factor causing variation in dose rate estimates (up to three orders of magnitude on mean total dose rates) was the soil-to-organism transfer of radionuclides that included variation in transfer parameter values as well as transfer calculation methods. Additional variation was associated with other modelling factors including: how participants conceptualised and modelled the exposure configurations (two orders of magnitude); which progeny to include with the parent radionuclide (typically less than one order of magnitude); and dose calculation parameters, including radiation weighting factors and dose conversion coefficients (typically less than one order of magnitude). Probabilistic approaches to model parameterisation were used to encompass and describe variable model parameters and outcomes. The study confirms the need for continued evaluation of the underlying mechanisms governing soil-to-organism transfer of radionuclides to improve estimation of dose rates to terrestrial wildlife. The exposure pathways and configurations available in most current codes are limited when considering instances where organisms access subsurface contamination through rooting, burrowing, or using different localised waste areas as part of their habitual routines. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Radiation streaming and skyshine evaluation for a proposed low-level radioactive waste assured isolation facility.

PubMed

Arno, Matthew; Hamilton, Ian S

2003-10-01

Texas is investigating the idea of building a long term waste storage facility, also known as an Assured Isolation Facility. This is an above-ground, retrievable low-level radioactive waste storage facility. A preliminary, scoping-level analysis has been extended to consider more complex scenarios of radiation streaming and skyshine by using MCNP to model the facility in greater detail. Using bounding source term assumptions, the radiation doses and dose rates are found to exceed applicable limits by an order of magnitude. By altering the facility design to fill in the hollow cores of the prefabricated concrete slabs used in the roof over the "high-gamma" rooms where the waste with greatest gamma radiation intensity is stored, dose rates outside the facility decrease by an order of magnitude. With the modified design, the annual dose at the site fenceline is less than the 1 mSv annual limit for exposure of the public. Within the site perimeter, modifying the roof results in an order of magnitude drop in the dose rate for personnel outside the facility and on the facility roof, as well as a significant drop inside the facility. Radiation streaming inside the facility can be lowered almost two orders of magnitude by placing operational restrictions to keep at least two rows of waste containers in front of the high-gamma room to cut down on the size of the path for streaming.

Psychopharmacology of theobromine in healthy volunteers.

PubMed

Baggott, Matthew J; Childs, Emma; Hart, Amy B; de Bruin, Eveline; Palmer, Abraham A; Wilkinson, Joy E; de Wit, Harriet

2013-07-01

Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited. We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug's effects in relation to genes related to their target receptors, but few associations were detected. This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative.

Psychopharmacology of theobromine in healthy volunteers

PubMed Central

Baggott, Matthew J.; Childs, Emma; Hart, Amy B.; de Bruin, Eveline; Palmer, Abraham A.; Wilkinson, Joy E.; de Wit, Harriet

2013-01-01

Background Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, currently evidence for this is limited. Objectives We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Results Caffeine had the expected effects on mood including feelings of alertness, and cardiovascular parameters. Theobromine responses differed according to dose: it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses we also examined individual differences in the drugs' effects in relation to genes related to their target receptors, but few associations were detected. Conclusions This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes effects become negative. PMID:23420115

A GREEN'S FUNCTION APPROACH FOR DETERMINING DOSE RATES FOR SMALL GRAM QUANTITIES IN SHIPPING PACKAGINGS

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

Nathan, S.

The Small Gram Quantity (SGQ) concept is based on the understanding that small amounts of hazardous materials, in this case radioactive materials (RAM), are significantly less hazardous than large amounts of the same materials. This paper describes a methodology designed to estimate an SGQ for several neutron and gamma emitting isotopes that can be shipped in a package in compliance with 10 CFR Part 71 external radiation level limits regulations. The neutron and photon sources were calculated using both ORIGEN-S and RASTA. The response from a unit source in each neutron and photon group was calculated using MCNP5 with eachmore » unshielded and shielded container configuration. Effects of self-shielding on both neutron and photon response were evaluated by including either plutonium oxide or iron in the source region for the case with no shielded container. For the cases of actinides mixed with light elements, beryllium is the bounding light element. The added beryllium (10 to 90 percent of the actinide mass) in the cases studied represents between 9 and 47 percent concentration of the total mixture mass. For beryllium concentrations larger than 50 percent, the increase in the neutron source term and dose rate tend to increase at a much lower rate than at concentrations lower than 50%. The intimately mixed actinide-beryllium form used in these models is very conservative and thus the limits presented in this report are practical bounds on the mass that can be safely shipped. The calculated dose rate from one gram of each isotope was then used to determin the maximum amount of a single isotope that could be shipped in the Model 9977 Package (or packagings having the same or larger external dimensions as well as similar structural materials) and have the external radiation level within the regulatory dose limits at the surface of the package. The estimates of the mass limits presented would also serve as conservative limits for both the Models 9975 and 9978 packages. If a package contains a mixture of isotopes, the acceptability for shipment can be determined by a sum of fractions approach. It should be noted that the SGQ masses presented in this report represent limits that would comply with the external radiation limits under 10CFR Part 71. They do not necessarily bound lower limits that may be required to comply with other factors such as heat load of the package.« less

Effects of UVB radiation on grazing of two cladocerans from high-altitude Andean lakes

PubMed Central

Rejas, Danny

2017-01-01

Climate change and water extraction may result in increased exposition of the biota to ultraviolet-B radiation (UVB) in high-altitude Andean lakes. Although exposition to lethal doses in these lakes is unlikely, sub-lethal UVB doses may have strong impacts in key compartments such as zooplankton. Here, we aimed at determining the effect of sub-lethal UVB doses on filtration rates of two cladoceran species (Daphnia pulicaria and Ceriodaphnia dubia). We firstly estimated the Incipient Limiting Concentration (ILC) and the Gut Passage Time (GPT) for both species. Thereafter we exposed clones of each species to four increasing UVB doses (treatments): i) DUV-0 (Control), ii) DUV-1 (0.02 MJ m2), iii) DUV-2 (0.03 MJ m2) and iv) DUV-3 (0.15 MJ m2); and estimated their filtration rates using fluorescent micro-spheres. Our results suggest that increasing sub-lethal doses of UVB radiation may strongly disturb the structure and functioning of high-altitude Andean lakes. Filtration rates of D. pulicaria were not affected by the lowest dose applied (DUV-1), but decreased by 50% in treatments DUV-2 and DUV-3. Filtration rates for C. dubia were reduced by more than 80% in treatments DUV-1 and DUV-2 and 100% of mortality occurred at the highest UVB dose applied (DUV-3). PMID:28379975

Implementing an Accurate and Rapid Sparse Sampling Approach for Low-Dose Atomic Resolution STEM Imaging

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

Kovarik, Libor; Stevens, Andrew J.; Liyu, Andrey V.

Aberration correction for scanning transmission electron microscopes (STEM) has dramatically increased spatial image resolution for beam-stable materials, but it is the sample stability rather than the microscope that often limits the practical resolution of STEM images. To extract physical information from images of beam sensitive materials it is becoming clear that there is a critical dose/dose-rate below which the images can be interpreted as representative of the pristine material, while above it the observation is dominated by beam effects. Here we describe an experimental approach for sparse sampling in the STEM and in-painting image reconstruction in order to reduce themore » electron dose/dose-rate to the sample during imaging. By characterizing the induction limited rise-time and hysteresis in scan coils, we show that sparse line-hopping approach to scan randomization can be implemented that optimizes both the speed of the scan and the amount of the sample that needs to be illuminated by the beam. The dose and acquisition time for the sparse sampling is shown to be effectively decreased by factor of 5x relative to conventional acquisition, permitting imaging of beam sensitive materials to be obtained without changing the microscope operating parameters. As a result, the use of sparse line-hopping scan to acquire STEM images is demonstrated with atomic resolution aberration corrected Z-contrast images of CaCO 3, a material that is traditionally difficult to image by TEM/STEM because of dose issues.« less

Implementing an Accurate and Rapid Sparse Sampling Approach for Low-Dose Atomic Resolution STEM Imaging

DOE PAGES

Kovarik, Libor; Stevens, Andrew J.; Liyu, Andrey V.; ...

2016-10-17

Aberration correction for scanning transmission electron microscopes (STEM) has dramatically increased spatial image resolution for beam-stable materials, but it is the sample stability rather than the microscope that often limits the practical resolution of STEM images. To extract physical information from images of beam sensitive materials it is becoming clear that there is a critical dose/dose-rate below which the images can be interpreted as representative of the pristine material, while above it the observation is dominated by beam effects. Here we describe an experimental approach for sparse sampling in the STEM and in-painting image reconstruction in order to reduce themore » electron dose/dose-rate to the sample during imaging. By characterizing the induction limited rise-time and hysteresis in scan coils, we show that sparse line-hopping approach to scan randomization can be implemented that optimizes both the speed of the scan and the amount of the sample that needs to be illuminated by the beam. The dose and acquisition time for the sparse sampling is shown to be effectively decreased by factor of 5x relative to conventional acquisition, permitting imaging of beam sensitive materials to be obtained without changing the microscope operating parameters. The use of sparse line-hopping scan to acquire STEM images is demonstrated with atomic resolution aberration corrected Z-contrast images of CaCO3, a material that is traditionally difficult to image by TEM/STEM because of dose issues.« less

High and low energy gamma beam dump designs for the gamma beam delivery system at ELI-NP

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

Yasin, Zafar, E-mail: zafar.yasin@eli-np.ro; Matei, Catalin; Ur, Calin A.

The Extreme Light Infrastructure - Nuclear Physics (ELI-NP) is under construction in Magurele, Bucharest, Romania. The facility will use two 10 PW lasers and a high intensity, narrow bandwidth gamma beam for stand-alone and combined laser-gamma experiments. The accurate estimation of particle doses and their restriction within the limits for both personel and general public is very important in the design phase of any nuclear facility. In the present work, Monte Carlo simulations are performed using FLUKA and MCNPX to design 19.4 and 4 MeV gamma beam dumps along with shielding of experimental areas. Dose rate contour plots from both FLUKAmore » and MCNPX along with numerical values of doses in experimental area E8 of the facility are performed. The calculated doses are within the permissible limits. Furthermore, a reasonable agreement between both codes enhances our confidence in using one or both of them for future calculations in beam dump designs, radiation shielding, radioactive inventory, and other calculations releated to radiation protection. Residual dose rates and residual activity calculations are also performed for high-energy beam dump and their effect is negligible in comparison to contributions from prompt radiation.« less

Dose-finding study of intensive weekly alternating schedule of docetaxel, 5-fluorouracil, and oxaliplatin, FD/FOx regimen, in metastatic gastric cancer.

PubMed

Bruera, Gemma; Massacese, Silvia; Galvano, Antonio; Mas, Antonella Dal; Guadagni, Stefano; Calvisi, Giuseppe; Ciacco, Eugenio; Russo, Antonio; Ricevuto, Enrico

2018-04-17

Proper administration timing, dose-intensity, efficacy/toxicity ratio of triplet docetaxel (DTX), 5-fluorouracil (5-FU), and oxaliplatin (OXP) should be improved to safely perform three-drugs intensive first line in advanced gastric cancer (GC). This dose-finding study investigated recommended 5-FU and OXP doses, safety of triplet regimen and preliminary activity. Schedule: 12h-timed-flat-infusion 5-FU 700-1000 mg/m 2 /d 1-2, 8-9, 15-16, 22-23, with 100 mg/m 2 /d increase for dose level; DTX 50 mg/m 2 d 1, 15 fixed dose, OXP at three increasing dose-levels 60-70-80 mg/m 2 d 8, 22, every 4 weeks. Intra- and inter-patients dose-escalation was planned. Ten fit <75 years patients were enrolled: median age 59; young-elderly 4 (40%). From first to fifth dose level, 5 patients (1 per cohort) were enrolled according to intra-patient dose escalation, no dose-limiting toxicity (DLT) were reported. At sixth level, 1 DLT, G2 diarrhea, was reported, thus other 2 patients were enrolled, DLT 1/3 patients (33%). Maximum tolerated dose (MTD) was not reached. 5-FU and OXP recommended doses (RD) were 1000 mg/m 2 /d and 80 mg/m 2 , respectively. To confirm RD, other 3 patients were enrolled, without DLT. Cumulative G3-4 toxicities were: neutropenia 50%, leucopenia 20%, hypoalbuminemia 10%, mucositis 10%, asthenia 20%. Limiting toxicity syndromes were 30%, 25% in young-elderly, all multiple site. Objective response rate intent-to-treat 60%, disease control rate 90%. After 15 months follow-up, progression-free and overall survival, 6 and 17 months, respectively. First line intensive FD/FOx regimen adding DXT/5-FU/OXP can be safely administered at recommended doses in advanced GC, with promising high activity and efficacy.

Dosimetric properties of a proton beamline dedicated to the treatment of ocular disease

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

Slopsema, R. L., E-mail: rslopsema@floridaproton.org; Mamalui, M.; Yeung, D.

2014-01-15

Purpose: A commercial proton eyeline has been developed to treat ocular disease. Radiotherapy of intraocular lesions (e.g., uveal melanoma, age-related macular degeneration) requires sharp dose gradients to avoid critical structures like the macula and optic disc. A high dose rate is needed to limit patient gazing times during delivery of large fractional dose. Dose delivery needs to be accurate and predictable, not in the least because current treatment planning algorithms have limited dose modeling capabilities. The purpose of this paper is to determine the dosimetric properties of a new proton eyeline. These properties are compared to those of existing systemsmore » and evaluated in the context of the specific clinical requirements of ocular treatments. Methods: The eyeline is part of a high-energy, cyclotron-based proton therapy system. The energy at the entrance of the eyeline is 105 MeV. A range modulator (RM) wheel generates the spread-out Bragg peak, while a variable range shifter system adjusts the range and spreads the beam laterally. The range can be adjusted from 0.5 up to 3.4 g/cm{sup 2}; the modulation width can be varied in steps of 0.3 g/cm{sup 2} or less. Maximum field diameter is 2.5 cm. All fields can be delivered with a dose rate of 30 Gy/min or more. The eyeline is calibrated according to the IAEA TRS-398 protocol using a cylindrical ionization chamber. Depth dose distributions and dose/MU are measured with a parallel-plate ionization chamber; lateral profiles with radiochromic film. The dose/MU is modeled as a function of range, modulation width, and instantaneous MU rate with fit parameters determined per option (RM wheel). Results: The distal fall-off of the spread-out Bragg peak is 0.3 g/cm{sup 2}, larger than for most existing systems. The lateral penumbra varies between 0.9 and 1.4 mm, except for fully modulated fields that have a larger penumbra at skin. The source-to-axis distance is found to be 169 cm. The dose/MU shows a strong dependence on range (up to 4%/mm). A linear increase in dose/MU as a function of instantaneous MU rate is observed. The dose/MU model describes the measurements with an accuracy of ±2%. Neutron dose is found to be 146 ± 102 μSv/Gy at the contralateral eye and 19 ± 13 μSv/Gy at the chest. Conclusions: Measurements show the proton eyeline meets the requirements to effectively treat ocular disease.« less

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

Slopsema, R. L., E-mail: rslopsema@floridaproton.org; Mamalui, M.; Yeung, D.

Purpose: A commercial proton eyeline has been developed to treat ocular disease. Radiotherapy of intraocular lesions (e.g., uveal melanoma, age-related macular degeneration) requires sharp dose gradients to avoid critical structures like the macula and optic disc. A high dose rate is needed to limit patient gazing times during delivery of large fractional dose. Dose delivery needs to be accurate and predictable, not in the least because current treatment planning algorithms have limited dose modeling capabilities. The purpose of this paper is to determine the dosimetric properties of a new proton eyeline. These properties are compared to those of existing systemsmore » and evaluated in the context of the specific clinical requirements of ocular treatments. Methods: The eyeline is part of a high-energy, cyclotron-based proton therapy system. The energy at the entrance of the eyeline is 105 MeV. A range modulator (RM) wheel generates the spread-out Bragg peak, while a variable range shifter system adjusts the range and spreads the beam laterally. The range can be adjusted from 0.5 up to 3.4 g/cm{sup 2}; the modulation width can be varied in steps of 0.3 g/cm{sup 2} or less. Maximum field diameter is 2.5 cm. All fields can be delivered with a dose rate of 30 Gy/min or more. The eyeline is calibrated according to the IAEA TRS-398 protocol using a cylindrical ionization chamber. Depth dose distributions and dose/MU are measured with a parallel-plate ionization chamber; lateral profiles with radiochromic film. The dose/MU is modeled as a function of range, modulation width, and instantaneous MU rate with fit parameters determined per option (RM wheel). Results: The distal fall-off of the spread-out Bragg peak is 0.3 g/cm{sup 2}, larger than for most existing systems. The lateral penumbra varies between 0.9 and 1.4 mm, except for fully modulated fields that have a larger penumbra at skin. The source-to-axis distance is found to be 169 cm. The dose/MU shows a strong dependence on range (up to 4%/mm). A linear increase in dose/MU as a function of instantaneous MU rate is observed. The dose/MU model describes the measurements with an accuracy of ±2%. Neutron dose is found to be 146 ± 102 μSv/Gy at the contralateral eye and 19 ± 13 μSv/Gy at the chest. Conclusions: Measurements show the proton eyeline meets the requirements to effectively treat ocular disease.« less

Subcutaneous Administration of Otelixizumab is Limited by Injection Site Reactions: Results of an Exploratory Study in Type 1 Diabetes Mellitus Patients.

PubMed

MacDonald, A; Ambery, P; Donaldson, J; Hicks, K; Keymeulen, B; Parkin, J

2016-05-01

Targeting CD3 antigens on human T lymphocytes with monoclonal antibodies has been shown to reduce the rate of decline of C-peptides in recent-onset type 1 diabetes mellitus patients. However, effective doses are associated with infusion reactions typical of "cytokine release syndrome" and appear to be dose-limiting when administered as short-duration infusions. A possible alternative approach, which may reduce the rate of T cell activation and consequent systemic cytokine release, is to inject subcutaneously. We investigated single- and repeat-dose subcutaneous administration of the anti-CD3 monoclonal antibody otelixizumab in small cohorts of patients with type 1 diabetes. Transient reductions in free or unbound CD3 antigen on CD4+ and CD8+ cells and absolute lymphocyte count were observed in the blood of these patients during treatment, consistent with the known mechanism of action of otelixizumab and other anti-CD3 monoclonal antibodies. This was despite the very low systemic exposure of antibodies measured during the same time period. With the exception of sporadic headaches, other symptoms associated with cytokine release syndrome, such as fever, nausea, vomiting, myalgia, and arthralgia, were absent in treated patients. However, treatment-related injection site reactions were consistently observed. The reactions were erythematous and their sizes were dose-dependent; in some cases, reactions persisted for up to 2 weeks following the start of treatment. While patients responded well to topical corticosteroid treatment and prophylaxis reduced the intensity of injection site reactions, the reactions were considered dose-limiting and higher doses were not investigated. © Georg Thieme Verlag KG Stuttgart · New York.

Spiromax, a New Dry Powder Inhaler: Dose Consistency under Simulated Real-World Conditions

PubMed Central

Canonica, Giorgio Walter; Arp, Jan; Keegstra, Johan René

2015-01-01

Abstract Background: Spiromax® is a novel dry powder inhaler for patients with asthma or chronic obstructive pulmonary disease (COPD). The studies presented here provide further data on attributes (in vitro dosing consistency with budesonide–formoterol (DuoResp) Spiromax; flow rates through empty versions of the Spiromax and Turbuhaler inhaler) of importance to patients with asthma or COPD. Methods: Dose-delivery studies were performed using low-, middle-, and high-strength DuoResp Spiromax. Dose consistency was assessed over inhaler life. Total emitted doses (TEDs) were measured at various flow rates, after exposure to high and low temperature or humidity, at different inhaler orientations, and after dropping the inhaler. The criterion for evaluating dose uniformity was whether mean TEDs were within the product specification limits. In separate studies, flow rates were measured after training, using the patient information leaflets, and again after enhanced training as part of a randomized, open-label, cross-over study. Results: Mean values for both budesonide and formoterol were within 85%–115% of the label claim for each strength of DuoResp Spiromax for initial dose uniformity and for the other investigated conditions (temperature, humidity, orientation, dropping, knocking), with the exception of approximately an 80% increase in first dose after dropping the inhaler (subsequent doses not affected). In the flow rate patient study, two patients' inhalations with Spiromax and six with Turbuhaler were <30 L/min. The majority of asthma patients [91% (Spiromax) versus 82% (Turbuhaler)] achieved the preferred flow rate of >60 L/min. Conclusions: DuoResp Spiromax consistently meets dose uniformity criteria, under controlled laboratory conditions and with variations intended to mimic real-world use. Following enhanced training, all patients in the flow study were able to achieve the minimal inspiratory flow rate of >30 L/min, which is required for effective treatment. PMID:26352860

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

Wang, C; Nguyen, G; Chung, Y

Purpose: Ureteroscopy involves fluoroscopy which potentially results in considerable amount of radiation dose to the patient. Purpose of this study was two-fold: (a) to develop the effective dose computational model for obese and non-obese patients undergoing left and right ureteroscopy, and (b) to evaluate the utility of a commercial Monte Carlo software for dose assessment in ureteroscopy. Methods: Organ dose measurements were performed on an adult male anthropomorphic phantom, representing the non-obese patients, with 20 high-sensitivity MOSFET detectors and two 0.18cc ionization chambers placed in selected organs. Fat-equivalent paddings were placed around the abdominal region to simulate for obese patients.more » Effective dose (ED) was calculated using ICRP 103 tissue weighting factors and normalized to the effective dose rate in miliSivert per second (mSv/s). In addition, a commercial Monte Carlo (MC) dose estimation program was used to estimate ED for the non-obese model, with table attenuation correction applied to simulate clinical procedure. Results: For the equipment and protocols involved in this study, the MOSFETderived ED rates for the obese patient model (‘Left’: 0.0092±0.0004 mSv/s; ‘Right’: 0.0086±0.0004 mSv/s) was found to be more than twice as much as that to the non-obese patient model (‘Left’: 0.0041±0.0003 mSv/s; ‘Right’: 0.0036±0.0007 mSv/s). The MC-derived ED rates for the non-obese patient model (‘Left’: 0.0041 mSv/s; ‘Right’: 0.0036 mSv/s; with statistical uncertainty of 1%) showed a good agreement with the MOSFET method. Conclusion: The significant difference in ED rate between the obese and non-obese patient models shows the limitation of directly applying commercial softwares for obese patients and leading to considerable underestimation of ED. Although commercial softwares offer a convenient means of dose estimation, but the utility may be limited to standard-man geometry as the software does not account for table attenuation, obese patient geometry, and differences between the anthropomorphic phantom and MC mathematical phantom.« less

Mathematical optimization of high dose-rate brachytherapy—derivation of a linear penalty model from a dose-volume model

NASA Astrophysics Data System (ADS)

Morén, B.; Larsson, T.; Carlsson Tedgren, Å.

2018-03-01

High dose-rate brachytherapy is a method for cancer treatment where the radiation source is placed within the body, inside or close to a tumour. For dose planning, mathematical optimization techniques are being used in practice and the most common approach is to use a linear model which penalizes deviations from specified dose limits for the tumour and for nearby organs. This linear penalty model is easy to solve, but its weakness lies in the poor correlation of its objective value and the dose-volume objectives that are used clinically to evaluate dose distributions. Furthermore, the model contains parameters that have no clear clinical interpretation. Another approach for dose planning is to solve mixed-integer optimization models with explicit dose-volume constraints which include parameters that directly correspond to dose-volume objectives, and which are therefore tangible. The two mentioned models take the overall goals for dose planning into account in fundamentally different ways. We show that there is, however, a mathematical relationship between them by deriving a linear penalty model from a dose-volume model. This relationship has not been established before and improves the understanding of the linear penalty model. In particular, the parameters of the linear penalty model can be interpreted as dual variables in the dose-volume model.

Space radiation dose analysis for solar flare of August 1989

NASA Technical Reports Server (NTRS)

Nealy, John E.; Simonsen, Lisa C.; Sauer, Herbert H.; Wilson, John W.; Townsend, Lawrence W.

1990-01-01

Potential dose and dose rate levels to astronauts in deep space are predicted for the solar flare event which occurred during the week of August 13, 1989. The Geostationary Operational Environmental Satellite (GOES-7) monitored the temporal development and energy characteristics of the protons emitted during this event. From these data, differential fluence as a function of energy was obtained in order to analyze the flare using the Langley baryon transport code, BRYNTRN, which describes the interactions of incident protons in matter. Dose equivalent estimates for the skin, ocular lens, and vital organs for 0.5 to 20 g/sq cm of aluminum shielding were predicted. For relatively light shielding (less than 2 g/sq cm), the skin and ocular lens 30-day exposure limits are exceeded within several hours of flare onset. The vital organ (5 cm depth) dose equivalent is exceeded only for the thinnest shield (0.5 g/sq cm). Dose rates (rem/hr) for the skin, ocular lens, and vital organs are also computed.

Space radiation dose analysis for solar flare of August 1989

NASA Astrophysics Data System (ADS)

Nealy, John E.; Simonsen, Lisa C.; Sauer, Herbert H.; Wilson, John W.; Townsend, Lawrence W.

1990-12-01

Potential dose and dose rate levels to astronauts in deep space are predicted for the solar flare event which occurred during the week of August 13, 1989. The Geostationary Operational Environmental Satellite (GOES-7) monitored the temporal development and energy characteristics of the protons emitted during this event. From these data, differential fluence as a function of energy was obtained in order to analyze the flare using the Langley baryon transport code, BRYNTRN, which describes the interactions of incident protons in matter. Dose equivalent estimates for the skin, ocular lens, and vital organs for 0.5 to 20 g/sq cm of aluminum shielding were predicted. For relatively light shielding (less than 2 g/sq cm), the skin and ocular lens 30-day exposure limits are exceeded within several hours of flare onset. The vital organ (5 cm depth) dose equivalent is exceeded only for the thinnest shield (0.5 g/sq cm). Dose rates (rem/hr) for the skin, ocular lens, and vital organs are also computed.

[Application of half-dose depot long-acting triptorelin in postoperative adjuvant therapy for endometriosis].

PubMed

Liu, Xia; Zhang, Hong-xia; Wang, Li-ping; Fu, Wei-ping

2013-01-15

To evaluate the efficacy and adverse effects of half-dose depot long-acting triptorelin in the therapy of endometriosis. The efficacy and adverse effects of routine-dose or half-dose triptorelin in postoperative endometriosis patients were prospectively observed. A total of 186 postoperative patients with moderate or severe endometriosis received an intramuscular injection of triptorelin every 28 days for 6 times. They were randomly divided into 3 groups, i.e. half-dose group (n = 99): 1.875 mg each time; "draw-back" group (n = 52): 3.75 mg first time, then 1.875 mg each time; and routine-dose group (n = 35): 3.75 mg each time. Amenorrhea was effectively induced in all patients after the second injection. There was no significant difference in the rate of serum E2 level at Day 28 of every injection below the upper limit of "estrogen threshold (110 - 146 pmol/L)" not stimulating ectopic endometrium proliferation among half-dose group, "draw-back" group and routine-dose group (99% vs 100% and 99.0%, P > 0.05), the percentage of E2 < 37 pmol/L in E2 < 110 pmol/L in half-dose group was significantly lower than that in "draw-back" and routine-dose groups after 2-5(th) injection (69% vs 79% and 85%, P < 0.01), but there was no significant difference after first half-dose and routine-dose injection (71% vs 73%, P > 0.05). No significant difference existed in the rate of pelvic pain relief during the first returning menstruation and the recurrence rate of endometriosis within 1 year postoperation among three groups (both P > 0.05). However, the incidences of menopausal syndrome and severe menopausal syndrome in half-dose group were significantly lower than those in "draw-back" and routine-dose groups (both P < 0.01). And the incompletion rate of six-time drug for severe menopause syndrome was also significantly lower (P < 0.05) while the completion rate of six-time drug use in half-dose group was significantly higher (P < 0.05). As a postoperative adjuvant, half-dose depot triptorelin therapy is efficacious for endometriosis. It reduces menopausal syndrome and treatment cost and enhances patient compliance.

Monte Carlo calculation of the neutron dose to a fetus at commercial flight altitudes

NASA Astrophysics Data System (ADS)

Alves, M. C.; Galeano, D. C.; Santos, W. S.; Hunt, John G.; d'Errico, Francesco; Souza, S. O.; de Carvalho Júnior, A. B.

2017-11-01

Aircrew members are exposed to primary cosmic rays as well as to secondary radiations from the interaction of cosmic rays with the atmosphere and with the aircraft. The radiation field at flight altitudes comprises neutrons, protons, electrons, positrons, photons, muons and pions. Generally, 50% of the effective dose to airplane passengers is due to neutrons. Care must be taken especially with pregnant aircrew members and frequent fliers so that the equivalent dose to the fetus will not exceed prescribed limits during pregnancy (1 mSv according to ICRP, and 5 mSv according to NCRP). Therefore, it is necessary to evaluate the equivalent dose to a fetus in the maternal womb. Up to now, the equivalent dose rate to a fetus at commercial flight altitudes was obtained using stylized pregnant-female phantom models. The aim of this study was calculating neutron fluence to dose conversion coefficients for a fetus of six months of gestation age using a new, realistic pregnant-female mesh-phantom. The equivalent dose rate to a fetus during an intercontinental flight was also calculated by folding our conversion coefficients with published spectral neutron flux data. The calculated equivalent dose rate to the fetus was 2.35 μSv.h-1, that is 1.5 times higher than equivalent dose rates reported in the literature. The neutron fluence to dose conversion coefficients for the fetus calculated in this study were 2.7, 3.1 and 3.9 times higher than those from previous studies using fetus models of 3, 6 and 9 months of gestation age, respectively. The differences between our study and data from the literature highlight the importance of using more realistic anthropomorphic phantoms to estimate doses to a fetus in pregnant aircrew members.

Predicting cancer rates in astronauts from animal carcinogenesis studies and cellular markers

NASA Technical Reports Server (NTRS)

Williams, J. R.; Zhang, Y.; Zhou, H.; Osman, M.; Cha, D.; Kavet, R.; Cuccinotta, F.; Dicello, J. F.; Dillehay, L. E.

1999-01-01

The radiation space environment includes particles such as protons and multiple species of heavy ions, with much of the exposure to these radiations occurring at extremely low average dose-rates. Limitations in databases needed to predict cancer hazards in human beings from such radiations are significant and currently do not provide confidence that such predictions are acceptably precise or accurate. In this article, we outline the need for animal carcinogenesis data based on a more sophisticated understanding of the dose-response relationship for induction of cancer and correlative cellular endpoints by representative space radiations. We stress the need for a model that can interrelate human and animal carcinogenesis data with cellular mechanisms. Using a broad model for dose-response patterns which we term the "subalpha-alpha-omega (SAO) model", we explore examples in the literature for radiation-induced cancer and for radiation-induced cellular events to illustrate the need for data that define the dose-response patterns more precisely over specific dose ranges, with special attention to low dose, low dose-rate exposure. We present data for multiple endpoints in cells, which vary in their radiosensitivity, that also support the proposed model. We have measured induction of complex chromosome aberrations in multiple cell types by two space radiations, Fe-ions and protons, and compared these to photons delivered at high dose-rate or low dose-rate. Our data demonstrate that at least three factors modulate the relative efficacy of Fe-ions compared to photons: (i) intrinsic radiosensitivity of irradiated cells; (ii) dose-rate; and (iii) another unspecified effect perhaps related to reparability of DNA lesions. These factors can produce respectively up to at least 7-, 6- and 3-fold variability. These data demonstrate the need to understand better the role of intrinsic radiosensitivity and dose-rate effects in mammalian cell response to ionizing radiation. Such understanding is critical in extrapolating databases between cellular response, animal carcinogenesis and human carcinogenesis, and we suggest that the SAO model is a useful tool for such extrapolation.

Biology relevant to space radiation

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

Fry, R J.M.

There are only very limited data on the health effects to humans from the two major components of the radiations in space, namely protons and heavy ions. As a result, predictions of the accompanying effects must be based either on (1) data generated through studies of experimental systems exposed on earth at rates and fluences higher than those in space, or (2) extrapolations from studies of gamma and x rays. Better information is needed about the doses, dose rates, and the energy and LET spectra of the radiations at the organ level that are anticipated to be encountered during extendedmore » space missions. In particular, there is a need for better estimates of the relationship between radiation quality and biological effects. In the case of deterministic effects, it is the threshold that is important. The possibility of the occurrence of a large solar particle event (SPE) requires that such effects be considered during extended space missions. Analyses suggest, however, that it is feasible to provide sufficient shielding so as to reduce such effects to acceptable levels, particularly if the dose rates can be limited. If these analyses prove correct, the primary biological risks will be the stochastic effects (latent cancer induction). The contribution of one large SPE to the risk of stochastic effects while undesirable will not be large in comparison to the potential total dose on a mission of long duration.« less

Twenty-year follow-up study of long-term survival of limited-stage small-cell lung cancer and overview of prognostic and treatment factors.

PubMed

Tai, Patricia; Tonita, Jon; Yu, Edward; Skarsgard, David

2003-07-01

To predict the long-term survival results of clinical trials earlier than using actuarial methods and to assess the factors predictive of long-term cure in patients with limited-stage small-cell lung cancer. Between 1981 and 1998, 1417 new cases of small-cell lung cancer were diagnosed in Saskatchewan, Canada, of which 244 were limited stage and treated with curative intent. They were followed to the end of February 2002. A parametric lognormal statistical model was retrospectively validated to determine whether long-term survival rates could be estimated several years earlier than is possible using the standard life-table actuarial method. The survival time of the uncured group followed a lognormal distribution. Four 2-year periods of diagnosis were combined, and patients were followed as a cohort for an additional 2 years. The estimated 10-year cause-specific survival rate was 13% by the lognormal model. The Kaplan-Meier calculation for 10-year cause-specific survival rate was 15% +/- 3%. The data also showed that the absence of mediastinal lymphadenopathy and higher chest radiotherapy dose were significant prognostic factors on multivariate analysis (p < 0.05). Among the 163 patients given prophylactic cranial irradiation, a higher biologically effective dose to the brain did not improve survival or decrease the incidence of brain metastases. The lognormal model has been validated for the estimation of survival in patients with limited-stage small-cell lung cancer. A higher biologically effective dose to the brain did not improve survival or decrease the incidence of brain metastases.

Quantitative Analysis of Electron Beam Damage in Organic Thin Films

PubMed Central

2017-01-01

In transmission electron microscopy (TEM) the interaction of an electron beam with polymers such as P3HT:PCBM photovoltaic nanocomposites results in electron beam damage, which is the most important factor limiting acquisition of structural or chemical data at high spatial resolution. Beam effects can vary depending on parameters such as electron dose rate, temperature during imaging, and the presence of water and oxygen in the sample. Furthermore, beam damage will occur at different length scales. To assess beam damage at the angstrom scale, we followed the intensity of P3HT and PCBM diffraction rings as a function of accumulated electron dose by acquiring dose series and varying the electron dose rate, sample preparation, and the temperature during acquisition. From this, we calculated a critical dose for diffraction experiments. In imaging mode, thin film deformation was assessed using the normalized cross-correlation coefficient, while mass loss was determined via changes in average intensity and standard deviation, also varying electron dose rate, sample preparation, and temperature during acquisition. The understanding of beam damage and the determination of critical electron doses provides a framework for future experiments to maximize the information content during the acquisition of images and diffraction patterns with (cryogenic) transmission electron microscopy. PMID:28553431

Quintupling Inhaled Glucocorticoids to Prevent Childhood Asthma Exacerbations.

PubMed

Jackson, Daniel J; Bacharier, Leonard B; Mauger, David T; Boehmer, Susan; Beigelman, Avraham; Chmiel, James F; Fitzpatrick, Anne M; Gaffin, Jonathan M; Morgan, Wayne J; Peters, Stephen P; Phipatanakul, Wanda; Sheehan, William J; Cabana, Michael D; Holguin, Fernando; Martinez, Fernando D; Pongracic, Jacqueline A; Baxi, Sachin N; Benson, Mindy; Blake, Kathryn; Covar, Ronina; Gentile, Deborah A; Israel, Elliot; Krishnan, Jerry A; Kumar, Harsha V; Lang, Jason E; Lazarus, Stephen C; Lima, John J; Long, Dayna; Ly, Ngoc; Marbin, Jyothi; Moy, James N; Myers, Ross E; Olin, J Tod; Raissy, Hengameh H; Robison, Rachel G; Ross, Kristie; Sorkness, Christine A; Lemanske, Robert F

2018-03-08

Asthma exacerbations occur frequently despite the regular use of asthma-controller therapies, such as inhaled glucocorticoids. Clinicians commonly increase the doses of inhaled glucocorticoids at early signs of loss of asthma control. However, data on the safety and efficacy of this strategy in children are limited. We studied 254 children, 5 to 11 years of age, who had mild-to-moderate persistent asthma and had had at least one asthma exacerbation treated with systemic glucocorticoids in the previous year. Children were treated for 48 weeks with maintenance low-dose inhaled glucocorticoids (fluticasone propionate at a dose of 44 μg per inhalation, two inhalations twice daily) and were randomly assigned to either continue the same dose (low-dose group) or use a quintupled dose (high-dose group; fluticasone at a dose of 220 μg per inhalation, two inhalations twice daily) for 7 days at the early signs of loss of asthma control ("yellow zone"). Treatment was provided in a double-blind fashion. The primary outcome was the rate of severe asthma exacerbations treated with systemic glucocorticoids. The rate of severe asthma exacerbations treated with systemic glucocorticoids did not differ significantly between groups (0.48 exacerbations per year in the high-dose group and 0.37 exacerbations per year in the low-dose group; relative rate, 1.3; 95% confidence interval, 0.8 to 2.1; P=0.30). The time to the first exacerbation, the rate of treatment failure, symptom scores, and albuterol use during yellow-zone episodes did not differ significantly between groups. The total glucocorticoid exposure was 16% higher in the high-dose group than in the low-dose group. The difference in linear growth between the high-dose group and the low-dose group was -0.23 cm per year (P=0.06). In children with mild-to-moderate persistent asthma treated with daily inhaled glucocorticoids, quintupling the dose at the early signs of loss of asthma control did not reduce the rate of severe asthma exacerbations or improve other asthma outcomes and may be associated with diminished linear growth. (Funded by the National Heart, Lung, and Blood Institute; STICS ClinicalTrials.gov number, NCT02066129 .).

Probabilistic dose assessment of normal operations and accident conditions for an assured isolation facility in Texas

NASA Astrophysics Data System (ADS)

Arno, Matthew Gordon

Texas is investigating building a long-term waste storage facility, also known as an Assured Isolation Facility. This is an above-ground low-level radioactive waste storage facility that is actively maintained and from which waste may be retrieved. A preliminary, scoping-level analysis has been extended to consider more complex scenarios of radiation streaming and skyshine by using the computer code Monte Carlo N-Particle (MCNP) to model the facility in greater detail. Accidental release scenarios have been studied in more depth to better assess the potential dose to off-site individuals. Using bounding source term assumptions, the projected radiation doses and dose rates are estimated to exceed applicable limits by an order of magnitude. By altering the facility design to fill in the hollow cores of the prefabricated concrete slabs used in the roof over the "high-gamma rooms," where the waste with the highest concentration of gamma emitting radioactive material is stored, dose rates outside the facility decrease by an order of magnitude. With the modified design, the annual dose at the site fenceline is estimated at 86 mrem, below the 100 mrem annual limit for exposure of the public. Within the site perimeter, the dose rates are lowered sufficiently such that it is not necessary to categorize many workers and contractor personnel as radiation workers, saving on costs as well as being advisable under ALARA principles. A detailed analysis of bounding accidents incorporating information on the local meteorological conditions indicate that the maximum committed effective dose equivalent from the passage of a plume of material released in an accident at any of the cities near the facility is 59 :rem in the city of Eunice, NM based on the combined day and night meteorological conditions. Using the daytime meteorological conditions, the maximum dose at any city is 7 :rem, also in the city of Eunice. The maximum dose at the site boundary was determined to be 230 mrem using the combined day and night meteorological conditions and 33 mrem using the daytime conditions.

Setting Age Limits for TT-OSL Dating - the Local Effect

NASA Astrophysics Data System (ADS)

Faershtein, G.; Porat, N.; Guralnik, B.; Matmon, A.

2017-12-01

Luminescence dating techniques, especially Optically Stimulated Luminescence (OSL) on quartz, are widely used for dating middle Pleistocene to late Holocene sediments from different geological settings. The dating limit of a particular luminescence method depends on signal saturation and its thermal stability. The OSL signal saturates at doses of 200 Gy, equivalent to ages of 150-300 ka. Thermally Transferred OSL (TT-OSL) is a developmental technique, which potentially extends the luminescence dating range up to 1000 ka. For the Chinese Loess Plateau, experiments have shown that the natural TT-OSL signal saturates at 2200 Gy (Chapot et al., 2016). Regarding thermal stability, different studies report a wide range of estimates (0.24-861 Ma), suggesting that the thermal lifetime of TT-OSL is (i) currently poorly constrained, and (ii) may vary both by sample and region. Here, we investigated the dating limit of TT-OSL, using quartz of Nilotic origin (Israel), obtained from two sediment sections of similar depth but different dose rates. Natural dose response curves (DRC) of the TT-OSL signal were constructed for each section separately. In both sections, luminescence intensity grows sub-linearly up to 450 Gy, beyond which it remains constant with depth. The absence of equivalent doses (De) over 600 Gy, at both sections (as well as elsewhere regionally), suggest that TT-OSL signal saturation may be an intrinsic property, related to quartz provenance, and independent of the specific ionizing dose rate at each section. The thermal stability of TT-OSL was investigated on a modern sample from one section, using a combination of analytical techniques (varying heating rates, and isothermal storage). The obtained TT-OSL lifetimes range between 105-107 ka, and reinforce a significant inter sample variability. A synthesis of our results suggests that TT-OSL ages of Nilotic quartz derived from De values over 450 Gy, are likely underestimates, and should be treated as minimum ages. The limiting value of 600 Gy for local quartz TT-OSL is likely representative of a steady-state between TT-OSL trap filling due to ionizing radiation, and the concurrent thermal empting of these traps.

Overdose and prescribed opioids: Associations among chronic non-cancer pain patients

PubMed Central

Dunn, Kate M; Saunders, Kathleen W; Rutter, Carolyn M; Banta-Green, Caleb J; Merrill, Joseph O; Sullivan, Mark D; Weisner, Constance M; Silverberg, Michael J; Campbell, Cynthia I; Psaty, Bruce M; Von Korff, Michael

2010-01-01

Background Chronic opioid therapy for chronic non-cancer pain (CNCP) is increasingly common in community practice. Concomitant with this practice change, rates of fatal opioid overdose have increased. It is not known to what extent overdose risks are elevated among patients receiving medically prescribed chronic opioid therapy. Objective To estimate rates of opioid overdose and their association with average prescribed daily opioid dose among patients receiving medically prescribed chronic opioid therapy. Design Cox proportional hazards models were used to estimate overdose risk as a function of average daily opioid dose (morphine equivalents) received at time of overdose. Setting Health maintenance organization. Patients Individuals (n=9940) who received 3+ opioid prescriptions within 90-days for CNCP between 1997 and 2005. Measurements Average daily opioid dose over the previous 90 days from automated pharmacy data. Primary outcomes, non-fatal and fatal overdoses, were identified through diagnostic codes from inpatient and outpatient care and death certificates and confirmed by medical record review. Results Fifty-one opioid-related overdoses were identified, including six deaths. Compared to patients receiving 1-20mg of opioids per day (0.2% annual overdose rate), patients receiving 50-99 mg had a 3.7 fold increase in overdose risk (95% C.I. 1.5, 9.5) and a 0.7% annual overdose rate. Patients receiving 100mg or more per day had an 8.9 fold increase in overdose risk (95% C.I. 4.0, 19.7) and a 1.8% annual overdose rate. Limitations Increased overdose risk among patients on higher dose regimens may be due to confounding by patient differences and by use of opioids in ways not intended by prescribing physicians. The small number of overdoses in the study cohort is also a limitation. Conclusions Patients receiving higher doses of prescribed opioids are at increased risk of opioid overdose, underscoring the need for close supervision of these patients. PMID:20083827

Eye doses to staff in a nuclear medicine department.

PubMed

Summers, Elizabeth C; Brown, Janis L E; Bownes, Peter J; Anderson, Shona E

2012-05-01

Occupational radiation doses to the Nuclear Medicine Department staff at Mount Vernon Hospital are routinely measured using optically stimulated luminescence dosemeters for whole-body effective dose and ring thermoluminescence dosemeters (TLDs) for finger dose. In 2002, a project was carried out using LiF:Mg,Cu,P Chinese TLDs to measure the dose to the lens of the eye received by staff during normal working procedures. Separate pairs of TLDs were worn by staff on their forehead between their eyes while dispensing and releasing in the radiopharmacy, injecting, and when administering I-131 capsules to patients. The dose received was calculated using calibration data from identical TLDs irradiated with Tc-99m, I-131, and the Ir-192 source of a Gammamed High Dose Rate (HDR) treatment unit. Data were collected over a 5-month period and the mean dose to the eye was calculated for each procedure. Using a typical yearly workload, the annual dose to the eye for a single member of staff was calculated and found to be 4.5 mSv. The occupational eye dose limit was, at the time, 150 mSv; therefore, staff were well below the level (3/10th of this limit) that would have required them to be classified. However, there have been large increases in radiopharmacy production and I-131 therapies administered at Mount Vernon in subsequent years. It is therefore expected that the eye dose received by staff will have increased to be significantly higher than 4.5 mSv and will in fact be greater than 6 mSv, which is 3/10th of the proposed new dose limit and would require these staff to become classified workers.

TU-D-201-05: Validation of Treatment Planning Dose Calculations: Experience Working with MPPG 5.a

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

Xue, J; Park, J; Kim, L

2016-06-15

Purpose: Newly published medical physics practice guideline (MPPG 5.a.) has set the minimum requirements for commissioning and QA of treatment planning dose calculations. We present our experience in the validation of a commercial treatment planning system based on MPPG 5.a. Methods: In addition to tests traditionally performed to commission a model-based dose calculation algorithm, extensive tests were carried out at short and extended SSDs, various depths, oblique gantry angles and off-axis conditions to verify the robustness and limitations of a dose calculation algorithm. A comparison between measured and calculated dose was performed based on validation tests and evaluation criteria recommendedmore » by MPPG 5.a. An ion chamber was used for the measurement of dose at points of interest, and diodes were used for photon IMRT/VMAT validations. Dose profiles were measured with a three-dimensional scanning system and calculated in the TPS using a virtual water phantom. Results: Calculated and measured absolute dose profiles were compared at each specified SSD and depth for open fields. The disagreement is easily identifiable with the difference curve. Subtle discrepancy has revealed the limitation of the measurement, e.g., a spike at the high dose region and an asymmetrical penumbra observed on the tests with an oblique MLC beam. The excellent results we had (> 98% pass rate on 3%/3mm gamma index) on the end-to-end tests for both IMRT and VMAT are attributed to the quality beam data and the good understanding of the modeling. The limitation of the model and the uncertainty of measurement were considered when comparing the results. Conclusion: The extensive tests recommended by the MPPG encourage us to understand the accuracy and limitations of a dose algorithm as well as the uncertainty of measurement. Our experience has shown how the suggested tests can be performed effectively to validate dose calculation models.« less

Atmospheric radiation modeling of galactic cosmic rays using LRO/CRaTER and the EMMREM model with comparisons to balloon and airline based measurements

NASA Astrophysics Data System (ADS)

Joyce, C. J.; Schwadron, N. A.; Townsend, L. W.; deWet, W. C.; Wilson, J. K.; Spence, H. E.; Tobiska, W. K.; Shelton-Mur, K.; Yarborough, A.; Harvey, J.; Herbst, A.; Koske-Phillips, A.; Molina, F.; Omondi, S.; Reid, C.; Reid, D.; Shultz, J.; Stephenson, B.; McDevitt, M.; Phillips, T.

2016-09-01

We provide an analysis of the galactic cosmic ray radiation environment of Earth's atmosphere using measurements from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) aboard the Lunar Reconnaissance Orbiter (LRO) together with the Badhwar-O'Neil model and dose lookup tables generated by the Earth-Moon-Mars Radiation Environment Module (EMMREM). This study demonstrates an updated atmospheric radiation model that uses new dose tables to improve the accuracy of the modeled dose rates. Additionally, a method for computing geomagnetic cutoffs is incorporated into the model in order to account for location-dependent effects of the magnetosphere. Newly available measurements of atmospheric dose rates from instruments aboard commercial aircraft and high-altitude balloons enable us to evaluate the accuracy of the model in computing atmospheric dose rates. When compared to the available observations, the model seems to be reasonably accurate in modeling atmospheric radiation levels, overestimating airline dose rates by an average of 20%, which falls within the uncertainty limit recommended by the International Commission on Radiation Units and Measurements (ICRU). Additionally, measurements made aboard high-altitude balloons during simultaneous launches from New Hampshire and California provide an additional comparison to the model. We also find that the newly incorporated geomagnetic cutoff method enables the model to represent radiation variability as a function of location with sufficient accuracy.

Cumulative Training Dose's Effects on Interrelationships Between Common Training-Load Models During Basketball Activity.

PubMed

Scanlan, Aaron T; Fox, Jordan L; Borges, Nattai R; Dascombe, Ben J; Dalbo, Vincent J

2017-02-01

The influence of various factors on training-load (TL) responses in basketball has received limited attention. This study aimed to examine the temporal changes and influence of cumulative training dose on TL responses and interrelationships during basketball activity. Ten state-level Australian male junior basketball players completed 4 × 10-min standardized bouts of simulated basketball activity using a circuit-based protocol. Internal TL was quantified using the session rating of perceived exertion (sRPE), summated heart-rate zones (SHRZ), Banister training impulse (TRIMP), and Lucia TRIMP models. External TL was assessed via measurement of mean sprint and circuit speeds. Temporal TL comparisons were performed between 10-min bouts, while Pearson correlation analyses were conducted across cumulative training doses (0-10, 0-20, 0-30, and 0-40 min). sRPE TL increased (P < .05) after the first 10-min bout of basketball activity. sRPE TL was only significantly related to Lucia TRIMP (r = .66-.69; P < .05) across 0-10 and 0-20 min. Similarly, mean sprint and circuit speed were significantly correlated across 0-20 min (r = .67; P < .05). In contrast, SHRZ and Banister TRIMP were significantly related across all training doses (r = .84-.89; P < .05). Limited convergence exists between common TL approaches across basketball training doses lasting beyond 20 min. Thus, the interchangeability of commonly used internal and external TL approaches appears dose-dependent during basketball activity, with various psychophysiological mediators likely underpinning temporal changes.

HLW Flexible jumper materials compatibility evaluation

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

Skidmore, T. E.

H-Tank Farm Engineering tasked SRNL/Materials Science & Technology (MS&T) to evaluate the compatibility of Goodyear Viper® chemical transfer hose with HLW solutions. The hose is proposed as a flexible Safety Class jumper for up to six months service. SRNL/MS&T performed various tests to evaluate the effects of radiation, high pH chemistry and elevated temperature on the hose, particularly the inner liner. Test results suggest an upper dose limit of 50 Mrad for the hose. Room temperature burst pressure values at 50 Mrad are estimated at 600- 800 psi, providing a safety factor of 4.0-5.3X over the anticipated operating pressure ofmore » 150 psi and a safety factor of 3.0-4.0X over the working pressure of the hose (200 psi), independent of temperature effects. Radiation effects are minimal at doses less than 10 Mrad. Doses greater than 50 Mrad may be allowed, depending on operating conditions and required safety factors, but cannot be recommended at this time. At 250 Mrad, burst pressure values are reduced to the hose working pressure. At 300 Mrad, burst pressures are below 150 psi. At a bounding continuous dose rate of 57,870 rad/hr, the 50 Mrad dose limit is reached within 1.2 months. Actual dose rates may be lower, particularly during non-transfer periods. Refined dose calculations are therefore recommended to justify longer service. This report details the tests performed and interpretation of the results. Recommendations for shelf-life/storage, component quality verification, and post-service examination are provided.« less

Patritumab plus trastuzumab and paclitaxel in human epidermal growth factor receptor 2-overexpressing metastatic breast cancer.

PubMed

Mukai, Hirofumi; Saeki, Toshiaki; Aogi, Kenjiro; Naito, Yoichi; Matsubara, Nobuaki; Shigekawa, Takashi; Ueda, Shigeto; Takashima, Seiki; Hara, Fumikata; Yamashita, Tomonari; Ohwada, Shoichi; Sasaki, Yasutsuna

2016-10-01

Human epidermal growth factor receptor 3 (HER3) expression in lung and breast cancers has a negative impact on survival. Patritumab, a human anti-HER3 mAb, has shown anticancer activity in preclinical models. This study examined the safety and pharmacokinetics of patritumab in combination with trastuzumab and paclitaxel in patients with HER2-overexpressing metastatic breast cancer. In this open-label, multicenter, dose-escalation, phase Ib study, patients received patritumab 9 or 18 mg/kg plus trastuzumab and paclitaxel at known tolerated doses. Safety and tolerability were assessed based on dose-limiting toxicities and other non-life threatening adverse events. The pharmacokinetic profile for patritumab was determined based on the target trough level. Clinical efficacy was evaluated based on the overall response rate and progression-free survival. Six patients received patritumab 9 mg/kg and 12 received 18 mg/kg. The most common adverse events were diarrhea, alopecia, leukopenia, neutropenia, and maculopapular rash. No dose-limiting toxicities were observed. The target trough serum concentration was achieved in all patients at a dose of 18 mg/kg. Overall response rate was 38.9% and median progression-free survival was 274 days. In conclusion, patritumab plus trastuzumab and paclitaxel was tolerable and efficacious at both doses. We recommend the dose level of 18 mg/kg for future phase II studies. (Clinical trial registration: JapicCTI-121772.). © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Cost-effectiveness of allopurinol and febuxostat for the management of gout.

PubMed

Jutkowitz, Eric; Choi, Hyon K; Pizzi, Laura T; Kuntz, Karen M

2014-11-04

Gout is the most common inflammatory arthritis in the United States. To evaluate the cost-effectiveness of urate-lowering treatment strategies for the management of gout. Markov model. Published literature and expert opinion. Patients for whom allopurinol or febuxostat is a suitable initial urate-lowering treatment. Lifetime. Health care payer. 5 urate-lowering treatment strategies were evaluated: no treatment; allopurinol- or febuxostat-only therapy; allopurinol-febuxostat sequential therapy; and febuxostat-allopurinol sequential therapy. Two dosing scenarios were investigated: fixed dose (80 mg of febuxostat daily, 0.80 success rate; 300 mg of allopurinol daily, 0.39 success rate) and dose escalation (≤120 mg of febuxostat daily, 0.82 success rate; ≤800 mg of allopurinol daily, 0.78 success rate). Discounted costs, discounted quality-adjusted life-years, and incremental cost-effectiveness ratios. In both dosing scenarios, allopurinol-only therapy was cost-saving. Dose-escalation allopurinol-febuxostat sequential therapy was more costly but more effective than dose-escalation allopurinol therapy, with an incremental cost-effectiveness ratio of $39 400 per quality-adjusted life-year. The relative rankings of treatments did not change. Our results were relatively sensitive to several potential variations of model assumptions; however, the cost-effectiveness ratios of dose escalation with allopurinol-febuxostat sequential therapy remained lower than the willingness-to-pay threshold of $109 000 per quality-adjusted life-year. Long-term outcome data for patients with gout, including medication adherence, are limited. Allopurinol single therapy is cost-saving compared with no treatment. Dose-escalation allopurinol-febuxostat sequential therapy is cost-effective compared with accepted willingness-to-pay thresholds. Agency for Healthcare Research and Quality.

The use of the long modular diagnostics shield module to mitigate shutdown dose rates in the ITER diagnostics equatorial ports

NASA Astrophysics Data System (ADS)

Juárez, R.; Guirao, J.; Kolsek, A.; Lopez, A.; Pedroche, G.; Bertalot, L.; Udintsev, V. S.; Walsh, M. J.; Sauvan, P.; Sanz, J.

2018-05-01

The ITER equatorial port plugs are submitted to a drained weight limit of 45 T. This limitation can conflict with their radiation shielding demands, although some weight margin is being discussed. The port interspaces are subject to a shutdown dose rate limit of 100 µSv h‑1 after 106 s of cooling time. To meet it, the port plugs must show a neutron flux attenuation comparable to their neighborhood, despite considering penetrations to host systems. Most of this task relies on the drawer shield module (DSM). In this work, two DSM concepts are analyzed with this perspective: the box-based DSM and the modular DSM. Regardless the penetrations, the box-based DSM leads to unsatisfactory port plugs to meet both weight and SDDR requirements. On the contrary, the modular DSM shows a performance which allows for the adoption of such DSM concept, or equivalent, a port may comply with both requirements at the same time, provided the penetrations are well designed.

A triplet combination with capecitabine/oxaliplatin/irinotecan (XELOXIRI) plus cetuximab as first-line therapy for patients with metastatic colorectal cancer: a dose escalation study.

PubMed

Sato, Yasushi; Hirakawa, Masahiro; Ohnuma, Hiroyuki; Takahashi, Minoru; Okamoto, Tetsuro; Okamoto, Koichi; Miyamoto, Hiroshi; Muguruma, Naoki; Furuhata, Tomohisa; Takemasa, Ichiro; Kato, Junji; Takayama, Tetsuji

2017-12-01

The addition of cetuximab to triplet chemotherapy can increase treatment efficacy for patients with metastatic colorectal cancer (mCRC). We explored the dose-limiting toxicity and feasibility of a triweekly capecitabine, oxaliplatin, irinotecan, plus cetuximab (XELOXIRI plus cetuximab) regimen in patients with wild-type KRAS mCRC. Patients received oxaliplatin (100 mg/m 2 , day 1), capecitabine (1700 mg/m 2 per day from day 2 to 15), irinotecan (100, 120, and 150 mg/m 2 for dose levels 1, 2, 3, respectively, on day 1), and cetuximab (400 mg/m 2 , day 1 and, thereafter, 250 mg/m 2 every week), repeated every 3 weeks. Dose-limiting toxicities (DLTs) were assessed in the first 2 treatment cycles to determine the maximum tolerated dose (MTD) and the recommended dose (RD). Twelve patients received a median of 7 cycles of therapy (range 2-10). The DLT was grade 4 neutropenia, observed in 1 of 6 patients at dose level 2. The MTD was not reached at dose level 3. Therefore, the RD of irinotecan was defined as 150 mg/m 2 . Most common grade ≥ 3 toxicities were neutropenia (50%), diarrhea (17%), and febrile neutropenia (8%). The response rate was 83% (complete and partial response: 1 and 9 patient(s), respectively), including 4 conversion cases. The combination of XELOXIRI and cetuximab is feasible and has an acceptable toxicity profile; neutropenia was the DLT. The RD of irinotecan is 150 mg/m 2 . The observed response rate was promising and warrants further investigation.

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

Miller, C A; Clarke, S D; Pozzi, S A

Purpose: To develop an instrument for measuring neutron and photon dose rates from mixed fields with a single device. Methods: Stilbene organic scintillators can be used to detect fast neutrons and photons. Stilbene was used to measure emission from mixed particle sources californium-252 (Cf-252) and plutonium-beryllium (PuBe). Many source detector configurations were used, along with varying amounts of shielding. Collected spectra were analyzed using pulse shape discrimination software, to separate neutron and photon interactions. With a measured light output to energy relationship the pulse height spectrum was converted to energy deposited in the detector. Energy deposited was converted to dosemore » with a variety of standard dose factors, for comparison to current methods. For validation, all measurements and processing was repeated using an EJ-309 liquid scintillator detector. Dose rates were also measured in the same configuration with commercially available dose meters for further validation. Results: Measurements of dose rates will show agreement across all methods. Higher accuracy of pulse shape discrimination at lower energies with stilbene leads to more accurate measurement of neutron and photon deposited dose. In strong fields of mixed particles discrimination can be performed well at a very low energy threshold. This shows accurate dose measurements over a large range of incident particle energy. Conclusion: Stilbene shows promise as a material for dose rate measurements due to its strong ability for separating neutrons and photon pulses and agreement with current methods. A dual particle dose meter would simplify methods which are currently limited to the measurement of only one particle type. Future work will investigate the use of a silicon photomultiplier to reduce the size and required voltage of the assembly, for practical use as a handheld survey meter, room monitor, or phantom installation. Funding From the United States Department of Energy and the National Nuclear Security Administration.« less

Solar particle dose rate buildup and distribution in critical body organs

NASA Technical Reports Server (NTRS)

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

1993-01-01

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

Radionuclides (210Po and 210Pb) and Some Heavy Metals in Fish and Sediments in Lake Bafa, Turkey, and the Contribution of 210Po to the Radiation Dose.

PubMed

Manav, Ramazan; Uğur Görgün, Aysun; Filizok, Işık

2016-11-09

The pollution level of Lake Bafa was investigated by collecting fish samples { Dicentrarchus labrax (sea bass), Liza ramada (mullet) and Anguilla anguilla (eel)}, surface sediment, and core samples. In all these samples, 210 Po and 210 Pb concentrations were estimated, and total annual dose rates were obtained for each species. Some heavy metal (Cr, Ni, Pb, Cd, Mn, Fe, and Zn) concentration levels were obtained for the fish and a core sample. The sediment mass accumulation rate was found to be 3.27 g·m -2 ·day -1 (0.119 g·cm -2 ·y -1 ) from a core sample. The heavy metal concentrations in the vertical profile of samples from the core were also observed. The measured concentration of Zn, Pb, Cd, and Cr were between the ERL (effects range low) and ERM (effects range median) limits, while Ni concentrations were higher than the ERM limit. The observed concentrations of Cd, Pb, and Zn in fish samples did not exceed the limits in accordance with Turkish Food Regulations. Further, the maximum effective dose equivalent of 210 Po in the area was found to be 1.169 µSv·y -1 .

The Effect of Measurement Area on Modelling UVR Dose to the Inner Canthus

NASA Astrophysics Data System (ADS)

Birt, Benjamin; Cowling, Ian; Coyne, Steve

People are exposed to varying amounts of UVR throughout their life from both natural and artificial light sources. The dose and rate of UVR exposure required for the formation of non-melanoma skin cancers is inconclusive. Certain regions on the face appear to exhibit a high rate of occurrence of Basal Cell Carcinomas (BCCs) in relation to the perceived dose of UVR. One of these regions is the inner canthus located on the medial side of the eye. The inner canthus appears to be well protected from large direct doses of ultraviolet radiation (UVR). Facial features such as eyelids, eye brow ridge, nasal bridge and cheek, combine to limit the solid angle of the field of view of the inner canthus to UVR from overhead sources. To explain the unexpected high rate of BCCs it is hypothesized that a percentage of the radiation incident on the eye is reflected onto the inner canthus. This paper showed that a portion of the radiation incident onto the eye was reflected towards the inner canthus. The percentage increase above the direct dose was only 2% across the whole region. As the detector elements decrease in size it is observed on a cellular level that some of the cells dose increased by 30% when the reflections were considered.

Definition of Small Gram Quantity Contents for Type B Radioactive Material Transportation Packages: Activity-Based Content Limitations

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

Sitaraman, S; Kim, S; Biswas, D

2010-10-27

Since the 1960's, the Department of Transportation Specification (DOT Spec) 6M packages have been used extensively for transportation of Type B quantities of radioactive materials between Department of Energy (DOE) facilities, laboratories, and productions sites. However, due to the advancement of packaging technology, the aging of the 6M packages, and variability in the quality of the packages, the DOT implemented a phased elimination of the 6M specification packages (and other DOT Spec packages) in favor of packages certified to meet federal performance requirements. DOT issued the final rule in the Federal Register on October 1, 2004 requiring that use ofmore » the DOT Specification 6M be discontinued as of October 1, 2008. A main driver for the change was the fact that the 6M specification packagings were not supported by a Safety Analysis Report for Packaging (SARP) that was compliant with Title 10 of the Code of Federal Regulations part 71 (10 CFR 71). Therefore, materials that would have historically been shipped in 6M packages are being identified as contents in Type B (and sometimes Type A fissile) package applications and addenda that are to be certified under the requirements of 10 CFR 71. The requirements in 10 CFR 71 include that the Safety Analysis Report for Packaging (SARP) must identify the maximum radioactivity of radioactive constituents and maximum quantities of fissile constituents (10 CFR 71.33(b)(1) and 10 CFR 71.33(b)(2)), and that the application (i.e., SARP submittal or SARP addendum) demonstrates that the external dose rate (due to the maximum radioactivity of radioactive constituents and maximum quantities of fissile constituents) on the surface of the packaging (i.e., package and contents) not exceed 200 mrem/hr (10 CFR 71.35(a), 10 CFR 71.47(a)). It has been proposed that a 'Small Gram Quantity' of radioactive material be defined, such that, when loaded in a transportation package, the dose rates at external points of an unshielded packaging not exceed the regulatory limits prescribed by 10 CFR 71 for non-exclusive shipments. The mass of each radioisotope presented in this paper is limited by the radiation dose rate on the external surface of the package, which per the regulatory limit should not exceed 200 mrem/hr. The results presented are a compendium of allowable masses of a variety of different isotopes (with varying impurity levels of beryllium in some of the actinide isotopes) that, when loaded in an unshielded packaging, do not result in an external dose rate on the surface of the package that exceeds 190 mrem/hr (190 mrem/hr was chosen to provide 5% conservatism relative to the regulatory limit). These mass limits define the term 'Small Gram Quantity' (SGQ) contents in the context of radioactive material transportation packages. The term SGQ is isotope-specific and pertains to contents in radioactive material transportation packages that do not require shielding and still satisfy the external dose rate requirements. Since these calculated mass limits are for contents without shielding, they are conservative for packaging materials that provide some limited shielding or if the contents are placed into a shielded package. The isotopes presented in this paper were chosen as the isotopes that Department of Energy (DOE) sites most likely need to ship. Other more rarely shipped isotopes, along with industrial and medical isotopes, are planned to be included in subsequent extensions of this work.« less

Characterization of the radiation environment for a large-area interim spent-nuclear-fuel storage facility

NASA Astrophysics Data System (ADS)

Fortkamp, Jonathan C.

Current needs in the nuclear industry and movements in the political arena indicate that authorization may soon be given for development of a federal interim storage facility for spent nuclear fuel. The initial stages of the design work have already begun within the Department of Energy and are being reviewed by the Nuclear Regulatory Commission. This dissertation addresses the radiation environment around an interim spent nuclear fuel storage facility. Specifically the dissertation characterizes the radiation dose rates around the facility based on a design basis source term, evaluates the changes in dose due to varying cask spacing configurations, and uses these results to define some applicable health physics principles for the storage facility. Results indicate that dose rates from the facility are due primarily from photons from the spent fuel and Co-60 activation in the fuel assemblies. In the modeled cask system, skyshine was a significant contribution to dose rates at distances from the cask array, but this contribution can be reduced with an alternate cask venting system. With the application of appropriate health physics principles, occupation doses can be easily maintained far below regulatory limits and maintained ALARA.

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

PubMed

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

2017-10-01

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

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

PubMed Central

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

2017-01-01

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

Evaluation of scattered radiation emitted from X-ray security scanners on occupational dose to airport personnel

NASA Astrophysics Data System (ADS)

Dalah, Entesar; Fakhry, Angham; Mukhtar, Asma; Al Salti, Farah; Bader, May; Khouri, Sara; Al-Zahmi, Reem

2017-06-01

Based on security issues and regulations airports are provided with luggage cargo scanners. These scanners utilize ionizing radiation that in principle present health risks toward humans. The study aims to investigate the amount of backscatter produced by passenger luggage and cargo toward airport personnel who are located at different distances from the scanners. To approach our investigation a Thermo Electron Radeye-G probe was used to quantify the backscattered radiation measured in terms of dose-rate emitted from airport scanners, Measurements were taken at the entrance and exit positions of the X-ray tunnel at three different distances (0, 50, and 100 cm) for two different scanners; both scanners include shielding curtains that reduce scattered radiation. Correlation was demonstrated using the Pearson coefficient test. Measurements confirmed an inverse relationship between dose rate and distance. An estimated occupational accumulative dose of 0.88 mSv/y, and 2.04 mSv/y were obtained for personnel working in inspection of carry-on, and cargo, respectively. Findings confirm that the projected dose of security and engineering staff are being well within dose limits.

Reprint of 'Evaluation of Scattered Radiation Emitted From X-ray Security Scanners on Occupational Dose to Airport Personnel'

NASA Astrophysics Data System (ADS)

Dalah, Entesar; Fakhry, Angham; Mukhtar, Asma; Al Salti, Farah; Bader, May; Khouri, Sara; Al-Zahmi, Reem

2017-11-01

Based on security issues and regulations airports are provided with luggage cargo scanners. These scanners utilize ionizing radiation that in principle present health risks toward humans. The study aims to investigate the amount of backscatter produced by passenger luggage and cargo toward airport personnel who are located at different distances from the scanners. To approach our investigation a Thermo Electron Radeye-G probe was used to quantify the backscattered radiation measured in terms of dose-rate emitted from airport scanners, Measurements were taken at the entrance and exit positions of the X-ray tunnel at three different distances (0, 50, and 100 cm) for two different scanners; both scanners include shielding curtains that reduce scattered radiation. Correlation was demonstrated using the Pearson coefficient test. Measurements confirmed an inverse relationship between dose rate and distance. An estimated occupational accumulative dose of 0.88 mSv/y, and 2.04 mSv/y were obtained for personnel working in inspection of carry-on, and cargo, respectively. Findings confirm that the projected dose of security and engineering staff are being well within dose limits.

Application of the Monte Carlo method to the analysis of doses and shielding around an X-ray fluorescence equipment

NASA Astrophysics Data System (ADS)

Ródenas, José; Juste, Belén; Gallardo, Sergio; Querol, Andrea

2017-09-01

An X-ray fluorescence equipment is used for practical exercises in the laboratory of Nuclear Engineering of the Polytechnic University of Valencia (Spain). This equipment includes a compact X-ray tube, ECLIPSE-III, and a Si-PIN XR-100T detector. The voltage (30 kV), and the current (100 μA) of the tube are low enough so that expected doses around the tube do not represent a risk for students working in the laboratory. Nevertheless, doses and shielding should be evaluated to accomplish the ALARA criterion. The Monte Carlo method has been applied to evaluate the dose rate around the installation provided with a shielding composed by a box of methacrylate. Dose rates calculated are compared with experimental measurements to validate the model. Obtained results show that doses are below allowable limits. Hence, no extra shielding is required for the X-ray beam. A previous Monte Carlo model was also developed to obtain the tube spectrum and validated by comparison with data from manufacturer.

A phase I study of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors potentially responsive to mitoxantrone

PubMed Central

Resta, Lee P.; Pili, Roberto; Eisenberger, Mario A.; Spitz, Avery; King, Serina; Porter, Jennifer; Franke, Amy; Boinpally, Ramesh; Sweeney, Christopher J.

2010-01-01

Purpose To find the maximum tolerated dose (MTD) of OSI-461 in combination with mitoxantrone in patients with advanced solid tumors. Methods This was a Phase I study using cohort dose escalation of OSI-461 dosed orally twice daily in combination with mitoxantrone 12 mg/m2 given on Day 1 of each 21-day cycle. Results OSI-461 dose was escalated to 1,000 mg po bid. One patient experienced a dose-limiting toxicity (DLT). Three patients discontinued the study due to adverse events (AE). Two patients (10%) had a partial response, and ten patients (50%) had stable disease as best response. Conclusion The combination of OSI-461 and mitoxantrone was well tolerated. Dose escalation was stopped because of toxicities in a concurrent Phase I trial. The response rate seen in patients with prostate cancer was comparable to response rates seen in trials of mitoxantrone and prednisone alone, and further studies of the combination of OSI-461 and mitoxantrone were not pursued. PMID:20445979

Advanced tertiary treatment of municipal wastewater using raw and modified diatomite.

PubMed

Wu, Jinlu; Yang, Y S; Lin, Jinhua

2005-12-09

Advanced technology for more efficient and effective wastewater treatment is always timely needed. The feasibility of using raw and modified diatomite for advanced treatment of secondary sewage effluents (SSE) was investigated in this study. Raw diatomite at a dosing rate of 300 mg/l showed a similar potential as activated carbon for removing most organic pollutants and toxic metals from SSE. Its performance was found poor in removal of arsenic and crop nutrient constituents (e.g. ammoniacal nitrogen and phosphate) and remained unsatisfactory even when the dosing rate increased up to 500 mg/l. Where modified diatomite was in lieu of raw diatomite, the removal efficiency for all target constituents was improved by 20-50%. At the dosing rate of 150 mg/l, modified diatomite enabled the post-treated effluents to satisfy the discharge consents, with the levels of all target constituents below the regulatory limits. Modified diatomite has advantages over raw diatomite in improving removal efficiency and reducing the dosing rate required for satisfactory treatment of SSE. It is concluded that modified diatomite is much more effective and efficient than raw diatomite, as an alternative to activated carbon, for economic treatment of SSE.

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

Russell Feder and Mahmoud Z. Yousef

Neutronics analysis to find nuclear heating rates and personnel dose rates were conducted in support of the integration of diagnostics in to the ITER Upper Port Plugs. Simplified shielding models of the Visible-Infrared diagnostic and of the ECH heating system were incorporated in to the ITER global CAD model. Results for these systems are representative of typical designs with maximum shielding and a small aperture (Vis-IR) and minimal shielding with a large aperture (ECH). The neutronics discrete-ordinates code ATTILA® and SEVERIAN® (the ATTILA parallel processing version) was used. Material properties and the 500 MW D-T volume source were taken frommore » the ITER “Brand Model” MCNP benchmark model. A biased quadrature set equivelant to Sn=32 and a scattering degree of Pn=3 were used along with a 46-neutron and 21-gamma FENDL energy subgrouping. Total nuclear heating (neutron plug gamma heating) in the upper port plugs ranged between 380 and 350 kW for the Vis-IR and ECH cases. The ECH or Large Aperture model exhibited lower total heating but much higher peak volumetric heating on the upper port plug structure. Personnel dose rates are calculated in a three step process involving a neutron-only transport calculation, the generation of activation volume sources at pre-defined time steps and finally gamma transport analyses are run for selected time steps. ANSI-ANS 6.1.1 1977 Flux-to-Dose conversion factors were used. Dose rates were evaluated for 1 full year of 500 MW DT operation which is comprised of 3000 1800-second pulses. After one year the machine is shut down for maintenance and personnel are permitted to access the diagnostic interspace after 2-weeks if dose rates are below 100 μSv/hr. Dose rates in the Visible-IR diagnostic model after one day of shutdown were 130 μSv/hr but fell below the limit to 90 μSv/hr 2-weeks later. The Large Aperture or ECH style shielding model exhibited higher and more persistent dose rates. After 1-day the dose rate was 230 μSv/hr but was still at 120 μSv/hr 4-weeks later. __________________________________________________« less

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

Russell E. Feder and Mahmoud Z. Youssef

Neutronics analysis to find nuclear heating rates and personnel dose rates were conducted in support of the integration of diagnostics in to the ITER Upper Port Plugs. Simplified shielding models of the Visible-Infrared diagnostic and of a large aperture diagnostic were incorporated in to the ITER global CAD model. Results for these systems are representative of typical designs with maximum shielding and a small aperture (Vis-IR) and minimal shielding with a large aperture. The neutronics discrete-ordinates code ATTILA® and SEVERIAN® (the ATTILA parallel processing version) was used. Material properties and the 500 MW D-T volume source were taken from themore » ITER “Brand Model” MCNP benchmark model. A biased quadrature set equivelant to Sn=32 and a scattering degree of Pn=3 were used along with a 46-neutron and 21-gamma FENDL energy subgrouping. Total nuclear heating (neutron plug gamma heating) in the upper port plugs ranged between 380 and 350 kW for the Vis-IR and Large Aperture cases. The Large Aperture model exhibited lower total heating but much higher peak volumetric heating on the upper port plug structure. Personnel dose rates are calculated in a three step process involving a neutron-only transport calculation, the generation of activation volume sources at pre-defined time steps and finally gamma transport analyses are run for selected time steps. ANSI-ANS 6.1.1 1977 Flux-to-Dose conversion factors were used. Dose rates were evaluated for 1 full year of 500 MW DT operation which is comprised of 3000 1800-second pulses. After one year the machine is shut down for maintenance and personnel are permitted to access the diagnostic interspace after 2-weeks if dose rates are below 100 μSv/hr. Dose rates in the Visible-IR diagnostic model after one day of shutdown were 130 μSv/hr but fell below the limit to 90 μSv/hr 2-weeks later. The Large Aperture style shielding model exhibited higher and more persistent dose rates. After 1-day the dose rate was 230 μSv/hr but was still at 120 μSv/hr 4-weeks later.« less

Micro-feeding and dosing of powders via a small-scale powder pump.

PubMed

Besenhard, M O; Fathollahi, S; Siegmann, E; Slama, E; Faulhammer, E; Khinast, J G

2017-03-15

Robust and accurate powder micro-feeding (<100mg/s) and micro-dosing (<5 mg) are major challenges, especially with regard to regulatory limitations applicable to pharmaceutical development and production. Since known micro-feeders that yield feed rates below 5mg/s use gravimetric feeding principles, feed rates depend primarily on powder properties. In contrast, volumetric powder feeders do not require regular calibration because their feed rates are primarily determined by the feeder's characteristic volume replacement. In this paper, we present a volumetric micro-feeder based on a cylinder piston system (i.e., a powder pump), which allows accurate micro-feeding and feed rates of a few grams per hours even for very fine powders. Our experimental studies addressed the influence of cylinder geometries, the initial conditions of bulk powder, and the piston speeds. Additional computational studies via Discrete Element Method simulations offered a better understanding of the feeding process, its possible limitations and ways to overcome them. The powder pump is a simple yet valuable tool for accurate powder feeding at feed rates of several orders of magnitude. Copyright © 2016 Elsevier B.V. All rights reserved.

Design and dosimetric characteristics of a new endocavitary contact radiotherapy system using an electronic brachytherapy source.

PubMed

Richardson, Susan; Garcia-Ramirez, Jose; Lu, Wei; Myerson, Robert J; Parikh, Parag

2012-11-01

To present design aspects and acceptance tests performed for clinical implementation of electronic brachytherapy treatment of early stage rectal adenocarcinoma. A dosimetric comparison is made between the historically used Philips RT-50 unit and the newly developed Axxent(®) Model S700 electronic brachytherapy source manufactured by Xoft (iCad, Inc.). Two proctoscope cones were manufactured by ElectroSurgical Instruments (ESI). Two custom surface applicators were manufactured by Xoft and were designed to fit and interlock with the proctoscope cones from ESI. Dose rates, half value layers (HVL), and percentage depth dose (PDD) measurements were made with the Xoft system and compared to historical RT-50 data. A description of the patient treatment approach and exposure rates during the procedure is also provided. The electronic brachytherapy system has a lower surface dose rate than the RT-50. The dose rate to water on the surface from the Xoft system is approximately 2.1 Gy∕min while the RT-50 is 10-12 Gy∕min. However, treatment times with Xoft are still reasonable. The HVLs and PDDs between the two systems were comparable resulting in similar doses to the target and to regions beyond the target. The exposure rate levels around a patient treatment were acceptable. The standard uncertainty in the dose rate to water on the surface is approximately ±5.2%. The Philips RT-50 unit is an out-of-date radiotherapy machine that is no longer manufactured with limited replacement parts. The use of a custom-designed proctoscope and Xoft surface applicators allows delivery of a well-established treatment with the ease of a modern radiotherapy device. While the dose rate is lower with the use of Xoft, the treatment times are still reasonable. Additionally, personnel may stand farther away from the Xoft radiation source, thus potentially reducing radiation exposure to the operator and other personnel.

The use of TLD-700H dosemeters in the assessment of external doses at the former Semipalatinsk nuclear test site.

PubMed

Hill, P; Dederichs, H; Pillath, J; Schlecht, W; Hille, R; Artemev, O; Ptitskaya, L; Akhmetov, M

2002-01-01

The joint projects performed since 1995 by the Jülich Research Centre in co-operation with the Kazakh National Nuclear Centre in the area of the former nuclear test site near Semipalatinsk, in eastern Kazakhstan, have assessed the current dose rate of the population at and around the test site, as well as determining retrospectively the dose rate of persons affected by the atmospheric tests. Measurements of the population by personal dosemeters depend on reliably wearing these dosemeters over prolonged periods of time, and of a sufficient dosemeter return. In the past, such measurements have been particularly successful whenever short wearing times were possible. This requires high sensitivity of the dosemeters. The suitability of the highly sensitive TLD material of the BICRON TLD 700H type for such personal dosimetry measurements was investigated. It was tested in practical field application at the Semipalatinsk nuclear test site in September 2000. Initial results are available from individual doses received by a group of geologists and a group of herdsmen at the test site. For the first time, the individual dose was measured directly in these population groups. Detection limits below 1 microSv permit informative measurements for wearing times of less than two weeks. Most individual doses did not arise significantly out of local fluctuations of natural background. A conservative assessment from the aspect of practical health physics yielded a mean personal dose of 0.55 microSv per day for the herdsmen, whereas the geologists received a mean personal dose of 0.45 microSv per day. For an annual exposure period of typically, about three months, the radiation dose received by the persons investigated, in addition to the natural radiation exposure, is thus well below the international limit value of 1 mSv x a(-1) for the population dose.

Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies

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

Kubicek, Gregory J.; Werner-Wasik, Maria; Machtay, Mitchell

Purpose: To evaluate the toxicity and response rate of bortezomib with concurrent radiotherapy and temozolomide in the treatment of patients with central nervous system malignancies. Patients and Methods: This open-label, dose-escalation, Phase I clinical study evaluated the safety of three dose levels of intravenously administered bortezomib (0.7, 1.0, and 1.3 mg/m{sup 2}/dose) on Days 1, 4, 8, and 11 of a 21-day cycle, in addition to concurrent radiotherapy and temozolomide at a daily dose of 75 mg/m{sup 2} starting on Day 1. The primary endpoint was dose-limiting toxicity, defined as any Grade 4-5 toxicity or Grade 3 toxicity directly attributablemore » to protocol treatment, requiring hospitalization and/or radiotherapy interruption. The secondary endpoints included feasibility, non-dose-limiting toxicity, and treatment response. Results: A total of 27 patients were enrolled, 23 of whom had high-grade glioma (10 recurrent and 13 newly diagnosed). No dose-limiting toxicities were noted in any dose group, including the highest (1.3 mg/m{sup 2}/dose). The most frequent toxicities were Grade 1 and 2 stomatitis, erythema, and alopecia. All 27 patients were evaluable for response. At a median follow-up of 15.0 months, 9 patients were still alive, with a median survival of 17.4 months for all patients and 15.0 months for patients with high-grade glioma. Conclusion: Bortezomib administered at its typical 'systemic' dose (1.3 mg/m{sup 2}) is well tolerated and safe combined with temozolomide and radiotherapy when used in the treatment of central nervous system malignancies. A Phase II study to characterize efficacy is warranted.« less

Radiation dose to patients and image quality evaluation from coronary 256-slice computed tomographic angiography

NASA Astrophysics Data System (ADS)

Chen, Liang-Kuang; Wu, Tung-Hsin; Yang, Ching-Ching; Tsai, Chia-Jung; Lee, Jason J. S.

2010-07-01

The aim of this study is to assess radiation dose and the corresponding image quality from suggested CT protocols which depends on different mean heart rate and high heart rate variability by using 256-slice CT. Fifty consecutive patients referred for a cardiac CT examination were included in this study. All coronary computed tomographic angiography (CCTA) examinations were performed on a 256-slice CT scanner with one of five different protocols: retrospective ECG-gating (RGH) with full dose exposure in all R-R intervals (protocol A), RGH of 30-80% pulsing window with tube current modulation (B), RGH of 78±5% pulsing window with tube current modulation (C), prospective ECG-triggering (PGT) of 78% R-R interval with 5% padding window (D) and PGT of 78% R-R interval without padding window (E). Radiation dose parameters and image quality scoring were determined and compared. In this study, no significant differences were found in comparison on image quality of the five different protocols. Protocol A obtained the highest radiation dose comparing with those of protocols B, C, D and E by a factor of 1.6, 2.4, 2.5 and 4.3, respectively ( p<0.001), which were ranged between 2.7 and 11.8 mSv. The PGT could significantly reduce radiation dose delivered to patients, as compared to the RGH. However, the use of PGT has limitations and is only good in assessing cases with lower mean heart rate and stable heart rate variability. With higher mean heart rate and high heart rate variability circumstances, the RGH within 30-80% of R-R interval pulsing window is suggested as a feasible technique for assessing diagnostic performance.

'Muscle-sparing' statins: preclinical profiles and future clinical use.

PubMed

Pfefferkorn, Jeffrey A

2009-03-01

Coronary heart disease (CHD) is a leading cause of death in the US, and hypercholesterolemia is a key risk factor for this disease. The current standard of care for treating hypercholesterolemia is the use of HMG-CoA reductase inhibitors, also known as statins, which block the rate-limiting step of cholesterol biosynthesis. In widespread clinical use, statins have proven safe and effective for both primary prevention of CHD and secondary prevention of coronary events. Results from several recent clinical trials have demonstrated that increasingly aggressive cholesterol-lowering therapy might offer additional protection against CHD compared with less aggressive treatment standards. While higher doses of current statin therapies are capable of achieving these more aggressive treatment goals, in certain cases statin-induced myalgia, the muscle pain or weakness that sometimes accompanies high-dose statin therapy, limits patient compliance with a treatment regimen. To address this limitation, efforts have been undertaken to develop highly hepatoselective statins that are capable of delivering best-in-class efficacy with minimized risk of dose-limiting myalgia. In this review, the preclinical and early clinical data for these next generation statins are discussed.

Technical Note: A proposal of air ventilation system design criteria for a clinical room in a heavy-ion medical facility.

PubMed

Kum, Oyeon

2018-06-01

An optimized air ventilation system design for a treatment room in Heavy-ion Medical Facility is an important issue in the aspects of nuclear safety because the activated air produced in a treatment room can directly affect the medical staff and the general public in the radiation-free area. Optimized design criteria of air ventilation system for a clinical room in 430 MeV/u carbon ion beam medical accelerator facility was performed by using a combination of MCNPX2.7.0 and CINDER'90 codes. Effective dose rate and its accumulated effective dose by inhalation and residual gamma were calculated for a normal treatment scenario (2 min irradiation for one fraction) as a function of decay time. Natural doses around the site were measured before construction and used as reference data. With no air ventilation system, the maximum effective dose rate was about 3 μSv/h (total dose of 90 mSv/y) and minimum 0.2 μSv/h (total dose of 6 mSv/y), which are over the legal limits for medical staff and for the general public. Although inhalation dose contribution was relatively small, it was considered seriously because of its long-lasting effects in the body. The integrated dose per year was 1.8 mSv/y in the radiation-free area with the 20-min rate of air ventilation system. An optimal air ventilation rate of 20 min is proposed for a clinical room, which also agrees with the best mechanical design value. © 2018 American Association of Physicists in Medicine.

Dose Escalation of Whole-Brain Radiotherapy for Brain Metastases From Melanoma

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

Rades, Dirk, E-mail: Rades.Dirk@gmx.ne; Heisterkamp, Christine; Huttenlocher, Stefan

2010-06-01

Purpose: The majority of patients with brain metastases from melanoma receive whole-brain radiotherapy (WBRT). However, the results are poor. Hypofractionation regimens failed to improve the outcome of these patients. This study investigates a potential benefit from escalation of the WBRT dose beyond the 'standard' regimen 30 Gy in 10 fractions (10x3 Gy). Methods and Materials: Data from 51 melanoma patients receiving WBRT alone were retrospectively analyzed. A dosage of 10x3 Gy (n = 33) was compared with higher doses including 40 Gy/20 fractions (n = 11) and 45 Gy/15 fractions (n = 7) for survival (OS) and local (intracerebral) controlmore » (LC). Additional potential prognostic factors were evaluated: age, gender, performance status, number of metastases, extracerebral metastases, and recursive partitioning analysis (RPA) class. Results: At 6 months, OS rates were 27% after 10x3 Gy and 50% after higher doses (p = 0.009). The OS rates at 12 months were 4% and 20%. On multivariate analysis, higher WBRT doses (p = 0.010), fewer than four brain metastases (p = 0.012), no extracerebral metastases (p = 0.006), and RPA class 1 (p = 0.005) were associated with improved OS. The LC rates at 6 months were 23% after 10x3 Gy and 50% after higher doses (p = 0.021). The LC rates at 12 months were 0% and 13%. On multivariate analysis, higher WBRT doses (p = 0.020) and fewer than brain metastases (p = 0.002) were associated with better LC. Conclusions: Given the limitations of a retrospective study, the findings suggest that patients with brain metastases from melanoma receiving WBRT alone may benefit from dose escalation beyond 10x3 Gy. The hypothesis generated by this study must be confirmed in a randomized trial stratifying for significant prognostic factors.« less

SU-F-T-653: Radiation Exposure from Cs-131 Permanent Seed Implants

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

Giaddui, T; Hardin, M; To, D

Purpose: Permanent seed implants have traditionally been used to treat prostate, lung and head or neck cancers using I-125 and Pd-103. Cs-131, which has higher dose rate is being used to treat brain, head and/or neck cancers in our clinic, therefore, we chose to monitor the dose received by surgeons during the extensive procedure. The aims of this work are to assess the level of radiation exposure to surgeons and the instantaneous exposure at bedside and 1 m from patients. Methods: Ten patients received Cs-131 implants for recurrent brain,head and/or neck cancer; the median implanted activity, number of implanted seedsmore » and prescription dose at 0.5 cm from the perpendicular plane of the implant were: 54.3 mCi (14.52 – 77); 19 (4 – 24) and 60 Gy (range 42 – 60) respectively. Radiation exposure was recorded at bedside and 1 m from the patient using Victoreen ion chamber (Fluke Biomedical, Cleveland, OH). Exposure to surgeons was measured using TLD (Mirion Technologies (GDS), Inc., USA). Results: The median equivalent dose rate at 1 m and bedside immediately following implantation were 1.49×10-2 mSv/h (8.77×10-3–2.63×10-2) and 7.76×10-2 mSv/h (3.1×10-2– 1.53×10-1) respectively. Median equivalent dose to surgeons’ hands was 0.60 mSv (0.33 – 1.48) and no doses were detected for whole-body. Surgical reconstruction for one patient was performed 71 days post-implant and resulted in zero exposure to surgeons. Conclusion: The recorded exposure rates were low when compared with the literature. Post procedure surveys at bed site and 1 m indicated that all patients were within safe limits for discharge (< 0.05 mSv/h at 1 m). However, as a precautionary measure, patients were advised to avoid direct contact with children and pregnant women within four weeks of the implant and stay at least at 3 ft from other people. Surgeons doses were well within occupational dose limits.« less

Phase I Trial Using Patupilone (Epothilone B) and Concurrent Radiotherapy for Central Nervous System Malignancies

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

Fogh, Shannon; Machtay, Mitchell; Werner-Wasik, Maria

Purpose: Based on preclinical data indicating the radiosensitizing potential of epothilone B, the present study was designed to evaluate the toxicity and response rate of patupilone, an epothilone B, with concurrent radiotherapy (RT) for the treatment of central nervous system malignancies. Methods and Materials: The present Phase I study evaluated the toxicities associated with patupilone combined with RT to establish the maximal tolerated dose. Eligible patients had recurrent gliomas (n = 10) primary (n = 5) or metastatic (n = 17) brain tumors. Dose escalation occurred if no dose-limiting toxicities, defined as any Grade 4-5 toxicity or Grade 3 toxicitymore » requiring hospitalization, occurred during treatment. Results: Of 14 patients, 5 were treated with weekly patupilone at 1.5 mg/m{sup 2}, 4 at 2.0 mg/m{sup 2}, 4 at 2.5 mg/m{sup 2}, and 1 at 4 mg/m{sup 2}. Of 18 patients, 7 were treated in the 6-mg/m{sup 2} group, 6 in the 8-mg/m{sup 2} group, and 5 in the 10-mg/m{sup 2} group. Primary central nervous system malignancies received RT to a median dose of 60 Gy. Central nervous system metastases received whole brain RT to a median dose of 37.4 Gy, and patients with recurrent gliomas underwent stereotactic RT to a median dose of 37.5 Gy. One dose-limiting toxicity (pneumonia) was observed in group receiving 8-mg/m{sup 2} every 3 weeks. At the subsequent dose level (10 mg/m{sup 2}), two Grade 4 dose-limiting toxicities occurred (renal failure and pulmonary hemorrhage); thus, 8 mg/m{sup 2} every 3 weeks was the maximal tolerated dose and the recommended Phase II dose. Conclusion: Combined with a variety of radiation doses and fractionation schedules, concurrent patupilone was well tolerated and safe, with a maximal tolerated dose of 8 mg/m{sup 2} every 3 weeks.« less

Modeling the effectiveness of shielding in the earth-moon-mars radiation environment using PREDICCS: five solar events in 2012

NASA Astrophysics Data System (ADS)

Quinn, Philip R.; Schwadron, Nathan A.; Townsend, Larry W.; Wimmer-Schweingruber, Robert F.; Case, Anthony W.; Spence, Harlan E.; Wilson, Jody K.; Joyce, Colin J.

2017-08-01

Radiation in the form of solar energetic particles (SEPs) presents a severe risk to the short-term health of astronauts and the success of human exploration missions beyond Earth's protective shielding. Modeling how shielding mitigates the dose accumulated by astronauts is an essential step toward reducing these risks. PREDICCS (Predictions of radiation from REleASE, EMMREM, and Data Incorporating the CRaTER, COSTEP, and other SEP measurements) is an online tool for the near real-time prediction of radiation exposure at Earth, the Moon, and Mars behind various levels of shielding. We compare shielded dose rates from PREDICCS with dose rates from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) onboard the Lunar Reconnaissance Orbiter (LRO) at the Moon and from the Radiation Assessment Detector (RAD) on the Mars Science Laboratory (MSL) during its cruise phase to Mars for five solar events in 2012 when Earth, MSL, and Mars were magnetically well connected. Calculations of the accumulated dose demonstrate a reasonable agreement between PREDICCS and RAD ranging from as little as 2% difference to 54%. We determine mathematical relationships between shielding levels and accumulated dose. Lastly, the gradient of accumulated dose between Earth and Mars shows that for the largest of the five solar events, lunar missions require aluminum shielding between 1.0 g cm-2 and 5.0 g cm-2 to prevent radiation exposure from exceeding the 30-day limits for lens and skin. The limits were not exceeded near Mars.

The increase in animal mortality risk following exposure to sparsely ionizing radiation is not linear quadratic with dose

DOE PAGES

Haley, Benjamin M.; Paunesku, Tatjana; Grdina, David J.; ...

2015-12-09

The US government regulates allowable radiation exposures relying, in large part, on the seventh report from the committee to estimate the Biological Effect of Ionizing Radiation (BEIR VII), which estimated that most contemporary exposures- protracted or low-dose, carry 1.5 fold less risk of carcinogenesis and mortality per Gy than acute exposures of atomic bomb survivors. This correction is known as the dose and dose rate effectiveness factor for the life span study of atomic bomb survivors (DDREF LSS). As a result, it was calculated by applying a linear-quadratic dose response model to data from Japanese atomic bomb survivors and amore » limited number of animal studies.« less

The increase in animal mortality risk following exposure to sparsely ionizing radiation is not linear quadratic with dose

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

Haley, Benjamin M.; Paunesku, Tatjana; Grdina, David J.

The US government regulates allowable radiation exposures relying, in large part, on the seventh report from the committee to estimate the Biological Effect of Ionizing Radiation (BEIR VII), which estimated that most contemporary exposures- protracted or low-dose, carry 1.5 fold less risk of carcinogenesis and mortality per Gy than acute exposures of atomic bomb survivors. This correction is known as the dose and dose rate effectiveness factor for the life span study of atomic bomb survivors (DDREF LSS). As a result, it was calculated by applying a linear-quadratic dose response model to data from Japanese atomic bomb survivors and amore » limited number of animal studies.« less

Correlates of individual differences in compensatory nicotine self-administration in rats following a decrease in nicotine unit dose

PubMed Central

Harris, Andrew C.; Pentel, Paul R.; LeSage, Mark G.

2013-01-01

Rationale The ability of tobacco harm reduction strategies to produce significant reductions in toxin exposure is limited by compensatory increases in smoking behavior. Characterizing factors contributing to the marked individual variability in compensation may be useful for understanding this phenomenon and assessing the feasibility of harm reduction interventions. Objective To use an animal model of human compensatory smoking that involves a decrease in unit dose supporting nicotine self-administration (NSA) to examine potential contributors to individual differences in compensation. Methods Rats were trained for NSA during daily 23 hr sessions at a unit dose of 0.06 mg/kg/inf until responding was stable. The unit dose was then reduced to 0.03 mg/kg/inf for at least 10 sessions. Following reacquisition of NSA at the training dose and extinction, single-dose nicotine pharmacokinetic parameters were determined. Results Decreases in nicotine intake following dose reduction were proportionally less than the decrease in unit dose, indicating partial compensation. Compensatory increases in infusion rates were observed across the course of the 23 hr sessions. The magnitude of compensation differed considerably between rats. Rats exhibiting the highest baseline infusion rates exhibited the lowest levels of compensation. Nicotine pharmacokinetic parameters were not significantly correlated with compensation. Infusion rates immediately returned to pre-reduction levels when baseline conditions were restored. Conclusions These findings provide initial insights into correlates of individual differences in compensation following a reduction in nicotine unit dose. The present assay may be useful for characterizing mechanisms and potential consequences of the marked individual differences in compensatory smoking observed in humans. PMID:19475400

Impact of high- versus low-dose neuromuscular blocking agent administration on unplanned 30-day readmission rates in retroperitoneal laparoscopic surgery.

PubMed

Boon, Martijn; Martini, Chris; Yang, H Keri; Sen, Shuvayu S; Bevers, Rob; Warlé, Michiel; Aarts, Leon; Niesters, Marieke; Dahan, Albert

2018-01-01

Recent data shows that a neuromuscular block (NMB) induced by administration of high doses of rocuronium improves surgical conditions in certain procedures. However, there are limited data on the effect such practices on postoperative outcomes. We performed a retrospective analysis to compare unplanned 30-day readmissions in patients that received high-dose versus low-dose rocuronium administration during general anesthesia for laparoscopic retroperitoneal surgery. This retrospective cohort study was performed in the Netherlands in an academic hospital where routine high-dose rocuronium NMB has been practiced since July 2015. Charts of patients receiving anesthesia between January 2014 and December 2016 were searched for surgical cases receiving high-dose rocuronium and matched with respect to procedure, age, sex and ASA classification to patients receiving low-dose rocuronium. The primary post-operative outcome was unplanned 30-day readmission rate. There were 130 patients in each cohort. Patients in the high- and low-dose rocuronium cohorts received 217 ± 49 versus 37 ± 5 mg rocuronium, respectively. In the high-dose rocuronium group neuromuscular activity was consistently monitored; matched patients were unreliably monitored. All patients receiving high-dose rocuronium were reversed with sugammadex, while just 33% of matched patients were reversed with sugammadex and 20% with neostigmine; the remaining patients were not reversed. Unplanned 30-day readmission rate was significantly lower in the high-dose compared to the low-dose rocuronium cohort (3.8% vs. 12.7%; p = 0.03; odds ratio = 0.33, 95% C.I. 0.12-0.95). This small retrospective study demonstrates a lower incidence of unplanned readmissions within 30-days following laparoscopic retroperitoneal surgery with high-dose relaxant anesthesia and sugammadex reversal in comparison to low-dose relaxant anesthesia. Further prospective studies are needed in larger samples to corroborate our findings and additionally assess the pharmacoeconomics of high-dose relaxant anesthesia taking into account the benefits (reduced readmissions) and harm (cost of relaxants and reversal agents) of such practice.

Relative radiological risks derived from different TENORM wastes in Malaysia.

PubMed

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

2011-11-01

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

Determination of the uncertainties in radiation doses from ingestion of strontium-90

NASA Astrophysics Data System (ADS)

Apostoaei, Andrei Iulian

Quantification of the uncertainties in the internal dosimetry is important because it can impact the outcome of dose reconstruction, risk assessment or epidemiological studies. This research focused on determination of the uncertainties in the dose factors from a single ingestion of 90Sr by adults, and analyzed the changes with age and the effect of gender. The uncertainties in the estimated dose factors are a factor of 6 for the bone surface, 5 for the red bone marrow, 2.5 for bladder and stomach, 2.2 for the small intestine, 2.1 for the upper large intestine and 2.7 for the lower large intestine. For the rest of the organs the uncertainty is a factor of 3. Only four parameters of the biokinetic model showed an age-dependency within the adult age group: the fractional transfers of strontium from plasma to cortical and trabecular bone, and the removal rates from the cortical and trabecular bone, respectively. When age-dependent biokinetic parameters were used, the estimated dose-factors are very close to the dose factors obtained using age-independent kinetics (within 40%). Thus, the dose factors based on age-independent parameters should suffice for most practical purposes. The dose factors and the associated uncertainties were also calculated as a function of age-at-exposure and attained age. These age dependent curves can be used for estimating doses from continuous intakes, or doses delivered over a limited portion of time. In addition to the committed dose, an expected dose is also estimated in this work. The expected dose is calculated using the dose rate weighted by the probability of surviving up to the age when the dose-rate is delivered. For exposure at young ages the expected dose and the committed dose are similar, but the committed dose decreases to zero when exposure occurs close to age 70, while the expected dose has elevated values pass age 70. No gender differences were found for bone surface, for red bone marrow, and the large intestine. The doses to the soft tissues for females are larger by 20% than the doses for males, because of the differences in the whole-body mass between males and females.

Low-voltage chest CT: another way to reduce the radiation dose in asbestos-exposed patients.

PubMed

Macía-Suárez, D; Sánchez-Rodríguez, E; Lopez-Calviño, B; Diego, C; Pombar, M

2017-09-01

To assess whether low voltage chest computed tomography (CT) can be used to successfully diagnose disease in patients with asbestos exposure. Fifty-six former employees of the shipbuilding industry, who were candidates to receive a standard-dose chest CT due to their occupational exposure to asbestos, underwent a routine CT. Immediately after this initial CT, they underwent a second acquisition using low-dose chest CT parameters, based on a low potential (80 kV) and limited tube current. The findings of the two CT protocols were compared based on typical diseases associated with asbestos exposure. The kappa coefficient for each parameter and for an overall rating (grouping them based on mediastinal, pleural, and pulmonary findings) were calculated in order to test for correlations between the two protocols. A good correlation between routine and low-dose CT was demonstrated for most parameters with a mean radiation dose reduction of up to 83% of the effective dose based on the dose-length product between protocols. Low-dose chest CT, based on a limited tube potential, is useful for patients with an asbestos exposure background. Low-dose chest CT can be successfully used to minimise the radiation dose received by patients, as this protocol produced an estimated mean effective dose similar to that of an abdominal or pelvis plain film. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Radionuclide transfer to wildlife at a 'Reference site' in the Chernobyl Exclusion Zone and resultant radiation exposures.

PubMed

Beresford, N A; Barnett, C L; Gashchak, S; Maksimenko, A; Guliaichenko, E; Wood, M D; Izquierdo, M

2018-02-27

This study addresses a significant data deficiency in the developing environmental protection framework of the International Commission on Radiological Protection, namely a lack of radionuclide transfer data for some of the Reference Animals and Plants (RAPs). It is also the first study that has sampled such a wide range of species (invertebrates, plants, amphibians and small mammals) from a single terrestrial site in the Chernobyl Exclusion Zone (CEZ). Samples were collected in 2014 from the 0.4 km 2 sampling site, located 5 km west of the Chernobyl Nuclear Power complex. We report radionuclide ( 137 Cs, 90 Sr, 241 Am and Pu-isotopes) and stable element concentrations in wildlife and soil samples and use these to determine whole organism-soil concentration ratios and absorbed dose rates. Increasingly, stable element analyses are used to provide transfer parameters for radiological models. The study described here found that for both Cs and Sr the transfer of the stable element tended to be lower than that of the radionuclide; this is the first time that this has been demonstrated for Sr, though it is in agreement with limited evidence previously reported for Cs. Studies reporting radiation effects on wildlife in the CEZ generally relate observations to ambient dose rates determined using handheld dose meters. For the first time, we demonstrate that ambient dose rates may underestimate the actual dose rate for some organisms by more than an order of magnitude. When reporting effects studies from the CEZ, it has previously been suggested that the area has comparatively low natural background dose rates. However, on the basis of data reported here, dose rates to wildlife from natural background radionuclides within the CEZ are similar to those in many areas of Europe. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis.

PubMed

Kloprogge, Frank; Workman, Lesley; Borrmann, Steffen; Tékété, Mamadou; Lefèvre, Gilbert; Hamed, Kamal; Piola, Patrice; Ursing, Johan; Kofoed, Poul Erik; Mårtensson, Andreas; Ngasala, Billy; Björkman, Anders; Ashton, Michael; Friberg Hietala, Sofia; Aweeka, Francesca; Parikh, Sunil; Mwai, Leah; Davis, Timothy M E; Karunajeewa, Harin; Salman, Sam; Checchi, Francesco; Fogg, Carole; Newton, Paul N; Mayxay, Mayfong; Deloron, Philippe; Faucher, Jean François; Nosten, François; Ashley, Elizabeth A; McGready, Rose; van Vugt, Michele; Proux, Stephane; Price, Ric N; Karbwang, Juntra; Ezzet, Farkad; Bakshi, Rajesh; Stepniewska, Kasia; White, Nicholas J; Guerin, Philippe J; Barnes, Karen I; Tarning, Joel

2018-06-01

The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations. A search in PubMed, Embase, ClinicalTrials.gov, Google Scholar, conference proceedings, and the WorldWide Antimalarial Resistance Network (WWARN) pharmacology database identified 31 relevant clinical studies published between 1 January 1990 and 31 December 2012, with 4,546 patients in whom lumefantrine concentrations were measured. Under the auspices of WWARN, relevant individual concentration-time data, clinical covariates, and outcome data from 4,122 patients were made available and pooled for the meta-analysis. The developed lumefantrine population pharmacokinetic model was used for dose optimisation through in silico simulations. Venous plasma lumefantrine concentrations 7 days after starting standard AL treatment were 24.2% and 13.4% lower in children weighing <15 kg and 15-25 kg, respectively, and 20.2% lower in pregnant women compared with non-pregnant adults. Lumefantrine exposure decreased with increasing pre-treatment parasitaemia, and the dose limitation on absorption of lumefantrine was substantial. Simulations using the lumefantrine pharmacokinetic model suggest that, in young children and pregnant women beyond the first trimester, lengthening the dose regimen (twice daily for 5 days) and, to a lesser extent, intensifying the frequency of dosing (3 times daily for 3 days) would be more efficacious than using higher individual doses in the current standard treatment regimen (twice daily for 3 days). The model was developed using venous plasma data from patients receiving intact tablets with fat, and evaluations of alternative dosing regimens were consequently only representative for venous plasma after administration of intact tablets with fat. The absence of artemether-dihydroartemisinin data limited the prediction of parasite killing rates and recrudescent infections. Thus, the suggested optimised dosing schedule was based on the pharmacokinetic endpoint of lumefantrine plasma exposure at day 7. Our findings suggest that revised AL dosing regimens for young children and pregnant women would improve drug exposure but would require longer or more complex schedules. These dosing regimens should be evaluated in prospective clinical studies to determine whether they would improve cure rates, demonstrate adequate safety, and thereby prolong the useful therapeutic life of this valuable antimalarial treatment.

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

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

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

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

Environmental radiology assessment in Lahad Datu, Sabah

NASA Astrophysics Data System (ADS)

Siti Fharhana, Yusof; Wan Muhamad Saridan, Wan Hassan; Ahmad Termizi, Ramli; Mohd Hilmi, Sahini; Mohammad Syazwan, Mohd Sanusi; Nor Afifah, Basri; Nor Zati Hani, Abu Hanifah

2017-10-01

Monitoring terrestial gamma radiation is crucial to prepare a baseline data for environmental radiological protection. Radiological research was carried out in Lahad Datu, Sabah to obtain the radioactivity status and terrestrial gamma radiation level in the area. We measure the terrestrial gamma radiation dose rates and analyse the radioactivity concentration of primordial radionuclides for radiological risk assessment. We identified that the annual estimation of dose effective for public is below the public dose limit, 1 mSv per year. Public and environment safety and health are remain secure. The obtained data and results can be used as reference for environmental radiology protection.

Exposure to cosmic radiation of British Airways flying crew on ultralonghaul routes.

PubMed

Bagshaw, M; Irvine, D; Davies, D M

1996-07-01

British Airways has carried out radiation monitoring in Concorde for more than 20 years and has used a heuristic model based on data quoted by the National Aeronautics and Space Administration (NASA) to model radiation exposure in all longhaul fleets. From these data it has been calculated that no flight deck crew would exceed the control level of 6 mSv/y currently under consideration by regulatory authorities, which is three tenths of the occupational dose limit of 20 mSv/y recommended by the International Commission on Radiological Protection (ICRP). The model suggested that less than 4% of cabin crew based in Tokyo flying only between London and Japan could reach or exceed the 6 mSv/y level, based on a predicted effective dose rate of 7 microSv/h. To validate this calculation a sampling measurement programme was carried out on nine round trips flown by a Boeing 747-400 between London and Tokyo. The radiation field was measured with dosimeters used for routine personal monitoring (thermoluminescence dosimeters (TLDs) and polyallydiglycol carbonate neutron dosimeters). The limitations of the methodology are acknowledged, but the results indicate that the effective dose rate was 6 microSv/h which is consistent with the predicted effective dose rate of 7 microSv/h. This result, which is in accordance with other reported studies indicates that it is unlikely that any of the cabin crew based in Tokyo exceeded the 6 mSv/y level. In accordance with "as low as reasonably achievable" principles British Airways will continue to monitor flying crew routes and hours flown to ensure compliance.

Radiation protection issues in galactic cosmic ray risk assessment

NASA Technical Reports Server (NTRS)

Sinclair, W. K.

1994-01-01

Radiation protection involves the limitation of exposure to below threshold doses for direct (or deterministic) effects and a knowledge of the risk of stochastic effects after low doses. The principal stochastic risk associated with low dose rate galactic cosmic rays is the increased risk of cancer. Estimates of this risk depend on two factors (a) estimates of cancer risk for low-LET radiation and (b) values of the appropriate radiation weighting factors, WR, for the high-LET radiations of galactic cosmic rays. Both factors are subject to considerable uncertainty. The low-LET cancer risk derived from the late effects of the atomic bombs is vulnerable to a number of uncertainties including especially that from projection in time, and from extrapolation from high to low dose rate. Nevertheless, recent low dose studies of workers and others tend to confirm these estimates. WR, relies on biological effects studied mainly in non-human systems. Additional laboratory studies could reduce the uncertainties in WR and thus produce a more confident estimate of the overall risk of galactic cosmic rays.

Radiation protection issues in galactic cosmic ray risk assessment.

PubMed

Sinclair, W K

1994-01-01

Radiation protection involves the limitation of exposure to below threshold doses for direct (or deterministic) effects and a knowledge of the risk of stochastic effects after low doses. The principal stochastic risk associated with low dose rate galactic cosmic rays is the increased risk of cancer. Estimates of this risk depend on two factors (a) estimates of cancer risk for low-LET radiation and (b) values of the appropriate radiation weighting factors, WR, for the high-LET radiations of galactic cosmic rays. Both factors are subject to considerable uncertainty. The low-LET cancer risk derived from the late effects of the atomic bombs is vulnerable to a number of uncertainties including especially that from projection in time, and from extrapolation from high to low dose rate. Nevertheless, recent low dose studies of workers and others tend to confirm these estimates. WR, relies on biological effects studied mainly in non-human systems. Additional laboratory studies could reduce the uncertainties in WR and thus produce a more confident estimate of the overall risk of galactic cosmic rays.

Reducing operator radiation exposure during cardiac resynchronization therapy.

PubMed

Brambilla, Marco; Occhetta, Eraldo; Ronconi, Martina; Plebani, Laura; Carriero, Alessandro; Marino, Paolo

2010-12-01

To quantify the reduction in equivalent dose at operator's hand that can be achieved by placement of a radiation-absorbing drape (RADPAD) during long-lasting cardiac resynchronization therapy (CRT) procedures. This is a prospective observational study that included 22 consecutive patients with drug-refractory heart failure who underwent implantation of a CRT device. The cases were randomly assigned to Group A (11 cases), performed without RADPAD, and to Group B (11 cases), performed using RADPAD. Dose equivalent at the examiner's hand was measured as H(p)(0.07) and as a time-adjusted H(p)(0.07) rate (mGy/min) with a direct reading dosimeter. The mean fluoroscopy time was 20.8 ± 7.7 min and the mean dose area product (DAP) was 118.6 ± 45.3 Gy cm(2). No significant differences were found between body mass index, fluoroscopy time, and DAP between patients examined with or without RADPAD. The correlation between the fluoroscopy time and the DAP was high (R(2) = 0.94, P < 0.001). Mean dose and dose rate measurement without the RADPAD at the finger and hand were H(p)(0.07) = 1.27 ± 0.47 mGy per procedure and H(p)(0.07) rate = 0.057 ± 0.011 mGy/min, respectively. The dosage was reduced with the RADPAD to H(p)(0.07) = 0.48 ± 0.20 (P < 0.05) and to H(p)(0.07) rate = 0.026 ± 0.008 (P < 0.001), respectively. A mean reduction of 54% in the equivalent dose rate to the operator's hand can be achieved with the use of RADPAD. The use of the RADPAD in CRT devices implantation will make unlikely the necessity of limiting the yearly number of implants for high volume operators.

Efficacy evaluation of low-dose aspirin in IVF/ICSI patients evidence from 13 RCTs: A systematic review and meta-analysis.

PubMed

Wang, Liping; Huang, Xiaman; Li, Xueli; Lv, Fang; He, Xiao; Pan, Yu; Wang, Li; Zhang, Xiaomei

2017-09-01

We conducted a systematic review and meta-analysis of existing literature to evaluate the different outcomes of low-dose aspirin on patients undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), including clinical pregnancy rate, implantation rate, live birth rate, miscarriage rate, fertilization rate, number of oocytes retrieved, and so forth. Electronic databases including PubMed, MEDLINE, and Embase were searched between 1997 and March 2016 to identity eligible studies. The following comparisons between treatment groups were included: aspirin versus placebo; aspirin versus control group; aspirin versus aspirin + prednisolone + control. Thirteen randomized controlled trials which included 3104 participants were selected. There were no significant differences in implantation rate (RR = 1.15; 95% CI = 0.78-1.70), live birth rate (RR = 1.06; 95% CI = 0.93-1.21), miscarriage rate (RR = 1.28; 95% CI = 0.93-1.77), fertilization rate (RR = 0.91; 95% CI = 0.75-1.11), and endometrial thickness (WMD = 0.15; 95% CI = -0.38-0.67). But the research showed that aspirin treatment may improve the clinical pregnancy rate (RR = 1.16; 95% CI = 1.04-1.28) compared to placebo or no treatment, and reduce the number of oocytes retrieved (WMD = -0.68; 95% CI = -0.91-0.46). Our findings suggest that low-dose aspirin may improve the pregnancy rate in IVF/ICSI, with the recommended clinical use dose of 100 mg/day. Considering the limitation of included studies, further well-designed large-scaled RCTs are necessary to clarify whether aspirin may improve assisted reproduction outcomes in IVF/ICSI patients.

Overview of epidemiologic studies of radiation and cancer risk based on medical series

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

Howe, G.R.

1997-03-01

Epidemiologic studies of individuals exposed to ionizing radiation for medical reasons have made important contributions to understanding of the relationship between such radiation and subsequent cancer risk. In this paper the strengths and limitations of medical studies are considered and their future potential usefulness is discussed. Studies may be broadly classified into two types, namely, those of individuals exposed for therapeutic purposes such as the study of ankylosing spondylytics and those of individuals exposed for diagnostic or examination purposes such as those of tuberculosis patients routinely examined by chest fluoroscopy. In general, studies of therapeutic exposures tend to involve highmore » doses of radiation given at high dose rates and in a relatively small number of fractions, whereas studies of diagnostic exposures tend to involve relatively low doses, low dose rates and many fractions. However, these generalizations are not always true: for example, in the fluoroscopy studies some patients received doses to organs such as breast and lung which were substantially higher than those experienced in the atomic bomb survivors study and in a study of Israeli children treated with radiation for tinea capitis the average thyroid dose was reported to be low, and only about 0.09 gray. These studies illustrate one of the most important advantages of medical series, namely the variety of such studies in terms of the characteristics of the radiation involved (linear energy transfer characteristics, dose range, dose rate, and fractionation), the organs exposed and hence potentially at risk, and the characteristics of those exposed to such radiation.« less

Combination of High-Dose Methylprednisolone and Defibrotide for Veno-Occlusive Disease in Pediatric Hematopoietic Stem Cell Transplant Recipients.

PubMed

Gloude, Nicholas J; Jodele, Sonata; Teusink-Cross, Ashley; Grimley, Michael; Davies, Stella M; Lane, Adam; Myers, Kasiani C

2018-01-01

Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplant (HSCT), with high mortality in severe cases and until recently very limited therapeutic options consisting largely of supportive care. Defibrotide was recently approved in the United States for the treatment of severe VOD in patients with renal or pulmonary dysfunction after HSCT. Our group previously published on the use of high-dose methylprednisolone (500 mg/m 2 per dose every 12 hours for 6 doses) in patients with VOD, showing good success. A small subset of these individuals were also treated with defibrotide, but additional studies using the combination of high-dose methylprednisolone and defibrotide for the treatment of VOD are lacking. We present a single-institution retrospective chart review of 15 HSCT patients with VOD treated with the combination of high-dose methylprednisolone and defibrotide. VOD developed at a median of 17 days post-HSCT, and combination therapy was initiated within 1 day of VOD diagnosis. Twelve of 15 patients (80%) had multiorgan failure. Our single-center experience using both high-dose methylprednisolone and defibrotide showed a day +100 survival rate of 73% and an overall VOD complete resolution rate of 66.7%, higher than the rates reported in the recent literature using defibrotide alone (40% to 50% day +100 overall survival). These data suggest that the combination of high-dose steroids and defibrotide may be superior to defibrotide alone and warrant further investigation. Copyright © 2017 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Analysis of the Body Distribution of Absorbed Dose in the Organs of Three Species of Fish from Sepetiba Bay

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

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

2008-08-07

The body distribution of Polonium-210 in three fishes from the Sepetiba Bay (Macrodon ancylodon, Micropogonias furnieri and Mugil curema) has been studied under the approach of the Department of Energy of the United States of America (DOE) that set the limit of absorbed dose rate in biota equal to 3.5x10{sup 3} {mu}Gy/y, and that also established the relation between dose rate (D) and radionuclide concentration (c) on a fish muscle fresh weight basis, as follows: D = 5.05 ExNxC, assuming that the radionuclide distribution is homogenous among organs. Two hypotheses were tested here, using statistical tools: 1) is the bodymore » distribution of absorbed dose homogenous among organs? and 2) is the body distribution of absorbed dose identical among studied fishes? It was concluded, as expected, that the distribution among organs is heterogeneous; but, unexpectedly, that the three fishes display identical body distribution pattern, although they belong to different trophic levels. Hence, concerning absorbed dose calculation, the statement that data distribution is homogenous must be understood merely as an approximation, at least in the case of Polonium-210.« less

Nuclear energy and health: and the benefits of low-dose radiation hormesis.

PubMed

Cuttler, Jerry M; Pollycove, Myron

2009-01-01

Energy needs worldwide are expected to increase for the foreseeable future, but fuel supplies are limited. Nuclear reactors could supply much of the energy demand in a safe, sustainable manner were it not for fear of potential releases of radioactivity. Such releases would likely deliver a low dose or dose rate of radiation, within the range of naturally occurring radiation, to which life is already accustomed. The key areas of concern are discussed. Studies of actual health effects, especially thyroid cancers, following exposures are assessed. Radiation hormesis is explained, pointing out that beneficial effects are expected following a low dose or dose rate because protective responses against stresses are stimulated. The notions that no amount of radiation is small enough to be harmless and that a nuclear accident could kill hundreds of thousands are challenged in light of experience: more than a century with radiation and six decades with reactors. If nuclear energy is to play a significant role in meeting future needs, regulatory authorities must examine the scientific evidence and communicate the real health effects of nuclear radiation. Negative images and implications of health risks derived by unscientific extrapolations of harmful effects of high doses must be dispelled.

Nuclear Energy and Health: And the Benefits of Low-Dose Radiation Hormesis

PubMed Central

Cuttler, Jerry M.; Pollycove, Myron

2009-01-01

Energy needs worldwide are expected to increase for the foreseeable future, but fuel supplies are limited. Nuclear reactors could supply much of the energy demand in a safe, sustainable manner were it not for fear of potential releases of radioactivity. Such releases would likely deliver a low dose or dose rate of radiation, within the range of naturally occurring radiation, to which life is already accustomed. The key areas of concern are discussed. Studies of actual health effects, especially thyroid cancers, following exposures are assessed. Radiation hormesis is explained, pointing out that beneficial effects are expected following a low dose or dose rate because protective responses against stresses are stimulated. The notions that no amount of radiation is small enough to be harmless and that a nuclear accident could kill hundreds of thousands are challenged in light of experience: more than a century with radiation and six decades with reactors. If nuclear energy is to play a significant role in meeting future needs, regulatory authorities must examine the scientific evidence and communicate the real health effects of nuclear radiation. Negative images and implications of health risks derived by unscientific extrapolations of harmful effects of high doses must be dispelled. PMID:19343116

Laboratory measures of methylphenidate effects in cocaine-dependent patients receiving treatment.

PubMed

Roache, J D; Grabowski, J; Schmitz, J M; Creson, D L; Rhoades, H M

2000-02-01

Two experiments examined the effects of methylphenidate in male and female patients enrolled in an outpatient treatment program for primary cocaine dependence. The first study was a component of a double-blind efficacy trial wherein 57 patients were first tested in a human laboratory for their initial responsiveness to medication. Patients were randomly assigned to receive either placebo or methylphenidate treatment and received their first dose in the human laboratory environment before continuing in outpatient treatment. Methylphenidate was given as a 20-mg sustained-release dose (twice daily) plus an additional 5-mg immediate-release dose combined with the morning dose. Methylphenidate increased heart rate and subjective ratings; however, the subjective effects were primarily of a "dysphoric" nature, and significant effects were limited to increases in anxiety, depression, and anger on the Profile of Mood States; shaky/jittery ratings on a visual analog scale; and dysphoria on the lysergic acid diethylamide (LSD) scale of the Addiction Research Center Inventory. Methylphenidate did not increase cocaine craving nor ratings suggesting abuse potential (i.e., Morphine-Benzedrine Group or drug-liking scores, etc.). None of the drug effects observed in the human laboratory was of clinical concern, and no subject was precluded from continuing in the outpatient study. After outpatient treatment completion, 12 patients were brought back into a second double-blind human laboratory study in which three doses (15, 30, and 60 mg) of immediate-release methylphenidate were administered in an ascending series preceded and followed by placebo. Methylphenidate produced dose-related increases in heart rate, subjective ratings of shaky/jittery, and LSD/dysphoria without significantly altering cocaine craving or stimulant euphoria ratings. These results suggest that stimulant substitution-type approaches to the treatment of cocaine dependence are not necessarily contraindicated because of cardiovascular toxicity or medication abuse potential. However, they also suggest that the subjective effects of methylphenidate may not be positive enough for an adequate replacement approach.

Low-dose (10-Gy) total skin electron beam therapy for cutaneous T-cell lymphoma: an open clinical study and pooled data analysis.

PubMed

Kamstrup, Maria R; Gniadecki, Robert; Iversen, Lars; Skov, Lone; Petersen, Peter Meidahl; Loft, Annika; Specht, Lena

2015-05-01

Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments is limited to 2 to 3 courses in a lifetime due to skin toxicity. This study aimed to determine the clinical effect of low-dose TSEBT in patients with MF and SS. In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over <2.5 weeks, receiving a total dose of 10 Gy in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. The overall response rate was 95% with a complete cutaneous response or a very good partial response rate (<1% skin involvement with patches or plaques) documented in 57% of the patients. Median duration of overall cutaneous response was 174 days (5.8 months; range: 60-675 days). TSEBT-related acute adverse events (grade 1 or 2) were observed in 60% of patients. Low-dose (10-Gy) TSEBT offers a high overall response rate and is relatively safe. With this approach, reirradiation at times of relapse or progression is likely to be less toxic than standard dose TSEBT. It remains to be established whether adjuvant and combination treatments can prolong the beneficial effects of low-dose TSEBT. Copyright © 2015 Elsevier Inc. All rights reserved.

Calculating evidence-based renal replacement therapy - Introducing an excel-based calculator to improve prescribing and delivery in renal replacement therapy - A before and after study.

PubMed

Cottle, Daniel; Mousdale, Stephen; Waqar-Uddin, Haroon; Tully, Redmond; Taylor, Benjamin

2016-02-01

Transferring the theoretical aspect of continuous renal replacement therapy to the bedside and delivering a given "dose" can be difficult. In research, the "dose" of renal replacement therapy is given as effluent flow rate in ml kg -1  h -1 . Unfortunately, most machines require other information when they are initiating therapy, including blood flow rate, pre-blood pump flow rate, dialysate flow rate, etc. This can lead to confusion, resulting in patients receiving inappropriate doses of renal replacement therapy. Our aim was to design an excel calculator which would personalise patient's treatment, deliver an effective, evidence-based dose of renal replacement therapy without large variations in practice and prolong filter life. Our calculator prescribes a haemodialfiltration dose of 25 ml kg -1  h -1 whilst limiting the filtration fraction to 15%. We compared the episodes of renal replacement therapy received by a historical group of patients, by retrieving their data stored on the haemofiltration machines, to a group where the calculator was used. In the second group, the data were gathered prospectively. The median delivered dose reduced from 41.0 ml kg -1  h -1 to 26.8 ml kg -1  h -1 with reduced variability that was significantly closer to the aim of 25 ml kg -1 .h -1 ( p  < 0.0001). The median treatment time increased from 8.5 h to 22.2 h ( p  = 0.00001). Our calculator significantly reduces variation in prescriptions of continuous veno-venous haemodiafiltration and provides an evidence-based dose. It is easy to use and provides personal care for patients whilst optimizing continuous veno-venous haemodiafiltration delivery and treatment times.

A double blind, randomized, active controlled study to assess the safety, tolerability and immunogenicity of measles, mumps rubella, and varicella vaccine (MMRV) manufactured using an alternative process.

PubMed

Marshall, Gary S; Senders, Shelly D; Shepard, Julie; Twiggs, Jerry D; Gardner, Julie; Hille, Darcy; Hartzel, Jonathan; Valenzuela, Rowan; Stek, Jon E; Helmond, Frans A

2016-08-02

Vaccination against measles, mumps, rubella, and varicella is recommended for all children in the US. Limitations manufacturing Oka/Merck strain varicella-zoster virus have hampered the availability of the combination vaccine (MMRV) against these 4 viruses, which drove the need to investigate an alternative manufacturing process. Healthy children 12-to-23 months of age at 71 US sites were randomized (1:1) to receive MMRV manufactured using an alternative process (MMRV AMP ) or the currently licensed MMRV. Subjects received 2 0.5 mL doses 3 months apart. Sera were collected before and 6 weeks after Dose-1. Adverse experiences (AEs) were collected for 42 d after each dose and serious AEs and events of special interest for 180 d after Dose-2. Overall, 706 subjects were randomized to MMRV AMP and 706 to MMRV and 698 and 702 received at least 1 dose of study vaccine, respectively. The risk difference in response rates and geometric mean concentrations of antibody to measles, mumps, rubella, and varicella viruses 6 weeks after Dose-1 met non-inferiority criteria for MMRV AMP versus, MMRV. Response rates met acceptability criteria for each virus, and the seroconversion rate to varicella-zoster virus was 99.5% in both groups. Vaccine-related AEs were mostly mild-to-moderate in intensity and somewhat more common after MMRV AMP . Febrile seizures occurred at similar rates in both groups during the first 42 d after each vaccine dose. MMRV AMP is non-inferior to MMRV and represents an important advancement in maintaining an adequate supply of vaccines against these diseases.

A double blind, randomized, active controlled study to assess the safety, tolerability and immunogenicity of measles, mumps rubella, and varicella vaccine (MMRV) manufactured using an alternative process

PubMed Central

Marshall, Gary S.; Senders, Shelly D.; Shepard, Julie; Twiggs, Jerry D.; Gardner, Julie; Hille, Darcy; Hartzel, Jonathan; Valenzuela, Rowan; Stek, Jon E.; Helmond, Frans A.

2016-01-01

ABSTRACT Vaccination against measles, mumps, rubella, and varicella is recommended for all children in the US. Limitations manufacturing Oka/Merck strain varicella-zoster virus have hampered the availability of the combination vaccine (MMRV) against these 4 viruses, which drove the need to investigate an alternative manufacturing process. Healthy children 12-to-23 months of age at 71 US sites were randomized (1:1) to receive MMRV manufactured using an alternative process (MMRVAMP) or the currently licensed MMRV. Subjects received 2 0.5 mL doses 3 months apart. Sera were collected before and 6 weeks after Dose-1. Adverse experiences (AEs) were collected for 42 d after each dose and serious AEs and events of special interest for 180 d after Dose-2. Overall, 706 subjects were randomized to MMRVAMP and 706 to MMRV and 698 and 702 received at least 1 dose of study vaccine, respectively. The risk difference in response rates and geometric mean concentrations of antibody to measles, mumps, rubella, and varicella viruses 6 weeks after Dose-1 met non-inferiority criteria for MMRVAMP versus, MMRV. Response rates met acceptability criteria for each virus, and the seroconversion rate to varicella-zoster virus was 99.5% in both groups. Vaccine-related AEs were mostly mild-to-moderate in intensity and somewhat more common after MMRVAMP. Febrile seizures occurred at similar rates in both groups during the first 42 d after each vaccine dose. MMRVAMP is non-inferior to MMRV and represents an important advancement in maintaining an adequate supply of vaccines against these diseases. PMID:27149048

Low-Dose (10-Gy) Total Skin Electron Beam Therapy for Cutaneous T-Cell Lymphoma: An Open Clinical Study and Pooled Data Analysis

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

Kamstrup, Maria R., E-mail: mkam0004@bbh.regionh.dk; Gniadecki, Robert; Iversen, Lars

2015-05-01

Purpose: Cutaneous T-cell lymphomas (CTCLs) are dominated by mycosis fungoides (MF) and Sézary syndrome (SS), and durable disease control is a therapeutic challenge. Standard total skin electron beam therapy (TSEBT) is an effective skin-directed therapy, but the possibility of retreatments is limited to 2 to 3 courses in a lifetime due to skin toxicity. This study aimed to determine the clinical effect of low-dose TSEBT in patients with MF and SS. Methods and Materials: In an open clinical study, 21 patients with MF/SS stages IB to IV were treated with low-dose TSEBT over <2.5 weeks, receiving a total dose of 10 Gymore » in 10 fractions. Data from 10 of these patients were published previously but were included in the current pooled data analysis. Outcome measures were response rate, duration of response, and toxicity. Results: The overall response rate was 95% with a complete cutaneous response or a very good partial response rate (<1% skin involvement with patches or plaques) documented in 57% of the patients. Median duration of overall cutaneous response was 174 days (5.8 months; range: 60-675 days). TSEBT-related acute adverse events (grade 1 or 2) were observed in 60% of patients. Conclusions: Low-dose (10-Gy) TSEBT offers a high overall response rate and is relatively safe. With this approach, reirradiation at times of relapse or progression is likely to be less toxic than standard dose TSEBT. It remains to be established whether adjuvant and combination treatments can prolong the beneficial effects of low-dose TSEBT.« less

Is a larger refuge always better? Dispersal and dose in pesticide resistance evolution

PubMed Central

Takahashi, Daisuke; Yamanaka, Takehiko; Sudo, Masaaki; Andow, David A.

2017-01-01

The evolution of resistance against pesticides is an important problem of modern agriculture. The high‐dose/refuge strategy, which divides the landscape into treated and nontreated (refuge) patches, has proven effective at delaying resistance evolution. However, theoretical understanding is still incomplete, especially for combinations of limited dispersal and partially recessive resistance. We reformulate a two‐patch model based on the Comins model and derive a simple quadratic approximation to analyze the effects of limited dispersal, refuge size, and dominance for high efficacy treatments on the rate of evolution. When a small but substantial number of heterozygotes can survive in the treated patch, a larger refuge always reduces the rate of resistance evolution. However, when dominance is small enough, the evolutionary dynamics in the refuge population, which is indirectly driven by migrants from the treated patch, mainly describes the resistance evolution in the landscape. In this case, for small refuges, increasing the refuge size will increase the rate of resistance evolution. Our analysis distils major driving forces from the model, and can provide a framework for understanding directional selection in source‐sink environments. PMID:28422284

Evaluation of GaAs low noise and power MMIC technologies to neutron, ionizing dose and dose rate effects

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

Derewonko, H.; Bosella, A.; Pataut, G.

1996-06-01

An evaluation program of Thomson CSF-TCS GaAs low noise and power MMIC technologies to 1 MeV equivalent neutron fluence levels, up to 1 {times} 10{sup 15} n/cm{sup 2}, ionizing 1.17--1.33 MeV CO{sup 60} dose levels in excess of 200 Mrad(GaAs) and dose rate levels reaching 1.89 {times} 10{sup 11} rad(GaAs)/s is presented in terms of proper components and parameter choices, DC/RF electrical measurements and test methods under irradiation. Experimental results are explained together with drift analyses of electrical parameters that have determined threshold limits of component degradations. Modelling the effects of radiation on GaAs components relies on degradation analysis ofmore » active layer which appears to be the most sensitive factor. MMICs degradation under neutron fluence was simulated from irradiated FET data. Finally, based on sensitivity of technological parameters, rad-hard design including material, technology and MMIC design enhancement is discussed.« less

Measurement of natural radioactivity in Jordanian building materials and their contribution to the public indoor gamma dose rate.

PubMed

Sharaf, J M; Hamideen, M S

2013-10-01

This study is undertaken to determine the activity concentration of (226)Ra, (232)Th and (40)K in samples of commonly used building materials in Jordan. Samples of seven different materials were collected from construction sites and local agencies supplying raw construction materials and analyzed using a HPGe gamma-ray spectrometer, taking into account self-attenuation in bulk samples. The average specific activity concentrations of (226)Ra, (232)Th, and (40)K ranged from 2.84 to 41.52, 0.78 to 58.42. and 3.74 to 897 Bq/kg, respectively. All the samples had radium equivalent activities well below the limit of 370 Bq/kg set by the Organization for Economic Cooperation and Development (OECD, 1979). External and internal hazard indices, absorbed dose and annual effective dose rate associated with the radionuclides of interest were calculated and compared with the international legislation and guidance. In general, most of the activities did not exceed the recommended international limits, except for granite and ceramic samples which are usually used as secondary building materials in Jordan. Copyright © 2013 Elsevier Ltd. All rights reserved.

Neutron dose rate analysis on HTGR-10 reactor using Monte Carlo code

NASA Astrophysics Data System (ADS)

Suwoto; Adrial, H.; Hamzah, A.; Zuhair; Bakhri, S.; Sunaryo, G. R.

2018-02-01

The HTGR-10 reactor is cylinder-shaped core fuelled with kernel TRISO coated fuel particles in the spherical pebble with helium cooling system. The outlet helium gas coolant temperature outputted from the reactor core is designed to 700 °C. One advantage HTGR type reactor is capable of co-generation, as an addition to generating electricity, the reactor was designed to produce heat at high temperature can be used for other processes. The spherical fuel pebble contains 8335 TRISO UO2 kernel coated particles with enrichment of 10% and 17% are dispersed in a graphite matrix. The main purpose of this study was to analysis the distribution of neutron dose rates generated from HTGR-10 reactors. The calculation and analysis result of neutron dose rate in the HTGR-10 reactor core was performed using Monte Carlo MCNP5v1.6 code. The problems of double heterogeneity in kernel fuel coated particles TRISO and spherical fuel pebble in the HTGR-10 core are modelled well with MCNP5v1.6 code. The neutron flux to dose conversion factors taken from the International Commission on Radiological Protection (ICRP-74) was used to determine the dose rate that passes through the active core, reflectors, core barrel, reactor pressure vessel (RPV) and a biological shield. The calculated results of neutron dose rate with MCNP5v1.6 code using a conversion factor of ICRP-74 (2009) for radiation workers in the radial direction on the outside of the RPV (radial position = 220 cm from the center of the patio HTGR-10) provides the respective value of 9.22E-4 μSv/h and 9.58E-4 μSv/h for enrichment 10% and 17%, respectively. The calculated values of neutron dose rates are compliant with BAPETEN Chairman’s Regulation Number 4 Year 2013 on Radiation Protection and Safety in Nuclear Energy Utilization which sets the limit value for the average effective dose for radiation workers 20 mSv/year or 10μSv/h. Thus the protection and safety for radiation workers to be safe from the radiation source has been fulfilled. From the result analysis, it can be concluded that the model of calculation result of neutron dose rate for HTGR-10 core has met the required radiation safety standards.

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

Hall, Matthew D.; Schultheiss, Timothy E., E-mail: schultheiss@coh.org; Smith, David D.

Purpose/Objective(s): To perform a meta-regression on published data and to model the 5-year probability of cataract development after hematopoietic stem cell transplantation (HSCT) with and without total body irradiation (TBI). Methods and Materials: Eligible studies reporting cataract incidence after HSCT with TBI were identified by a PubMed search. Seventeen publications provided complete information on radiation dose schedule, fractionation, dose rate, and actuarial cataract incidence. Chemotherapy-only regimens were included as zero radiation dose regimens. Multivariate meta-regression with a weighted generalized linear model was used to model the 5-year cataract incidence and contributory factors. Results: Data from 1386 patients in 21 seriesmore » were included for analysis. TBI was administered to a total dose of 0 to 15.75 Gy with single or fractionated schedules with a dose rate of 0.04 to 0.16 Gy/min. Factors significantly associated with 5-year cataract incidence were dose, dose times dose per fraction (D•dpf), pediatric versus adult status, and the absence of an ophthalmologist as an author. Dose rate, graft versus host disease, steroid use, hyperfractionation, and number of fractions were not significant. Five-fold internal cross-validation showed a model validity of 83% ± 8%. Regression diagnostics showed no evidence of lack-of-fit and no patterns in the studentized residuals. The α/β ratio from the linear quadratic model, estimated as the ratio of the coefficients for dose and D•dpf, was 0.76 Gy (95% confidence interval [CI], 0.05-1.55). The odds ratio for pediatric patients was 2.8 (95% CI, 1.7-4.6) relative to adults. Conclusions: Dose, D•dpf, pediatric status, and regimented follow-up care by an ophthalmologist were predictive of 5-year cataract incidence after HSCT. The low α/β ratio indicates the importance of fractionation in reducing cataracts. Dose rate effects have been observed in single institution studies but not in the combined data analyzed here. Although data were limited to articles with 5-year actuarial estimates, the development of radiation-induced cataracts extends beyond this time.« less

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

Unkelbach, J; Perko, Z; Wolfgang, J

Purpose: Stereotactic body radiotherapy (SBRT) has become an established treatment option for liver cancer. For patients with large tumors, the prescription dose is often limited by constraints on the mean liver dose, leading to tumor recurrence. In this work, we demonstrate that spatiotemporal fractionation schemes, ie delivering distinct dose distributions in different fractions, may allow for a 10% increase in biologically effective dose (BED) in the tumor compared to current practice where each fraction delivers the same dose distribution. Methods: We consider rotation therapy delivered with x-ray beams. Treatment plan optimization is performed using objective functions evaluated for the cumulativemore » BED delivered at the end of treatment. This allows for simultaneously optimizing multiple distinct treatment plans for different fractions. Results: The treatment that optimally exploits fractionation effects is designed such that each fraction delivers a similar dose bath to the uninvolved liver while delivering high single fraction doses to complementary parts of the target volume. Thereby, partial hypofractionation in the tumor is achieved along with near uniform fractionation in the surrounding liver - leading to an improvement in the therapeutic ratio. The benefit of such spatiotemporal fractionation schemes depends on tumor geometry and location as well as the number of fractions. For 5-fraction treatments (allowing for 5 distinct dose distributions) an improvement in the order of 10% is observed. Conclusion: Delivering distinct dose distributions in different fractions, purely motivated by fractionation effects rather than geometric changes, may improve the therapeutic ratio. For treatment sites where the prescriptions dose is limited by mean dose constraints in the surrounding organ, such as liver cancer, this approach may facilitate biological dose escalation and improved cure rates.« less

The nonuniformity of antibody distribution in the kidney and its influence on dosimetry.

PubMed

Flynn, Aiden A; Pedley, R Barbara; Green, Alan J; Dearling, Jason L; El-Emir, Ethaar; Boxer, Geoffrey M; Boden, Robert; Begent, Richard H J

2003-02-01

The therapeutic efficacy of radiolabeled antibody fragments can be limited by nephrotoxicity, particularly when the kidney is the major route of extraction from the circulation. Conventional dose estimates in kidney assume uniform dose deposition, but we have shown increased antibody localization in the cortex after glomerular filtration. The purpose of this study was to measure the radioactivity in cortex relative to medulla for a range of antibodies and to assess the validity of the assumption of uniformity of dose deposition in the whole kidney and in the cortex for these antibodies with a range of radionuclides. Storage phosphor plate technology (radioluminography) was used to acquire images of the distributions of a range of antibodies of various sizes, labeled with 125I, in kidney sections. This allowed the calculation of the antibody concentration in the cortex relative to the medulla. Beta-particle point dose kernels were then used to generate the dose-rate distributions from 14C, 131I, 186Re, 32P and 90Y. The correlation between the actual dose-rate distribution and the corresponding distribution calculated assuming uniform antibody distribution throughout the kidney was used to test the validity of estimating dose by assuming uniformity in the kidney and in the cortex. There was a strong inverse relationship between the ratio of the radioactivity in the cortex relative to that in the medulla and the antibody size. The nonuniformity of dose deposition was greatest with the smallest antibody fragments but became more uniform as the range of the emissions from the radionuclide increased. Furthermore, there was a strong correlation between the actual dose-rate distribution and the distribution when assuming a uniform source in the kidney for intact antibodies along with medium- to long-range radionuclides, but there was no correlation for small antibody fragments with any radioisotope or for short-range radionuclides with any antibody. However, when the cortex was separated from the whole kidney, the correlation between the actual dose-rate distribution and the assumed dose-rate distribution, if the source was uniform, increased significantly. During radioimmunotherapy, the extent of nonuniformity of dose deposition in the kidney depends on the properties of the antibody and radionuclide. For dosimetry estimates, the cortex should be taken as a separate source region when the radiopharmaceutical is small enough to be filtered by the glomerulus.

Feasibility of Administering High-Dose 131I-MIBG Therapy to Children with High-Risk Neuroblastoma without Lead-Lined Rooms

PubMed Central

Chu, Bae P.; Horan, Christopher; Basu, Ellen; Dauer, Lawrence; Williamson, Matthew; Carrasquillo, Jorge A.; Pandit-Taskar, Neeta; Modak, Shakeel

2015-01-01

Background Although 131I-metaiodobenzylguanidine therapy (131I-MIBG) is increasingly used for children with high-risk neuroblastoma, a paucity of lead-lined rooms limits its wider use. We implemented radiation safety procedures to comply with New York City Department of Health and Mental Hygiene regulations for therapeutic radioisotopes and administered 131I-MIBG using rolling lead shields. Procedure Patients received 0.67GBq (18mCi)/kg/dose 131I-MIBG on an IRB-approved protocol (NCT00107289). Radiation safety procedures included private room with installation of rolling lead shields to maintain area dose rates ≤0.02mSv/h outside the room, patient isolation until dose rate <0.07mSv/h at 1m and retention of a urinary catheter with collection of urine in lead boxes. Parents were permitted in the patient’s room behind lead shields, trained in radiation safety principles and given real-time radiation monitors. Results Records on 16 131I-MIBG infusions among 10 patients (age 2–11 years) were reviewed. Mean ± standard deviation 131I-MIBG administered was 17.67±11.14 (range: 6.11–40.59) GBq. Mean maximum dose rates outside treatment rooms were 0.013±0.008 mSv/hr. Median time-to-discharge was 3 days post-131I-MIBG. Exposure of medical staff and parents was below regulatory limits. Cumulative whole-body dose received by the physician, nurse and radiation safety officer during treatment was 0.098±0.058, 0.056±0.045, 0.055±0.050 mSv respectively. Cumulative exposure to parents was 0.978±0.579mSv. Estimated annual radiation exposure for inpatient nurses was 0.096±0.034mSv/nurse. Thyroid bioassay scans on all medical personnel were

Phase I/II trial of doxorubicin and fixed dose-rate infusion gemcitabine in advanced soft tissue sarcomas: a GEIS study

PubMed Central

López-Pousa, A; Losa, R; Martín, J; Maurel, J; Fra, J; Sierra, M; Casado, A; García del Muro, J; Poveda, A; Balañá, C; Martínez-Trufero, J; Esteban, E; Buesa, J M

2006-01-01

The aim of the study was to determine the dose-limiting toxicity and maximum tolerated dose of a first-line combination of doxorubicin and gemcitabine in adult patients with advanced soft tissue sarcomas and to explore its activity and toxicity, and the presence of possible interactions between these agents. Patients with measurable disease were initially treated with doxorubicin 60 mg m−2 by i.v. bolus on day 1 followed by gemcitabine at 800 mg m−2 over 80 min on days 1 and 8, every 21 days. Concentrations of gemcitabine and 2′,2′-difluorodeoxyuridine in plasma, and gemcitabine triphosphate levels in peripheral blood mononuclear cells were determined during 8 h after the start of gemcitabine infusion. Myelosuppression and stomatitis were limiting toxicities, and the initial dose level was applied for the Phase II trial, where grade 3–4 granulocytopenia occurred in 70% of patients, grade 3 stomatitis in 46% and febrile neutropenia in 20%. Objective activity in 36 patients was 22% (95% CI: 9–35%), and a 50% remission rate was noted in leiomyosarcomas. Administration of doxorubicin preceding gemcitabine significantly reduced the synthesis of gemcitabine triphosphate. Clinical activity, similar to that of single-agent doxorubicin, and the toxicity encountered do not justify further studies with this schedule of administration. PMID:16721358

A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

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

Monjazeb, Arta M., E-mail: arta.monjazeb@ucdmc.ucdavis.edu; Ayala, Deandra; Jensen, Courtney

2012-02-01

Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patientsmore » experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.« less

A randomized two-by-two comparison of high-dose bolus tirofiban versus abciximab and unfractionated heparin versus bivalirudin during percutaneous coronary revascularization and stent placement: the tirofiban evaluation of novel dosing versus abciximab with clopidogrel and inhibition of thrombin (TENACITY) study trial.

PubMed

Moliterno, David J

2011-06-01

In the absence of high-dose thienopyridines, placebo-controlled trials have demonstrated a reduction in ischemic events with intravenous glycoprotein IIb/IIIa antagonists during percutaneous coronary intervention (PCI). One head-to-head trial comparing abciximab and tirofiban among PCI patients found tirofiban to be inferior, and laboratory evidence confirmed that the bolus dose of tirofiban tested in that trial to be less effective than abciximab. Whether a higher bolus dose of tirofiban would be as efficacious as abciximab during PCI is uncertain. Patients undergoing PCI were randomized equally to abciximab or to tirofiban, given as high-dose bolus (25 μg/kg) plus 12-hr infusion (0.15 μg/kg/min). All patients received aspirin and clopidogrel and were additionally randomized to unfractionated heparin or bivalirudin. Approximately 8,000 patients were to be studied, but after 383 were enrolled, the study sponsor discontinued the trial for financial reasons. The primary endpoint of 30-day death, myocardial infarction, or urgent target vessel revascularization occurred in 8.8% of patients randomized to abciximab and 6.9% of those randomized to tirofiban. The respective rates of major bleeding were 1.5 and 1.6%. Additionally, the primary endpoint occurred in 8.1% of patients randomized to unfractionated heparin and 7.6% of those randomized to bivalirudin. The respective rates of major bleeding were 2.5% and 0.5%. With limited assessment, this direct comparison of high-dose bolus tirofiban versus abciximab produced encouraging results and suggests that further study of this tirofiban dose regimen is warranted. The limited assessments comparing heparin and bivalirudin are consistent with prior observations. Copyright © 2010 Wiley-Liss, Inc.

A phase I-II study of paclitaxel, ifosfamide, and vinorelbine with filgrastim (rhG-CSF) support in advanced non-small-cell lung cancer.

PubMed

Masters, G A; Mauer, A M; Hoffman, P C; Wyka, D; Samuels, B L; Krauss, S A; Watson, S; Golomb, H; Vokes, E E

1998-06-01

We designed a phase I-II trial of three active agents, paclitaxel, ifosfamide, and vinorelbine, in advanced non-small-cell lung cancer (NSCLC) to: 1) define the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of paclitaxel with filgrastim (G-CSF) support; and 2) determine the overall response rate and median survival of patients treated on this regimen. We treated cohorts of patients with stage IIIB or IV NSCLC with ifosfamide 1.2-1.6 g/m2/day x 3 and vinorelbine 20-25 mg/m2/day x 3 and escalating doses of paclitaxel at 100-175 mg/m2 on day 2 with G-CSF support on a 21-day cycle. One prior experimental single-agent chemotherapy regimen was allowed. Fifty-six patients, were enrolled on this trial: 27 on the phase I portion of the study and an additional 29 at the recommended phase II dose (RPTD). Thirteen patients had received prior chemotherapy. Paclitaxel doses of 175 mg/m2 and 150 mg/m2 produced dose-limiting myelosuppression, and the RPTD was determined to be paclitaxel 135 mg/m2 with ifosfamide 1.2 g/m2/day on days 1-3 and vinorelbine 20 mg/m2/ day on days 1-3 with G-CSF support. The overall response rate was 18%, with a median survival of 6.1 months. Six of 35 patients (17%) treated at the RPTD achieved a partial response to therapy. Grade IV neutropenia was observed in 19 of 35 patients at this dose, with eight patients suffering febrile neutropenia. This non-cisplatin-containing three-drug regimen has substantial toxicity and low activity in advanced NSCLC, and does not seem to improve on prior regimens. It is unclear whether the lack of efficacy relates to an antagonistic reaction between the specific drugs, administration schedule, or to subtherapeutic doses of the individual agents.

High Dose Hyperfractionated Radiotherapy for Adults with Glioblastomas

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

Koukourakis, Michael; Scarlatos, John; Yiannakakis, Dimitrios

2015-01-15

From 1989 to 1991, 27 patients with glioblastoma multiforme or anaplastic astrocytoma of the brain were treated with radiotherapy. Fifteen of twenty-seven patients were treated through limited volume fields, with a thrice-a-day (1.1 Gy/f) or twice-a-day (1.4 Gy/f) hyperfractionated regimen to a total physical dose of 62–92 Gy (median dose 76 Gy). The remaining 12 were treated with whole brain irradiation (40 Gy of total conventionally fractionated dose) and a localised boost to a total dose of 60 Gy. The hyperfractionated regimen was well tolerated and there was no sign of increased brain oedema to indicate the insertion of amore » split. Of six patients who received a NTD10 (normalised total dose for α/β =10) higher than 71 Gy, five showed CR (83% CR rate) versus three of 21 patients who received a lower NTD10 (14% CR rate). For 13 patients who received a NTD10 higher than 66 Gy, the 18-months survival was 61% (8/13) versus 28% (4/14) for 14 patients who received a NTD10 less than 66 Gy. As far as the late morbidity is concerned, of six patients treated with 76-92 Gy of physical dose, none died because of radiation-induced brain necrosis within 18-42 months of follow-up, and three of them are without evidence of disease 18-31 months after the end of radiation treatment. None of our 15 patients who received less than whole brain irradiation relapsed outside the radiation portals. The present study strongly suggests the use of limited volume hyperfractionated radiotherapy schemes, so as to increase the local tumor dose (NTD10) to values higher than 79 Gy, at the same time keeping the NTD2 (NTD for α/β = 2) below 68 Gy.« less

Multiscale analysis of the radiooxidative degradation of EVA/EPDM composites. ATH filler and dose rate effect

NASA Astrophysics Data System (ADS)

Sidi, Ahmedou; Colombani, Juliette; Larché, Jean-François; Rivaton, Agnès

2018-01-01

This study is focused on the radiooxidative degradation of polymeric insulation of electric cables used in Nuclear Power Plants (NPPs). In order to investigate the degradation mechanisms of the insulation, model composites with ATH (Aluminium TriHydrate) filler and blends (without filler) based on a cross-linked mixture of EVA (Ethylene Vinyl Acetate) and EPDM (Ethylene Propylene Diene Monomer) were submitted to gamma-rays. In normal operating conditions of a NPP, the dose rate which electric cables are exposed to is around 0.1 Gy h-1. In this work, artificial accelerated ageing test process has been applied at a relatively low dose rate of 7 Gy h-1. Gamma-irradiations at higher dose rates typically used to accelerate the ageing, in the range 0.2-1 kGy h-1, were also carried out. The first part of the study is focused on irradiations performed at relatively low dose rate and is devoted to the highlighting of the radiooxidative degradation mechanisms of EVA/EPDM blend with and without ATH filler. Correlations between the evolutions of the chemical, morphological and mechanical/electrical properties of the materials occurring after the ageing process are presented. It is shown that the degradation process is governed by radical oxidation mechanism involving chain scissions leading to the formation of carboxylic acids as end-groups. One of the main effects of the ATH filler is the progressive loss of the mechanical properties of the composite upon radiooxidation whereas they are maintained in the case of the unfilled sample. Despite the oxidation of the polymer, no change in the electrical properties of the blend and of the composite could be observed. The second part of the study focuses on the dose rate effect. It is shown that one of the main consequences of an increase of the dose rate from 7 Gy h-1 to 0.2-1 kGy h-1 is a reduction of the chain scission process yield by a factor of about 20. Therefore, an important and consistent finding is that there are some limits that must not be exceeded in terms of dose rate to ensure a global satisfactorily representativeness of the accelerated ageing process.

Assessment of background gamma radiation levels using airborne gamma ray spectrometer data over uranium deposits, Cuddapah Basin, India - A comparative study of dose rates estimated by AGRS and PGRS.

PubMed

Srinivas, D; Ramesh Babu, V; Patra, I; Tripathi, Shailesh; Ramayya, M S; Chaturvedi, A K

2017-02-01

The Atomic Minerals Directorate for Exploration and Research (AMD) has conducted high-resolution airborne gamma ray spectrometer (AGRS), magnetometer and time domain electromagnetic (TDEM) surveys for uranium exploration, along the northern margins of Cuddapah Basin. The survey area includes well known uranium deposits such as Lambapur-Peddagattu, Chitrial and Koppunuru. The AGRS data collected for uranium exploration is utilised for estimating the average absorbed rates in air due to radio-elemental (potassium in %, uranium and thorium in ppm) distribution over these known deposit areas. Further, portable gamma ray spectrometer (PGRS) was used to acquire data over two nearby locations one from Lambapur deposit, and the other from known anomalous zone and subsequently average gamma dose rates were estimated. Representative in-situ rock samples were also collected from these two areas and subjected to radio-elemental concentration analysis by gamma ray spectrometer (GRS) in the laboratory and then dose rates were estimated. Analyses of these three sets of results complement one another, thereby providing a comprehensive picture of the radiation environment over these deposits. The average absorbed area wise dose rate level is estimated to be 130 ± 47 nGy h -1 in Lambapur-Peddagattu, 186 ± 77 nGy h -1 in Chitrial and 63 ± 22 nGy h -1 in Koppunuru. The obtained average dose levels are found to be higher than the world average value of 54 nGy h -1 . The gamma absorbed dose rates in nGy h -1 were converted to annual effective dose rates in mSv y -1 as proposed by the United Nations Scientific Committee on the Effect of Atomic Radiation (UNSCEAR). The annual average effective dose rates for the entire surveyed area is 0.12 mSv y -1 , which is much lower than the recommended limit of 1 mSv y -1 by International Commission on Radiation protection (ICRP). It may be ascertained here that the present study establishes a reference data set (baseline) in these areas to assess any changes in gamma radiation levels due to mining and milling activities in future. Copyright © 2016 Elsevier Ltd. All rights reserved.

Niagara Falls Storage Site annual site environmental monitoring report. Calendar year 1985

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

Not Available

1986-04-01

During 1985, an environmental monitoring program was continued at the Niagara Falls Storage Site (NFSS), a United States Department of Energy (DOE) surplus facility located in Niagara County, New York, presently used for the interim storage of low-level radioactive residues and contaminated soils and rubble. The monitoring program is being conducted by Bechtel National, Inc. Monitoring results show that the NFSS is in compliance with DOE concentration guides and radiation protection standards. Derived Concentration Guides (DCGs) represent the concentrations of radionuclides in air or water that would limit the radiation dose to 100 mrem/yr. The applicable limits have been revisedmore » since the 1984 environmental monitoring report was published. The limits applied in 1984 were based on a radiation protection standard of 500 mrem/yr; the limits applied for the 1985 are based on a standard of 100 mrem/yr. To determine whether the site is in compliance with DOE standards, environmental measurements are expressed as percentages of the applicable DCG, while the calculated doses to the public are expressed as percentages of the applicable radiation protection standard. The monitoring program measured radon gas concentrations in air; uranium and radium concentrations in surface water, groundwater, and sediments; and external gamma dose rates. Environmental samples collected were analyzed to determine compliance with applicable standards. Potential radiation doses to the public were also calculated.« less

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

Phase II Dose Escalation Study of Caspofungin for Invasive Aspergillosis ▿ §

PubMed Central

Cornely, O. A.; Vehreschild, J. J.; Vehreschild, M. J. G. T.; Würthwein, G.; Arenz, D.; Schwartz, S.; Heussel, C. P.; Silling, G.; Mahne, M.; Franklin, J.; Harnischmacher, U.; Wilkens, A.; Farowski, F.; Karthaus, M.; Lehrnbecher, T.; Ullmann, A. J.; Hallek, M.; Groll, A. H.

2011-01-01

Our objective was to evaluate the maximum tolerated dose of caspofungin for invasive aspergillosis (IA). The safety and pharmacokinetics of escalating dosages of caspofungin were investigated in IA. Eight patients each received caspofungin 70, 100, 150, or 200 mg once a day (QD). Dose-limiting toxicity (DLT) was defined as the same non-hematological treatment-related adverse event of grade ≥4 in 2 of 8 patients or ≥3 in 4 of 8 patients in a cohort. A total of 46 patients (median age, 61 years; 21 female; 89% with hematological malignancies) received caspofungin (9, 8, 9, and 20 patients in the 70-, 100-, 150-, and 200-mg cohorts) for a median of 24.5 days. Plasma pharmacokinetics were linear across the investigated dosages and followed a two-compartment model, with weight as the covariate on clearance and sex as the covariate on central volume of distribution. Simulated peak plasma concentrations at steady state ranged from 14.2 to 40.6 mg/liter (28%), trough concentrations from 4.1 to 11.8 mg/liter (58%), and area under the concentration-time curve from 175 to 500 mg/liter/h (32%) (geometric mean, geometric coefficient of variation). Treatment was well tolerated without dose-limiting toxicity. The rate of complete or partial responses was 54.3%, and the overall mortality at 12-week follow-up was 28.3%. In first-line treatment of invasive aspergillosis, daily doses of up to 200 mg caspofungin were well tolerated and the maximum tolerated dose was not reached. Pharmacokinetics was linear. Response rates were similar to those previously reported for voriconazole and liposomal amphotericin. PMID:21911573

Measured and Calculated Neutron Spectra and Dose Equivalent Rates at High Altitudes; Relevance to SST Operations and Space Research

NASA Technical Reports Server (NTRS)

Foelsche, T.; Mendell, R. B.; Wilson, J. W.; Adams, R. R.

1974-01-01

Results of the NASA Langley-New York University high-altitude radiation study are presented. Measurements of the absorbed dose rate and of secondary fast neutrons (1 to 10 MeV energy) during the years 1965 to 1971 are used to determine the maximum radiation exposure from galactic and solar cosmic rays of supersonic transport (SST) and subsonic jet occupants. The maximum dose equivalent rates that the SST crews might receive turn out to be 13 to 20 percent of the maximum permissible dose rate (MPD) for radiation workers (5 rem/yr). The exposure of passengers encountering an intense giant-energy solar particle event could exceed the MPD for the general population (0.5 rem/yr), but would be within these permissible limits if in such rare cases the transport descends to subsonic altitude; it is in general less than 12 percent of the MPD. By Monte Carlo calculations of the transport and buildup of nucleons in air for incident proton energies E of 0.02 to 10 GeV, the measured neutron spectra were extrapolated to lower and higher energies and for galactic cosmic rays were found to continue with a relatively high intensity to energies greater than 400 MeV, in a wide altitude range. This condition, together with the measured intensity profiles of fast neutrons, revealed that the biologically important fast and energetic neutrons penetrate deep into the atmosphere and contribute approximately 50 percent of the dose equivalant rates at SST and present subsonic jet altitudes.

Radiological assessment of water treatment processes in a water treatment plant in Saudi Arabia: Water and sludge radium content, radon air concentrations and dose rates.

PubMed

Al-Jaseem, Q Kh; Almasoud, Fahad I; Ababneh, Anas M; Al-Hobaib, A S

2016-09-01

There is an increase demand for clean water sources in Saudi Arabia and, yet, renewable water resources are very limited. This has forced the authorities to explore deep groundwater which is known to contain large concentrations of radionuclides, mainly radium isotopes. Lately, there has been an increase in the number of water treatment plants (WTPs) around the country. In this study, a radiological assessment of a WTP in Saudi Arabia was performed. Raw water was found to have total radium activity of 0.23Bq/L, which exceeds the international limit of 0.185Bq/L (5pCi/L). The WTP investigated uses three stages of treatment: flocculation/sedimentation, sand filtration and reverse osmosis. The radium removal efficiency was evaluated for each stage and the respective values were 33%, 22% and 98%. Moreover, the activity of radium in the solid waste generated from the WTP in the sedimentation and sand filtrations stages were measured and found to be 4490 and 6750Bq/kg, respectively, which exceed the national limit of 1000Bq/kg for radioactive waste. A radiological assessment of the air inside the WTP was also performed by measuring the radon concentrations and dose rates and were found in the ranges of 2-18Bq/m(3) and 70-1000nSv/h, respectively. The annual effective dose was calculated and the average values was found to be 0.3mSv which is below the 1mSv limit. Copyright © 2016 Elsevier B.V. All rights reserved.

Comparison of TID Effects in Space-Like Variable Dose Rates and Constant Dose Rates

NASA Technical Reports Server (NTRS)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Evans, Robin W.; Jun, Insoo

2008-01-01

The degradation of the LM193 dual voltage comparator has been studied at different TID dose rate profiles, including several different constant dose rates and a variable dose rate that simulates the behavior of a solar flare. A comparison of results following constant dose rate vs. variable dose rates is made to explore how well the constant dose rates used for typical part testing predict the performance during a simulated space-like mission. Testing at a constant dose rate equal to the lowest dose rate seen during the simulated flare provides an extremely conservative estimate of the overall amount of degradation. A constant dose rate equal to the average dose rate is also more conservative than the variable rate. It appears that, for this part, weighting the dose rates by the amount of total dose received at each rate (rather than the amount of time at each dose rate) results in an average rate that produces an amount of degradation that is a reasonable approximation to that received by the variable rate.

High-dose transdermal nicotine replacement for tobacco cessation.

PubMed

Brokowski, Laurie; Chen, Jiahui; Tanner, Sara

2014-04-15

The safety and efficacy of high-dose transdermal nicotine-replacement therapy (NRT) for the treatment of tobacco-use cessation were reviewed. Transdermal nicotine doses of 7, 14, and 21 mg daily are approved by the Food and Drug Administration for use in tobacco cessation. However, studies have suggested that these doses are more adequate for people who smoke fewer than 20 cigarettes per day. A literature search was conducted to identify English-language studies that evaluated the use of transdermal nicotine doses of ≥42 mg daily. A total of 11 articles were identified, representing 10 separate trials. In terms of safety, the majority of the trials had no reports of serious adverse events related to transdermal NRT at doses of ≥42 mg daily. A dose-response relationship with adverse events occurred in most trials. In terms of efficacy, a numerically higher abstinence rate was achieved with high-dose transdermal NRT in all trials but 1. However, none of the studies showed significant differences in final abstinence rates at follow-up. Some reasons why statistical significance was not achieved in these trials may be related to the limitations of these trials, such as their small samples and the lack of a power calculation. A more robust trial is needed to support higher nicotine transdermal doses in tobacco cessation and to help elucidate which patient population would be most suitable for their use. The safety and efficacy of high-dose transdermal NRT for tobacco cessation have not been established in the medical literature.

Radiological risk from consuming fish and wildlife to Native Americans on the Hanford Site (USA).

PubMed

Delistraty, Damon; Van Verst, Scott; Rochette, Elizabeth A

2010-02-01

Historical operations at the Hanford Site (Washington State, USA) have released a wide array of non-radionuclide and radionuclide contaminants into the environment. As a result of stakeholder concerns, Native American exposure scenarios have been integrated into Hanford risk assessments. Because its contribution to radiological risk to Native Americans is culturally and geographically specific but quantitatively uncertain, a fish and wildlife ingestion pathway was examined in this study. Adult consumption rates were derived from 20 Native American scenarios (based on 12 studies) at Hanford, and tissue concentrations of key radionuclides in fish, game birds, and game mammals were compiled from the Hanford Environmental Information System (HEIS) database for a recent time interval (1995-2007) during the post-operational period. It was assumed that skeletal muscle comprised 90% of intake, while other tissues accounted for the remainder. Acknowledging data gaps, median concentrations of eight radionuclides (i.e., Co-60, Cs-137, Sr-90, Tc-99, U-234, U-238, Pu-238, and Pu-239/240) in skeletal muscle and other tissues were below 0.01 and 1 pCi/g wet wt, respectively. These radionuclide concentrations were not significantly different (Bonferroni P>0.05) on and off the Hanford Site. Despite no observed difference between onsite and offsite tissue concentrations, radiation dose and risk were calculated for the fish and wildlife ingestion pathway using onsite data. With median consumption rates and radionuclide tissue concentrations, skeletal muscle provided 42% of the dose, while other tissues (primarily bone and carcass) accounted for 58%. In terms of biota, fish ingestion was the largest contributor to dose (64%). Among radionuclides, Sr-90 was dominant, accounting for 47% of the dose. At median intake and radionuclide levels, estimated annual dose (0.36 mrem/yr) was below a dose limit of 15 mrem/yr recommended by the United States Environmental Protection Agency (USEPA), as well as below a dose limit of 100 mrem/yr proposed by the International Commission on Radiation Protection (ICRP). Similarly, lifetime cancer risk (1.7E-5), calculated with median inputs, was below risk levels corresponding to these dose limits. However, our dose and risk estimates apply to only one pathway within a multidimensional exposure scenario for Native Americans. On the other hand, radiation dose and risk corresponding to onsite tissue concentrations were not significantly different from those corresponding to offsite (background) concentrations. Recognizing uncertainties in exposure and toxicity assessments, our results may facilitate informed decision making and optimize resource allocation within a risk assessment framework at the Hanford Site. (c) 2009 Elsevier Inc. All rights reserved.

Radiological risk from consuming fish and wildlife to Native Americans on the Hanford Site (USA)

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

Delistraty, Damon, E-mail: DDEL461@ecy.wa.gov; Verst, Scott Van; Rochette, Elizabeth A.

Historical operations at the Hanford Site (Washington State, USA) have released a wide array of non-radionuclide and radionuclide contaminants into the environment. As a result of stakeholder concerns, Native American exposure scenarios have been integrated into Hanford risk assessments. Because its contribution to radiological risk to Native Americans is culturally and geographically specific but quantitatively uncertain, a fish and wildlife ingestion pathway was examined in this study. Adult consumption rates were derived from 20 Native American scenarios (based on 12 studies) at Hanford, and tissue concentrations of key radionuclides in fish, game birds, and game mammals were compiled from themore » Hanford Environmental Information System (HEIS) database for a recent time interval (1995-2007) during the post-operational period. It was assumed that skeletal muscle comprised 90% of intake, while other tissues accounted for the remainder. Acknowledging data gaps, median concentrations of eight radionuclides (i.e., Co-60, Cs-137, Sr-90, Tc-99, U-234, U-238, Pu-238, and Pu-239/240) in skeletal muscle and other tissues were below 0.01 and 1 pCi/g wet wt, respectively. These radionuclide concentrations were not significantly different (Bonferroni P>0.05) on and off the Hanford Site. Despite no observed difference between onsite and offsite tissue concentrations, radiation dose and risk were calculated for the fish and wildlife ingestion pathway using onsite data. With median consumption rates and radionuclide tissue concentrations, skeletal muscle provided 42% of the dose, while other tissues (primarily bone and carcass) accounted for 58%. In terms of biota, fish ingestion was the largest contributor to dose (64%). Among radionuclides, Sr-90 was dominant, accounting for 47% of the dose. At median intake and radionuclide levels, estimated annual dose (0.36 mrem/yr) was below a dose limit of 15 mrem/yr recommended by the United States Environmental Protection Agency (USEPA), as well as below a dose limit of 100 mrem/yr proposed by the International Commission on Radiation Protection (ICRP). Similarly, lifetime cancer risk (1.7E-5), calculated with median inputs, was below risk levels corresponding to these dose limits. However, our dose and risk estimates apply to only one pathway within a multidimensional exposure scenario for Native Americans. On the other hand, radiation dose and risk corresponding to onsite tissue concentrations were not significantly different from those corresponding to offsite (background) concentrations. Recognizing uncertainties in exposure and toxicity assessments, our results may facilitate informed decision making and optimize resource allocation within a risk assessment framework at the Hanford Site.« less

Image perception by expert readers as a function of patient skin entrance dose levels in digital radiography

NASA Astrophysics Data System (ADS)

Lehnert, T.; Korkusuz, H.; Khan, F.; Vogl, T. J.; Mack, M. G.

2008-03-01

In this study, image quality was based on required clinical criteria, in order to investigate to what degree entrance dose could be lowered and what kind of added filtration can be used without impinging on radiologist confidence levels in diagnosing. Images were taken of extremities from a cadaver using stepwise decreasing dose levels and variation of added filtration (no filtration, aluminum, aluminum/copper) under digital projection radiography (Kodak DirectView DR7500). The starting point dose level for all body parts imaged was the current x-ray technique. Two experienced and two resident radiologists were presented the images in a blinded fashion and rated each with an image quality score from 1 to 9 indicated very satisfied and 1 as very unsatisfied indicating loss of diagnostic value. The readers were not aware of which dose level and added filtration corresponded to which image. Dose levels considered were 100%, 75%, 50% and 25% of the normal and customary x-ray techniques used for the particular body part and projection. Images were reviewed on a clinical diagnostic workstation with no time limits imposed. Readers were also able to change the image presentation by adjusting the window width and level. Without added filtration image quality mean score was rated with 6.3 (dose level 100%), 6.2 (dose level 75%), 5.3 (dose level 50%) and with 4.4 (dose level 25%). An added aluminum filtration induced an image quality mean score of 6.3 (dose level 100%), 6.0 (dose level 75%), 5.1 (dose level 50%) and of 4.2 (dose level 25%). Using aluminum/copper filtration image quality mean score was rated with 6.0 (dose level 100%), 6.1 (dose level 75%), 5.0 (dose level 50%) and with 3.8 (dose level 25%). Regardless of the added filtration a differentiation between dose levels 100% and 75% was possible in 38.9%, between dose levels 75% and 50% in 66.7%, and between dose levels 50% and 25% in 70.0% of the cases. It is possible, in the case of extremities, to lower entrance doses up to 75 % of the normal value, a reduction of 25% in dose, under simultaneous use of added aluminum or aluminum/copper filtration, without comprising the diagnostic value required.

MO-F-CAMPUS-I-02: Occupational Conceptus Doses From Fluoroscopically-Guided Interventional Procedures

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

Damilakis, J; Perisinakis, K; Solomou, G

Purpose: The aim of this method was to provide dosimetric data on conceptus dose for the pregnant employee who participates in fluoroscopically-guided interventional procedures. Methods: Scattered air-kerma dose rates were obtained for 17 fluoroscopic projections involved in interventional procedures. These projections were simulated on an anthropomorphic phantom placed on the examination table supine. The operating theater was divided into two grids relative to the long table sides. Each grid consisted of 33 cells spaced 0.50 m apart. During the simulated exposures, at each cell, scatter air-kerma rate was measured at 110 cm from the floor i.e. at the height ofmore » the waist of the pregnant worker. Air-kerma rates were divided by the dose area product (DAP) rate of each exposure to obtain normalized data. For each projection, measurements were performed for 3 kVp and 3 filtration values i.e. for 9 different x-ray spectra. All measurements were performed by using a modern C-arm angiographic system (Siemens Axiom Artis, Siemens, Germany) and a radiation meter equipped with an ionization chamber. Results: The results consist of 153 iso-dose maps, which show the spatial distribution of DAP-normalized scattered air-kerma doses at the waist level of a pregnant worker. Conceptus dose estimation is possible using air-kerma to embryo/fetal dose conversion coefficients published in a previous study (J Cardiovasc Electrophysiol, Vol. 16, pp. 1–8, July 2005). Using these maps, occupationally exposed pregnant personnel may select a working position for a certain projection that keeps abdominal dose as low as reasonably achievable. Taking into consideration the regulatory conceptus dose limit for occupational exposure, determination of the maximum workload allowed for the pregnant personnel is also possible. Conclusion: Data produced in this work allow for the anticipation of conceptus dose and the determination of the maximum workload for a pregnant worker from any fluoroscopically-guided interventional procedure. This study was supported by the Greek Ministry of Education and Religious Affairs, General Secretariat for Research and Technology, Operational Program ‘Education and Lifelong Learning’, ARISTIA (Research project: CONCERT)« less

Circulating Cytokine/Chemokine Concentrations Respond to Ionizing Radiation Doses but not Radiation Dose Rates: Granulocyte-Colony Stimulating Factor and Interleukin-18.

PubMed

Kiang, Juliann G; Smith, Joan T; Hegge, Sara R; Ossetrova, Natalia I

2018-06-01

Exposure to ionizing radiation is a crucial life-threatening factor in nuclear and radiological incidents. It is known that ionizing radiation affects cytokine/chemokine concentrations in the blood of B6D2F1 mice. It is not clear whether radiation dose rates would vary the physiological response. Therefore, in this study we utilized data from two experiments using B6D2F1 female mice exposed to six different dose rates ranging from low to high rates. In one experiment, mice received a total dose of 8 Gy (LD 0/30 ) of 60 Co gamma radiation at four dose rates: 0.04, 0.15, 0.30 and 0.47 Gy/min. Blood samples from mice were collected at 24 and 48 h postirradiation for cytokine/chemokine measurements, including interleukin (IL)-1β, IL-6, IL-10, keratinocyte cytokine (KC), IL-12p70, IL-15, IL-17A, IL-18, granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage (GM)-CSF, macrophage (M)-CSF, monokine induced by gamma interferon (MIG), tumor necrosis factor (TNF)-α, fibroblast growth factor (FGF)-basic, vascular endothelial growth factor (VEGF) and platelet-derived growth factor basic (PDGF-bb). At 24 h after ionizing irradiation at dose rate of 0.04 Gy/min, significant increases were observed only in G-CSF and M-CSF ( P < 0.05). At 0.15 Gy/min, IL-10, IL-17A, G-CSF and GM-CSF concentrations were increased. At 0.3 Gy/min, IL-15, IL-18, G-CSF, GM-CSF, M-CSF, MCP-1, MIP-2, MIG, FGF-basic, VEGF and PDGF-bb were significantly elevated ( P < 0.05). At 0.47 Gy/min, IL-6, KC, IL-10, MCP-1, G-CSF, GM-CSF and M-CSF were significantly increased. At 48 h postirradiation, all cytokines/chemokines except MCP-1 returned to or were below their baselines, suggesting these increases are transient at LD 0/30 irradiation. Of note, there is a limitation on day 2 because cytokines/chemokines are either at or below their baselines. Other parameters such as fms-like tyrosine kinase receptor-3 ligand (Flt-3 ligand) concentrations and lymphocyte counts, which have proven to be unaffected by radiation dose rates, can be used instead for assessing the radiation dose. However, in a separate radiation dose and time-course experiment, increases in IL-18 and G-CSF depended on the radiation doses but showed no significant differences between 0.58 and 1.94 Gy/min ( P > 0.05) at 3 and 6 Gy but not 12 Gy. G-CSF continued to increase up to day 7, whereas IL-18 increased on day 4 and remained above baseline level on day 7. Therefore, time after irradiation at different doses should be taken into consideration. To our knowledge, these results are the first to suggest that ionizing radiation, even at a very low-dose-rate (0.04 Gy/min), induces circulating G-CSF increases but not others for selected time points; radiation-induced increases in IL-18 at radiation dose rates between 0.15 and 1.94 Gy/min are also not in a radiation dose-rate-dependent manner. C-CSF, lymphocyte counts and circulating Flt-3 ligand should be explored further as possible biomarkers of radiation exposure at early time points. IL-18 is also worthy of further study as a potential biomarker at later time points.

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

PubMed

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

2005-06-01

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

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

PubMed

Lensen, Sarah F; Wilkinson, Jack; Leijdekkers, Jori A; La Marca, Antonio; Mol, Ben Willem J; Marjoribanks, Jane; Torrance, Helen; Broekmans, Frank J

2018-02-01

During a cycle of in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI), women receive daily doses of gonadotropin follicle-stimulating hormone (FSH) to induce multifollicular development in the ovaries. Generally, the dose of FSH is associated with the number of eggs retrieved. A normal response to stimulation is often considered desirable, for example the retrieval of 5 to 15 oocytes. Both poor and hyper-response are associated with increased chance of cycle cancellation. Hyper-response is also associated with increased risk of ovarian hyperstimulation syndrome (OHSS). Clinicians often individualise the FSH dose using patient characteristics predictive of ovarian response such as age. More recently, clinicians have begun using ovarian reserve tests (ORTs) to predict ovarian response based on the measurement of various biomarkers, including basal FSH (bFSH), antral follicle count (AFC), and anti-Müllerian hormone (AMH). It is unclear whether individualising FSH dose based on these markers improves clinical outcomes. To assess the effects of individualised gonadotropin dose selection using markers of ovarian reserve in women undergoing IVF/ICSI. We searched the Cochrane Gynaecology and Fertility Group Specialised Register, Cochrane Central Register of Studies Online, MEDLINE, Embase, CINAHL, LILACS, DARE, ISI Web of Knowledge, ClinicalTrials.gov, and the World Health Organisation International Trials Registry Platform search portal from inception to 27th July 2017. We checked the reference lists of relevant reviews and included studies. We included trials that compared different doses of FSH in women with a defined ORT profile (i.e. predicted low, normal or high responders based on AMH, AFC, and/or bFSH) and trials that compared an individualised dosing strategy (based on at least one ORT measure) versus uniform dosing or a different individualised dosing algorithm. We used standard methodological procedures recommended by Cochrane. Primary outcomes were live birth/ongoing pregnancy and severe OHSS. Secondary outcomes included clinical pregnancy, moderate or severe OHSS, multiple pregnancy, oocyte yield, cycle cancellations, and total dose and duration of FSH administration. We included 20 trials (N = 6088); however, we treated those trials with multiple comparisons as separate trials for the purpose of this review. Meta-analysis was limited due to clinical heterogeneity. Evidence quality ranged from very low to moderate. The main limitations were imprecision and risk of bias associated with lack of blinding.Direct dose comparisons in women according to predicted responseAll evidence was low or very low quality.Due to differences in dose comparisons, caution is warranted in interpreting the findings of five small trials assessing predicted low responders. The effect estimates were very imprecise, and increased FSH dosing may or may not have an impact on rates of live birth/ongoing pregnancy, OHSS, and clinical pregnancy.Similarly, in predicted normal responders (nine studies, three comparisons), higher doses may or may not impact the probability of live birth/ongoing pregnancy (e.g. 200 versus 100 international units: OR 0.88, 95% CI 0.57 to 1.36; N = 522; 2 studies; I 2 = 0%) or clinical pregnancy. Results were imprecise, and a small benefit or harm remains possible. There were too few events for the outcome of OHSS to enable any inferences.In predicted high responders, lower doses may or may not have an impact on rates of live birth/ongoing pregnancy (OR 0.98, 95% CI 0.66 to 1.46; N = 521; 1 study), OHSS, and clinical pregnancy. However, lower doses probably reduce the likelihood of moderate or severe OHSS (Peto OR 2.31, 95% CI 0.80 to 6.67; N = 521; 1 study).ORT-algorithm studiesFour trials compared an ORT-based algorithm to a non-ORT control group. Rates of live birth/ongoing pregnancy and clinical pregnancy did not appear to differ by more than a few percentage points (respectively: OR 1.04, 95% CI 0.88 to 1.23; N = 2823, 4 studies; I 2 = 34%; OR 0.96, 95% CI 0.82 to 1.13, 4 studies, I 2 =0%, moderate-quality evidence). However, ORT algorithms probably reduce the likelihood of moderate or severe OHSS (Peto OR 0.58, 95% CI 0.34 to 1.00; N = 2823; 4 studies; I 2 = 0%, low quality evidence). There was insufficient evidence to determine whether the groups differed in rates of severe OHSS (Peto OR 0.54, 95% CI 0.14 to 1.99; N = 1494; 3 studies; I 2 = 0%, low quality evidence). Our findings suggest that if the chance of live birth with a standard dose is 26%, the chance with ORT-based dosing would be between 24% and 30%. If the chance of moderate or severe OHSS with a standard dose is 2.5%, the chance with ORT-based dosing would be between 0.8% and 2.5%. These results should be treated cautiously due to heterogeneity in the study designs. We did not find that tailoring the FSH dose in any particular ORT population (low, normal, high ORT), influenced rates of live birth/ongoing pregnancy but we could not rule out differences, due to sample size limitations. In predicted high responders, lower doses of FSH seemed to reduce the overall incidence of moderate and severe OHSS. Moderate-quality evidence suggests that ORT-based individualisation produces similar live birth/ongoing pregnancy rates to a policy of giving all women 150 IU. However, in all cases the confidence intervals are consistent with an increase or decrease in the rate of around five percentage points with ORT-based dosing (e.g. from 25% to 20% or 30%). Although small, a difference of this magnitude could be important to many women. Further, ORT algorithms reduced the incidence of OHSS compared to standard dosing of 150 IU, probably by facilitating dose reductions in women with a predicted high response. However, the size of the effect is unclear. The included studies were heterogeneous in design, which limited the interpretation of pooled estimates, and many of the included studies had a serious risk of bias.Current evidence does not provide a clear justification for adjusting the standard dose of 150 IU in the case of poor or normal responders, especially as increased dose is generally associated with greater total FSH dose and therefore greater cost. However, a decreased dose in predicted high responders may reduce OHSS.

OBJECT KINETIC MONTE CARLO SIMULATIONS OF RADIATION DAMAGE IN BULK TUNGSTEN

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

Nandipati, Giridhar; Setyawan, Wahyu; Heinisch, Howard L.

2015-09-22

We used our recently developed lattice based OKMC code; KSOME [1] to carryout simulations of radiation damage in bulk W. We study the effect of dimensionality of self interstitial atom (SIA) diffusion i.e. 1D versus 3D on the defect accumulation during irradiation with a primary knock-on atom (PKA) energy of 100 keV at 300 K for the dose rates of 10-5 and 10-6 dpa/s. As expected 3D SIA diffusion significantly reduces damage accumulation due to increased probability of recombination events. In addition, dose rate, over the limited range examined here, appears to have no effect in both cases of SIAmore » diffusion.« less

Boosting subsurface life: is subseafloor sediment a natural catalyst for radiolytic hydrogen production?

NASA Astrophysics Data System (ADS)

Sauvage, J.; Graham, D.; Spivack, A. J.; Dunlea, A. G.; Murray, R. W.; D'Hondt, S.

2014-12-01

Naturally occurring production of molecular hydrogen (H2) by water radiolysis may be a fundamentally important source of electron donors (energy) for life in subsurface environments where organic matter is scarce. Previous studies with very high gamma radiation rates and wet mineral phases have reported high H2 production relative to production from water radiolysis in the absence of solid phases. Numerical calculations by other previous studies have predicted enhanced H2 production from seawater radiolysis relative to pure water radiolysis, due to the interaction of anions with hydroxyl radicals. Given these reports, the potential catalytic influences of solid and dissolved chemical phases on radiolytic H2 production need to be carefully quantified in order to fully evaluate the role of radiolytic H2 as a microbial energy source. For such quantification, we undertook gamma-irradiation experiments with pure water, deep ocean water and mixtures (slurries, φ = 0.85) of seawater with: North Pacific abyssal clay and calcareous oozes, coastal sediment, zirconium dioxide, and zeolite. We carried out our experiments at the Rhode Island Nuclear Science Center using a 37Cesium source at low dose rates (up to 0.1 Gy/hr). Our results to date include the following. First, the per-dose radiolytic H2 yield of pure water at low dose rates is directly comparable to the per-dose yield at much higher dose rates (ca. 1 kGy/hr); this result indicates that H2 production rate is linearly related to radiation dose rate across four orders of magnitude. Second, there is no statistically significant difference (90% confidence limit) between the radiolytic H2 yield from pure water and that from seawater; this result rules out influence of abundant seawater salts on H2 yield from water radiolysis. Third, H2 production from a mixture of abyssal clay and seawater is 25% higher than the yield from pure water. This enhanced yield is consistent with catalysis of radiolytic H2 production by zeolite.

Intensity-modulated radiotherapy in the standard management of head and neck cancer: promises and pitfalls.

PubMed

Mendenhall, William M; Amdur, Robert J; Palta, Jatinder R

2006-06-10

The purpose of this article is to review the role of intensity-modulated radiotherapy (IMRT) in the standard management of patients with head and neck cancer through a critical review of the pertinent literature. IMRT may result in a dose distribution that is more conformal than that achieved with three-dimensional conformal radiotherapy (3D CRT), allowing dose reduction to normal structures and thus decreasing toxicity and possibly enhancing locoregional control through dose escalation. Disadvantages associated with IMRT include increased risk of a marginal miss, decreased dose homogeneity, increased total body dose, and increased labor and expense. Outcomes data after IMRT are limited, and follow-up is relatively short. Locoregional control rates appear to be comparable to those achieved with 3D CRT and, depending on the location and extent of the tumor, late toxicity may be lower. Despite limited data on clinical outcomes, IMRT has been widely adopted as a standard technique in routine practice and clinical trials. The use of IMRT involves a learning curve for the practitioner and will continue to evolve, requiring continuing education and monitoring of outcomes from routine practice. Additional standards pertaining to a variety of issues, including target definitions and dose specification, need to be developed. Phase III trials will better define the role of IMRT in coming years.

Prospective study of proton-beam radiation therapy for limited-stage small cell lung cancer.

PubMed

Rwigema, Jean-Claude M; Verma, Vivek; Lin, Liyong; Berman, Abigail T; Levin, William P; Evans, Tracey L; Aggarwal, Charu; Rengan, Ramesh; Langer, Corey; Cohen, Roger B; Simone, Charles B

2017-11-01

Existing data supporting the use of proton-beam therapy (PBT) for limited-stage small cell lung cancer (LS-SCLC) are limited to a single 6-patient case series. This is the first prospective study to evaluate clinical outcomes and toxicities of PBT for LS-SCLC. This study prospectively analyzed patients with primary, nonrecurrent LS-SCLC definitively treated with PBT and concurrent chemotherapy from 2011 to 2016. Clinical backup intensity-modulated radiotherapy (IMRT) plans were generated for each patient and were compared with PBT plans. Outcome measures included local control (LC), recurrence-free survival (RFS), and overall survival (OS) rates and toxicities. Thirty consecutive patients were enrolled and evaluated. The median dose was 63.9 cobalt gray equivalents (range, 45-66.6 cobalt gray equivalents) in 33 to 37 fractions delivered daily (n = 18 [60.0%]) or twice daily (n = 12 [40.0%]). The concurrent chemotherapy was cisplatin/etoposide (n = 21 [70.0%]) or carboplatin/etoposide (n = 9 [30.0%]). In comparison with the backup IMRT plans, PBT allowed statistically significant reductions in the cord, heart, and lung mean doses and the volume receiving at least 5 Gy but not in the esophagus mean dose or the lung volume receiving at least 20 Gy. At a median follow-up of 14 months, the 1-/2-year LC and RFS rates were 85%/69% and 63%/42%, respectively. The median OS was 28.2 months, and the 1-/2-year OS rates were 72%/58%. There was 1 case each (3.3%) of grade 3 or higher esophagitis, pneumonitis, anorexia, and pericardial effusion. Grade 2 pneumonitis and esophagitis were seen in 10.0% and 43.3% of patients, respectively. In the first prospective registry study and largest analysis to date of PBT for LS-SCLC, PBT was found to be safe with a limited incidence of high-grade toxicities. Cancer 2017;123:4244-4251. © 2017 American Cancer Society. © 2017 American Cancer Society.

Implementing smart infusion pumps with dose-error reduction software: real-world experiences.

PubMed

Heron, Claire

2017-04-27

Intravenous (IV) drug administration, especially with 'smart pumps', is complex and susceptible to errors. Although errors can occur at any stage of the IV medication process, most errors occur during reconstitution and administration. Dose-error reduction software (DERS) loaded on to infusion pumps incorporates a drug library with predefined upper and lower drug dose limits and infusion rates, which can reduce IV infusion errors. Although this is an important advance for patient safety at the point of care, uptake is still relatively low. This article discuses the challenges and benefits of implementing DERS in clinical practice as experienced by three UK trusts.

Self-limiting atomic layer deposition of conformal nanostructured silver films

NASA Astrophysics Data System (ADS)

Golrokhi, Zahra; Chalker, Sophia; Sutcliffe, Christopher J.; Potter, Richard J.

2016-02-01

The controlled deposition of ultra-thin conformal silver nanoparticle films is of interest for applications including anti-microbial surfaces, plasmonics, catalysts and sensors. While numerous techniques can produce silver nanoparticles, few are able to produce highly conformal coatings on high aspect ratio surfaces, together with sub-nanometre control and scalability. Here we develop a self-limiting atomic layer deposition (ALD) process for the deposition of conformal metallic silver nanoparticle films. The films have been deposited using direct liquid injection ALD with ((hexafluoroacetylacetonato)silver(I)(1,5-cyclooctadiene)) and propan-1-ol. An ALD temperature window between 123 and 128 °C is identified and within this range self-limiting growth is confirmed with a mass deposition rate of ∼17.5 ng/cm2/cycle. The effects of temperature, precursor dose, co-reactant dose and cycle number on the deposition rate and on the properties of the films have been systematically investigated. Under self-limiting conditions, films are metallic silver with a nano-textured surface topography and nanoparticle size is dependent on the number of ALD cycles. The ALD reaction mechanisms have been elucidated using in-situ quartz crystal microbalance (QCM) measurements, showing chemisorption of the silver precursor, followed by heterogeneous catalytic dehydrogenation of the alcohol to form metallic silver and an aldehyde.

Assessment of natural radioactivity and radiological hazards in building materials used in Yan'an, China.

PubMed

Lu, Xinwei; Li, Nan; Yang, Guang; Zhao, Caifeng

2013-03-01

The concentration of natural radionuclides in commonly used building materials collected from Yan'an, China, was determined using gamma ray spectroscopy with a NaI(Tl) detector. The activity concentration of ²²⁶Ra, ²³²Th, and ⁴⁰K in the studied building materials ranges from 9.4-73.1, 11.5-86.9, and 258.9-1,055.1 Bq kg⁻¹, respectively. The concentrations for these natural radionuclides were compared with the reported data of other countries and the world mean values for soil. The radium equivalent activity (Raeq), external hazard index (Hex), internal hazard index (Hin), indoor air absorbed dose rate, and annual effective dose rate due to natural radionuclides in samples were estimated to assess radiological hazards for people living in dwellings made of the studied building materials. The calculated Raeq values of all building materials (75.7-222.1 Bq kg⁻¹) are lower than the limit of 370 Bq kg⁻¹. The values of Hex and Hin are less than unity. The mean values of indoor air absorbed dose rates of all building materials (101.0 ± 14.1-177.0 ± 6.8 nGy h⁻¹) are higher than the world population-weighted average of 84 nGy h⁻¹, while the mean values of annual effective dose range from 0.50 ± 0.07-0.87 ± 0.03 mSv y⁻¹, which are lower than the recommended limit of 1 mSv y⁻¹. It is found that these materials may be used safely as construction materials and do not pose significant radiation hazards to inhabitants.

Exposure to cosmic radiation of British Airways flying crew on ultralonghaul routes.

PubMed Central

Bagshaw, M; Irvine, D; Davies, D M

1996-01-01

British Airways has carried out radiation monitoring in Concorde for more than 20 years and has used a heuristic model based on data quoted by the National Aeronautics and Space Administration (NASA) to model radiation exposure in all longhaul fleets. From these data it has been calculated that no flight deck crew would exceed the control level of 6 mSv/y currently under consideration by regulatory authorities, which is three tenths of the occupational dose limit of 20 mSv/y recommended by the International Commission on Radiological Protection (ICRP). The model suggested that less than 4% of cabin crew based in Tokyo flying only between London and Japan could reach or exceed the 6 mSv/y level, based on a predicted effective dose rate of 7 microSv/h. To validate this calculation a sampling measurement programme was carried out on nine round trips flown by a Boeing 747-400 between London and Tokyo. The radiation field was measured with dosimeters used for routine personal monitoring (thermoluminescence dosimeters (TLDs) and polyallydiglycol carbonate neutron dosimeters). The limitations of the methodology are acknowledged, but the results indicate that the effective dose rate was 6 microSv/h which is consistent with the predicted effective dose rate of 7 microSv/h. This result, which is in accordance with other reported studies indicates that it is unlikely that any of the cabin crew based in Tokyo exceeded the 6 mSv/y level. In accordance with "as low as reasonably achievable" principles British Airways will continue to monitor flying crew routes and hours flown to ensure compliance. PMID:8704876

Radiation concurrent with gemcitabine for locally advanced head and neck cancer: a phase I trial and intracellular drug incorporation study.

PubMed

Eisbruch, A; Shewach, D S; Bradford, C R; Littles, J F; Teknos, T N; Chepeha, D B; Marentette, L J; Terrell, J E; Hogikyan, N D; Dawson, L A; Urba, S; Wolf, G T; Lawrence, T S

2001-02-01

To examine the feasibility and dose-limiting toxicity (DLT) of once-weekly gemcitabine at doses predicted in preclinical studies to produce radiosensitization, concurrent with a standard course of radiation for locally advanced head and neck cancer. Tumor incorporation of gemcitabine triphosphate (dFdCTP) was measured to assess whether adequate concentrations were achieved at each dose level. Twenty-nine patients with unresectable head and neck cancer received a course of radiation (70 Gy over 7 weeks, 5 days weekly) concurrent with weekly infusions of low-dose gemcitabine. Tumor biopsies were performed after the first gemcitabine infusion (before radiation started), and the intracellular concentrations of dFdCTP were measured. Severe acute and late mucosal and pharyngeal-related DLT required de-escalation of gemcitabine dose in successive patient cohorts receiving dose levels of 300 mg/m(2)/wk, 150 mg/m(2)/wk, and 50 mg/m(2)/wk. No DLT was observed at 10 mg/m(2)/wk. The rate of endoscopy- and biopsy-assessed complete tumor response was 66% to 87% in the various cohorts. Tumor dFdCTP levels were similar in patients receiving 50 to 300 mg/m(2) (on average, 1.55 pmol/mg, SD 1.15) but were barely or not detectable at 10 mg/m(2). A high rate of acute and late mucosa-related DLT and a high rate of complete tumor response were observed in this regimen at the dose levels of 50 to 300 mg/m(2), which also resulted in similar, subcytotoxic intracellular dFdCTP concentrations. These results demonstrate significant tumor and normal tissue radiosensitization by low-dose gemcitabine. Different regimens of combined radiation and gemcitabine should be evaluated, based on newer preclinical data promising an improved therapeutic ratio.

Monte Carlo simulations of the secondary neutron ambient and effective dose equivalent rates from surface to suborbital altitudes and low Earth orbit

NASA Astrophysics Data System (ADS)

El-Jaby, Samy; Richardson, Richard B.

2015-07-01

Occupational exposures from ionizing radiation are currently regulated for airline travel (<20 km) and for missions to low-Earth orbit (∼300-400 km). Aircrew typically receive between 1 and 6 mSv of occupational dose annually, while aboard the International Space Station, the area radiation dose equivalent measured over just 168 days was 106 mSv at solar minimum conditions. It is anticipated that space tourism vehicles will reach suborbital altitudes of approximately 100 km and, therefore, the annual occupational dose to flight crew during repeated transits is expected to fall somewhere between those observed for aircrew and astronauts. Unfortunately, measurements of the radiation environment at the high altitudes reached by suborbital vehicles are sparse, and modelling efforts have been similarly limited. In this paper, preliminary MCNPX radiation transport code simulations are developed of the secondary neutron flux profile in air from surface altitudes up to low Earth orbit at solar minimum conditions and excluding the effects of spacecraft shielding. These secondary neutrons are produced by galactic cosmic radiation interacting with Earth's atmosphere and are among the sources of radiation that can pose a health risk. Associated estimates of the operational neutron ambient dose equivalent, used for radiation protection purposes, and the neutron effective dose equivalent that is typically used for estimates of stochastic health risks, are provided in air. Simulations show that the neutron radiation dose rates received at suborbital altitudes are comparable to those experienced by aircrew flying at 7 to 14 km. We also show that the total neutron dose rate tails off beyond the Pfotzer maximum on ascension from surface up to low Earth orbit.

Monte Carlo simulations of the secondary neutron ambient and effective dose equivalent rates from surface to suborbital altitudes and low Earth orbit.

PubMed

El-Jaby, Samy; Richardson, Richard B

2015-07-01

Occupational exposures from ionizing radiation are currently regulated for airline travel (<20 km) and for missions to low-Earth orbit (∼300-400 km). Aircrew typically receive between 1 and 6 mSv of occupational dose annually, while aboard the International Space Station, the area radiation dose equivalent measured over just 168 days was 106 mSv at solar minimum conditions. It is anticipated that space tourism vehicles will reach suborbital altitudes of approximately 100 km and, therefore, the annual occupational dose to flight crew during repeated transits is expected to fall somewhere between those observed for aircrew and astronauts. Unfortunately, measurements of the radiation environment at the high altitudes reached by suborbital vehicles are sparse, and modelling efforts have been similarly limited. In this paper, preliminary MCNPX radiation transport code simulations are developed of the secondary neutron flux profile in air from surface altitudes up to low Earth orbit at solar minimum conditions and excluding the effects of spacecraft shielding. These secondary neutrons are produced by galactic cosmic radiation interacting with Earth's atmosphere and are among the sources of radiation that can pose a health risk. Associated estimates of the operational neutron ambient dose equivalent, used for radiation protection purposes, and the neutron effective dose equivalent that is typically used for estimates of stochastic health risks, are provided in air. Simulations show that the neutron radiation dose rates received at suborbital altitudes are comparable to those experienced by aircrew flying at 7 to 14 km. We also show that the total neutron dose rate tails off beyond the Pfotzer maximum on ascension from surface up to low Earth orbit. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Integrated protection of humans and the environment: a view from Japan.

PubMed

Sakai, K

2018-01-01

Six and a half years after the accident at Fukushima Daiichi nuclear power plant, an area of existing exposure situation remains. One of the main concerns of people is the higher level of ionising radiation than before the accident, although this is not expected to have any discernible health effect. Since the accident, several 'abnormalities' in environmental organisms have been reported. It is still not clear if these abnormalities were induced by radiation. It appears that the impact of the released radioactivity has not been sufficient to threaten the maintenance of biological diversity, the conservation of species, or the health and status of natural habitats, which are the focus in environmental protection. This highlights a difference between the protection of humans and protection of the environment (individuals for humans and populations/species for the environment). The system for protection of the environment has been developed with a similar approach as the system for protection of humans. Reference Animals and Plants (RAPs) were introduced to connect exposure and doses in a way similar to that for Reference Male and Reference Female. RAPs can also be used as a tool to associate the level of radiation (dose rate) with the biological effects on an organism. A difference between the protection of humans and that of the environment was identified: an effect on humans is measured in terms of dose, and an effect on the environment is measured in terms of dose rate. In other words, protection criteria for humans are expressed in term of dose (as dose limits, dose constraints, and reference levels), whereas those for the environment are expressed in terms of dose rate (as derived consideration reference levels).

Vaccine wastage in Nigeria: An assessment of wastage rates and related vaccinator knowledge, attitudes and practices.

PubMed

Wallace, Aaron S; Willis, Fred; Nwaze, Eric; Dieng, Boubacar; Sipilanyambe, Naawa; Daniels, Danni; Abanida, Emmanuel; Gasasira, Alex; Mahmud, Mustapha; Ryman, Tove K

2017-12-04

The introduction of new vaccines highlights concerns about high vaccine wastage, knowledge of wastage policies and quality of stock management. However, an emphasis on minimizing wastage rates may cause confusion when recommendations are also being made to reduce missed opportunities to routinely vaccinate children. This concern is most relevant for lyophilized vaccines without preservatives [e.g. measles-containing vaccine (MCV)], which can be used for a limited time once reconstituted. We sampled 54 health facilities within 11 local government areas (LGAs) in Nigeria and surveyed health sector personnel regarding routine vaccine usage and wastage-related knowledge and practices, conducted facility exit interviews with caregivers of children about missed opportunities for routine vaccination, and abstracted vaccine stock records and vaccination session data over a 6-month period to calculate wastage rates and vaccine vial usage patterns. Nearly half of facilities had incomplete vaccine stock data for calculating wastage rates. Among facilities with sufficient data, mean monthly facility-level wastage rates were between 18 and 35% across all reviewed vaccines, with little difference between lyophilized and liquid vaccines. Most (98%) vaccinators believed high wastage led to recent vaccine stockouts, yet only 55% were familiar with the multi-dose vial policy for minimizing wastage. On average, vaccinators reported that a minimum of six children must be present prior to opening a 10-dose MCV vial. Third dose of diphtheria-tetanus-pertussis vaccine (DTP3) was administered in 84% of sessions and MCV in 63%; however, the number of MCV and DTP3 doses administered were similar indicating the number of children vaccinated with DTP3 and MCV were similar despite less frequent MCV vaccination opportunities. Among caregivers, 30% reported being turned away for vaccination at least once; 53% of these children had not yet received the missed dose. Our findings show inadequate implementation of vaccine management guidelines, missed opportunities to vaccinate, and lyophilized vaccine wastage rates below expected rates. Missed opportunities for vaccination may occur due to how the health system's contradicting policies may force health workers to prioritize reduced wastage rates over vaccine administration, particularly for multi-dose vials. Published by Elsevier Ltd.

Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis

PubMed Central

Borrmann, Steffen; Tékété, Mamadou; Lefèvre, Gilbert; Hamed, Kamal; Piola, Patrice; Ursing, Johan; Kofoed, Poul Erik; Mårtensson, Andreas; Ngasala, Billy; Björkman, Anders; Friberg Hietala, Sofia; Aweeka, Francesca; Parikh, Sunil; Mwai, Leah; Davis, Timothy M. E.; Karunajeewa, Harin; Newton, Paul N.; Mayxay, Mayfong; Deloron, Philippe; van Vugt, Michele; Karbwang, Juntra; Ezzet, Farkad; Bakshi, Rajesh; Stepniewska, Kasia; Barnes, Karen I.

2018-01-01

Background The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations. Methods and findings A search in PubMed, Embase, ClinicalTrials.gov, Google Scholar, conference proceedings, and the WorldWide Antimalarial Resistance Network (WWARN) pharmacology database identified 31 relevant clinical studies published between 1 January 1990 and 31 December 2012, with 4,546 patients in whom lumefantrine concentrations were measured. Under the auspices of WWARN, relevant individual concentration-time data, clinical covariates, and outcome data from 4,122 patients were made available and pooled for the meta-analysis. The developed lumefantrine population pharmacokinetic model was used for dose optimisation through in silico simulations. Venous plasma lumefantrine concentrations 7 days after starting standard AL treatment were 24.2% and 13.4% lower in children weighing <15 kg and 15–25 kg, respectively, and 20.2% lower in pregnant women compared with non-pregnant adults. Lumefantrine exposure decreased with increasing pre-treatment parasitaemia, and the dose limitation on absorption of lumefantrine was substantial. Simulations using the lumefantrine pharmacokinetic model suggest that, in young children and pregnant women beyond the first trimester, lengthening the dose regimen (twice daily for 5 days) and, to a lesser extent, intensifying the frequency of dosing (3 times daily for 3 days) would be more efficacious than using higher individual doses in the current standard treatment regimen (twice daily for 3 days). The model was developed using venous plasma data from patients receiving intact tablets with fat, and evaluations of alternative dosing regimens were consequently only representative for venous plasma after administration of intact tablets with fat. The absence of artemether-dihydroartemisinin data limited the prediction of parasite killing rates and recrudescent infections. Thus, the suggested optimised dosing schedule was based on the pharmacokinetic endpoint of lumefantrine plasma exposure at day 7. Conclusions Our findings suggest that revised AL dosing regimens for young children and pregnant women would improve drug exposure but would require longer or more complex schedules. These dosing regimens should be evaluated in prospective clinical studies to determine whether they would improve cure rates, demonstrate adequate safety, and thereby prolong the useful therapeutic life of this valuable antimalarial treatment. PMID:29894518

Dosimetric quality, accuracy, and deliverability of modulated radiotherapy treatments for spinal metastases

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

Kairn, Tanya, E-mail: t.kairn@gmail.com; School of Chemistry, Physics, and Mechanical Engineering, Queensland University of Technology, Brisbane; Papworth, Daniel

2016-10-01

Cancer often metastasizes to the vertebra, and such metastases can be treated successfully using simple, static posterior or opposed-pair radiation fields. However, in some cases, including when re-irradiation is required, spinal cord avoidance becomes necessary and more complex treatment plans must be used. This study evaluated 16 sample intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans designed to treat 6 typical vertebral and paraspinal volumes using a standard prescription, with the aim of investigating the advantages and limitations of these treatment techniques and providing recommendations for their optimal use in vertebral treatments. Treatment plan quality and beammore » complexity metrics were evaluated using the Treatment And Dose Assessor (TADA) code. A portal-imaging–based quality assurance (QA) system was used to evaluate treatment delivery accuracy, and radiochromic film measurements were used to provide high-resolution verification of treatment plan dose accuracy, especially in the steep dose gradient regions between each vertebral target and spinal cord. All treatment modalities delivered approximately the same doses and the same levels of dose heterogeneity to each planning target volume (PTV), although the minimum PTV doses in the vertebral plans were substantially lower than the prescription, because of the requirement that the plans meet a strict constraint on the dose to the spinal cord and cord planning risk volume (PRV). All plans met required dose constraints on all organs at risk, and all measured PTV-cord dose gradients were steeper than planned. Beam complexity analysis suggested that the IMRT treatment plans were more deliverable (less complex, leading to greater QA success) than the VMAT treatment plans, although the IMRT plans also took more time to deliver. The accuracy and deliverability of VMAT treatment plans were found to be substantially increased by limiting the number of monitor units (MU) per beam at the optimization stage, and thereby limiting beam modulation complexity. The VMAT arcs that were optimized with MU limitation had higher QA pass rates as well as higher modulation complexity scores (less complexity), lower modulation indices (less modulation), lower MU per beam, larger beam segments, and fewer small apertures than the VMAT arcs that were optimized without MU limitation. It is recommended that VMAT treatments for vertebral volumes, where the PTV abuts or surrounds the spinal cord, should be optimized with MU limitation. IMRT treatments may be preferable to the VMAT treatments, for dosimetry and deliverability reasons, but may be inappropriate for some patients because of their increased treatment delivery time.« less

A phase I trial of two sequence-specific schedules of decitabine and vorinostat in patients with acute myeloid leukemia

PubMed Central

How, Jonathan; Minden, Mark D.; Brian, Leber; Chen, Eric X.; Brandwein, Joseph; Schuh, Andre C.; Schimmer, Aaron D.; Gupta, Vikas; Webster, Sheila; Degelder, Tammy; Haines, Patricia; Stayner, Lee-Anne; McGill, Shauna; Wang, Lisa; Piekarz, Richard; Wong, Tracy; Siu, Lillian L.; Espinoza-Delgado, Igor; Holleran, Julianne L.; Egorin, Merrill J.; Yee, Karen W. L.

2015-01-01

This phase I trial evaluated two schedules of escalating vorinostat in combination with decitabine every 28 days: (i) sequential or (ii) concurrent. There were three dose-limiting toxicities: grade 3 fatigue and generalized muscle weakness on the sequential schedule (n = 1) and grade 3 fatigue on the concurrent schedule (n = 2). The maximum tolerated dose was not reached on both planned schedules. The overall response rate (ORR) was 23% (three complete response [CR], two CR with incomplete incomplete blood count recovery [CRi], one partial response [PR] and two morphological leukemic free state [MLFS]). The ORR for all and previously untreated patients in the sequential arm was 13% (one CRi; one MLFS) and 0% compared to 30% (three CR; one CRi; one PR; one MLFS) and 36% in the concurrent arm (p = 0.26 for both), respectively. Decitabine plus vorinostat was safe and has clinical activity in patients with previously untreated acute myeloid leukemia. Responses appear higher with the concurrent dose schedule. Cumulative toxicities may limit long-term usage on the current dose/schedules. PMID:25682963

Phase I study of carboplatin combined with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer.

PubMed

Takeoka, Hiroaki; Yamada, Kazuhiko; Azuma, Koichi; Zaizen, Yoshiaki; Yamashita, Fumie; Yoshida, Tsukasa; Naito, Yoshiko; Okayama, Yusuke; Miyamoto, Maki; Hoshino, Tomoaki

2014-05-01

The primary objective of this study was to evaluate the safety and tolerability of carboplatin plus pemetrexed for elderly patients (≥75 years) with chemotherapy-naïve advanced non-squamous non-small cell lung cancer. Patients received escalated doses of carboplatin at an area under the concentration-time curve of 4 (Level 1) or 5 (Level 2) plus pemetrexed (500 mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation was decided according to whether dose-limiting toxicity occurred in the first cycle of chemotherapy. A total of 20 patients (6 at Level 1, 14 at Level 2) were enrolled. No dose-limiting toxicities were observed in patients at Level 1 or the first six patients at Level 2, and therefore the combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was considered to be the recommended dose. Among a total of 14 patients in Level 2, only 1 patient experienced dose-limiting toxicity: Grade 3 febrile neutropenia and urticaria. The major toxicities were neutropenia, thrombocytopenia and anemia. Liver dysfunction, fatigue and anorexia were also common, but generally manageable. Six patients showed partial responses, giving the overall response rate of 30%. The median progression-free survival period was 4.8 months (95% confidence interval 2.9-6.7 months). The combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was determined as the recommended dose in chemotherapy-naïve elderly patients (≥75 years) with advanced non-squamous non-small cell lung cancer, in view of overall safety and tolerability.

Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline.

PubMed

Arrossi, Silvina; Temin, Sarah; Garland, Suzanne; Eckert, Linda O'Neal; Bhatla, Neerja; Castellsagué, Xavier; Alkaff, Sharifa Ezat; Felder, Tamika; Hammouda, Doudja; Konno, Ryo; Lopes, Gilberto; Mugisha, Emmanuel; Murillo, Rául; Scarinci, Isabel C; Stanley, Margaret; Tsu, Vivien; Wheeler, Cosette M; Adewole, Isaac Folorunso; de Sanjosé, Silvia

2017-10-01

To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally. The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/biostatistics, health economics, behavioral/implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings. Existing sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75%. In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age ≥ 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if ≥ 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus-related cancers and diseases. Basic settings: vaccinating boys is not recommended. It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Benchmarking of MCNP for calculating dose rates at an interim storage facility for nuclear waste.

PubMed

Heuel-Fabianek, Burkhard; Hille, Ralf

2005-01-01

During the operation of research facilities at Research Centre Jülich, Germany, nuclear waste is stored in drums and other vessels in an interim storage building on-site, which has a concrete shielding at the side walls. Owing to the lack of a well-defined source, measured gamma spectra were unfolded to determine the photon flux on the surface of the containers. The dose rate simulation, including the effects of skyshine, using the Monte Carlo transport code MCNP is compared with the measured dosimetric data at some locations in the vicinity of the interim storage building. The MCNP data for direct radiation confirm the data calculated using a point-kernel method. However, a comparison of the modelled dose rates for direct radiation and skyshine with the measured data demonstrate the need for a more precise definition of the source. Both the measured and the modelled dose rates verified the fact that the legal limits (<1 mSv a(-1)) are met in the area outside the perimeter fence of the storage building to which members of the public have access. Using container surface data (gamma spectra) to define the source may be a useful tool for practical calculations and additionally for benchmarking of computer codes if the discussed critical aspects with respect to the source can be addressed adequately.

Natural and anthropogenic radionuclides in rocks and beach sands from Ezine region (Canakkale), Western Anatolia, Turkey.

PubMed

Orgün, Y; Altinsoy, N; Sahin, S Y; Güngör, Y; Gültekin, A H; Karahan, G; Karacik, Z

2007-06-01

This paper represents the first reports on the natural and anthropogenic radionuclides in Kestanbol granitic pluton and surrounding rocks, and coastal region of the Ezine town. To assess the radiological hazard of the natural radioactivity, the radium equivalent activity, the absorbed dose rate and the external hazard index were calculated, and in situ gamma dose rates were measured. The high-activity concentrations were measured in the pluton and sands, which was originated mainly from the pluton, due to the presence of zircon, allanite, monazite, thorite, uranothorite and apatite. The average activity concentrations of (238)U, (232)Th and (40)K are 174.78, 204.69 and 1171.95 Bq kg(-1) for pluton, and 290.36, 532.04 and 1160.75 Bq kg(-1) for sands, respectively. (137)Cs in Ezine region ranged from 0-6.57 Bq kg(-1). The average absorbed dose rate for the granitic and sand samples were calculated to be 251.6 and 527.92 nGy h(-1), respectively. The maximum contribution to the total absorbed gamma dose rate in air was due to the (232)Th (52.3% for pluton and 67.1% for sands). The Raeq activities of the pluton and sands are higher than the recommended maximum value of 370 Bq kg(-1) criterion limit of Raeq activity for building materials.

Annual limits on intake (ALI) values in ICRP 61 and 10 CFR Part 20 (1991)

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

Zhu, M.; Kearfott, K.J.

The newest major revision of Nuclear Regulatory Commission`s 10 CFR Part 20 (1991) incorporates the new dose methodology system, revised limits, and improved internal dose computations presented in International Commission on Radiation Protection (ICRP) Publication 30 (1979). A year before the issue of this revised 10 CFR Part 20, the ICRP dispatched Publication 61 (1990). This new ICRP report employed different dose limits, in addition to incorporating more recent biological information and variations in physiological and different tissue weighing factors for various organs. An investigation of the numerical differences in the Annual Limit on Intake (ALI) reported in this moremore » recent international regulations and those of the new regulations was thus undertaken. Overall means, medians, modes, maximum, minimum, and ranges of the percent changes are almost identical for ingestion and inhalation, although the percent difference between 10 CFR and ICRP Publication 61 showed minor differences for individual radionuclides. Approximately 334 of 1,351 radionuclides for inhalation and 173 of 771 radionuclides for ingestion have much less restrictive ALIs in the new ICRP recommendations than in the old, with some of those limits increased by at least a factor of two. Approximately 51% of the radionuclides for ingestion intake and 48% of radionuclides for inhalation intake showed changes of greater than 25%. The radionuclides observed to have much less restrictive ALIs are primarily the radionuclides of thorium, mercury, plutonium, uranium, and americium which have short effective clearance rates. While many countries have already applied the ICRP 61 recommendations to their radiation protection standards, using the ICRP 30 recommendation in the United States does not match the international standards even when the values of the ALIs are adjusted for differences in dose limits.« less

Altitudinal characteristics of atmospheric deposition of aerosols in mountainous regions: Lessons from the Fukushima Daiichi Nuclear Power Station accident.

PubMed

Sanada, Yukihisa; Katata, Genki; Kaneyasu, Naoki; Nakanishi, Chika; Urabe, Yoshimi; Nishizawa, Yukiyasu

2018-03-15

To understand the formation process of radiologically contaminated areas in eastern Japan caused by the Fukushima Daiichi Nuclear Power Station (FDNPS) accident, the deposition mechanisms over complex topography are the key factors to be investigated. To characterize the atmospheric deposition processes of radionuclides over complex mountainous topography, we investigated the altitudinal distributions of the radiocesium deposited during the accident. In five selected areas, altitudinal characteristics of the air dose rates observed using airborne surveys were analyzed. To examine the deposition mechanisms, we supplementarily used vertical profiles of radiocesium deposition in each area calculated in the latest atmospheric dispersion model. In southern Iwate, the vertical profile of the observed air dose rate was uniform regardless of altitude. In western Tochigi, the areas with the highest levels of contamination were characteristically distributed in the middle of the mountains, while in southern Fukushima, the areas with the highest contamination levels were enhanced near the summits of mountains. In central Fukushima, high air dose rates were limited to the bottoms of basin-like valley. In the region northwest of FDNPS, the air dose rate was the highest at the bottom of valley topography and decreased gradually with altitude. The simulation results showed that calculated wet deposition and observed vertical profiles of total deposition were similar in areas of southern Iwate and northwest of FDNPS qualitatively, suggesting that the dominant deposition mechanism was wet deposition. In contrast, the atmospheric dispersion model failed to reproduce either the timing of precipitation events or vertical profiles of radiocesium deposition in three other areas. Although it was difficult to elucidate the deposition mechanisms in these areas due to uncertainties of the present model results, potential mechanisms such as cloud water deposition were still proposed based on circumstantial evidences of limited meteorological data during the early stage of the accident. Copyright © 2017 Elsevier B.V. All rights reserved.

Phase I trial of combination chemotherapy with docetaxel, cisplatin and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer.

PubMed

Tahara, M; Araki, K; Okano, S; Kiyota, N; Fuse, N; Minashi, K; Yoshino, T; Doi, T; Zenda, S; Kawashima, M; Ogino, T; Hayashi, R; Minami, H; Ohtsu, A

2011-01-01

we investigated the maximum tolerated dose (MTD) of combination therapy with docetaxel, cisplatin, and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer (HNC). treatment consisted of docetaxel (Taxotere) at doses of 50, 60, and 70 mg/m(2); cisplatin at 70 mg·m(2)/day on day 1; and S-1 twice daily on days 1-14 at doses of 40, 60, and 80 mg·m(2)/day, repeated every 3 or 4 weeks. forty patients were enrolled. MTD was not reached until level 4. Subjects at expanded dose were limited to patients with locally advanced disease. Two dose-limiting toxic effects (DLTs) were observed at dose level 5 (TPS: 70/70/80 mg·m(2)/day, every 3 weeks), namely one grade 3 infection and one grade 3 hyperbilirubinemia, establishing this as the MTD. Of 12 patients treated at dose level 6 (TPS: 70/70/60 mg·m(2)/day, every 3 weeks), 2 DLTs were seen. Six achieved a complete response and 22 a partial response, giving a response rate of 70%. TPS was well tolerated. The recommended phase II dose as induction chemotherapy for locally advanced HNC was determined as 70/70/60 mg·m(2)/day every 3 weeks. Antitumor activity was highly promising and warrants further investigation.

Global transport and deposition of 137Cs following the Fukushima nuclear power plant accident in Japan: emphasis on Europe and Asia using high-resolution model versions and radiological impact assessment of the human population and the environment using interactive tools.

PubMed

Evangeliou, Nikolaos; Balkanski, Yves; Cozic, Anne; Møller, Anders Pape

2013-06-04

The earthquake and the subsequent tsunami that occurred offshore of Japan resulted in an important loss of life and a serious accident at the nuclear facility of Fukushima. The "hot spots" of the release are evaluated here applying the model LMDZORINCA for (137)Cs. Moreover, an assessment is attempted for the population and the environment using the dosimetric scheme of the WHO and the interactive tool ERICA, respectively. Cesium-137 was deposited mostly in Pacific and Atlantic Oceans and North Pole (80%), whereas the rest in the continental areas of North America and Eurasia contributed slightly to the natural background (0.5-5.0 kBq m(-2)). The effective dose from (137)Cs and (134)Cs (radiocesium) irradiation during the first 3 months was estimated between 1-5 mSv in Fukushima and the neighboring prefectures. In the rest of Japan, the respective doses were found to be less than 0.5 mSv, whereas in the rest of the world it was less than 0.1 mSv. Such doses are equivalent with the obtained dose from a simple X-ray; for the highly contaminated regions, they are close to the dose limit for exposure due to radon inhalation (10 mSv). The calculated dose rates from radiocesium exposure on reference organisms ranged from 0.03 to 0.18 μGy h(-1), which are 2 orders of magnitude below the screening dose limit (10 μGy h(-1)) that could result in obvious effects on the population. However, these results may underestimate the real situation, since stable soil density was used in the calculations, a zero radiocesium background was assumed, and dose only from two radionuclides was estimated, while more that 40 radionuclides have been deposited in the vicinity of the facility. When monitoring data applied, much higher dose rates were estimated certifying ecological risk for small mammals and reptiles in terms of cytogenetic damage and reproduction.

Global transport of Fukushima-derived radionuclides from Japan to Asia, North America and Europe. Estimated doses and expected health effects

NASA Astrophysics Data System (ADS)

Evangeliou, Nikolaos; Stohl, Andreas; Balkanski, Yves

2017-04-01

The earthquake and the subsequent tsunami that occurred offshore of Japan resulted in a serious accident at the nuclear facility of Fukushima. A large number of fission products were released and transported worldwide. We estimate that around 23% of the released 137Cs remained into Japan, while 76% deposited in the oceans. Around 163 TBq deposited over North America, among which 95 TBq over USA, 40 TBq over Canada and 5 TBq over Greenland). About 14 TBq deposited over Europe (mostly in the European part of Russia, Sweden and Norway) and 47 TBq over Asia (mostly in the Asian part of Russia, Philippines and South Korea), while traces were observed over Africa, Oceania and Antarctica. Since the radioactive plume followed a northward direction before its arrival to USA and then to Europe, a significant amount of about 69 TBq deposited in the Arctic, as well. An attempt to assess exposure of the population and the environment showed that the effective dose from gamma irradiation during the first 3 months was estimated between 1-5 mSv in Fukushima and the neighbouring prefectures. In the rest of Japan, the respective doses were found to be less than 0.5 mSv, whereas in the rest of the world it was less than 0.1 mSv. Such doses are equivalent with the obtained dose from a simple X-ray; for the highly contaminated regions, they are close to the dose limit for exposure due to radon inhalation (10 mSv). The calculated dose rates from radiocesium exposure on reference organisms ranged from 0.03 to 0.18 μGy h-1, which are 2 orders of magnitude below the screening dose limit (10 μGy h-1) that could result in obvious effects on the population. However, monitoring data have shown that much higher dose rates were committed to organisms raising ecological risk for small mammals and reptiles in terms of cytogenetic damage and reproduction.

Factors Influencing Pulmonary Toxicity in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in the Setting of Total Body Irradiation-Based Myeloablative Conditioning.

PubMed

Abugideiri, Mustafa; Nanda, Ronica H; Butker, Charlotte; Zhang, Chao; Kim, Sungjin; Chiang, Kuang-Yueh; Butker, Elizabeth; Khan, Mohammad K; Haight, Ann E; Chen, Zhengjia; Esiashvili, Natia

2016-02-01

This study evaluated factors associated with increased risk of pulmonary toxicity (PT) from any cause in pediatric patients after myeloablative conditioning, using total body irradiation (TBI), followed by allogeneic hematopoietic stem cell transplantation (HSCT). The records of 129 consecutive pediatric patients (range: 1-21 years of age) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI doses ranged from 10.5 to 14 Gy, lung doses were limited to 10 Gy with partial transmission blocks. TBI dose rates ranged from 5.6 cGy/min to 20.9 cGy/min. PT was classified using clinical symptoms, radiographic evidence, and ventilatory defects on pulmonary function tests. Noninfectious (idiopathic) pneumonia syndrome (IPS) was characterized by patients exhibiting PT while demonstrating no signs of infection throughout the follow-up period. PT from any cause developed in 70.5% of patients and was significantly associated with increased transplantation-related mortality (TRM) (P=.03) and decreased overall survival (OS) (P=.02). IPS developed in 23.3% of patients but was not associated with increased TRM (P=.6) or decreased OS (P=.5). Acute graft-versus-host disease (GVHD) significantly affected PT (P=.001) but did not significantly influence the development of IPS (P=.4). Infection was a leading cause of PT (75.8%). TBI dose rate significantly affected development of overall PT (P=.02) and was the sole factor to significantly influence the incidence of IPS (P=.002). TBI total dose, dose per fraction, disease type, transplantation chemotherapy, age of patient, sex, and donor type did not significantly impact overall PT or IPS. A high incidence of PT was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. TBI dose rates affected overall PT and strongly influenced IPS. TBI dose rate is a contributing factor influencing pulmonary toxicity and rates less than 15 cGy/min should be considered to decrease the risk of IPS. Copyright © 2016 Elsevier Inc. All rights reserved.

Dosimetric Consistency of Co-60 Teletherapy Unit- a ten years Study.

PubMed

Baba, Misba H; Mohib-Ul-Haq, M; Khan, Aijaz A

2013-01-01

The goal of the Radiation standards and Dosimetry is to ensure that the output of the Teletherapy Unit is within ±2% of the stated one and the output of the treatment dose calculation methods are within ±5%. In the present paper, we studied the dosimetry of Cobalt-60 (Co-60) Teletherapy unit at Sher-I-Kashmir Institute of Medical Sciences (SKIMS) for last 10 years. Radioactivity is the phenomenon of disintegration of unstable nuclides called radionuclides. Among these radionuclides, Cobalt-60, incorporated in Telecobalt Unit, is commonly used in therapeutic treatment of cancer. Cobalt-60 being unstable decays continuously into Ni-60 with half life of 5.27 years thereby resulting in the decrease in its activity, hence dose rate (output). It is, therefore, mandatory to measure the dose rate of the Cobalt-60 source regularly so that the patient receives the same dose every time as prescribed by the radiation oncologist. The under dosage may lead to unsatisfactory treatment of cancer and over dosage may cause radiation hazards. Our study emphasizes the consistency between actual output and output obtained using decay method. The methodology involved in the present study is the calculations of actual dose rate of Co-60 Teletherapy Unit by two techniques i.e. Source to Surface Distance (SSD) and Source to Axis Distance (SAD), used for the External Beam Radiotherapy, of various cancers, using the standard methods. Thereby, a year wise comparison has been made between average actual dosimetric output (dose rate) and the average expected output values (obtained by using decay method for Co-60.). The present study shows that there is a consistency in the average output (dose rate) obtained by the actual dosimetry values and the expected output values obtained using decay method. The values obtained by actual dosimetry are within ±2% of the expected values. The results thus obtained in a year wise comparison of average output by actual dosimetry done regularly as a part of Quality Assurance of the Telecobalt Radiotherapy Unit and its deviation from the expected output data is within the permissible limits. Thus our study shows a trend towards uniformity and a better dose delivery.

Factors Influencing Pulmonary Toxicity in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in the Setting of Total Body Irradiation-Based Myeloablative Conditioning

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

Abugideiri, Mustafa, E-mail: Mabugid@emory.edu; Nanda, Ronica H.; Butker, Charlotte

Purpose: This study evaluated factors associated with increased risk of pulmonary toxicity (PT) from any cause in pediatric patients after myeloablative conditioning, using total body irradiation (TBI), followed by allogeneic hematopoietic stem cell transplantation (HSCT). Methods and Materials: The records of 129 consecutive pediatric patients (range: 1-21 years of age) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI doses ranged from 10.5 to 14 Gy, lung doses were limited to 10 Gy with partial transmission blocks. TBI dose rates ranged from 5.6 cGy/min to 20.9 cGy/min. PT was classified usingmore » clinical symptoms, radiographic evidence, and ventilatory defects on pulmonary function tests. Noninfectious (idiopathic) pneumonia syndrome (IPS) was characterized by patients exhibiting PT while demonstrating no signs of infection throughout the follow-up period. Results: PT from any cause developed in 70.5% of patients and was significantly associated with increased transplantation-related mortality (TRM) (P=.03) and decreased overall survival (OS) (P=.02). IPS developed in 23.3% of patients but was not associated with increased TRM (P=.6) or decreased OS (P=.5). Acute graft-versus-host disease (GVHD) significantly affected PT (P=.001) but did not significantly influence the development of IPS (P=.4). Infection was a leading cause of PT (75.8%). TBI dose rate significantly affected development of overall PT (P=.02) and was the sole factor to significantly influence the incidence of IPS (P=.002). TBI total dose, dose per fraction, disease type, transplantation chemotherapy, age of patient, sex, and donor type did not significantly impact overall PT or IPS. Conclusions: A high incidence of PT was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. TBI dose rates affected overall PT and strongly influenced IPS. TBI dose rate is a contributing factor influencing pulmonary toxicity and rates less than 15 cGy/min should be considered to decrease the risk of IPS.« less

Developing A Directional High-Dose Rate (d-HDR) Brachytherapy Source

NASA Astrophysics Data System (ADS)

Heredia, Athena Yvonne

Conventional sources used in brachytherapy provide nearly isotropic or radially symmetric dose distributions. Optimizations of dose distributions have been limited to varied dwell times at specified locations within a given treatment volume, or manipulations in source position for seed implantation techniques. In years past, intensity modulated brachytherapy (IMBT) has been used to reduce the amount of radiation to surrounding sensitive structures in select intracavitary cases by adding space or partial shields. Previous work done by Lin et al., at the University of Wisconsin-Madison, has shown potential improvements in conformality for brachytherapy treatments using a directionally shielded low dose rate (LDR) source for treatments in breast and prostate. Directional brachytherapy sources irradiate approximately half of the radial angles around the source, and adequately shield a quarter of the radial angles on the opposite side, with sharp gradient zones between the treated half and shielded quarter. With internally shielded sources, the radiation can be preferentially emitted in such a way as to reduce toxicities in surrounding critical organs. The objective of this work is to present findings obtained in the development of a new directional high dose rate (d-HDR) source. To this goal, 103Pd (Z = 46) is reintroduced as a potential radionuclide for use in HDR brachytherapy. 103Pd has a low average photon energy (21 keV) and relatively short half -life (17 days), which is why it has historically been used in low dose rate applications and implantation techniques. Pd-103 has a carrier-free specific activity of 75000 Ci/g. Using cyclotron produced 103Pd, near carrier-free specific activities can be achieved, providing suitability for high dose rate applications. The evolution of the d-HDR source using Monte Carlo simulations is presented, along with dosimetric parameters used to fully characterize the source. In addition, a discussion on how to obtain elemental palladium, Pd(0), will be discussed in detail. Directional HDR has the potential to improve upon current treatments, providing better dose conformality to the target volume, while maintaining the benefits of HDR applications.

Analysis of the dose-sparing effect of adjuvanted Sabin-inactivated poliovirus vaccine (sIPV).

PubMed

Li, Zhuofan; Ding, Wenting; Guo, Qi; Liu, Ze; Zhu, Zhe; Song, Shaohui; Li, Weidong; Liao, Guoyang

2018-03-30

Sabin-based inactivated poliovirus vaccine(sIPV) is gradually replacing live-attenuated oral polio vaccine(OPV). Sabin-inactivated poliovirus vaccine(sIPV) has played a vital role in reducing economic burden of poliomyelitis and maintaining appropriate antibody levels in the population. However, due to its high cost and limited manufacturing capacity, sIPV cannot reach its full potential for global poliovirus eradication in developing countries. Therefore, to address this situation, we designed this study to evaluate the dose-sparing effects of AS03, CpG oligodeoxynucleotides (CpG-ODN) and polyinosinic:polycytidylic acid (PolyI:C) admixed with sIPV in rats. Our results showed that a combination of 1/4-dose sIPV adjuvanted with AS03 or AS03 with BW006 provides a seroconversion rate similar to that of full-dose sIPV without adjuvant and that, this rate is 5-fold higher than that of 1/4-dose sIPV without adjuvant after the first immunization. The combination of AS03 or AS03 with BW006 as an adjuvant effectively reduced sIPV dose by at least 4-fold and induced both humoral and cellular immune responses. Therefore, our study revealed that the combination of AS03 or AS03 with BW006 is a promising adjuvant for sIPV development.

Effects of low dose ibogaine on subjective mood state and psychological performance.

PubMed

Forsyth, Bridget; Machado, Liana; Jowett, Tim; Jakobi, Hannah; Garbe, Kira; Winter, Helen; Glue, Paul

2016-08-02

Root bark from Tabernanthe iboga has been used traditionally in West Africa as a psychoactive substance in religious rituals. In smaller doses it is reported anecdotally to have stimulant properties. To evaluate the influence of a single 20mg ibogaine dose on psychological variables reflecting subjective mood state and a range of cognitive functions. 21 healthy male volunteers received single 20mg doses of ibogaine after 6 days pretreatment with double-blind paroxetine or placebo. We compared responses to a battery of psychometric tests and subjective mood ratings performed before and 2h after ibogaine dosing, and assessed relationships between changes in test scores and concentrations of active moiety (the sum of molar noribogaine and ibogaine concentrations). Psychological tests were chosen based on responsiveness to opioid and serotonergic ligands. Ibogaine had minimal influence on psychological tests and mood ratings. The ability to selectively ignore distracting spatial information showed some evidence of modulation; however because this effect was limited to the less challenging condition calls into question the reliability of this result. We were unable to identify stimulant effects after single 20mg doses of ibogaine. Future research is needed to confirm whether active moiety concentrations impact selective attention abilities while leaving other cognitive functions and mood state unaffected. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Measurements of the linear energy transfer spectra on the Mir orbital station and comparison with radiation transport models

NASA Technical Reports Server (NTRS)

Badhwar, G. D.; Konradi, A.; Atwell, W.; Golightly, M. J.; Cucinotta, F. A.; Wilson, J. W.; Petrov, V. M.; Tchernykh, I. V.; Shurshakov, V. A.; Lobakov, A. P.

1996-01-01

A tissue equivalent proportional counter designed to measure the linear energy transfer spectra (LET) in the range 0.2-1250 keV/micrometer was flown in the Kvant module on the Mir orbital station during September 1994. The spacecraft was in a 51.65 degrees inclination, elliptical (390 x 402 km) orbit. This is nearly the lower limit of its flight altitude. The total absorbed dose rate measured was 411.3 +/- 4.41 microGy/day with an average quality factor of 2.44. The galactic cosmic radiation (GCR) dose rate was 133.6 microGy/day with a quality factor of 3.35. The trapped radiation belt dose rate was 277.7 microGy/day with an average quality factor of 1.94. The peak rate through the South Atlantic Anomaly was approximately 12 microGy/min and nearly constant from one pass to another. A detailed comparison of the measured LET spectra has been made with radiation transport models. The GCR results are in good agreement with model calculations; however, this is not the case for radiation belt particles and again points to the need for improving the AP8 omni-directional trapped proton models.

Recent international regulations: low dose-low rate radiation protection and the demise of reason.

PubMed

Okkalides, Demetrios

2008-01-01

The radiation protection measures suggested by the International Committee for Radiation Protection (ICRP), national regulating bodies and experts, have been becoming ever more strict despite the decrease of any information supporting the existence of the Linear no Threshold model (LNT) and of any adverse effects of Low Dose Low Rate (LDLR) irradiation. This tendency arises from the disproportionate response of human society to hazards that are currently in fashion and is unreasonable. The 1 mSv/year dose limit for the public suggested by the ICRP corresponds to a 1/18,181 detriment-adjusted cancer risk and is much lower than other hazards that are faced by modern societies such as e.g. driving and smoking which carry corresponding rate risks of 1/2,100 and 1/2,000. Even worldwide deadly work accidents rate is higher at 1/ 8,065. Such excessive safety measures against minimal risks from man made radiation sources divert resources from very real and much greater hazards. In addition they undermine research and development of radiation technology and tend to subjugate science and the quest for understanding nature to phobic practices.

Clinical applications of advanced rotational radiation therapy

NASA Astrophysics Data System (ADS)

Nalichowski, Adrian

Purpose: With a fast adoption of emerging technologies, it is critical to fully test and understand its limits and capabilities. In this work we investigate new graphic processing unit (GPU) based treatment planning algorithm and its applications in helical tomotherapy dose delivery. We explore the limits of the system by applying it to challenging clinical cases of total marrow irradiation (TMI) and stereotactic radiosurgery (SRS). We also analyze the feasibility of alternative fractionation schemes for total body irradiation (TBI) and TMI based on reported historical data on lung dose and interstitial pneumonitis (IP) incidence rates. Methods and Materials: An anthropomorphic phantom was used to create TMI plans using the new GPU based treatment planning system and the existing CPU cluster based system. Optimization parameters were selected based on clinically used values for field width, modulation factor and pitch. Treatment plans were also created on Eclipse treatment planning system (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) for dose delivery on IX treatment unit. A retrospective review was performed of 42 publications that reported IP rates along with lung dose, fractionation regimen, dose rate and chemotherapy. The analysis consisted of nearly thirty two hundred patients and 34 unique radiation regimens. Multivariate logistic regression was performed to determine parameters associated with IP and establish does response function. Results: The results showed very good dosimetric agreement between the GPU and CPU calculated plans. The results from SBRT study show that GPU planning system can maintain 90% target coverage while meeting all the constraints of RTOG 0631 protocol. Beam on time for Tomotherapy and flattening filter free RapidArc was much faster than for Vero or Cyberknife. Retrospective data analysis showed that lung dose and Cyclophosphomide (Cy) are both predictors of IP in TBI/TMI treatments. The dose rate was not found to be an independent risk factor for IP. The model failed to establish accurate dose response function, but the discrete data indicated a radiation dose threshold of 7.6Gy (EQD2_repair) and 120 mg/kg of Cy below which no IP cases were reported. Conclusion: The TomoTherapy GPU based dose engine is capable of calculating TMI treatment plans with plan quality nearly identical to plans calculated using the traditional CPU/cluster based system, while significantly reducing the time required for optimization and dose calculation. The new system was able to achieve more uniform dose distribution throughout the target volume and steeper dose fall off, resulting in superior OAR sparing when compared to Eclipse treatment planning system for VMAT delivery. The machine optimization parameters tested for TMI cases provide a comprehensive overview of the capabilities of the treatment planning station and associated helical delivery system. The new system also proved to be dosimetrically compatible with other leading modalities for treatments of small and complicated target volumes and was even superior when treatment delivery times were compared. These finding demonstrate that the advanced treatment planning and delivery system from TomoTherapy is well suitable for treatments of complicated cases such as TMI and SRS and it's often dosimetrically and/or logistically superior to other modalities. The new planning system can easily meet the constraint of threshold lung dose established in this study. The results presented here on the capabilities of Tomotherapy and on the identified lung dose threshold provide an opportunity to explore alternative fractionation schemes without sacrificing target coverage or lung toxicity. (Abstract shortened by ProQuest.).

Eye lens exposure to medical staff during endoscopic retrograde cholangiopancreatography.

PubMed

Zagorska, A; Romanova, K; Hristova-Popova, J; Vassileva, J; Katzarov, K

2015-11-01

The paper presents a study of the radiation doses to eye lens of medical staff during endoscopic retrograde cholangiopancreatography (ERCP) procedures performed in a busy gastroenterology department. For each procedure the dose equivalent to the eye, exposure time, dose rate, Kerma Area Product and fluoroscopy time were recorded. Measurements were performed for a period of two months in four main positions of the operating staff, and then extrapolated to estimate annual doses. The fluoroscopy time per ERCP procedure varied between 1.0 min and 28.8 min, with a mean value of 4.6 min. The calculated mean eye dose per procedure varied between 34.9 μSv and 93.3 μSv. The results demonstrated that if eye protection is not used, annual doses to the eye lens of the gastroenterologist performing the procedure and the anesthesiologist can exceed the dose limit of 20 mSv per year. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Charged particles radiation measurements with Liulin-MO dosimeter of FREND instrument aboard ExoMars Trace Gas Orbiter during the transit and in high elliptic Mars orbit

NASA Astrophysics Data System (ADS)

Semkova, Jordanka; Koleva, Rositza; Benghin, Victor; Dachev, Tsvetan; Matviichuk, Yuri; Tomov, Borislav; Krastev, Krasimir; Maltchev, Stephan; Dimitrov, Plamen; Mitrofanov, Igor; Malahov, Alexey; Golovin, Dmitry; Mokrousov, Maxim; Sanin, Anton; Litvak, Maxim; Kozyrev, Andrey; Tretyakov, Vladislav; Nikiforov, Sergey; Vostrukhin, Andrey; Fedosov, Fedor; Grebennikova, Natalia; Zelenyi, Lev; Shurshakov, Vyacheslav; Drobishev, Sergey

2018-03-01

ExoMars is a joint ESA-Rosscosmos program for investigating Mars. Two missions are foreseen within this program: one consisting of the Trace Gas Orbiter (TGO), that carries scientific instruments for the detection of trace gases in the Martian atmosphere and for the location of their source regions, plus an Entry, Descent and landing demonstrator Module (EDM), launched on March 14, 2016; and the other, featuring a rover and a surface platform, with a launch date of 2020. On October 19, 2016 TGO was inserted into high elliptic Mars' orbit. The dosimetric telescope Liulin-MO for measuring the radiation environment onboard the ExoMars 2016 TGO is a module of the Fine Resolution Epithermal Neutron Detector (FREND). Here we present first results from measurements of the charged particle fluxes, dose rates, Linear Energy Transfer (LET) spectra and estimation of dose equivalent rates in the interplanetary space during the cruise of TGO to Mars and first results from dosimetric measurements in high elliptic Mars' orbit. A comparison is made with the dose rates obtained by RAD instrument onboard Mars Science Laboratory during the cruise to Mars in 2011-2012 and with the Galactic Cosmic Rays (GCR) count rates provided by other particle detectors currently in space. The average measured dose rate in Si from GCR during the transit to Mars for the period April 22-September 15, 2016 is 372 ± 37 μGy d-1 and 390 ± 39 μGy d-1 in two perpendicular directions. The dose equivalent rate from GCR for the same time period is about 2 ± 0.3 mSv d-1. This is in good agreement with RAD results for radiation dose rate in Si from GCR in the interplanetary space, taking into account the different solar activity during the measurements of both instruments. About 10% increase of the dose rate, and 15% increase of the dose equivalent rate for 10.5 months flight is observed. It is due to the increase of Liulin-MO particle fluxes for that period and corresponds to the overall GCR intensity increase during the declining phase of the solar activity. Data show that during the cruise to Mars and back (6 months in each direction), taken during the declining of solar activity, the crewmembers of future manned flights to Mars will accumulate at least 60% of the total dose limit for the cosmonaut's/astronaut's career in case their shielding conditions are close to the average shielding of Liulin-MO detectors-about 10 g cm-2. The dosimetric measurements in high elliptic Mars' orbit demonstrate strong dependence of the GCR fluxes near the TGO pericenter on satellite's field of view shadowed by Mars.

NAIRAS aircraft radiation model development, dose climatology, and initial validation.

PubMed

Mertens, Christopher J; Meier, Matthias M; Brown, Steven; Norman, Ryan B; Xu, Xiaojing

2013-10-01

[1] The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway.

NAIRAS aircraft radiation model development, dose climatology, and initial validation

NASA Astrophysics Data System (ADS)

Mertens, Christopher J.; Meier, Matthias M.; Brown, Steven; Norman, Ryan B.; Xu, Xiaojing

2013-10-01

The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway.

NAIRAS aircraft radiation model development, dose climatology, and initial validation

PubMed Central

Mertens, Christopher J; Meier, Matthias M; Brown, Steven; Norman, Ryan B; Xu, Xiaojing

2013-01-01

[1] The Nowcast of Atmospheric Ionizing Radiation for Aviation Safety (NAIRAS) is a real-time, global, physics-based model used to assess radiation exposure to commercial aircrews and passengers. The model is a free-running physics-based model in the sense that there are no adjustment factors applied to nudge the model into agreement with measurements. The model predicts dosimetric quantities in the atmosphere from both galactic cosmic rays (GCR) and solar energetic particles, including the response of the geomagnetic field to interplanetary dynamical processes and its subsequent influence on atmospheric dose. The focus of this paper is on atmospheric GCR exposure during geomagnetically quiet conditions, with three main objectives. First, provide detailed descriptions of the NAIRAS GCR transport and dosimetry methodologies. Second, present a climatology of effective dose and ambient dose equivalent rates at typical commercial airline altitudes representative of solar cycle maximum and solar cycle minimum conditions and spanning the full range of geomagnetic cutoff rigidities. Third, conduct an initial validation of the NAIRAS model by comparing predictions of ambient dose equivalent rates with tabulated reference measurement data and recent aircraft radiation measurements taken in 2008 during the minimum between solar cycle 23 and solar cycle 24. By applying the criterion of the International Commission on Radiation Units and Measurements (ICRU) on acceptable levels of aircraft radiation dose uncertainty for ambient dose equivalent greater than or equal to an annual dose of 1 mSv, the NAIRAS model is within 25% of the measured data, which fall within the ICRU acceptable uncertainty limit of 30%. The NAIRAS model predictions of ambient dose equivalent rate are generally within 50% of the measured data for any single-point comparison. The largest differences occur at low latitudes and high cutoffs, where the radiation dose level is low. Nevertheless, analysis suggests that these single-point differences will be within 30% when a new deterministic pion-initiated electromagnetic cascade code is integrated into NAIRAS, an effort which is currently underway. PMID:26213513

American Brachytherapy Society consensus report for accelerated partial breast irradiation using interstitial multicatheter brachytherapy.

PubMed

Hepel, Jaroslaw T; Arthur, Douglas; Shaitelman, Simona; Polgár, Csaba; Todor, Dorin; Zoberi, Imran; Kamrava, Mitchell; Major, Tibor; Yashar, Catheryn; Wazer, David E

To develop a consensus report for the quality practice of accelerated partial breast irradiation (APBI) using interstitial multicatheter brachytherapy (IMB). The American Brachytherapy Society Board appointed an expert panel with clinical and research experience with breast brachytherapy to provide guidance for the current practice of IMB. This report is based on a comprehensive literature review with emphasis on randomized data and expertise of the panel. Randomized trials have demonstrated equivalent efficacy of APBI using IMB compared with whole breast irradiation for select patients with early-stage breast cancer. Several techniques for placement of interstitial catheters are described, and importance of three-dimensional planning with appropriate optimization is reviewed. Optimal target definition is outlined. Commonly used dosing schemas include 50 Gy delivered in pulses of 0.6-0.8 Gy/h using pulsed-dose-rate technique and 34 Gy in 10 fractions, 32 Gy in eight fractions, or 30 Gy in seven fractions using high-dose-rate technique. Potential toxicities and strategies for toxicity avoidance are described in detail. Dosimetric constraints include limiting whole breast volume that receives ≥50% of prescription dose to <60%, skin dose to ≤100% of prescription dose (≤60-70% preferred), chest wall dose to ≤125% of prescription dose, Dose Homogeneity Index to >0.75 (>0.85 preferred), V 150  < 45 cc, and V 200  < 14 cc. Using an optimal implant technique coupled with optimal planning and appropriate dose constraints, a low rate of toxicity and a good-to-excellent cosmetic outcome of ≥90% is expected. IMB is an effective technique to deliver APBI for appropriately selected women with early-stage breast cancer. This consensus report has been created to assist clinicians in the appropriate practice of APBI using IMB. Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

A phase 2 trial of high dose lenalidomide in patients with relapsed/refractory higher-risk myelodysplastic syndromes and acute myeloid leukaemia with trilineage dysplasia.

PubMed

Zeidan, Amer M; Smith, B Douglas; Carraway, Hetty E; Gojo, Ivana; DeZern, Amy; Gore, Steven D

2017-01-01

Limited therapies exist for patients with refractory and relapsed (RR) higher-risk myelodysplastic syndromes (HR-MDS) and acute myeloid leukaemia with trilineage dysplasia (AML-TD). High dose (HD) lenalidomide (50 mg) has activity as frontline therapy in elderly AML but there is limited data in the RR setting. This phase II trial included patients with RR HR-MDS or AML-TD at 2 doses of lenalidomide (15 or 50 mg) on days 1-28 of 42-day cycles. The primary endpoint was response rate using the 2006 International Working Group criteria. Overall survival (OS) was estimated by Kaplan-Meier methods. Of 27 patients enrolled, 59% had HR-MDS and 31% AML-TD. No patient had isolated del5q; 41% had poor-risk karyotype. Of 9 patients treated at 15 mg, 56% completed ≥2 cycles with no responses. Of 18 patients treated at 50 mg, 39% completed ≥2 cycles and 11% responded but all experienced grade 3/4 neutropenic fever/infection. The 60-day mortality rate was 30%. Median OS was 114 days with 19% surviving ≥1 year. The study was terminated due to lack of robust clinical activity. In conclusion, lenalidomide at 15 mg is ineffective in RR myeloid malignancies. Continous high dosing schedules are poorly tolerated and minimally active. Further evaluation should be considered in upfront intensive chemotherapy-ineligible patients. © 2016 John Wiley & Sons Ltd.

Medium doses of daily vitamin D decrease falls and higher doses of daily vitamin D3 increase falls: A randomized clinical trial.

PubMed

Smith, Lynette M; Gallagher, J Christopher; Suiter, Corinna

2017-10-01

Falls are a serious health problem in the aging population. Because low levels of vitamin D have been associated with increased fall rates, many trials have been performed with vitamin D; two meta-analyses showed either a small effect or no effect of vitamin D on falls. We conducted a study of the effect of vitamin D on serum 25 hydroxyvitamin D (25OHD) and data on falls was collected as a secondary outcome. In a 12-month double blind randomized placebo trial, elderly women, mean age 66 years, were randomized to one of seven daily oral doses of vitamin D or placebo. The main inclusion criterion for study was a baseline serum 25OHD<20ng/ml (50nmol/L). A history of falls was collected at baseline and fall events were collected every 3 months. Results showed that the effect of vitamin D on falls followed a U-shaped curve whether analyzed by dose or serum 25OHD levels. There was no decrease in falls on low vitamin D doses 400, 800 IU, a significant decrease on medium doses 1600, 2400,3200 IU (p=0.020) and no decrease on high doses 4000, 4800 IU compared to placebo (p=0.55). When compared to 12-month serum 25OHD quintiles, the faller rate was 60% in the lowest quintile <25ng/ml (<50nmol/L), 21% in the low middle quintile 32-38ng/ml (80-95nmo/L), 72% in the high middle quintile 38-46ng/ml (95-115nmo/L) and 45% in the highest quintile 46-66ng/ml (115-165nmol/L). In the subgroup with a fall history, fall rates were 68% on low dose, 27% on medium doses and 100% on higher doses. Fall rates on high doses were increased compared to medium doses (Odds Ratio 5.6.95% CI: 2.1-14.8). In summary, the maximum decrease in falls corresponds to a 12- month serum 25OHD of 32-38ng/ml (80-95nmol/L) and faller rates increase as serum 25OHD exceed 40-45ng/ml (100-112.5nmol/L). The Tolerable upper limit (TUL) recently increased in 2010 from 2000 to 4000 IU/day may need to be reduced in elderly women especially in those with a fall history. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessment of radiological hazard parameters due to natural radioactivity in soils from granite-rich regions in Kütahya Province, Turkey.

PubMed

Sahin, Latife; Hafızoğlu, Nurgül; Çetinkaya, Hakan; Manisa, Kaan; Bozkurt, Engin; Biçer, Ahmet

2017-05-01

The analysis of natural radioactivity from 238 U, 232 Th and 40 K in 357 soil samples collected from the province of Kütahya was carried out using a NaI(Tl) gamma-ray spectroscopy system at the Nuclear Physics Research Laboratory, Dumlupınar University, Kütahya, Turkey. The specific activities of 238 U, 232 Th and 40 K in the soil samples were evaluated. From the activity concentrations of 238 U, 232 Th and 40 K, the total absorbed outdoor gamma-ray dose rates and the corresponding annual effective dose rates were determined. The corresponding values of the external and internal hazard indices of all the soil samples were also calculated. The external gamma-ray dose rate at 1 m above the ground was directly measured at each collected soil sample location. The results obtained in this study were compared within the limits of values obtained in other cities of Turkey, those in other countries. Radiological maps of Kütahya Province were constructed from the results of this study.

Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

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

McGarry, Ronald C.; Papiez, Lech; Williams, Mark

Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy),more » but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.« less

Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study.

PubMed

Swords, Ronan T; Erba, Harry P; DeAngelo, Daniel J; Bixby, Dale L; Altman, Jessica K; Maris, Michael; Hua, Zhaowei; Blakemore, Stephen J; Faessel, Hélène; Sedarati, Farhad; Dezube, Bruce J; Giles, Francis J; Medeiros, Bruno C

2015-05-01

This trial was conducted to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the first in class NEDD8-activating enzyme (NAE) inhibitor, pevonedistat, and to investigate pevonedistat pharmacokinetics and pharmacodynamics in patients with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Pevonedistat was administered via a 60-min intravenous infusion on days 1, 3 and 5 (schedule A, n = 27), or days 1, 4, 8 and 11 (schedule B, n = 26) every 21-days. Dose escalation proceeded using a standard '3 + 3' design. Responses were assessed according to published guidelines. The MTD for schedules A and B were 59 and 83 mg/m(2) , respectively. On schedule A, hepatotoxicity was dose limiting. Multi-organ failure (MOF) was dose limiting on schedule B. The overall complete (CR) and partial (PR) response rate in patients treated at or below the MTD was 17% (4/23, 2 CRs, 2 PRs) for schedule A and 10% (2/19, 2 PRs) for schedule B. Pevonedistat plasma concentrations peaked after infusion followed by elimination in a biphasic pattern. Pharmacodynamic studies of biological correlates of NAE inhibition demonstrated target-specific activity of pevonedistat. In conclusion, administration of the first-in-class agent, pevonedistat, was feasible in patients with MDS and AML and modest clinical activity was observed. © 2015 John Wiley & Sons Ltd.

Measurement of 238U and 232Th radionuclides in ilmenite and synthetic rutile

NASA Astrophysics Data System (ADS)

Idris, M. I.; Siong, K. K.; Fadzil, S. M.

2018-01-01

The only factory that currently processes ilmenite to produce synthetic rutile is Tor Minerals in Ipoh, Perak, Malaysia. These two minerals contain radioactive elements such as uranium and thorium. Furthermore, this factory was built close to the residential areas. Thus, the primary issues are radiation exposure attributed to the decay of the radionuclides. Hence, the objectives of this study are to measure the dose and to evaluate activity levels of uranium and thorium. Dose rates from surrounding area of factory indicate the normal range for both on the surface and 1 meter above the ground (0.3-0.7 μSv/hr) lower than the global range of 0.5-1.3 μSv/hr set by UNSCEAR. The mean activity levels of uranium and thorium for ilmenite are 235 Bq/kg and 503 Bq/kg while for synthetic rutile are 980 Bq/kg and 401 Bq/kg, respectively. The result shows that uranium activity levels of synthetic rutile is 4 times higher than ilmenite but it is still lower than the regulatory exemption limit of 1000 Bq/kg set by IAEA Basic Safety Standards. Even though the dose rates at the factory and the activity levels are within safe limits, safety precautions must be followed by the factory management to prevent any unwanted accident to occur.

epsilon-N-trimethyllysine availability regulates the rate of carnitine biosynthesis in the growing rat

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

Rebouche, C.J.; Lehman, L.J.; Olson, L.

1986-05-01

Rates of carnitine biosynthesis in mammals depend on the availability of substrates and the activity of enzymes subserving the pathway. This study was undertaken to test the hypothesis that the availability of epsilon-N-trimethyllysine is rate-limiting for synthesis of carnitine in the growing rat and to evaluate diet as a source of this precursor for carnitine biosynthesis. Rats apparently absorbed greater than 90% of a tracer dose of (methyl-/sup 3/H)epsilon-N-trimethyllysine, and approximately 30% of that was incorporated into tissues as (/sup 3/H)carnitine. Rats given oral supplements of epsilon-N-trimethyllysine (0.5-20 mg/d), but no dietary carnitine, excreted more carnitine than control animals receivingmore » no dietary epsilon-N-trimethyllysine or carnitine. Rates of carnitine excretion increased in a dose-dependent manner. Tissue and serum levels of carnitine also increased with dietary epsilon-N-trimethyllysine supplementation. There was no evidence that the capacity for carnitine biosynthesis was saturated even at the highest level of oral epsilon-N-trimethyllysine supplementation. Common dietary proteins (casein, soy protein and wheat gluten) were found to be poor sources of epsilon-N-trimethyllysine for carnitine biosynthesis. The results of this study indicate that the availability of epsilon-N-trimethyllysine limits the rate of carnitine biosynthesis in the growing rat.« less

Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

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

Shinoto, Makoto, E-mail: shinoto@saga-himat.jp; Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu; Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka

Purpose: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. Methods and Materials: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m{sup 2} under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions undermore » the fixed recommended gemcitabine dose determined. Results: Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m{sup 2}. The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m{sup 2}) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. Conclusions: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.« less

TEM characterization of irradiated microstructure of Fe-9%Cr ODS and ferritic-martensitic alloys

NASA Astrophysics Data System (ADS)

Swenson, M. J.; Wharry, J. P.

2018-04-01

The objective of this study is to evaluate the effects of irradiation dose and dose rate on defect cluster (i.e. dislocation loops and voids) evolution in a model Fe-9%Cr oxide dispersion strengthened steel and commercial ferritic-martensitic steels HCM12A and HT9. Complimentary irradiations using Fe2+ ions, protons, or neutrons to doses ranging from 1 to 100 displacements per atom (dpa) at 500 °C are conducted on each alloy. The irradiated microstructures are characterized using transmission electron microscopy (TEM). Dislocation loops exhibit limited growth after 1 dpa upon Fe2+ and proton irradiation, while any voids observed are small and sparse. The average size and number density of loops are statistically invariant between Fe2+, proton, and neutron irradiated specimens at otherwise fixed irradiation conditions of ∼3 dpa, 500 °C. Therefore, we conclude that higher dose rate charged particle irradiations can reproduce the neutron irradiated loop microstructure with temperature shift governed by the invariance theory; this temperature shift is ∼0 °C for the high sink strength alloys studied herein.

Stereotactic Body Radiotherapy in the Management of Oligometastatic Disease.

PubMed

Ahmed, Kamran A; Torres-Roca, Javier F

2016-01-01

The treatment of oligometastatic disease has become common as imaging techniques have advanced and the management of systemic disease has improved. Use of highly targeted, hypofractionated regimens of stereotactic body radiotherapy (SBRT) is now a primary management option for patients with oligometastatic disease. The properties of SBRT are summarized and the results of retrospective and prospective studies of SBRT use in the management of oligometastases are reviewed. Future directions of SBRT, including optimizing dose and fractionation schedules, are also discussed. SBRT can deliver highly conformal, dosed radiation treatments for ablative tumors in a few treatment sessions. Phase 1/2 trials and retrospective institutional results support use of SBRT as a treatment option for oligometastatic disease metastasized to the lung, liver, and spine, and SBRT offers adequate toxicity profiles with good rates of local control. Future directions will involve optimizing dose and fractionation schedules for select histologies to improve rates of local control while limiting toxicity to normal structures. SBRT offers an excellent management option for patients with oligometastases. However, additional research is still needed to optimize dose and fractionation schedules.

Dose-rate effects on the radiation-induced oxidation of electric cable used in nuclear power plants

NASA Astrophysics Data System (ADS)

Reynolds, A. B.; Bell, R. M.; Bryson, N. M. N.; Doyle, T. E.; Hall, M. B.; Mason, L. R.; Quintric, L.; Terwilliger, P. L.

1995-01-01

Dose-rate effects were measured for typical ethylene propylene rubber (EPR) and crosslinked polyethylene (XLPE) electric cable used in nuclear power plants. The radiation source was the 60Co Irradiation Facility at the University of Virginia. Dose rates were varied from 5 Gy/h to 2500 Gy/h. It was found that there is little or no dose-rate effect at low doses for four of the five EPR cable products tested from 2500 Gy/h down to dose rates of 5 Gy/h but perhaps a small dose-rate effect at high doses for dose rates above 340 Gy/h. A small dose-rate exists for the fifth EPR above 340 Gy/h at all doses. A dose-rate effect exists above 40 Gy/h for two of the three XLPE cable products tested, but there is no dose-rate for these XLPE's between 40 Gy/h and 5 Gy/h. These results indicate that the dose-rate effects observed are due to oxygen diffusion effects during heterogeneous aging and suggest that there is no dose-rate effect for either EPR or XLPE during homogeneous aging.

Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer

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

Kelsey, Chris R., E-mail: christopher.kelsey@duke.edu; Das, Shiva; Gu, Lin

2015-12-01

Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standardmore » 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.« less

Typical doses and dose rates in studies pertinent to radiation risk inference at low doses and low dose rates

PubMed Central

Rühm, Werner; Azizova, Tamara; Bouffler, Simon; Cullings, Harry M; Grosche, Bernd; Little, Mark P; Shore, Roy S; Walsh, Linda; Woloschak, Gayle E

2018-01-01

Abstract In order to quantify radiation risks at exposure scenarios relevant for radiation protection, often extrapolation of data obtained at high doses and high dose rates down to low doses and low dose rates is needed. Task Group TG91 on ‘Radiation Risk Inference at Low-dose and Low-dose Rate Exposure for Radiological Protection Purposes’ of the International Commission on Radiological Protection is currently reviewing the relevant cellular, animal and human studies that could be used for that purpose. This paper provides an overview of dose rates and doses typically used or present in those studies, and compares them with doses and dose rates typical of those received by the A-bomb survivors in Japan. PMID:29432579

Radiation safety standards: space hazards vs. terrestrial hazards.

PubMed

Sinclair, W K

1983-01-01

The standards currently recommended for use in space travel were perhaps the first risk derived recommendations for dose limitations developed for quasi-occupational circumstances. They were based on data, considerations, and philosophy existing prior to 1970 and considered carcinogenesis primarily. In the intervening twelve years, not only has radiation risk information improved markedly but considerations relating to risk in general have become better known. The earlier recommendations have been examined with respect to changes in risk estimation and it is noted that the same philosophy used today, would probably lead to different dose limitations. However, other philosophies might be used; in particular a comparison of risks between terrestrial occupational radiation circumstances and also with fatal accident rates in a range of industries can be made and might be used in a modified philosophy with respect to risks from carcinogenesis. Developments have also taken place with respect to the knowledge of the biological effects of HZE particles but whether these effects are limiting as compared with radiation induced carcinogenesis is not yet clear. More studies on the effects of HZE particles, now becoming available, are needed. It is recommended that an in depth reexamination be undertaken of the biological effectiveness of space radiations and the philosophy of dose limitations in comparison with other risks.

Strategies to eradicate minimal residual disease in small cell lung cancer: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

PubMed

Krug, L M; Grant, S C; Miller, V A; Ng, K K; Kris, M G

1999-10-01

In the last 25 years, treatment for small cell lung cancer (SCLC) has improved with advances in chemotherapy and radiotherapy. Standard chemotherapy regimens can yield 80% to 90% response rates and some cures when combined with thoracic irradiation in limited-stage patients. Nonetheless, small cell lung cancer has a high relapse rate due to drug resistance; this has resulted in poor survival for most patients. Attacking this problem requires a unique approach to eliminate resistant disease remaining after induction therapy. This review will focus on three potential strategies: high-dose chemotherapy with autologous bone marrow transplantation, matrix metalloproteinase inhibitors, and BEC2 plus BCG vaccination.

High-dose-rate intraoperative radiation therapy: the nuts and bolts of starting a program

PubMed Central

Moningi, Shalini; Armour, Elwood P.; Terezakis, Stephanie A.; Efron, Jonathan E.; Gearhart, Susan L.; Bivalacqua, Trinity J.; Kumar, Rachit; Le, Yi; Kien Ng, Sook; Wolfgang, Christopher L.; Zellars, Richard C.; Ellsworth, Susannah G.; Ahuja, Nita

2014-01-01

High-dose-rate intraoperative radiation therapy (HDR-IORT) has historically provided effective local control (LC) for patients with unresectable and recurrent tumors. However, IORT is limited to only a few specialized institutions and it can be difficult to initiate an HDR-IORT program. Herein, we provide a brief overview on how to initiate and implement an HDR-IORT program for a selected group of patients with gastrointestinal and pelvic solid tumors using a multidisciplinary approach. Proper administration of HDR-IORT requires institutional support and a joint effort among physics staff, oncologists, surgeons, anesthesiologists, and nurses. In order to determine the true efficacy of IORT for various malignancies, collaboration among institutions with established IORT programs is needed. PMID:24790628

Cytogenetic damage analysis in mice chronically exposed to low-dose internal tritium beta-particle radiation.

PubMed

Roch-Lefèvre, Sandrine; Grégoire, Eric; Martin-Bodiot, Cécile; Flegal, Matthew; Fréneau, Amélie; Blimkie, Melinda; Bannister, Laura; Wyatt, Heather; Barquinero, Joan-Francesc; Roy, Laurence; Benadjaoud, Mohamed; Priest, Nick; Jourdain, Jean-René; Klokov, Dmitry

2018-06-08

The aim of this study was to carry out a comprehensive examination of potential genotoxic effects of low doses of tritium delivered chronically to mice and to compare these effects to the ones resulting from equivalent doses of gamma-irradiation. Mice were chronically exposed for one or eight months to either tritiated water (HTO) or organically bound tritium (OBT) in drinking water at concentrations of 10 kBq/L, 1 MBq/L or 20 MBq/L. Dose rates of internal β-particle resulting from such tritium treatments were calculated and matching external gamma-exposures were carried out. We measured cytogenetic damage in bone marrow and in peripheral blood lymphocytes (PBLs) and the cumulative tritium doses (0.009 - 181 mGy) were used to evaluate the dose-response of OBT in PBLs, as well as its relative biological effectiveness (RBE). Neither tritium, nor gamma exposures produced genotoxic effects in bone marrow. However, significant increases in chromosome damage rates in PBLs were found as a result of chronic OBT exposures at 1 and 20 M Bq/L, but not at 10 kBq/L. When compared to an external acute gamma-exposure ex vivo , the RBE of OBT for chromosome aberrations induction was evaluated to be significantly higher than 1 at cumulative tritium doses below 10 mGy. Although found non-existent at 10 kBq/L (the WHO limit), the genotoxic potential of low doses of tritium (>10 kBq/L), mainly OBT, may be higher than currently assumed.

Low-dose intradermal and intramuscular vaccination against hepatitis B.

PubMed

Bryan, J P; Sjogren, M H; Perine, P L; Legters, L J

1992-03-01

Hepatitis B and its sequelae are global problems preventable by immunization. Expense limits the use of hepatitis B vaccines, but low-dose intradermal immunization has been evaluated as a cost-saving strategy in numerous studies. With few exceptions, low-dose intradermal plasma-derived vaccines have elicited protective levels of antibody in 82%-100% of young healthy adults--a proportion similar to that noted with full-dose regimens; peak levels of antibody to hepatitis B surface antigen (HBsAg) are lower with reduced doses, however. Although children respond well to low-dose intradermal immunization, this procedure is technically difficult in neonates and should not be used for those born to HBsAg-positive mothers. For persons at high risk, antibody to HBsAg must be assessed after immunization to determine the need for a booster dose. A fourth dose 1-2 years after the initial series substantially increases antibody concentrations. In low intradermal doses, recombinant vaccine elicits lower rates of seroconversion than plasma-derived vaccine. However, low intramuscular doses of recombinant vaccine give favorable results. In short, low-dose intradermal or intramuscular immunization offers protection against hepatitis B at significant savings and may be useful for mass immunization of populations at high risk.

Modeling to optimize operational practices to limit shallow dose and dose to the lens at the Weldon Spring Site Remedial Action Project.

PubMed

Hillman, D J; Green, S W

1994-10-01

The Weldon Spring Site Remedial Action Project (WSSRAP) began remediation of its chemical plant buildings in June 1992. The chemical plant was used by the Atomic Energy Commission in the 1950's and 1960's to process uranium ore and natural thorium. Many remaining equipment surfaces were highly contaminated with uranium and thorium product residues, which are relatively weak gamma emitters, but are strong beta emitters that deposit the majority of their energy within the first centimeter of tissue. An essential part of the remediation, therefore, is to control the dose to the skin, extremities, and the lens of the eye from the broad range of betas emitted by uranium and thorium decay series radionuclides. The WSSRAP planned to quantitatively record the dose to the skin, extremities, and the lens of the eye, when warranted, through selection and use of appropriate passive dosimeters. That would not, however, constitute control. A direct-reading instrument was needed that could be used by field technicians to anticipate and prevent work methods and situations that would otherwise result in the unnecessary commitment of dose. However, the interpretation of real-time instrument readings produced by a broad spectrum of beta energies is typically challenging at best, particularly when the shallow dose rate and the lens dose rate are both of interest. The purpose of this effort was, therefore, to (1) select a direct-reading instrument for use in the buildings that could be used to provide rule-of-thumb action levels for field technicians, which, if exceeded, would warrant worker protective measures; (2) determine the approximate conversions between the instrument readings and the shallow (including extremity) dose rate and lens of the eye dose rate; and (3) specify protective measures and dosimetry for the lens of the eye, if warranted. Methods described in the literature are used to estimate action levels for direct instrument readings and to demonstrate that lens dosimetry and special protective measures for the lens of the eye are not necessary at the WSSRAP.

Impact of whole brain radiation therapy on CSF penetration ability of Icotinib in EGFR-mutated non-small cell lung cancer patients with brain metastases: Results of phase I dose-escalation study.

PubMed

Zhou, Lin; He, Jiazhuo; Xiong, Weijie; Liu, Yongmei; Xiang, Jing; Yu, Qin; Liang, Maozhi; Zhou, Xiaojuan; Ding, Zhenyu; Huang, Meijuan; Ren, Li; Zhu, Jiang; Li, Lu; Hou, Mei; Ding, Lieming; Tan, Fenlai; Lu, You

2016-06-01

Whole-brain radiation therapy (WBRT) and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are both treatment options for EGFR-mutated non-small cell lung cancer (NSCLC) patients with brain metastases. However, the dose-escalation toxicity and efficacy of combination therapy, and the effect of WBRT on cerebrospinal fluid (CSF) penetration of EGFR-TKIs are still unclear. EGFR-mutated NSCLC patients with brain metastases were enrolled in this study, and the cohorts were constructed with a 3+3 design. The patients received icotinib with escalating doses (125-625mg, tid), and the concurrent WBRT (37.5Gy/15f/3weeks) started a week later. The CSF penetration rates of icotinib were tested before, immediately after, and 4 weeks after WBRT, respectively. Potential toxicities and benefits from dose-escalation treatment were analyzed. Fifteen patients were included in this study, 3 at each dose level from 125mg-375mg and 6 at 500mg with 3 occurred dose-limiting toxicities. The maximal tolerated dose of icotinib was 375mg tid in this combination therapy. There was a significant correlation between icotinib concentration in the CSF and plasma (R(2)=0.599, P<0.001). The CSF penetration rate of icotinib, from 1.2% to 9.7%, reached a maximum at 375mg (median, 6.1%). There was no significant difference for CSF penetration rates among the three test points (median, 4.1% vs. 2.8% vs. 2.8%, P=0.16). The intracranial objective response rate and median intracranial progression free survival are 80% and 18.9 months. WBRT plus concurrent icotinib is well tolerated in EGFR-mutated NSCLC patients with brain metastases, up to an icotinib dose of 375mg tid. The icotinib CSF concentration seemed to have a potential ceiling effect with the dose escalation, and WBRT seemed to have no significant impact on CSF penetration of icotinib till 4 weeks after the treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Contribution of liver alcohol dehydrogenase to metabolism of alcohols in rats.

PubMed

Plapp, Bryce V; Leidal, Kevin G; Murch, Bruce P; Green, David W

2015-06-05

The kinetics of oxidation of various alcohols by purified rat liver alcohol dehydrogenase (ADH) were compared with the kinetics of elimination of the alcohols in rats in order to investigate the roles of ADH and other factors that contribute to the rates of metabolism of alcohols. Primary alcohols (ethanol, 1-propanol, 1-butanol, 2-methyl-1-propanol, 3-methyl-1-butanol) and diols (1,3-propanediol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol) were eliminated in rats with zero-order kinetics at doses of 5-20 mmol/kg. Ethanol was eliminated most rapidly, at 7.9 mmol/kgh. Secondary alcohols (2-propanol-d7, 2-propanol, 2-butanol, 3-pentanol, cyclopentanol, cyclohexanol) were eliminated with first order kinetics at doses of 5-10 mmol/kg, and the corresponding ketones were formed and slowly eliminated with zero or first order kinetics. The rates of elimination of various alcohols were inhibited on average 73% (55% for 2-propanol to 90% for ethanol) by 1 mmol/kg of 4-methylpyrazole, a good inhibitor of ADH, indicating a major role for ADH in the metabolism of the alcohols. The Michaelis kinetic constants from in vitro studies (pH 7.3, 37 °C) with isolated rat liver enzyme were used to calculate the expected relative rates of metabolism in rats. The rates of elimination generally increased with increased activity of ADH, but a maximum rate of 6±1 mmol/kg h was observed for the best substrates, suggesting that ADH activity is not solely rate-limiting. Because secondary alcohols only require one NAD(+) for the conversion to ketones whereas primary alcohols require two equivalents of NAD(+) for oxidation to the carboxylic acids, it appears that the rate of oxidation of NADH to NAD(+) is not a major limiting factor for metabolism of these alcohols, but the rate-limiting factors are yet to be identified. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Contribution of Liver Alcohol Dehydrogenase to Metabolism of Alcohols in Rats

PubMed Central

Plapp, Bryce V.; Leidal, Kevin G.; Murch, Bruce P.; Green, David W.

2015-01-01

The kinetics of oxidation of various alcohols by purified rat liver alcohol dehydrogenase (ADH) were compared with the kinetics of elimination of the alcohols in rats in order to investigate the roles of ADH and other factors that contribute to the rates of metabolism of alcohols. Primary alcohols (ethanol, 1-propanol, 1-butanol, 2-methyl-1-propanol, 3-methyl-1-butanol) and diols (1,3-propanediol, 1,3-butanediol, 1,4-butanediol, 1,5-pentanediol) were eliminated in rats with zero-order kinetics at doses of 5–20 mmole/kg. Ethanol was eliminated most rapidly, at 7.9 mmole/kg•h. Secondary alcohols (2-propanol-d7, 2-propanol, 2-butanol, 3-pentanol, cyclopentanol, cyclohexanol) were eliminated with first order kinetics at doses of 5–10 mmole/kg, and the corresponding ketones were formed and slowly eliminated with zero or first order kinetics. The rates of elimination of various alcohols were inhibited on average 73% (55% for 2-propanol to 90% for ethanol) by 1 mmole/kg of 4-methylpyrazole, a good inhibitor of ADH, indicating a major role for ADH in the metabolism of the alcohols. The Michaelis kinetic constants from in vitro studies (pH 7.3, 37 °C) with isolated rat liver enzyme were used to calculate the expected relative rates of metabolism in rats. The rates of elimination generally increased with increased activity of ADH, but a maximum rate of 6 ± 1 mmole/kg•h was observed for the best substrates, suggesting that ADH activity is not solely rate-limiting. Because secondary alcohols only require one NAD+ for the conversion to ketones whereas primary alcohols require two equivalents of NAD+ for oxidation to the carboxylic acids, it appears that the rate of oxidation of NADH to NAD+ is not a major limiting factor for metabolism of these alcohols, but the rate-limiting factors are yet to be identified. PMID:25641189

Effect of increasing radiation dose on pathologic complete response in rectal cancer patients treated with neoadjuvant chemoradiation therapy.

PubMed

Hall, Matthew D; Schultheiss, Timothy E; Smith, David D; Fakih, Marwan G; Wong, Jeffrey Y C; Chen, Yi-Jen

2016-12-01

Neoadjuvant chemoradiation therapy (CRT) increases pathological complete response (pCR) rates compared to radiotherapy alone in patients with stage II-III rectal cancer. Limited evidence addresses whether radiotherapy dose escalation further improves pCR rates. Our purpose is to measure the effects of radiotherapy dose and other factors on post-therapy pathologic tumor (ypT) and nodal stage in rectal cancer patients treated with neoadjuvant CRT followed by mesorectal excision. A non-randomized comparative effectiveness analysis was performed of rectal cancer patients treated in 2000-2013 from the National Oncology Data Alliance™ (NODA), a pooled database of cancer registries from >150 US hospitals. The NODA contains the same data submitted to state cancer registries and SEER combined with validated radiotherapy and chemotherapy records. Eligible patients were treated with neoadjuvant CRT followed by proctectomy and had complete data on treatment start dates, radiotherapy dose, clinical tumor (cT) and ypT stage, and number of positive nodes at surgery (n = 3298 patients). Multivariable logistic regression was used to assess the predictive value of independent variables on achieving a pCR. On multivariable regression, radiotherapy dose, cT stage, and time interval between CRT and surgery were significant predictors of achieving a pCR. After adjusting for the effect of other variates, patients treated with higher radiotherapy doses were also more likely to have negative nodes at surgery and be downstaged from cT3-T4 and/or node positive disease to ypT0-T2N0 after neoadjuvant CRT. Our study suggests that increasing dose significantly improved pCR rates and downstaging in rectal cancer patients treated with neoadjuvant CRT followed by surgery.

Dose rate mapping of VMAT treatments

NASA Astrophysics Data System (ADS)

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

2016-06-01

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

Background radiation: natural and man-made.

PubMed

Thorne, M C

2003-03-01

A brief overview and comparison is given of dose rates arising from natural background radiation and the fallout from atmospheric testing of nuclear weapons. Although there are considerable spatial variations in exposure to natural background radiation, it is useful to give estimates of worldwide average overall exposures from the various components of that background. Cosmic-ray secondaries of low linear energy transfer (LET), mainly muons and photons, deliver about 280 microSv a(-1). Cosmic-ray neutrons deliver about another 100 microSv a(-1). These low- and high-LET exposures are relatively uniform to the whole body. The effective dose rate from cosmogenic radionuclides is dominated by the contribution of 12 microSv a(-1) from 14C. This is due to relatively uniform irradiation of all organs and tissues from low-energy beta particles. Primordial radionuclides and their progeny (principally the 238U and 232Th series, and 40K) contribute about 480 microSv a(-1) of effective dose by external irradiation. This is relatively uniform photon irradiation of the whole body. Internally incorporated 40K contributes a further 165 microSv a(-1) of effective dose in adults, mainly from beta particles, but with a significant gamma component. Equivalent doses from 40K are somewhat higher in muscle than other soft tissues, but the distinction is less than a factor of three. Uranium and thorium series radionuclides give rise to an average effective dose rate of around 120 microSv a(-1). This includes a major alpha particle component, and exposures of radiosensitive tissues in lung, liver, kidney and the skeleton are recognised as important contributors to effective dose. Overall, these various sources give a worldwide average effective dose rate of about 1160 microSv a(-1). Exposure to 222Rn, 220Rn and their short-lived progeny has to be considered separately. This is very variable both within and between countries. For 222Rn and its progeny, a worldwide average effective dose rate is about 1105 microSv a(-1). For 220Rn and its progeny, the corresponding value is 91 microSv a(-1). In both cases, the effective dose is mainly due to a particle irradiation of the bronchial tissues of the lungs. Overall, the worldwide average effective dose rate from natural background is about 2400 microSv a(-1) or 2.4 mSv a(-1). For comparison, worldwide average effective dose rates from weapons fallout peaked at 113 microSv a(-1) (about 5% of natural background) in 1963 and have since fallen to about 5.5 microSv a(-1) (about 0.2% of natural background). These values perhaps serve to emphasise that even gross insults to the natural environment from anthropogenic releases of radioactive materials are likely to be of limited significance when set in the context of the ambient radioactive environment within which all organisms, including humans, have developed.

Probability Distribution of Dose and Dose-Rate Effectiveness Factor for use in Estimating Risks of Solid Cancers From Exposure to Low-Let Radiation.

PubMed

Kocher, David C; Apostoaei, A Iulian; Hoffman, F Owen; Trabalka, John R

2018-06-01

This paper presents an analysis to develop a subjective state-of-knowledge probability distribution of a dose and dose-rate effectiveness factor for use in estimating risks of solid cancers from exposure to low linear energy transfer radiation (photons or electrons) whenever linear dose responses from acute and chronic exposure are assumed. A dose and dose-rate effectiveness factor represents an assumption that the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation, RL, differs from the risk per Gy at higher acute doses, RH; RL is estimated as RH divided by a dose and dose-rate effectiveness factor, where RH is estimated from analyses of dose responses in Japanese atomic-bomb survivors. A probability distribution to represent uncertainty in a dose and dose-rate effectiveness factor for solid cancers was developed from analyses of epidemiologic data on risks of incidence or mortality from all solid cancers as a group or all cancers excluding leukemias, including (1) analyses of possible nonlinearities in dose responses in atomic-bomb survivors, which give estimates of a low-dose effectiveness factor, and (2) comparisons of risks in radiation workers or members of the public from chronic exposure to low linear energy transfer radiation at low dose rates with risks in atomic-bomb survivors, which give estimates of a dose-rate effectiveness factor. Probability distributions of uncertain low-dose effectiveness factors and dose-rate effectiveness factors for solid cancer incidence and mortality were combined using assumptions about the relative weight that should be assigned to each estimate to represent its relevance to estimation of a dose and dose-rate effectiveness factor. The probability distribution of a dose and dose-rate effectiveness factor for solid cancers developed in this study has a median (50th percentile) and 90% subjective confidence interval of 1.3 (0.47, 3.6). The harmonic mean is 1.1, which implies that the arithmetic mean of an uncertain estimate of the risk of a solid cancer per Gy at low acute doses or low dose rates of low linear energy transfer radiation is only about 10% less than the mean risk per Gy at higher acute doses. Data were also evaluated to define a low acute dose or low dose rate of low linear energy transfer radiation, i.e., a dose or dose rate below which a dose and dose-rate effectiveness factor should be applied in estimating risks of solid cancers.

A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced solid tumors.

PubMed

Papadopoulos, Kyriakos P; Burris, Howard A; Gordon, Michael; Lee, Peter; Sausville, Edward A; Rosen, Peter J; Patnaik, Amita; Cutler, Richard E; Wang, Zhengping; Lee, Susan; Jones, Suzanne F; Infante, Jeffery R

2013-10-01

Tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of carfilzomib, a selective proteasome inhibitor, administered twice weekly by 2-10-min intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 in 28-day cycles, were assessed in patients with advanced solid tumors in this phase I/II study. Adult patients with solid tumors progressing after ≥1 prior therapies were enrolled. The dose was 20 mg/m(2) in week 1 of cycle 1 and 20, 27, or 36 mg/m(2) thereafter. The maximum tolerated dose or protocol-defined maximum planned dose (MPD) identified during dose escalation was administered to an expansion cohort and to patients with small cell lung, non-small cell lung, ovarian, and renal cancer in phase II tumor-specific cohorts. Fourteen patients received carfilzomib during dose escalation. The single dose-limiting toxicity at 20/36 mg/m(2) was grade 3 fatigue, establishing the MPD as the expansion and phase II dose. Sixty-five additional patients received carfilzomib at the MPD. Adverse events included fatigue, nausea, anorexia, and dyspnea. Carfilzomib PK was dose proportional with a half-life <1 h. All doses resulted in at least 80 % proteasome inhibition in blood. Partial responses occurred in two patients in phase I, with 21.5 % stable disease after four cycles in evaluable patients in the expansion and phase II cohorts. Carfilzomib 20/36 mg/m(2) was well tolerated when administered twice weekly by 2-10-min IV infusion. At this dose and infusion rate, carfilzomib inhibited the proteasome in blood but demonstrated limited antitumor activity in patients with advanced solid tumors.

The impact of the oxygen scavenger on the dose-rate dependence and dose sensitivity of MAGIC type polymer gels

NASA Astrophysics Data System (ADS)

Khan, Muzafar; Heilemann, Gerd; Kuess, Peter; Georg, Dietmar; Berg, Andreas

2018-03-01

Recent developments in radiation therapy aimed at more precise dose delivery along with higher dose gradients (dose painting) and more efficient dose delivery with higher dose rates e.g. flattening filter free (FFF) irradiation. Magnetic-resonance-imaging based polymer gel dosimetry offers 3D information for precise dose delivery techniques. Many of the proposed polymer gels have been reported to exhibit a dose response, measured as relaxation rate ΔR2(D), which is dose rate dependent. A lack of or a reduced dose-rate sensitivity is very important for dosimetric accuracy, especially with regard to the increasing clinical use of FFF irradiation protocols with LINACs at high dose rates. Some commonly used polymer gels are based on Methacrylic-Acid-Gel-Initiated-by-Copper (MAGIC). Here, we report on the dose sensitivity (ΔR2/ΔD) of MAGIC-type gels with different oxygen scavenger concentration for their specific dependence on the applied dose rate in order to improve the dosimetric performance, especially for high dose rates. A preclinical x-ray machine (‘Yxlon’, E  =  200 kV) was used for irradiation to cover a range of dose rates from low \\dot{D} min  =  0.6 Gy min-1 to high \\dot{D} max  =  18 Gy min-1. The dose response was evaluated using R2-imaging of the gel on a human high-field (7T) MR-scanner. The results indicate that all of the investigated dose rates had an impact on the dose response in polymer gel dosimeters, being strongest in the high dose region and less effective for low dose levels. The absolute dose rate dependence \\frac{(Δ R2/Δ D)}{Δ \\dot{D}} of the dose response in MAGIC-type gel is significantly reduced using higher concentrations of oxygen scavenger at the expense of reduced dose sensitivity. For quantitative dose evaluations the relative dose rate dependence of a polymer gel, normalized to its sensitivity is important. Based on this normalized sensitivity the dose rate sensitivity was reduced distinctly using an increased oxygen scavenger concentration with reference to standard MAGIC-type gel formulation at high dose rate levels. The proposed gel composition with high oxygen scavenger concentration exhibits a larger linear active dose response and might be used especially in FFF-radiation applications and preclinical dosimetry at high dose rates. We propose in general to use high dose rates for calibration and evaluation as the change in relative dose sensitivity is reduced at higher dose rates in all of the investigated gel types.

Radiotherapy in the treatment of solitary plasmacytoma.

PubMed

Jyothirmayi, R; Gangadharan, V P; Nair, M K; Rajan, B

1997-05-01

Solitary plasmacytoma of bone (SPB) and extramedullary plasmacytoma (EMP) are rare. High local control rates are reported with radiotherapy, although the optimal dose and extent of radiotherapy portals remains controversial. Between 1983 and 1993, 30 patients with solitary plasmacytoma were seen at the Regional Cancer Centre, Trivandrum, India. 23 patients had SPB and seven EMP. The mean age was 52 years and the male to female ratio 3.2:1. Diagnosis of SPB was confirmed by biopsy in 16 patients and tumour excision in seven. 20 patients received megavoltage radiotherapy to the bone lesion with limited margins, and one received chemotherapy. Two patients who underwent complete tumour excision received no further treatment. All seven patients with EMP received megavoltage radiotherapy, four following biopsy and three after tumour excision. Local control was achieved in all patients with SPB. Nine progressed to multiple myeloma and one developed a solitary plasmacytoma in another bone. Six patients with EMP achieved local control. Three later progressed to multiple myeloma and one had local relapse. Median time to relapse was 28 months in SPB and 30 months in EMP. 5-year overall survival rates were 82% and 57% for patients with SPB and EMP, respectively. The corresponding progression free survival rates were 55% and 50%, respectively. Age, sex, site of tumour, serum M protein and haemoglobin levels did not significantly influence progression free survival. The extent of surgery, radiotherapy dose or time to relapse were not significant prognostic factors. Radiotherapy appears to be an effective modality of treatment of solitary plasmacytoma. No dose-response relationship is observed, and high local control rates are achieved with limited portals. Progression to multiple myeloma is the commonest pattern of failure, although no prognostic factors for progression are identified. The role of chemotherapy in preventing disease progression needs further evaluation.

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External Exposure § 835.207 Occupational dose limits for minors. The dose limits for minors occupationally exposed...

Evaluation of a 15-week CHOP protocol for the treatment of canine multicentric lymphoma.

PubMed

Burton, J H; Garrett-Mayer, E; Thamm, D H

2013-12-01

Dose intense CHOP protocols have been shown to improve outcome for people with non-Hodgkin's lymphoma, but evaluation of dose intense CHOP protocols for canine lymphoma is currently limited. The hypothesis of this retrospective study was that a 15-week dose intense CHOP protocol would have shorter treatment duration with similar efficacy to other doxorubicin-based multidrug protocols. Thirty-one client owned dogs with multicentric lymphoma were treated with a 15-week CHOP chemotherapy protocol with an overall response rate of 100% and a median progression-free interval (PFI) of 140 days [95% confidence interval (CI) 91-335 days]. Dogs that had two or more treatment delays had significantly prolonged PFI and overall survival in multivariate analysis. Dose intensity did not correlate with patient outcome. Dogs experiencing multiple treatment delays secondary to adverse events may receive their individual maximally tolerated dose while dogs with no adverse events may be underdosed. Future studies should focus on individual patient dose optimization. © 2012 Blackwell Publishing Ltd.

[Thyroid status peculiarities of elderly patients 5 years after operation depending on the volume of surgical intervention].

PubMed

Aristarhov, V G; Danilov, N V; Aristarkhov, R V; Puzin, D A; Birykov, C V

2016-01-01

Long-term results of treatment of 180 patients operated 5 years ago for benign thyroid nodular pathology have been analyzed in the present paper, the results being analyzed depending on the volume of surgical intervention. The rate of postoperative hypothyrodism is lower in patients who had undergone limited thyroid resection, recurrent cases are more frequent, but they are not clinically significant and seldom require reoperation. It should also be noted that those patients have fewer cardiac complaints as the dose of hormone replacement therapy preparations is small. Elder patients who had undergone functionally significant thyroidectomy and need to take great doses of Thyroxin (107-150 mcg/day) have cardiac complaints more often (43 %) comparing to those who had undergone limited resections (35 %).

International Comparison of Adult Height in Children with Growth Hormone Deficiency and Limitations of Growth Hormone Treatment in Japan.

PubMed

Tanaka, Toshiaki

2017-03-01

The approved therapeutic dose of growth hormone (GH) for growth hormone deficiency (GHD) varies depending on the country. Japan has the lowest therapeutic dose globally, with a single dose of 0.175 mg/kg/week. GH treatment for GHD is considered as a replacement therapy and in fact, a dose of 0.175 mg/kg/week is slightly higher than GH secretion in prepubertal healthy children but nearly the same as that of pubertal children. Although the same growth rate as that of healthy children is expected in response to replacement therapy, the catch-up growth observed for the first 1 to 2 years of GH treatment was misinterpreted as an effect of the GH replacement therapy. The real effect of the GH replacement therapy was the growth rate appeared after more than 3 years of GH therapy, when patients showed nearly the same growth rate as healthy children. Therefore, children with GHD can have a higher growth rate than healthy children only for the first 1 to 2 years of GH therapy, after which their growth rate begins to wane. In the United States and Europe, the various therapeutic doses and high-dose treatment are accepted and the SD score of adult height after treatment is higher than that in Japan. The improvement degree of the height SD score and the adult height SD score with GH therapy are lower in Japan compared with other countries that administer a similar therapeutic dose. This suggests that the response to GH can be affected by race. Actual comparison of the response to GH between Japanese and Caucasian patients using KIGS (Pharmacia International Growth Database) data showed that both the short-term response and the effect on adult height were reduced in Japanese patients. As there is a strong positive correlation between adult height and height at the onset of puberty, treatment methods that can increase pubertal growth will be considered in the future for patients with GDH who enter puberty with short stature. Copyright© of YS Medical Media ltd.

Phase I/II Trial Evaluating Carbon Ion Radiotherapy for Salvaging Treatment of Locally Recurrent Nasopharyngeal Carcinoma.

PubMed

Kong, Lin; Hu, Jiyi; Guan, Xiyin; Gao, Jing; Lu, Rong; Lu, Jiade J

2016-01-01

Radiation therapy is the mainstay strategy for the treatment of nasopharyngeal cancer (NPC). Intensity-modulated X-ray therapy (IMXT) alone is the current standard for stage I and II NPC. For stage III and IV A/B diseases, concurrent chemotherapy should be provided in addition to IMXT. However, optimal treatment for locally recurrent NPC after previous definitive dose of radiotherapy is lacking. Various techniques including brachytherapy, IMXT, stereotactic radiosurgery or radiotherapy (SRS or SBRT) have been used in the management of locally recurrent NPC. Due to the inherent limitation of these techniques, i.e., limited range of irradiation or over-irradiation to surrounding normal tissues, moderate efficacy has been observed at the cost of severe toxicities. Carbon ion radiotherapy (CIRT) offers potential physical and biological advantages over photon and proton radiotherapy. Due to the inverted dose profile of particle beams and their greater energy deposition within the Bragg peak, precise dose delivery to the target volume(s) without exposing the surrounding organs at risk to extra doses is possible. In addition, CIRT provides an increased relative biological effectiveness (RBE) as compared to photon and proton radiotherapy. Such advantages may translate to improved outcomes after irradiation in terms of disease control in radio-resistant and previously treated, recurrent malignancies. It is therefore reasonable to postulate that recurrent NPC after high-dose radiotherapy could be more resistant to re-irradiation using photons. Reports on the treatment of radio-resistant malignancies in the head and neck region such as melanoma, sarcoma, and adenoid cystic carcinoma (ACC) have demonstrated superior local control rates from CIRT as compared to photon irradiation. Thus patients with recurrent NPC are likely to benefit from the enhanced biological effectiveness of carbon ions. As effective retreatment strategy is lacking for locally recurrent NPC, carbon ion radiation therapy offers an ideal alternate to conventional X-ray irradiation. The recommended dose of re-irradiation using CIRT for locally recurrent NPC will be determined in the dose-escalating phase (Phase I) of the study. Efficacy in terms of local progression-free survival (LPFS) and overall survival (OS) will be studied in the second phase of the study. Increasing doses of CIRT using raster scanning technology from 55GyE (22×2.5 GyE) to 65 GyE (26× 2.5 GyE) will be delivered in the Phase I part of the study. The primary endpoint of the Phase I part of the study is acute and sub-acute toxicities; the primary endpoint in the Phase II part is local progression-free survival and overall survival. Using the historical 2-year OS rate of 50% in locally recurrent NPC patients treated with photon or proton, we hypothesize that CIRT can improve the 2-year OS rate to 70%. The utilization of conventional radiation techniques including IMXT, brachytherapy, or stereotactic radiation therapy provides moderate efficacy in the treatment of locally recurrent NPC due to the limitations in dose distribution and biological effectiveness. Improved outcome in terms of treatment-induced toxicity, LC, LPFS, and OS are expected using CIRT due to the physical and biological characteristics of carbon ion beam. However, the recommended dose of CIRT used in re-irradiation for the local NPC focus remain to be determined. The recommended dose as well as the efficacy of CIRT in the treatment of locally recurrent NPC will be evaluated in the present trial.

Is there a place for brachytherapy in the salvage treatment of cervical lymph node metastases of head and neck cancers?

PubMed

Bartochowska, Anna; Skowronek, Janusz; Wierzbicka, Malgorzata; Leszczynska, Malgorzata; Szyfter, Witold

2015-01-01

Therapeutic options are limited for unresectable isolated cervical lymph node recurrences. The purpose of the study was to evaluate the feasibility, safety, and efficacy of high-dose-rate (HDR) and pulsed-dose-rate (PDR) brachytherapy (BT) in such cases. Sixty patients have been analyzed. All them had previously been treated with radical radiotherapy or chemoradiotherapy with or without surgery. PDR-BT and HDR-BT were used in 49 and 11 patients, respectively. In PDR-BT, a dose per pulse of 0.6-0.8 Gy (median 0.7 Gy) was given up to a median total dose of 20 Gy (range, 20-40 Gy). HDR-BT delivered a median total dose of 24 Gy (range, 7-60 Gy) in 3-10 fractions at 3-6 Gy per fraction. The overall survival and lymph node control rates at 1 and 2 years were estimated for 31.7% and 19%, and 41.4% and 27.3%, respectively. Serious late side effects (soft tissue necrosis) were observed in 11.7% of patients. Adverse events occurred statistically more often in patients >59 years (p = 0.02). HDR-BT and PDR-BT are feasible in previously irradiated patients with isolated regional lymph node metastases of head and neck cancers. The techniques should be considered if surgery is contraindicated. They provide acceptable toxicity and better tumor control than chemotherapy alone. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

The Effect of Dose Rate on Composite Durability When Exposed to a Simulated Long-Term Lunar Radiation Environment

NASA Technical Reports Server (NTRS)

Rojdev, Kristina; O'Rourke, Mary Jane; Hill, Charles; Nutt, Steven; Atwell, William

2011-01-01

Human exploration of space beyond low Earth orbit (LEO) requires a safe living and working environment for crew. Composite materials are one type of material being investigated by NASA as a multi-functional structural approach to habitats for long-term use in space or on planetary surfaces with limited magnetic fields and atmosphere. These materials provide high strength with the potential for decreased weight and increased radiation protection of crew and electronics when compared with conventional aluminum structures. However, these materials have not been evaluated in a harsh radiation environment, as would be experienced outside of LEO or on a planetary surface. Thus, NASA has been investigating the durability of select composite materials in a long-term radiation environment. Previously, NASA exposed composite samples to a simulated, accelerated 30-year radiation treatment and tensile stresses similar to those of a habitat pressure vessel. The results showed evidence of potential surface oxidation and enhanced cross-linking of the matrix. As a follow-on study, we performed the same accelerated exposure alongside an exposure with a decreased dose rate. The slower dose ]rate is comparable to a realistic scenario, although still accelerated. Strain measurements were collected during exposure and showed that with a fastdose rate, the strain decreased with time, but with a slow ]dose rate, the strain increased with time. After the radiation exposures, samples were characterized via tensile tests, flexure tests, Fourier Transform Infrared Spectroscopy (FTIR), and Differential Scanning Calorimetry (DSC). The results of these tests will be discussed.

Uncertainties in estimating health risks associated with exposure to ionising radiation.

PubMed

Preston, R Julian; Boice, John D; Brill, A Bertrand; Chakraborty, Ranajit; Conolly, Rory; Hoffman, F Owen; Hornung, Richard W; Kocher, David C; Land, Charles E; Shore, Roy E; Woloschak, Gayle E

2013-09-01

The information for the present discussion on the uncertainties associated with estimation of radiation risks and probability of disease causation was assembled for the recently published NCRP Report No. 171 on this topic. This memorandum provides a timely overview of the topic, given that quantitative uncertainty analysis is the state of the art in health risk assessment and given its potential importance to developments in radiation protection. Over the past decade the increasing volume of epidemiology data and the supporting radiobiology findings have aided in the reduction of uncertainty in the risk estimates derived. However, it is equally apparent that there remain significant uncertainties related to dose assessment, low dose and low dose-rate extrapolation approaches (e.g. the selection of an appropriate dose and dose-rate effectiveness factor), the biological effectiveness where considerations of the health effects of high-LET and lower-energy low-LET radiations are required and the transfer of risks from a population for which health effects data are available to one for which such data are not available. The impact of radiation on human health has focused in recent years on cancer, although there has been a decided increase in the data for noncancer effects together with more reliable estimates of the risk following radiation exposure, even at relatively low doses (notably for cataracts and cardiovascular disease). New approaches for the estimation of hereditary risk have been developed with the use of human data whenever feasible, although the current estimates of heritable radiation effects still are based on mouse data because of an absence of effects in human studies. Uncertainties associated with estimation of these different types of health effects are discussed in a qualitative and semi-quantitative manner as appropriate. The way forward would seem to require additional epidemiological studies, especially studies of low dose and low dose-rate occupational and perhaps environmental exposures and for exposures to x rays and high-LET radiations used in medicine. The development of models for more reliably combining the epidemiology data with experimental laboratory animal and cellular data can enhance the overall risk assessment approach by providing biologically refined data to strengthen the estimation of effects at low doses as opposed to the sole use of mathematical models of epidemiological data that are primarily driven by medium/high doses. NASA's approach to radiation protection for astronauts, although a unique occupational group, indicates the possible applicability of estimates of risk and their uncertainty in a broader context for developing recommendations on: (1) dose limits for occupational exposure and exposure of members of the public; (2) criteria to limit exposures of workers and members of the public to radon and its short-lived decay products; and (3) the dosimetric quantity (effective dose) used in radiation protection.

Compact Tissue-equivalent Proportional Counter for Deep Space Human Missions.

PubMed

Straume, T; Braby, L A; Borak, T B; Lusby, T; Warner, D W; Perez-Nunez, D

2015-10-01

Effects on human health from the complex radiation environment in deep space have not been measured and can only be simulated here on Earth using experimental systems and beams of radiations produced by accelerators, usually one beam at a time. This makes it particularly important to develop instruments that can be used on deep-space missions to measure quantities that are known to be relatable to the biological effectiveness of space radiation. Tissue-equivalent proportional counters (TEPCs) are such instruments. Unfortunately, present TEPCs are too large and power intensive to be used beyond low Earth orbit (LEO). Here, the authors describe a prototype of a compact TEPC designed for deep space applications with the capability to detect both ambient galactic cosmic rays and intense solar particle event radiation. The device employs an approach that permits real-time determination of yD (and thus quality factor) using a single detector. This was accomplished by assigning sequential sampling intervals as detectors “1” and “2” and requiring the intervals to be brief compared to the change in dose rate. Tests with g rays show that the prototype instrument maintains linear response over the wide dose-rate range expected in space with an accuracy of better than 5% for dose rates above 3 mGy h(-1). Measurements of yD for 200 MeV n(-1) carbon ions were better than 10%. Limited tests with fission spectrum neutrons show absorbed dose-rate accuracy better than 15%.

Compact Tissue-equivalent Proportional Counter for Deep Space Human Missions

PubMed Central

Straume, T.; Braby, L.A.; Borak, T.B.; Lusby, T.; Warner, D.W.; Perez-Nunez, D.

2015-01-01

Abstract Effects on human health from the complex radiation environment in deep space have not been measured and can only be simulated here on Earth using experimental systems and beams of radiations produced by accelerators, usually one beam at a time. This makes it particularly important to develop instruments that can be used on deep-space missions to measure quantities that are known to be relatable to the biological effectiveness of space radiation. Tissue-equivalent proportional counters (TEPCs) are such instruments. Unfortunately, present TEPCs are too large and power intensive to be used beyond low Earth orbit (LEO). Here, the authors describe a prototype of a compact TEPC designed for deep space applications with the capability to detect both ambient galactic cosmic rays and intense solar particle event radiation. The device employs an approach that permits real-time determination of (and thus quality factor) using a single detector. This was accomplished by assigning sequential sampling intervals as detectors “1” and “2” and requiring the intervals to be brief compared to the change in dose rate. Tests with γ rays show that the prototype instrument maintains linear response over the wide dose-rate range expected in space with an accuracy of better than 5% for dose rates above 3 mGy h−1. Measurements of for 200 MeV n−1 carbon ions were better than 10%. Limited tests with fission spectrum neutrons show absorbed dose-rate accuracy better than 15%. PMID:26313585

Mannitol dosing error during interfacility transfer for intracranial emergencies.

PubMed

Elliott, Cameron A; MacKenzie, Mark; O'Kelly, Cian J

2015-11-01

Mannitol is commonly used to treat elevated intracranial pressure (ICP). The authors analyzed mannitol dosing errors at peripheral hospitals prior to or during transport to tertiary care facilities for intracranial emergencies. They also investigated the appropriateness of mannitol use based on the 2007 Brain Trauma Foundation guidelines for severe traumatic brain injury. The authors conducted a retrospective review of the Shock Trauma Air Rescue Society (STARS) electronic patient database of helicopter medical evacuations in Alberta, Canada, between 2004 and 2012, limited to patients receiving mannitol before transfer. They extracted data on mannitol administration and patient characteristics, including diagnosis, mechanism, Glasgow Coma Scale score, weight, age, and pupil status. A total of 120 patients with an intracranial emergency received a mannitol infusion initiated at a peripheral hospital (median Glasgow Coma Scale score 6; range 3-13). Overall, there was a 22% dosing error rate, which comprised an underdosing rate (<0.25 g/kg) of 8.3% (10 of 120 patients), an overdosing rate (>1.5 g/kg) of 7.5% (9 of 120), and a nonbolus administration rate (>1 hour) of 6.7% (8 of 120). Overall, 72% of patients had a clear indication to receive mannitol as defined by meeting at least one of the following criteria based on Brain Trauma Foundation guidelines: neurological deterioration (11%), severe traumatic brain injury (69%), or pupillary abnormality (25%). Mannitol administration at peripheral hospitals is prone to dosing error. Strategies such as a pretransport checklist may mitigate this risk.

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).

Multidisciplinary European Low Dose Initiative (MELODI): strategic research agenda for low dose radiation risk research.

PubMed

Kreuzer, M; Auvinen, A; Cardis, E; Durante, M; Harms-Ringdahl, M; Jourdain, J R; Madas, B G; Ottolenghi, A; Pazzaglia, S; Prise, K M; Quintens, R; Sabatier, L; Bouffler, S

2018-03-01

MELODI (Multidisciplinary European Low Dose Initiative) is a European radiation protection research platform with focus on research on health risks after exposure to low-dose ionising radiation. It was founded in 2010 and currently includes 44 members from 18 countries. A major activity of MELODI is the continuous development of a long-term European Strategic Research Agenda (SRA) on low-dose risk for radiation protection. The SRA is intended to identify priorities for national and European radiation protection research programs as a basis for the preparation of competitive calls at the European level. Among those key priorities is the improvement of health risk estimates for exposures close to the dose limits for workers and to reference levels for the population in emergency situations. Another activity of MELODI is to ensure the availability of European key infrastructures for research activities, and the long-term maintenance of competences in radiation research via an integrated European approach for training and education. The MELODI SRA identifies three key research topics in low dose or low dose-rate radiation risk research: (1) dose and dose rate dependence of cancer risk, (2) radiation-induced non-cancer effects and (3) individual radiation sensitivity. The research required to improve the evidence base for each of the three key topics relates to three research lines: (1) research to improve understanding of the mechanisms contributing to radiogenic diseases, (2) epidemiological research to improve health risk evaluation of radiation exposure and (3) research to address the effects and risks associated with internal exposures, differing radiation qualities and inhomogeneous exposures. The full SRA and associated documents can be downloaded from the MELODI website ( http://www.melodi-online.eu/sra.html ).

In Vivo Dosimetry of High-Dose-Rate Interstitial Brachytherapy in the Pelvic Region: Use of a Radiophotoluminescence Glass Dosimeter for Measurement of 1004 Points in 66 Patients With Pelvic Malignancy

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

Nose, Takayuki; Department of Physics, Cancer Institute of the Japanese Foundation for Cancer Research, Tokyo; Koizumi, Masahiko

2008-02-01

Purpose: To perform the largest in vivo dosimetry study for interstitial brachytherapy yet to be undertaken using a new radiophotoluminescence glass dosimeter (RPLGD) in patients with pelvic malignancy and to study the limits of contemporary planning software based on the results. Patients and Methods: Sixty-six patients with pelvic malignancy were treated with high-dose-rate interstitial brachytherapy, including prostate (n = 26), gynecological (n = 35), and miscellaneous (n = 5). Doses for a total of 1004 points were measured by RPLGDs and calculated with planning software in the following locations: rectum (n = 549), urethra (n = 415), vagina (n =more » 25), and perineum (n = 15). Compatibility (measured dose/calculated dose) was analyzed according to dosimeter location. Results: The compatibility for all dosimeters was 0.98 {+-} 0.23, stratified by location: rectum, 0.99 {+-} 0.20; urethra, 0.96 {+-} 0.26; vagina, 0.91 {+-} 0.08; and perineum, 1.25 {+-} 0.32. Conclusions: Deviations between measured and calculated doses for the rectum and urethra were greater than 20%, which is attributable to the independent movements of these organs and the applicators. Missing corrections for inhomogeneity are responsible for the 9% negative shift near the vaginal cylinder (specific gravity = 1.24), whereas neglect of transit dose contributes to the 25% positive shift in the perineal dose. Dose deviation of >20% for nontarget organs should be taken into account in the planning process. Further development of planning software and a real-time dosimetry system are necessary to use the current findings and to achieve adaptive dose delivery.« less

Cost and Effectiveness of Decontamination Strategies in Radiation Contaminated Areas in Fukushima in Regard to External Radiation Dose

PubMed Central

Yasutaka, Tetsuo; Naito, Wataru; Nakanishi, Junko

2013-01-01

The objective of the present study is to evaluate the cost and effectiveness of decontamination strategies in the special decontamination areas in Fukushima in regard to external radiation dose. A geographical information system (GIS) was used to relate the predicted external dose in the affected areas to the number of potential inhabitants and the land use in the areas. A comprehensive review of the costs of various decontamination methods was conducted as part of the analysis. The results indicate that aerial decontamination in the special decontamination areas in Fukushima would be effective for reducing the air dose rate to the target level in a short period of time in some but not all of the areas. In a standard scenario, analysis of cost and effectiveness suggests that decontamination costs for agricultural areas account for approximately 80% of the total decontamination cost, of which approximately 60% is associated with storage. In addition, the costs of decontamination per person per unit area are estimated to vary greatly. Appropriate selection of decontamination methods may significantly decrease decontamination costs, allowing more meaningful decontamination in terms of the limited budget. Our analysis can help in examining the prioritization of decontamination areas from the viewpoints of cost and effectiveness in reducing the external dose. Decontamination strategies should be determined according to air dose rates and future land-use plans. PMID:24069398

Cost and effectiveness of decontamination strategies in radiation contaminated areas in Fukushima in regard to external radiation dose.

PubMed

Yasutaka, Tetsuo; Naito, Wataru; Nakanishi, Junko

2013-01-01

The objective of the present study is to evaluate the cost and effectiveness of decontamination strategies in the special decontamination areas in Fukushima in regard to external radiation dose. A geographical information system (GIS) was used to relate the predicted external dose in the affected areas to the number of potential inhabitants and the land use in the areas. A comprehensive review of the costs of various decontamination methods was conducted as part of the analysis. The results indicate that aerial decontamination in the special decontamination areas in Fukushima would be effective for reducing the air dose rate to the target level in a short period of time in some but not all of the areas. In a standard scenario, analysis of cost and effectiveness suggests that decontamination costs for agricultural areas account for approximately 80% of the total decontamination cost, of which approximately 60% is associated with storage. In addition, the costs of decontamination per person per unit area are estimated to vary greatly. Appropriate selection of decontamination methods may significantly decrease decontamination costs, allowing more meaningful decontamination in terms of the limited budget. Our analysis can help in examining the prioritization of decontamination areas from the viewpoints of cost and effectiveness in reducing the external dose. Decontamination strategies should be determined according to air dose rates and future land-use plans.

Impact of inadequate doses of rituximab in the treatment of diffuse large B cell lymphoma in Malaysian patients.

PubMed

Gan, Gin Gin; Subramaniam, Rajaletchumy; Bee, Ping Chong; Chin, Edmund Fui Min; Abdul-Halim, Habibah; Tai, Mei Chee

2014-01-01

The current standard treatment for patients with newly diagnosed diffuse large B cell lymphoma (DLBCL) is rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). A significant number of patients were not treated with recommended dose of rituximab due to limited financial resources in Malaysia. This study evaluates the efficacy of R-CHOP like chemotherapy in Malaysian patients with DLBCL. The study comprised a retrospective analysis of patients with DLBCL treated at a single centre. The outcome was compared with patients who were treated with R-CHOP like and CHOP like chemotherapy. Patients who were treated with lower dose of rituximab was subanalysed for outcome. A total of 86 patients who had CHOP-like chemotherapy were included. Only 39 (45%) patients had rituximab and only 12 (29%) patients had the recommended dose. The overall response (OR) and complete response (CR) rates were 88% and 81% respectively. There was no significant difference in OR and CR in patients who had rituximab and those without rituxmab. Those with International Prognostic Index (IPI) score of ≤ 2 had significant higher CR rate, progression free survival (PFS) and overall survival (p<0.001). The lack of significant improvement in CR and DFS in our patients may be due to an inadequate dose of rituximab.

Measurement of natural radioactivity and assessment of associated radiation hazards in soil around Baoji second coal-fired thermal power plant, China.

PubMed

Lu, Xinwei; Li, Xiaoxue; Yun, Pujun; Luo, Dacheng; Wang, Lijun; Ren, Chunhui; Chen, Cancan

2012-01-01

Activity concentrations of natural radionuclides (226)Ra, (232)Th and (40)K in soil around Baoji Second coal-fired thermal power plant of China were determined using gamma ray spectrometry. The mean activity concentrations of (226)Ra, (232)Th and (40)K in soil were found to be 40.3 ± 3.5, 59.6 ± 3.1 and 751.2 ± 12.4 Bq kg(-1), respectively, which are all higher than the corresponding average values in Shaanxi, Chinese and world soil. The radium equivalent activity (Ra(eq)), the air absorbed dose rate (D), the annual effective dose (E), the external hazard index (H(ex)) and internal hazard index (H(in)) were evaluated and compared with the internationally reported or reference values. All the soil samples have Ra(eq) lower than the limit of 370 Bq kg(-1) and H(ex) and H(in) less than unity. The overall mean outdoor terrestrial gamma air absorbed dose rate is ∼86.6 ± 3.4 nGy h(-1) and the corresponding outdoor annual effective dose is 0.106 ± 0.004 mSv, which is higher than the worldwide average (0.07 mSv y(-1)) for outdoor's annual effective dose.

Fludarabine and rituximab with escalating doses of lenalidomide followed by lenalidomide/rituximab maintenance in previously untreated chronic lymphocytic leukaemia (CLL): the REVLIRIT CLL-5 AGMT phase I/II study.

PubMed

Egle, Alexander; Steurer, Michael; Melchardt, Thomas; Weiss, Lukas; Gassner, Franz Josef; Zaborsky, Nadja; Geisberger, Roland; Catakovic, Kemal; Hartmann, Tanja Nicole; Pleyer, Lisa; Voskova, Daniela; Thaler, Josef; Lang, Alois; Girschikofsky, Michael; Petzer, Andreas; Greil, Richard

2018-06-04

Despite recent advances, chemoimmunotherapy remains a standard for fit previously untreated chronic lymphocytic leukaemia patients. Lenalidomide had activity in early monotherapy trials, but tumour lysis and flare proved major obstacles in its development. We combined lenalidomide in increasing doses with six cycles of fludarabine and rituximab (FR), followed by lenalidomide/rituximab maintenance. In 45 chemo-naive patients, included in this trial, individual tolerability of the combination was highly divergent and no systematic toxicity determining a maximum tolerated dose was found. Grade 3/4 neutropenia (71%) was high, but only 7% experienced grade 3 infections. No tumour lysis or flare > grade 2 was observed, but skin toxicity proved dose-limiting in nine patients (20%). Overall and complete response rates after induction were 89 and 44% by intention-to-treat, respectively. At a median follow-up of 78.7 months, median progression-free survival (PFS) was 60.3 months. Minimal residual disease and immunoglobulin variable region heavy chain mutation state predicted PFS and TP53 mutation most strongly predicted OS. Baseline clinical factors did not predict tolerance to the immunomodulatory drug lenalidomide, but pretreatment immunophenotypes of T cells showed exhausted memory CD4 cells to predict early dose-limiting non-haematologic events. Overall, combining lenalidomide with FR was feasible and effective, but individual changes in the immune system seemed associated with limiting side effects. clinicaltrials.gov (NCT00738829) and EU Clinical Trials Register ( www.clinicaltrialsregister.eu , 2008-001430-27).

AN INTEGRATED PHARMACOKINETIC AND PHARMACODYNAMIC STUDY OF ARSENITE ACTION 2. HEME OXYGENASE INDUCTION IN MICE

EPA Science Inventory

Heme oxygenase (HO) is the rate-limiting enzyme in heme degradation and its activity has a significant impact on intracellular heme pools. Rat studies indicate that HO induction is a sensitive, dose-dependent response to arsenite (AsIII) exposure in both liver and kidney. The o...

Assessment of radioactive materials and heavy metals in the surface soil around uranium mining area of Tongliao, China.

PubMed

Haribala; Hu, Bitao; Wang, Chengguo; Gerilemandahu; Xu, Xiao; Zhang, Shuai; Bao, Shanhu; Li, Yuhong

2016-08-01

Natural and artificial radionuclides and heavy metals in the surface soil of the uranium mining area of Tongliao, China, were measured using gamma spectrometry, flame atomic absorption spectrophotometry, graphite furnace atomic absorption spectrophotometry and microwave dissolution atomic fluorescence spectrometry respectively. The estimated average activity concentrations of (238)U, (232)Th, (226)Ra, (40)K and (137)Cs are 27.53±16.01, 15.89±5.20, 12.64±4.27, 746.84±38.24 and 4.23±4.76Bq/kg respectively. The estimated average absorbed dose rate in the air and annual effective dose rate are 46.58±5.26nGy/h and 57.13±6.45μSv, respectively. The radium equivalent activity, external and internal hazard indices were also calculated and their mean values are within the acceptable limits. The heavy metal concentrations of Pb, Cd, Cu, Zn, Hg and As from the surface soil were measured and their health risks were then determined. Although the content of Cd is much higher than the average background in China, its non-cancer and cancer risk indices are all within the acceptable ranges. These calculated hazard indices to estimate the potential radiological health risk in soil and the dose rate are well below their permissible limit. In addition the correlations between the radioactivity concentrations of the radionuclides and the heavy metals in soil were determined by the Pearson linear coefficient. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluating the accuracy of technicians and pharmacists in checking unit dose medication cassettes.

PubMed

Ambrose, Peter J; Saya, Frank G; Lovett, Larry T; Tan, Sandy; Adams, Dale W; Shane, Rita

2002-06-15

The accuracy rates of board-registered pharmacy technicians and pharmacists in checking unit dose medication cassettes in the inpatient setting at two separate institutions were examined. Cedars-Sinai Medical Center and Long Beach Memorial Medical Center, both in Los Angeles county, petitioned the California State Board of Pharmacy to approve a waiver of the California Code of Regulations to conduct an experimental program to compare the accuracy of unit dose medication cassettes checked by pharmacists with that of cassettes checked by trained, certified pharmacy technicians. The study consisted of three parts: assessing pharmacist baseline checking accuracy (Phase I), developing a technician-training program and certifying technicians who completed the didactic and practical training (Phase II), and evaluating the accuracy of certified technicians checking unit dose medication cassettes as a daily function (Phase III). Twenty-nine pharmacists and 41 technicians (3 of whom were pharmacy interns) participated in the study. Of the technicians, all 41 successfully completed the didactic and practical training, 39 successfully completed the audits and became certified checkers, and 2 (including 1 of the interns) did not complete the certification audits because they were reassigned to another work area or had resigned. In Phase II, the observed accuracy rate and its lower confidence limit exceeded the predetermined minimum requirement of 99.8% for a certified checker. The mean accuracy rates for technicians were identical at the two institutions (p = 1.0). The difference in mean accuracy rates between pharmacists (99.52%; 95% confidence interval [CI] 99.44-99.58%) and technicians, (99.89%; 95% CI 99.87-99.90%) was significant (p < 0.0001). Inpatient technicians who had been trained and certified in a closely supervised program that incorporated quality assurance mechanisms could safely and accurately check unit dose medication cassettes filled by other technicians.

Immunogenicity and safety of one dose of diphtheria, tetanus, acellular pertussis and poliomyelitis vaccine (Repevax®) followed by two doses of diphtheria, tetanus and poliomyelitis vaccine (Revaxis®) in adults aged ≥ 40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years.

PubMed

Dominicus, Rolf; Galtier, Florence; Richard, Patrick; Baudin, Martine

2014-06-30

The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years. This open-label, multicentre study was conducted in adults aged ≥ 40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥ 0.1IU/mL by seroneutralization assay [SNA]); tetanus (≥ 0.1IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥ 8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥ 5EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥ 0.01IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose. Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5-96.8); tetanus and poliomyelitis, 100% (CI: 98.8-100). Percentage of participants with an antibody titre ≥ 5EU/mL against pertussis antigens was ≥ 95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8-100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%). This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an adult population to achieve maximal protection against diphtheria, tetanus, poliomyelitis and pertussis simultaneously. Copyright © 2014 Elsevier Ltd. All rights reserved.

Dose rate effect of pulsed electron beam on micronucleus frequency in human peripheral blood lymphocytes.

PubMed

Acharya, Santhosh; Sanjeev, Ganesh; Bhat, Nagesh N; Narayana, Yerol

2010-03-01

The micronucleus assay in human peripheral blood lymphocytes is a sensitive indicator of radiation damage and could serve as a biological dosimeter in evaluating suspected overexposure to ionising radiation. Micronucleus (MN) frequency as a measure of chromosomal damage has also extensively been employed to quantify the effects of radiation dose rate on biological systems. Here we studied the effects of 8 MeV pulsed electron beam emitted by Microtron electron accelerator on MN induction at dose rates between 35 Gy min-1 and 352.5 Gy min-1. These dose rates were achieved by varying the pulse repetition rate (PRR). Fricke dosimeter was employed to measure the absorbed dose at different PRR and to ensure uniform dose distribution of the electron beam. To study the dose rate effect, blood samples were irradiated to an absorbed dose of (4.7+/-0.2) Gy at different rates and cytogenetic damage was quantified using the micronucleus assay. The obtained MN frequency showed no dose rate dependence within the studied dose rate range. Our earlier dose effect study using 8 MeV electrons revealed that the response of MN was linear-quadratic. Therefore, in the event of an accident, dose estimation can be made using linear-quadratic dose response parameters, without adding dose rate as a correction factor.

Diffraction measurements using the LHC Beam Loss Monitoring System

NASA Astrophysics Data System (ADS)

Kalliokoski, Matti

2017-03-01

The Beam Loss Monitoring (BLM) system of the Large Hadron Collider protects the machine from beam induced damage by measuring the absorbed dose rates of beam losses, and by triggering beam dump if the rates increase above the allowed threshold limits. Although the detection time scales are optimized for multi-turn losses, information on fast losses can be recovered from the loss data. In this paper, methods in using the BLM system in diffraction studies are discussed.

Brachytherapy Boost Utilization and Survival in Unfavorable-risk Prostate Cancer.

PubMed

Johnson, Skyler B; Lester-Coll, Nataniel H; Kelly, Jacqueline R; Kann, Benjamin H; Yu, James B; Nath, Sameer K

2017-11-01

There are limited comparative survival data for prostate cancer (PCa) patients managed with a low-dose rate brachytherapy (LDR-B) boost and dose-escalated external-beam radiotherapy (DE-EBRT) alone. To compare overall survival (OS) for men with unfavorable PCa between LDR-B and DE-EBRT groups. Using the National Cancer Data Base, we identified men with unfavorable PCa treated between 2004 and 2012 with androgen suppression (AS) and either EBRT followed by LDR-B or DE-EBRT (75.6-86.4Gy). Treatment selection was evaluated using logistic regression and annual percentage proportions. OS was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards, and propensity score matching. We identified 25038 men between 2004 and 2012, during which LDR-B boost utilization decreased from 29% to 14%. LDR-B was associated with better OS on univariate (7-yr OS: 82% vs 73%; p<0.001) and multivariate analyses (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.64-0.77). Propensity score matching verified an OS benefit associated with LDR-B boost (HR 0.74, 95% CI 0.66-0.89). The OS benefit of LDR-B boost persisted when limited to men aged <60 yr with no comorbidities. On subset analysis, there was no interaction between treatment and age, risk group, or radiation dose. Limitations include the retrospective design, nonrandomized selection bias, and the absence of treatment toxicity, hormone duration, and cancer-specific outcomes. Between 2004 and 2012, LDR-B boost utilization declined and was associated with better OS compared to DE-EBRT alone. LDR-B boost is probably the ideal treatment option for men with unfavorable PCa, pending long-term results of randomized trials. We compared radiotherapy utilization and survival for prostate cancer (PCa) patients using a national database. We found that low-dose rate brachytherapy (LDR-B) boost, a method being used less frequently, was associated with better overall survival when compared to dose-escalated external-beam radiotherapy alone for men with unfavorable PCa. Randomized trials are needed to confirm that LDR-B boost is the ideal treatment. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Enhanced Low Dose Rate Sensitivity at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Pease, Ronald; Forney, James; Carts, Martin; Phan, Anthony; Cox, Stephen; Kruckmeyer, Kriby; Burns, Sam; Albarian, Rafi; Holcombe, Bruce;

The Effects of ELDRS at Ultra-Low Dose Rates

NASA Technical Reports Server (NTRS)

Chen, Dakai; Forney, James; Carts, Martin; Phan, Anthony; Pease, Ronald; Kruckmeyer, Kirby; Cox, Stephen; LaBel, Kenneth; Burns, Samuel; Albarian, Rafi;

Sex differences in the subjective effects of oral Δ9-THC in cannabis users.

PubMed

Fogel, Jessica S; Kelly, Thomas H; Westgate, Philip M; Lile, Joshua A

2017-01-01

Previous studies suggest that there are sex differences in endocannabinoid function and the response to exogenous cannabinoids, though data from clinical studies comparing acute cannabinoid effects in men and women under controlled laboratory conditions are limited. To further explore these potential differences, data from 30 cannabis users (N=18 M, 12 F) who completed previous Δ 9 -tetrahydrocannabinol (Δ 9 -THC) discrimination studies were combined for this retrospective analysis. In each study, subjects learned to discriminate between oral Δ 9 -THC and placebo and then received a range of Δ 9 -THC doses (0, 5, 15 and a "high" dose of either 25 or 30mg). Responses on a drug-discrimination task, subjective effects questionnaire, psychomotor performance tasks, and physiological measures were assessed. Δ 9 -THC dose-dependently increased drug-appropriate responding, ratings on "positive" Visual Analog Scale (VAS) items (e.g., good effects, like drug, take again), and items related to intoxication (e.g., high, stoned). Δ 9 -THC also dose-dependently impaired performance on psychomotor tasks and elevated heart rate. Sex differences on VAS items emerged as a function of dose. Women exhibited significantly greater subjective responses to oral drug administration than men at the 5mg Δ 9 -THC dose, whereas men were more sensitive to the subjective effects of the 15mg dose of Δ 9 -THC than women. These results demonstrate dose-dependent separation in the subjective response to oral Δ 9 -THC administration by sex, which might contribute to the differential development of problematic cannabis use. Copyright © 2015 Elsevier Inc. All rights reserved.

Dosimetric Consistency of Co-60 Teletherapy Unit- a ten years Study

PubMed Central

Baba, Misba H; Mohib-ul-Haq, M.; Khan, Aijaz A.

2013-01-01

Objective The goal of the Radiation standards and Dosimetry is to ensure that the output of the Teletherapy Unit is within ±2% of the stated one and the output of the treatment dose calculation methods are within ±5%. In the present paper, we studied the dosimetry of Cobalt-60 (Co-60) Teletherapy unit at Sher-I-Kashmir Institute of Medical Sciences (SKIMS) for last 10 years. Radioactivity is the phenomenon of disintegration of unstable nuclides called radionuclides. Among these radionuclides, Cobalt-60, incorporated in Telecobalt Unit, is commonly used in therapeutic treatment of cancer. Cobalt-60 being unstable decays continuously into Ni-60 with half life of 5.27 years thereby resulting in the decrease in its activity, hence dose rate (output). It is, therefore, mandatory to measure the dose rate of the Cobalt-60 source regularly so that the patient receives the same dose every time as prescribed by the radiation oncologist. The under dosage may lead to unsatisfactory treatment of cancer and over dosage may cause radiation hazards. Our study emphasizes the consistency between actual output and output obtained using decay method. Methodology The methodology involved in the present study is the calculations of actual dose rate of Co-60 Teletherapy Unit by two techniques i.e. Source to Surface Distance (SSD) and Source to Axis Distance (SAD), used for the External Beam Radiotherapy, of various cancers, using the standard methods. Thereby, a year wise comparison has been made between average actual dosimetric output (dose rate) and the average expected output values (obtained by using decay method for Co-60.) Results The present study shows that there is a consistency in the average output (dose rate) obtained by the actual dosimetry values and the expected output values obtained using decay method. The values obtained by actual dosimetry are within ±2% of the expected values. Conclusion The results thus obtained in a year wise comparison of average output by actual dosimetry done regularly as a part of Quality Assurance of the Telecobalt Radiotherapy Unit and its deviation from the expected output data is within the permissible limits. Thus our study shows a trend towards uniformity and a better dose delivery. PMID:23559901

Efficacy of Single-Dose and Triple-Dose Albendazole and Mebendazole against Soil-Transmitted Helminths and Taenia spp.: A Randomized Controlled Trial

PubMed Central

Steinmann, Peter; Utzinger, Jürg; Du, Zun-Wei; Jiang, Jin-Yong; Chen, Jia-Xu; Hattendorf, Jan; Zhou, Hui; Zhou, Xiao-Nong

2011-01-01

Background The control of soil-transmitted helminth (STH) infections currently relies on the large-scale administration of single-dose oral albendazole or mebendazole. However, these treatment regimens have limited efficacy against hookworm and Trichuris trichiura in terms of cure rates (CR), whereas fecal egg reduction rates (ERR) are generally high for all common STH species. We compared the efficacy of single-dose versus triple-dose treatment against hookworm and other STHs in a community-based randomized controlled trial in the People's Republic of China. Methodology/Principal findings The hookworm CR and fecal ERR were assessed in 314 individuals aged ≥5 years who submitted two stool samples before and 3–4 weeks after administration of single-dose oral albendazole (400 mg) or mebendazole (500 mg) or triple-dose albendazole (3×400 mg over 3 consecutive days) or mebendazole (3×500 mg over 3 consecutive days). Efficacy against T. trichiura, Ascaris lumbricoides, and Taenia spp. was also assessed. Albendazole cured significantly more hookworm infections than mebendazole in both treatment regimens (single dose: respective CRs 69% (95% confidence interval [CI]: 55–81%) and 29% (95% CI: 20–45%); triple dose: respective CRs 92% (95% CI: 81–98%) and 54% (95% CI: 46–71%)). ERRs followed the same pattern (single dose: 97% versus 84%; triple dose: 99.7% versus 96%). Triple-dose regimens outperformed single doses against T. trichiura; three doses of mebendazole – the most efficacious treatment tested – cured 71% (95% CI: 57–82%). Both single and triple doses of either drug were highly efficacious against A. lumbricoides (CR: 93–97%; ERR: all >99.9%). Triple dose regimens cured all Taenia spp. infections, whereas single dose applications cured only half of them. Conclusions/Significance Single-dose oral albendazole is more efficacious against hookworm than mebendazole. To achieve high CRs against both hookworm and T. trichiura, triple-dose regimens are warranted. Trial Registration www.controlled-trials.com ISRCTN47375023 PMID:21980373

RadNuc: A graphical user interface to deliver dose rate patterns encountered in nuclear medicine with a 137Cs irradiator

PubMed Central

Pasternack, Jordan B.; Howell, Roger W.

2012-01-01

The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy are generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Methods Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. Results The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/hr and a minimum dose rate of 0.01 cGy/hr. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/hr. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. Conclusion The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides. PMID:23265668

RadNuc: a graphical user interface to deliver dose rate patterns encountered in nuclear medicine with a 137Cs irradiator.

PubMed

Pasternack, Jordan B; Howell, Roger W

2013-02-01

The temporal variations in absorbed dose rates to organs and tissues in the body are very large in diagnostic and therapeutic nuclear medicine. The response of biological endpoints of relevance to radiation safety and therapeutic efficacy is generally modulated by dose rate. Therefore, it is important to understand how the complex dose rate patterns encountered in nuclear medicine impact relevant biological responses. Accordingly, a graphical user interface (GUI) was created to control a cesium-137 irradiator to deliver such dose rate patterns. Visual Basic 6.0 was used to create a user-friendly GUI to control the dose rate by varying the thickness of a mercury attenuator. The GUI facilitates the delivery of a number of dose rate patterns including constant, exponential increase or decrease, and multi-component exponential. Extensive visual feedback is provided by the GUI during both the planning and delivery stages. The GUI controlled irradiator can achieve a maximum dose rate of 40 cGy/h and a minimum dose rate of 0.01 cGy/h. Addition of machined lead blocks can be used to further reduce the minimum dose rate to 0.0001 cGy/h. Measured dose rate patterns differed from programmed dose rate patterns in total dose by 3.2% to 8.4%. The GUI controlled irradiator is able to accurately create dose rate patterns encountered in nuclear medicine and other related fields. This makes it an invaluable tool for studying the effects of chronic constant and variable low dose rates on biological tissues in the contexts of both radiation protection and clinical administration of internal radionuclides. Copyright © 2013 Elsevier Inc. All rights reserved.

The antitumor effect and hepatotoxicity of a hexokinase II inhibitor 3-bromopyruvate: in vivo investigation of intraarterial administration in a rabbit VX2 hepatoma model.

PubMed

Jae, Hwan Jun; Chung, Jin Wook; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo-Cheol; Yoon, Jung Hwan; Chung, Hesson; Park, Jae Hyung

2009-01-01

The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. The tumor necrosis rate was significantly higher in the high dose group (93% +/- 7.6 [mean +/- SD]) than that in the control group (48% +/- 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% +/- 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% +/- 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method.

The Antitumor Effect and Hepatotoxicity of a Hexokinase II Inhibitor 3-Bromopyruvate: In Vivo Investigation of Intraarterial Administration in a Rabbit VX2 Hepatoma Model

PubMed Central

Jae, Hwan Jun; Park, Hee Sun; Lee, Min Jong; Lee, Ki Chang; Kim, Hyo-Cheol; Yoon, Jung Hwan; Chung, Hesson; Park, Jae Hyung

2009-01-01

Objective The purpose of this study was to compare the antitumor effect and hepatotoxicity of an intraarterial delivery of low-dose and high-dose 3-bromopyruvate (3-BrPA) and those of a conventional Lipiodol-doxorubicin emulsion in a rabbit VX2 hepatoma model. Materials and Methods This experiment was approved by the animal care committee at our institution. VX2 carcinoma was implanted in the livers of 36 rabbits. Transcatheter intraarterial administration was performed using low dose 3-BrPA (25 mL in a 1 mM concentration, n = 10), high dose 3-BrPA (25 mL in a 5 mM concentration, n = 10) and Lipiodol-doxorubicin emulsion (1.6 mg doxorubicin/ 0.4 mL Lipiodol, n = 10), and six rabbits were treated with normal saline alone as a control group. One week later, the proportion of tumor necrosis was calculated based on histopathologic examination. The hepatotoxicity was evaluated by biochemical analysis. The differences between these groups were statistically assessed with using Mann-Whitney U tests and Kruskal-Wallis tests. Results The tumor necrosis rate was significantly higher in the high dose group (93% ± 7.6 [mean ± SD]) than that in the control group (48% ± 21.7) (p = 0.0002), but the tumor necrosis rate was not significantly higher in the low dose group (62% ± 20.0) (p = 0.2780). However, the tumor necrosis rate of the high dose group was significantly lower than that of the Lipiodol-doxorubicin treatment group (99% ± 2.7) (p = 0.0015). The hepatotoxicity observed in the 3-BrPA groups was comparable to that of the Lipiodol-doxorubicin group. Conclusion Even though intraarterial delivery of 3-BrPA shows a dose-related antitumor effect, single session treatment seems to have limited efficacy when compared with the conventional method. PMID:19885316

Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial.

PubMed

Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

2010-07-01

Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1-4, prednisone at a dose of 1.5 mg/kg also on days 1-4 and thalidomide at a dose of 50-100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1-4 and 1.6, 3.2, or 4.8 g on days 5-35. Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3-4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1-4 followed by 4.8 g p.o. on days 5-35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs.

Melphalan, prednisone, thalidomide and defibrotide in relapsed/refractory multiple myeloma: results of a multicenter phase I/II trial

PubMed Central

Palumbo, Antonio; Larocca, Alessandra; Genuardi, Mariella; Kotwica, Katarzyna; Gay, Francesca; Rossi, Davide; Benevolo, Giulia; Magarotto, Valeria; Cavallo, Federica; Bringhen, Sara; Rus, Cecilia; Masini, Luciano; Iacobelli, Massimo; Gaidano, Gianluca; Mitsiades, Constantine; Anderson, Kenneth; Boccadoro, Mario; Richardson, Paul

2010-01-01

Background Defibrotide is a novel orally bioavailable polydisperse oligonucleotide with anti-thrombotic and anti-adhesive effects. In SCID/NOD mice, defibrotide showed activity in human myeloma xenografts. This phase I/II study was conducted to identify the most appropriate dose of defibrotide in combination with melphalan, prednisone and thalidomide in patients with relapsed and relapsed/refractory multiple myeloma, and to determine its safety and tolerability as part of this regimen. Design and Methods This was a phase I/II, multicenter, dose-escalating, non-comparative, open label study. Oral melphalan was administered at a dose of 0.25 mg/kg on days 1–4, prednisone at a dose of 1.5 mg/kg also on days 1–4 and thalidomide at a dose of 50–100 mg/day continuously. Defibrotide was administered orally at three dose-levels: 2.4, 4.8 or 7.2 g on days 1–4 and 1.6, 3.2, or 4.8 g on days 5–35. Results Twenty-four patients with relapsed/refractory multiple myeloma were enrolled. No dose-limiting toxicity was observed. In all patients, the complete response plus very good partial response rate was 9%, and the partial response rate was 43%. The 1-year progression-free survival and 1-year overall survival rates were 34% and 90%, respectively. The most frequent grade 3–4 adverse events included neutropenia, thrombocytopenia, anemia and fatigue. Deep vein thrombosis was reported in only one patient. Conclusions This combination of melphalan, prednisone and thalidomide together with defibrotide showed anti-tumor activity with a favorable tolerability. The maximum tolerated dose of defibrotide was identified as 7.2 g p.o. on days 1–4 followed by 4.8 g p.o. on days 5–35. Further trials are needed to confirm the role of this regimen and to evaluate the combination of defibrotide with new drugs (ClinicalTrials.gov Identifier: NCT00406978). PMID:20053869

Dose--effect relationships for femoral fractures after multimodality limb-sparing therapy of soft-tissue sarcomas of the proximal lower extremity.

PubMed

Pak, Daniel; Vineberg, Karen A; Griffith, Kent A; Sabolch, Aaron; Chugh, Rashmi; Ben-Josef, Edgar; Biermann, Janet Sybil; Feng, Mary

2012-07-15

We investigated the clinical and dosimetric predictors for radiation-associated femoral fractures in patients with proximal lower extremity soft tissue sarcomas (STS). We examined 131 patients with proximal lower extremity STS who received limb-sparing surgery and external-beam radiation therapy between 1985 and 2006. Five (4%) patients sustained pathologic femoral fractures. Dosimetric analysis was limited to 4 fracture patients with full three-dimensional dose information, who were compared with 59 nonfracture patients. The mean doses and volumes of bone (V(d)) receiving specified doses (≥30 Gy, 45 Gy, 60 Gy) at the femoral body, femoral neck, intertrochanteric region, and subtrochanteric region were compared. Clinical predictive factors were also evaluated. Of 4 fracture patients in our dosimetric series, there were three femoral neck fractures with a mean dose of 57.6 ± 8.9 Gy, V30 of 14.5 ± 2.3 cc, V45 of 11.8 ± 1.1 cc, and V60 of 7.2 ± 2.2 cc at the femoral neck compared with 22.9 ± 20.8 Gy, 4.8 ± 5.6 cc, 2.5 ± 3.9 cc, and 0.8 ± 2.7 cc, respectively, for nonfracture patients (p < 0.03 for all). The femoral neck fracture rate was higher than at the subtrochanteric region despite lower mean doses at these subregions. All fracture sites received mean doses greater than 40 Gy. Also, with our policy of prophylactic femoral intramedullary nailing for high-risk patients, there was no significant difference in fracture rates between patients with and without periosteal excision. There were no significant differences in age, sex, tumor size, timing of radiation therapy, and use of chemotherapy between fracture and nonfracture patients. These dose-volume toxicity relationships provide RT optimization goals to guide future efforts for reducing pathologic fracture rates. Prophylactic femoral intramedullary nailing may also reduce fracture risk for susceptible patients. Copyright © 2012 Elsevier Inc. All rights reserved.

Ultra-Shallow Junctions Fabrication by Plasma Immersion Implantation on PULSION registered Followed by Laser Thermal Processing

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

Torregrosa, Frank; Etienne, Hasnaa; Sempere, Guillaume

In order to achieve the requirements for P+/N junctions for <45 nm ITRS nodes, ultra low energy and high dose implantations are needed. Classical beamline implantation is now limited in low energies, compared to Plasma Immersion Ion Implantation (PIII) which efficiency is no more to prove for the realization of Ultra-Shallow Junctions (USJ) in semiconductor applications : this technique allows to get ultimate shallow profiles (as implanted) due to no lower limitation of energy and high dose rate. Electrical activation is also a big issue since it has to afford high electrical activation rate with very low diffusion. Laser annealingmore » is one of the candidates for the 45 nm node. This paper presents electrical and physico-chemical characterizations of junctions realized with BF3 PIII followed by laser thermal processing with aim to obtain ultra-shallow junctions. Different implantation conditions (acceleration voltage/dose) and laser conditions (laser types, fluence/number of shots) are used for this study. Pre-amorphization is also used to confine the junction depth, and is shown to have a positive effect on junction depth but leads in higher junction leakage due to the remaining of EOR defects. The characterization is done using Optical characterization tool (SEMILAB) for sheet resistance and junction leakage measurements. SIMS is used for Boron profile and junction depth.« less

Review of the safety and efficacy of vitamin A supplementation in the treatment of children with severe acute malnutrition.

PubMed

Iannotti, Lora L; Trehan, Indi; Manary, Mark J

2013-09-12

World Health Organization (WHO) guidelines recommend for children with severe acute malnutrition (SAM), high-dose vitamin A (VA) supplements be given on day 1 of admission, and on days 2 and 14 in the case of clinical signs of vitamin A deficiency (VAD). Daily low-dose VA follows, delivered in a premix added to F-75 and F-100. This study aimed to systematically review the evidence for safety and effectiveness of high-dose VA supplementation (VAS) in treatment of children with SAM. A comprehensive literature review was undertaken for all relevant randomized controlled trials (RCT) and observational studies from 1950 to 2012. Studies identified for full review were evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology using a set of pre-defined criteria: indirectness; inconsistency; imprecision; and study limitations. A quality rating of high, moderate, or low was then assigned to each study, and only those attaining moderate to high were considered in making recommendations. Of the 2072 abstracts screened, 38 met criteria for full review, and 20 were rated moderate to high quality. Only one study replicated the WHO VA protocol in children with SAM. Indirectness was a critical limitation, as studies were not exclusive to children with SAM. There was inconsistency across trials for definitions of malnutrition, morbidities, and ages studied; and imprecision arising from sub-group analyses and small sample sizes. Evidence showed improved outcomes associated with low-dose compared to high-dose VAS, except in cases presenting with signs of VAD, measles, and severe diarrhea or shigellosis. Adverse outcomes related to respiratory infection, diarrhea, and growth were associated with high-dose VAS in children who were predominantly adequately nourished. No adverse effects of the high dose were found in children with SAM in the trial that replicated the WHO VA guideline. This is the first systematic review of the safety and efficacy of high-dose VAS in treatment of SAM. We recommend a low-dose VAS regimen for children with SAM, except in cases presenting with measles, severe diarrhea (shigellosis), and any indication of VAD. Further research is needed in exclusively malnourished children and to explore alternate delivery strategies.

Dose rate in brachytherapy using after-loading machine: pulsed or high-dose rate?

PubMed

Hannoun-Lévi, J-M; Peiffert, D

2014-10-01

Since February 2014, it is no longer possible to use low-dose rate 192 iridium wires due to the end of industrial production of IRF1 and IRF2 sources. The Brachytherapy Group of the French society of radiation oncology (GC-SFRO) has recommended switching from iridium wires to after-loading machines. Two types of after-loading machines are currently available, based on the dose rate used: pulsed-dose rate or high-dose rate. In this article, we propose a comparative analysis between pulsed-dose rate and high-dose rate brachytherapy, based on biological, technological, organizational and financial considerations. Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Monte Carlo Shielding Comparative Analysis Applied to TRIGA HEU and LEU Spent Fuel Transport

NASA Astrophysics Data System (ADS)

Margeanu, C. A.; Margeanu, S.; Barbos, D.; Iorgulis, C.

2010-12-01

The paper is a comparative study of LEU and HEU fuel utilization effects for the shielding analysis during spent fuel transport. A comparison against the measured data for HEU spent fuel, available from the last stage of spent fuel repatriation fulfilled in the summer of 2008, is also presented. All geometrical and material data for the shipping cask were considered according to NAC-LWT Cask approved model. The shielding analysis estimates radiation doses to shipping cask wall surface, and in air at 1 m and 2 m, respectively, from the cask, by means of 3D Monte Carlo MORSE-SGC code. Before loading into the shipping cask, TRIGA spent fuel source terms and spent fuel parameters have been obtained by means of ORIGEN-S code. Both codes are included in ORNL's SCALE 5 programs package. The actinides contribution to total fuel radioactivity is very low in HEU spent fuel case, becoming 10 times greater in LEU spent fuel case. Dose rates for both HEU and LEU fuel contents are below regulatory limits, LEU spent fuel photon dose rates being greater than HEU ones. Comparison between HEU spent fuel theoretical and measured dose rates in selected measuring points shows a good agreement, calculated values being greater than the measured ones both to cask wall surface (about 34% relative difference) and in air at 1 m distance from cask surface (about 15% relative difference).

Steady γ-Ray Effects on the Performance of PPP-BOTDA and TW-COTDR Fiber Sensing

PubMed Central

Planes, Isabelle; Girard, Sylvain; Boukenter, Aziz; Marin, Emmanuel; Delepine-Lesoille, Sylvie; Marcandella, Claude; Ouerdane, Youcef

2017-01-01

We investigated the evolution of the performances of Pulse Pre Pump-Brillouin Time Domain Analysis (PPP-BOTDA) and Tunable Wavelength Coherent Optical Time Domain Reflectometry (TW-COTDR) fiber-based temperature and strain sensors when the sensing optical fiber is exposed to two γ-ray irradiation conditions: (i) at room temperature and a dose rate of 370 Gy(SiO2)/h up to a total ionizing dose (TID) of 56 kGy; (ii) at room temperature and a dose rate of 25 kGy(SiO2)/h up to a TID of 10 MGy. Two main different classes of single-mode optical fibers have been tested in situ, radiation-tolerant ones: fluorine-doped or nitrogen-doped core fibers, as well as Telecom-grade germanosilicate ones. Brillouin and Rayleigh Sensitivities of N-Doped fibers were not reported yet, and these characterizations pave the way for a novel and alternative sensing scheme. Moreover, in these harsh conditions, our results showed that the main parameter affecting the sensor sensitivity remains the Radiation Induced Attenuation (RIA) at its operation wavelength of 1550 nm. RIA limits the maximal sensing range but does not influence the measurement uncertainty. F-doped fiber is the most tolerant against RIA with induced losses below 8 dB/km after a 56 kGy accumulated dose whereas the excess losses of other fibers exceed 22 dB/km. Both Rayleigh and Brillouin signatures that are exploited by the PPP-BOTDA and the TW-COTDR remain unchanged (within our experimental uncertainties). The strain and temperature coefficients of the various fibers under test are not modified by radiations, at these dose/dose rate levels. Consequently, this enables the design of a robust strain and temperature sensing architecture for the monitoring of radioactive waste disposals. PMID:28218652

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

PubMed

Hunt, G J

1997-04-01

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

Feasibility study on the verification of actual beam delivery in a treatment room using EPID transit dosimetry.

PubMed

Baek, Tae Seong; Chung, Eun Ji; Son, Jaeman; Yoon, Myonggeun

2014-12-04

The aim of this study is to evaluate the ability of transit dosimetry using commercial treatment planning system (TPS) and an electronic portal imaging device (EPID) with simple calibration method to verify the beam delivery based on detection of large errors in treatment room. Twenty four fields of intensity modulated radiotherapy (IMRT) plans were selected from four lung cancer patients and used in the irradiation of an anthropomorphic phantom. The proposed method was evaluated by comparing the calculated dose map from TPS and EPID measurement on the same plane using a gamma index method with a 3% dose and 3 mm distance-to-dose agreement tolerance limit. In a simulation using a homogeneous plastic water phantom, performed to verify the effectiveness of the proposed method, the average passing rate of the transit dose based on gamma index was high enough, averaging 94.2% when there was no error during beam delivery. The passing rate of the transit dose for 24 IMRT fields was lower with the anthropomorphic phantom, averaging 86.8% ± 3.8%, a reduction partially due to the inaccuracy of TPS calculations for inhomogeneity. Compared with the TPS, the absolute value of the transit dose at the beam center differed by -0.38% ± 2.1%. The simulation study indicated that the passing rate of the gamma index was significantly reduced, to less than 40%, when a wrong field was erroneously irradiated to patient in the treatment room. This feasibility study suggested that transit dosimetry based on the calculation with commercial TPS and EPID measurement with simple calibration can provide information about large errors for treatment beam delivery.

Steady γ-Ray Effects on the Performance of PPP-BOTDA and TW-COTDR Fiber Sensing.

PubMed

Planes, Isabelle; Girard, Sylvain; Boukenter, Aziz; Marin, Emmanuel; Delepine-Lesoille, Sylvie; Marcandella, Claude; Ouerdane, Youcef

2017-02-17

We investigated the evolution of the performances of Pulse Pre Pump-Brillouin Time Domain Analysis (PPP-BOTDA) and Tunable Wavelength Coherent Optical Time Domain Reflectometry (TW-COTDR) fiber-based temperature and strain sensors when the sensing optical fiber is exposed to two γ-ray irradiation conditions: (i) at room temperature and a dose rate of 370 Gy(SiO2)/h up to a total ionizing dose (TID) of 56 kGy; (ii) at room temperature and a dose rate of 25 kGy(SiO2)/h up to a TID of 10 MGy. Two main different classes of single-mode optical fibers have been tested in situ, radiation-tolerant ones: fluorine-doped or nitrogen-doped core fibers, as well as Telecom-grade germanosilicate ones. Brillouin and Rayleigh Sensitivities of N-Doped fibers were not reported yet, and these characterizations pave the way for a novel and alternative sensing scheme. Moreover, in these harsh conditions, our results showed that the main parameter affecting the sensor sensitivity remains the Radiation Induced Attenuation (RIA) at its operation wavelength of 1550 nm. RIA limits the maximal sensing range but does not influence the measurement uncertainty. F-doped fiber is the most tolerant against RIA with induced losses below 8 dB/km after a 56 kGy accumulated dose whereas the excess losses of other fibers exceed 22 dB/km. Both Rayleigh and Brillouin signatures that are exploited by the PPP-BOTDA and the TW-COTDR remain unchanged (within our experimental uncertainties). The strain and temperature coefficients of the various fibers under test are not modified by radiations, at these dose/dose rate levels. Consequently, this enables the design of a robust strain and temperature sensing architecture for the monitoring of radioactive waste disposals.

Estimation of the indoor radon and the annual effective dose from granite samples

NASA Astrophysics Data System (ADS)

Sola, P.; Srinuttrakul, W.; Kewsuwan, P.

2015-05-01

Inhalation of radon and thoron daughters increases the risk of lung cancer. The main sources of indoor radon are building materials. The aim of this research is to estimate the indoor radon and the annual effective dose from the building materials. Eighteen granite samples bought from the markets in Thailand were measured using an ionization chamber (ATMOS 12 DPX) for the radon concentration in air. Radon exhalation rates were calculated from the radon concentration in chamber. The indoor radon from the granite samples ranged from 10.04 to 55.32 Bq·m-2·h-1 with an average value of 20.30 Bq·m-2·h-1 and the annual effective dose ranged from 0.25 to 1.39 mSv·y-1 with an average value of 0.48 mSv·y-1. The results showed that the annual effective doses of three granite samples were higher than the annual exposure limit for the general public (1 mSv·y-1) recommended by the International Commission on Radiological Protection (ICRP). In addition, the relationship between the colours and radon exhalation rates of granite samples was also explained.

Is a larger refuge always better? Dispersal and dose in pesticide resistance evolution.

PubMed

Takahashi, Daisuke; Yamanaka, Takehiko; Sudo, Masaaki; Andow, David A

2017-06-01

The evolution of resistance against pesticides is an important problem of modern agriculture. The high-dose/refuge strategy, which divides the landscape into treated and nontreated (refuge) patches, has proven effective at delaying resistance evolution. However, theoretical understanding is still incomplete, especially for combinations of limited dispersal and partially recessive resistance. We reformulate a two-patch model based on the Comins model and derive a simple quadratic approximation to analyze the effects of limited dispersal, refuge size, and dominance for high efficacy treatments on the rate of evolution. When a small but substantial number of heterozygotes can survive in the treated patch, a larger refuge always reduces the rate of resistance evolution. However, when dominance is small enough, the evolutionary dynamics in the refuge population, which is indirectly driven by migrants from the treated patch, mainly describes the resistance evolution in the landscape. In this case, for small refuges, increasing the refuge size will increase the rate of resistance evolution. Our analysis distils major driving forces from the model, and can provide a framework for understanding directional selection in source-sink environments. © 2017 The Author(s). Evolution published by Wiley Periodicals, Inc. on behalf of The Society for the Study of Evolution.

Cost-effectiveness of hepatitis A vaccination in Indonesia.

PubMed

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

2014-01-01

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

Cost-effectiveness of hepatitis A vaccination in Indonesia

PubMed Central

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

2014-01-01

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

The causes and prevention of cancer: gaining perspective.

PubMed Central

Ames, B N; Gold, L S

1997-01-01

Epidemiological studies have identified several factors that are likely to have a major effect on reducing rates of cancer: reduction of smoking, increased consumption of fruits and vegetables, and control of infections. Other factors include avoidance of intense sun exposure, increased physical activity, and reduced consumption of alcohol and possibly red meat. Risks of many types of cancer can already be reduced, and the potential for further reductions is great. In the United States, cancer death rates for all cancers combined are decreasing, if lung cancer (90% of which is due to smoking), is excluded from the analysis. We review the research on causes of cancer and show why much cancer is preventable. The idea that traces of synthetic chemicals, such as DDT, are major contributors to human cancer is not supported by the evidence, yet public concern and resource allocation for reduction of chemical pollution are very high, in part because standard risk assessment uses linear extrapolation from limited data in high-dose animal cancer tests. These tests are done at the maximum tolerated dose (MTD) and are typically misinterpreted to mean that low doses of synthetic chemicals and industrial pollutants are relevant to human cancer. About half the chemicals tested, whether synthetic or natural, are carcinogenic to rodents at such high doses. Almost all chemicals in the human diet are natural. For example, 99.99% of the pesticides we eat are naturally present in plants to ward off insects and other predators. Half of the natural pesticides that have been tested at the MTD are rodent carcinogens. Cooking food produces large numbers of natural dietary chemicals. Roasted coffee, for example, contains more than 1000 chemicals: of 27 tested, 19 are rodent carcinogens. Increasing evidence supports the idea that the high frequency of positive results in rodent bioassays is due to testing at the MTD, which frequently can cause chronic cell killing and consequent cell replacement-a risk factor for cancer that can be limited to high doses. Because default risk assessments use linear extrapolation, which ignores effects of the high dose itself, low-dose risks are often exaggerated. PMID:9255573

The causes and prevention of cancer: gaining perspective.

PubMed

Ames, B N; Gold, L S

1997-06-01

Epidemiological studies have identified several factors that are likely to have a major effect on reducing rates of cancer: reduction of smoking, increased consumption of fruits and vegetables, and control of infections. Other factors include avoidance of intense sun exposure, increased physical activity, and reduced consumption of alcohol and possibly red meat. Risks of many types of cancer can already be reduced, and the potential for further reductions is great. In the United States, cancer death rates for all cancers combined are decreasing, if lung cancer (90% of which is due to smoking), is excluded from the analysis. We review the research on causes of cancer and show why much cancer is preventable. The idea that traces of synthetic chemicals, such as DDT, are major contributors to human cancer is not supported by the evidence, yet public concern and resource allocation for reduction of chemical pollution are very high, in part because standard risk assessment uses linear extrapolation from limited data in high-dose animal cancer tests. These tests are done at the maximum tolerated dose (MTD) and are typically misinterpreted to mean that low doses of synthetic chemicals and industrial pollutants are relevant to human cancer. About half the chemicals tested, whether synthetic or natural, are carcinogenic to rodents at such high doses. Almost all chemicals in the human diet are natural. For example, 99.99% of the pesticides we eat are naturally present in plants to ward off insects and other predators. Half of the natural pesticides that have been tested at the MTD are rodent carcinogens. Cooking food produces large numbers of natural dietary chemicals. Roasted coffee, for example, contains more than 1000 chemicals: of 27 tested, 19 are rodent carcinogens. Increasing evidence supports the idea that the high frequency of positive results in rodent bioassays is due to testing at the MTD, which frequently can cause chronic cell killing and consequent cell replacement-a risk factor for cancer that can be limited to high doses. Because default risk assessments use linear extrapolation, which ignores effects of the high dose itself, low-dose risks are often exaggerated.

Primary Prevention of Cervical Cancer: American Society of Clinical Oncology Resource-Stratified Guideline

PubMed Central

Arrossi, Silvina; Temin, Sarah; Garland, Suzanne; Eckert, Linda O’Neal; Bhatla, Neerja; Castellsagué, Xavier; Alkaff, Sharifa Ezat; Felder, Tamika; Hammouda, Doudja; Konno, Ryo; Lopes, Gilberto; Mugisha, Emmanuel; Murillo, Rául; Scarinci, Isabel C.; Stanley, Margaret; Tsu, Vivien; Wheeler, Cosette M.; Adewole, Isaac Folorunso; de Sanjosé, Silvia

2017-01-01

Purpose To provide resource-stratified (four tiers), evidence-based recommendations on the primary prevention of cervical cancer globally. Methods The American Society of Clinical Oncology convened a multidisciplinary, multinational panel of oncology, obstetrics/gynecology, public health, cancer control, epidemiology/biostatistics, health economics, behavioral/implementation science, and patient advocacy experts. The Expert Panel reviewed existing guidelines and conducted a modified ADAPTE process and a formal consensus-based process with additional experts (consensus ratings group) for one round of formal ratings. Results Existing sets of guidelines from five guideline developers were identified and reviewed; adapted recommendations formed the evidence base. Five systematic reviews, along with cost-effectiveness analyses, provided evidence to inform the formal consensus process, which resulted in agreement of ≥ 75%. Recommendations In all resource settings, two doses of human papillomavirus vaccine are recommended for girls age 9 to 14 years, with an interval of at least 6 months and possibly up to 12 to 15 months. Individuals with HIV positivity should receive three doses. Maximal and enhanced settings: if girls are age ≥ 15 years and received their first dose before age 15 years, they may complete the series; if no doses were received before age 15 years, three doses should be administered; in both scenarios, vaccination may be through age 26 years. Limited and basic settings: if sufficient resources remain after vaccinating girls age 9 to 14 years, girls who received one dose may receive additional doses between age 15 and 26 years. Maximal, enhanced, and limited settings: if ≥ 50% coverage in the priority female target population, sufficient resources, and cost effectiveness, boys may be vaccinated to prevent other noncervical human papillomavirus–related cancers and diseases. Basic settings: vaccinating boys is not recommended. It is the view of the American Society of Clinical Oncology that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines. PMID:29094100

Induction and concurrent chemotherapy with high-dose thoracic conformal radiation therapy in unresectable stage IIIA and IIIB non-small-cell lung cancer: a dose-escalation phase I trial.

PubMed

Socinski, Mark A; Morris, David E; Halle, Jan S; Moore, Dominic T; Hensing, Thomas A; Limentani, Steven A; Fraser, Robert; Tynan, Maureen; Mears, Andrea; Rivera, M Patricia; Detterbeck, Frank C; Rosenman, Julian G

2004-11-01

Local control rates at conventional radiotherapy doses (60 to 66 Gy) are poor in stage III non-small-cell lung cancer (NSCLC). Dose escalation using three-dimensional thoracic conformal radiation therapy (TCRT) is one strategy to improve local control and perhaps survival. Stage III NSCLC patients with a good performance status (PS) were treated with induction chemotherapy (carboplatin area under the curve [AUC] 5, irinotecan 100 mg/m(2), and paclitaxel 175 mg/m(2) days 1 and 22) followed by concurrent chemotherapy (carboplatin AUC 2 and paclitaxel 45 mg/m(2) weekly for 7 to 8 weeks) beginning on day 43. Pre- and postchemotherapy computed tomography scans defined the initial clinical target volume (CTV(I)) and boost clinical target volume (CTV(B)), respectively. The CTV(I) received 40 to 50 Gy; the CTV(B) received escalating doses of TCRT from 78 Gy to 82, 86, and 90 Gy. The primary objective was to escalate the TCRT dose from 78 to 90 Gy or to the maximum-tolerated dose. Twenty-nine patients were enrolled (25 assessable patients; median age, 59 years; 62% male; 45% stage IIIA; 38% PS 0; and 38% > or = 5% weight loss). Induction CIP was well tolerated (with filgrastim support) and active (partial response rate, 46.2%; stable disease, 53.8%; and early progression, 0%). The TCRT dose was escalated from 78 to 90 Gy without dose-limiting toxicity. The primary acute toxicity was esophagitis (16%, all grade 3). Late toxicity consisted of grade 2 esophageal stricture (n = 3), bronchial stenosis (n = 2), and fatal hemoptysis (n = 2). The overall response rate was 60%, with a median survival time and 1-year survival probability of 24 months and 0.73 (95% CI, 0.55 to 0.89), respectively. CONCLUSION Escalation of the TCRT dose from 78 to 90 Gy in the context of induction and concurrent chemotherapy was accomplished safely in stage III NSCLC patients.

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.

A quality assurance device for measuring afterloader performance and transit dose for nasobiliary high-dose-rate brachytherapy.

PubMed

Deufel, Christopher L; Mullins, John P; Zakhary, Mark J

2018-05-17

Nasobiliary high-dose-rate (HDR) brachytherapy has emerged as an effective tool to boost the radiation dose for patients with unresectable perihilar cholangiocarcinoma. This work describes a quality assurance (QA) tool for measuring the HDR afterloader's performance, including the transit dose, when the source wire travels through a tortuous nasobiliary catheter path. The nasobiliary QA device was designed to mimic the anatomical path of a nasobiliary catheter, including the nasal, stomach, duodenum, and bile duct loops. Two of these loops, the duodenum and bile duct loops, have adjustable radii of curvature, resulting in the ability to maximize stress on the source wire in transit. The device was used to measure the performance over time for the HDR afterloader and the differences between intraluminal catheter lots. An upper limit on the transit dose was also measured using radiochromic film and compared with a simple theoretical model. The QA device was capable of detecting performance variations among nasobiliary catheter lots and following radioactive source replacement. The transit dose from a nasobiliary treatment increased by up to one order of magnitude when the source wire encountered higher than normal friction. Three distinct travel speeds of the source wire were observed: 5.2, 17.4, and 54.7 cm/s. The maximum transit dose was 0.3 Gy at a radial distance of 5 mm from a 40.3 kU 192 Ir source. The source wire encounters substantially greater friction when it navigates through the nasobiliary brachytherapy catheter. A QA tool that mimics the nasal, stomach, duodenum, and bile duct loops may be used to evaluate transit dose and the afterloader's performance over time. Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

The comparison of microdose flare-up and multiple dose antagonist protocols based on hCG day estradiol (E2), progesterone (P) and P/E2 ratio among poor responder patients in ICSI-ET cycles.

PubMed

Cicek, M N; Kahyaoglu, I; Kahyaoglu, S

2015-02-01

Elevated progesterone levels surpassing exact treshold values impede endometrial receptivity and decrease clinical pregnancy rates in different responder patients during assisted reproductive techniques. A progesterone (P): estradiol (E2) ratio of > 1 on the day of hCG administration has also been suggested to be a manifestation of low ovarian reserve. The clinical significance of P/E2 ratio on the day of hCG administration was investigated among poor responder patients. Based on the ESHRE Bologna consensus criteria related to poor ovarian response diagnosis, 48 poor responder patients were treated with the microdose flare-up regimen and 34 patients were treated with the multiple-dose GnRH antagonist protocol. All patients were destined to perform a ICSI-ET procedure at the end of the stimulation protocols. Progesterone levels and P/E2 ratios have been detected during controlled ovarian hyperstimulation. In the microdose flare-up group; the duration of stimulation, total gonadotropin dose used and hCG day E2 levels were significantly higher than the multiple dose antagonist group. However, the mean hCG day P/E2 rate in the microdose flare-up group was less than that in the multiple-dose antagonist group. The clinical pregnancy rates were non significantly higher in the multiple dose antagonist protocol group than in microdose flare-up group. Impaired endometrial receptivity caused by elevated P levels results with lower pregnancy rates. Regardless of the selected stimulation protocol, poor responder patients are not prone to exhibit high P and E2 secretion. Increased P/E2 ratio of > 1 on hCG day has limited value to predict cycle outcomes in poor responder patients because of ovarian follicle depletion.

Shielding design of the Mayo Clinic Scottsdale cyclotron vault

NASA Astrophysics Data System (ADS)

Riper, Kenneth A. Van; Metzger, Robert L.; Nelson, Kevin

2017-09-01

Mayo Clinic Scottsdale (Scottsdale, Arizona) is building a cyclotron vault containing a cyclotron with adjacent targets and a beam line leading to an external target. The targets are irradiated by high energy (15 to 16.5 MeV) protons for the production of radioisotopes. We performed Monte Carlo radiation transport simulations to calculate the radiation dose outside of the vault during irradiation of the cyclotron and external targets. We present the Monte Carlo model including the geometry, sources, and variance reduction methods. Mesh tallies surrounding the vault show the external dose rate is within acceptable limits.

Preclinical dose number and its application in understanding drug absorption risk and formulation design for preclinical species.

PubMed

Wuelfing, W Peter; Daublain, Pierre; Kesisoglou, Filippos; Templeton, Allen; McGregor, Caroline

2015-04-06

In the drug discovery setting, the ability to rapidly identify drug absorption risk in preclinical species at high doses from easily measured physical properties is desired. This is due to the large number of molecules being evaluated and their high attrition rate, which make resource-intensive in vitro and in silico evaluation unattractive. High-dose in vivo data from rat, dog, and monkey are analyzed here, using a preclinical dose number (PDo) concept based on the dose number described by Amidon and other authors (Pharm. Res., 1993, 10, 264-270). PDo, as described in this article, is simply calculated as dose (mg/kg) divided by compound solubility in FaSSIF (mg/mL) and approximates the volume of biorelevant media per kilogram of animal that would be needed to fully dissolve the dose. High PDo values were found to be predictive of difficulty in achieving drug exposure (AUC)-dose proportionality in in vivo studies, as could be expected; however, this work analyzes a large data set (>900 data points) and provides quantitative guidance to identify drug absorption risk in preclinical species based on a single solubility measurement commonly carried out in drug discovery. Above the PDo values defined, >50% of all in vivo studies exhibited poor AUC-dose proportionality in rat, dog, and monkey, and these values can be utilized as general guidelines in discovery and early development to rapidly assess risk of solubility-limited absorption for a given compound. A preclinical dose number generated by biorelevant dilutions of formulated compounds (formulated PDo) was also evaluated and defines solubility targets predictive of suitable AUC-dose proportionality in formulation development efforts. Application of these guidelines can serve to efficiently identify compounds in discovery that are likely to present extreme challenges with respect to solubility-limited absorption in preclinical species as well as reduce the testing of poor formulations in vivo, which is a key ethical and resource matter.

TU-AB-201-06: Evaluation of Electromagnetically Guided High- Dose Rate Brachytherapy for Ablative Treatment of Lung Metastases

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

Pinkham, D.W.; Shultz, D.; Loo, B.W.

Purpose: The advent of electromagnetic navigation bronchoscopy has enabled minimally invasive access to peripheral lung tumors previously inaccessible by optical bronchoscopes. As an adjunct to Stereotactic Ablative Radiosurgery (SABR), implantation of HDR catheters can provide focal treatments for multiple metastases and sites of retreatments. The authors evaluate a procedure to deliver ablative doses via Electromagnetically-Guided HDR (EMG-HDR) to lung metastases, quantify the resulting dosimetry, and assess its role in the comprehensive treatment of lung cancer. Methods: A retrospective study was conducted on ten patients, who, from 2009 to 2011, received a hypo-fractionated SABR regimen with 6MV VMAT to lesions inmore » various lobes ranging from 1.5 to 20 cc in volume. A CT visible pathway was delineated for EM guided placement of an HDR applicator (catheter) and dwell times were optimized to ensure at least 98% prescription dose coverage of the GTV. Normal tissue doses were calculated using inhomogeneity corrections via a grid-based Boltzmann solver (Acuros-BV-1.5.0). Results: With EMG-HDR, an average of 83% (+/−9% standard deviation) of each patient’s GTV received over 200% of the prescription dose, as compared to SABR where the patients received an average maximum dose of 125% (+/−5%). EMG-HDR enabled a 59% (+/−12%) decrease in the aorta maximum dose, a 63% (+/−26%) decrease in the spinal cord max dose, and 57% (+/−23%) and 70% (+/−17%) decreases in the volume of the body receiving over 50% and 25% of the prescription dose, respectively. Conclusion: EMG-HDR enables delivery of higher ablative doses to the GTV, while concurrently reducing surrounding normal tissue doses. The single catheter approach shown here is limited to targets smaller than 20 cc. As such, the technique enables ablation of small lesions and a potentially safe and effective retreatment option in situations where external beam utility is limited by normal tissue constraints.« less

Bruton Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Has Significant Activity in Patients With Relapsed/Refractory B-Cell Malignancies

PubMed Central

Buggy, Joseph J.; Sharman, Jeff P.; Smith, Sonali M.; Boyd, Thomas E.; Grant, Barbara; Kolibaba, Kathryn S.; Furman, Richard R.; Rodriguez, Sara; Chang, Betty Y.; Sukbuntherng, Juthamas; Izumi, Raquel; Hamdy, Ahmed; Hedrick, Eric; Fowler, Nathan H.

2013-01-01

Purpose Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies. Patients and Methods Patients with relapsed or refractory B-cell lymphoma and chronic lymphocytic leukemia received escalating oral doses of ibrutinib. Two schedules were evaluated: one, 28 days on, 7 days off; and two, once-daily continuous dosing. Occupancy of BTK by ibrutinib in peripheral blood was monitored using a fluorescent affinity probe. Dose escalation proceeded until either the maximum-tolerated dose (MTD) was achieved or, in the absence of MTD, until three dose levels above full BTK occupancy by ibrutinib. Response was evaluated every two cycles. Results Fifty-six patients with a variety of B-cell malignancies were treated over seven cohorts. Most adverse events were grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without reaching MTD. Pharmacokinetic data indicated rapid absorption and elimination, yet BTK occupancy was maintained for at least 24 hours, consistent with the irreversible mechanism. Objective response rate in 50 evaluable patients was 60%, including complete response of 16%. Median progression-free survival in all patients was 13.6 months. Conclusion Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies. PMID:23045577

Bruton tyrosine kinase inhibitor ibrutinib (PCI-32765) has significant activity in patients with relapsed/refractory B-cell malignancies.

PubMed

Advani, Ranjana H; Buggy, Joseph J; Sharman, Jeff P; Smith, Sonali M; Boyd, Thomas E; Grant, Barbara; Kolibaba, Kathryn S; Furman, Richard R; Rodriguez, Sara; Chang, Betty Y; Sukbuntherng, Juthamas; Izumi, Raquel; Hamdy, Ahmed; Hedrick, Eric; Fowler, Nathan H

2013-01-01

Survival and progression of mature B-cell malignancies depend on signals from the B-cell antigen receptor, and Bruton tyrosine kinase (BTK) is a critical signaling kinase in this pathway. We evaluated ibrutinib (PCI-32765), a small-molecule irreversible inhibitor of BTK, in patients with B-cell malignancies. Patients with relapsed or refractory B-cell lymphoma and chronic lymphocytic leukemia received escalating oral doses of ibrutinib. Two schedules were evaluated: one, 28 days on, 7 days off; and two, once-daily continuous dosing. Occupancy of BTK by ibrutinib in peripheral blood was monitored using a fluorescent affinity probe. Dose escalation proceeded until either the maximum-tolerated dose (MTD) was achieved or, in the absence of MTD, until three dose levels above full BTK occupancy by ibrutinib. Response was evaluated every two cycles. Fifty-six patients with a variety of B-cell malignancies were treated over seven cohorts. Most adverse events were grade 1 and 2 in severity and self-limited. Dose-limiting events were not observed, even with prolonged dosing. Full occupancy of the BTK active site occurred at 2.5 mg/kg per day, and dose escalation continued to 12.5 mg/kg per day without reaching MTD. Pharmacokinetic data indicated rapid absorption and elimination, yet BTK occupancy was maintained for at least 24 hours, consistent with the irreversible mechanism. Objective response rate in 50 evaluable patients was 60%, including complete response of 16%. Median progression-free survival in all patients was 13.6 months. Ibrutinib, a novel BTK-targeting inhibitor, is well tolerated, with substantial activity across B-cell histologies.

ELDRS Characterization for a Very High Dose Mission

NASA Technical Reports Server (NTRS)

Harris, Richard D.; McClure, Steven S.; Rax, Bernard G.; Kenna, Aaron J.; Thorbourn, Dennis O.; Clark, Karla B.; Yan, Tsun-Yee

2010-01-01

Evaluation of bipolar linear parts which may have Enhanced Low Dose Rate Sensitivity (ELDRS) is problematic for missions that have very high dose radiation requirements. The accepted standards for evaluating parts that display ELDRS require testing at a very low dose rate which could be prohibitively long for very high dose missions. In this work, a methodology for ELDRS characterization of bipolar parts for mission doses up to 1 Mrad(Si) is evaluated. The procedure employs an initial dose rate of 0.01 rad(Si)/s to a total dose of 50 krad(Si) and then changes to 0.04 rad(Si)/s to a total dose of 1 Mrad(Si). This procedure appears to work well. No change in rate of degradation with dose has been observed when the dose rate is changed from 0.01 to 0.04 rad(Si)/s. This is taken as an indication that the degradation due to the higher dose rate is equivalent to that at the lower dose rate at the higher dose levels, at least for the parts studied to date. In several cases, significant parameter degradation or functional failure not observed at HDR was observed at fairly high total doses (50 to 250 krad(Si)) at LDR. This behavior calls into question the use of dose rate trend data and enhancement factors to predict LDR performance.

Dialysis Cannot be Dosed

PubMed Central

Meyer, Timothy W.; Sirich, Tammy L.; Hostetter, Thomas H.

2014-01-01

Adequate dialysis is difficult to define because we have not identified the toxic solutes that contribute most to uremic illness. Dialysis prescriptions therefore cannot be adjusted to control the levels of these solutes. The current solution to this problem is to define an adequate dose of dialysis on the basis of fraction of urea removed from the body. This has provided a practical guide to treatment as the dialysis population has grown over the past 25 years. Indeed, a lower limit to Kt/Vurea (or the related urea reduction ratio) is now established as a quality indicator by the Centers for Medicare and Medicaid for chronic hemodialysis patients in the United States. For the present, this urea-based standard provides a useful tool to avoid grossly inadequate dialysis. Dialysis dosing, however, based on measurement of a single, relatively nontoxic solute can provide only a very limited guide toward improved treatment. Prescriptions which have similar effects on the index solute can have widely different effects on other solutes. The dose concept discourages attempts to increase the removal of such solutes independent of the index solute. The dose concept further assumes that important solutes are produced at a constant rate relative to body size, and discourages attempts to augment dialysis treatment by reducing solute production. Identification of toxic solutes would provide a more rational basis for the prescription of dialysis and ultimately for improved treatment of patients with renal failure. PMID:21929590

Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study).

PubMed

Hegarty, Joanne Elizabeth; Harding, Jane Elizabeth; Gamble, Gregory David; Crowther, Caroline Anne; Edlin, Richard; Alsweiler, Jane Marie

2016-10-01

Neonatal hypoglycaemia is common, affecting up to 15% of newborns, and can cause brain damage. Currently, there are no strategies, beyond early feeding, to prevent neonatal hypoglycaemia. Our aim was to determine a dose of 40% oral dextrose gel that will prevent neonatal hypoglycaemia in newborn babies at risk. We conducted a randomised, double-blind, placebo-controlled dose-finding trial of buccal dextrose gel to prevent neonatal hypoglycaemia at two hospitals in New Zealand. Babies at risk of hypoglycaemia (infant of a mother with diabetes, late preterm delivery, small or large birthweight, or other risk factors) but without indication for admission to a neonatal intensive care unit (NICU) were randomly allocated either to one of four treatment groups: 40% dextrose at one of two doses (0.5 ml/kg = 200 mg/kg, or 1 ml/kg = 400 mg/kg), either once at 1 h of age or followed by three additional doses of dextrose (0.5 ml/kg before feeds in the first 12 h); or to one of four corresponding placebo groups. Treatments were administered by massaging gel into the buccal mucosa. The primary outcome was hypoglycaemia (<2.6 mM) in the first 48 h. Secondary outcomes included admission to a NICU, admission for hypoglycaemia, and breastfeeding at discharge and at 6 wk. Prespecified potential dose limitations were tolerance of gel, time taken to administer, messiness, and acceptability to parents. From August 2013 to November 2014, 416 babies were randomised. Compared to babies randomised to placebo, the risk of hypoglycaemia was lowest in babies randomised to a single dose of 200 mg/kg dextrose gel (relative risk [RR] 0.68; 95% confidence interval [CI] 0.47-0.99, p = 0.04) but was not significantly different between dose groups (p = 0.21). Compared to multiple doses, single doses of gel were better tolerated, quicker to administer, and less messy, but these limitations were not different between dextrose and placebo gel groups. Babies who received any dose of dextrose gel were less likely to develop hypoglycaemia than those who received placebo (RR 0.79; 95% CI 0.64-0.98, p = 0.03; number needed to treat = 10, 95% CI 5-115). Rates of NICU admission were similar (RR 0.64; 95% CI 0.33-1.25, p = 0.19), but admission for hypoglycaemia was less common in babies randomised to dextrose gel (RR 0.46; 95% CI 0.21-1.01, p = 0.05). Rates of breastfeeding were similar in both groups. Adverse effects were uncommon and not different between groups. A limitation of this study was that most of the babies in the trial were infants of mothers with diabetes (73%), which may reduce the applicability of the results to babies from other risk groups. The incidence of neonatal hypoglycaemia can be reduced with a single dose of buccal 40% dextrose gel 200 mg/kg. A large randomised trial (Hypoglycaemia Prevention with Oral Dextrose [hPOD]) is under way to determine the effects on NICU admission and later outcomes. Australian New Zealand Clinical Trials Registry ACTRN12613000322730.

Radiation exposures during space flight and their measurement.

PubMed

Benton, E V; Henke, R P

1983-01-01

The paper reviews radiation exposures recorded during space flights of the US and USSR. Most of the data are from manned missions and include discussion of absorbed dose and dose rates as a function of parameters such as altitude, inclination, spacecraft type and shielding. Preliminary data exist on the neutron and HZE-particle component, as well as the LET spectra. For low Earth-orbit missions, the dose encountered is strongly altitude-dependent, with a weaker dependence upon inclination. The doses range from about 6 millirad per day for the Space Transportation System No. 3 flight to about 90 mrad per day for Skylab. The effective quality factor (QF) for the near-Earth orbits and free space has been estimated to be about 1.5 and about 5.5 respectively. Complete shielding from the galactic cosmic rays does not appear practical because of spacecraft weight limitations.

Engineering the thermal conductivity along an individual silicon nanowire by selective helium ion irradiation.

PubMed

Zhao, Yunshan; Liu, Dan; Chen, Jie; Zhu, Liyan; Belianinov, Alex; Ovchinnikova, Olga S; Unocic, Raymond R; Burch, Matthew J; Kim, Songkil; Hao, Hanfang; Pickard, Daniel S; Li, Baowen; Thong, John T L

2017-06-27

The ability to engineer the thermal conductivity of materials allows us to control the flow of heat and derive novel functionalities such as thermal rectification, thermal switching and thermal cloaking. While this could be achieved by making use of composites and metamaterials at bulk length-scales, engineering the thermal conductivity at micro- and nano-scale dimensions is considerably more challenging. In this work, we show that the local thermal conductivity along a single Si nanowire can be tuned to a desired value (between crystalline and amorphous limits) with high spatial resolution through selective helium ion irradiation with a well-controlled dose. The underlying mechanism is understood through molecular dynamics simulations and quantitative phonon-defect scattering rate analysis, where the behaviour of thermal conductivity with dose is attributed to the accumulation and agglomeration of scattering centres at lower doses. Beyond a threshold dose, a crystalline-amorphous transition was observed.

Rare problems with RhD immunoglobulin for postnatal prophylaxis after large fetomaternal haemorrhage

PubMed Central

Kidson-Gerber, Giselle

2015-01-01

We report a case of unusually large fetomaternal haemorrhage in a RhD- patient; of symptomatic non-sustained haemolysis of fetal red cells in the maternal circulation with infusion of intravenous high-dose RhD immunoglobulin; and of a failure to prevent RhD alloimmunisation. The haemolytic reaction is not previously reported in this patient group and we suggest would be limited to patients where the number of fetal red cells in the circulation is high. We advocate caution in treatment and spaced dosing of RhD immunoglobulin where the required dose is high, and refer readers to the WinRhoSDF™ RhD immunoglobulin product information for their updated dosing recommendations. There is a need for better understanding of pathophysiology and RhD immunoglobulin effects, to further reduce alloimmunisation rates, and we support the reporting of prophylaxis failures to haemovigilance programmes as is in place in the United Kingdom. PMID:27512480

Engineering the thermal conductivity along an individual silicon nanowire by selective helium ion irradiation

PubMed Central

Zhao, Yunshan; Liu, Dan; Chen, Jie; Zhu, Liyan; Belianinov, Alex; Ovchinnikova, Olga S.; Unocic, Raymond R.; Burch, Matthew J.; Kim, Songkil; Hao, Hanfang; Pickard, Daniel S.; Li, Baowen; Thong, John T. L.

2017-01-01

The ability to engineer the thermal conductivity of materials allows us to control the flow of heat and derive novel functionalities such as thermal rectification, thermal switching and thermal cloaking. While this could be achieved by making use of composites and metamaterials at bulk length-scales, engineering the thermal conductivity at micro- and nano-scale dimensions is considerably more challenging. In this work, we show that the local thermal conductivity along a single Si nanowire can be tuned to a desired value (between crystalline and amorphous limits) with high spatial resolution through selective helium ion irradiation with a well-controlled dose. The underlying mechanism is understood through molecular dynamics simulations and quantitative phonon-defect scattering rate analysis, where the behaviour of thermal conductivity with dose is attributed to the accumulation and agglomeration of scattering centres at lower doses. Beyond a threshold dose, a crystalline-amorphous transition was observed. PMID:28653663

Engineering the thermal conductivity along an individual silicon nanowire by selective helium ion irradiation

DOE PAGES

Zhao, Yunshan; Liu, Dan; Chen, Jie; ...

2017-06-27

The ability to engineer the thermal conductivity of materials allows us to control the flow of heat and derive novel functionalities such as thermal rectification, thermal switching and thermal cloaking. While this could be achieved by making use of composites and metamaterials at bulk length-scales, engineering the thermal conductivity at micro- and nano-scale dimensions is considerably more challenging. Here, we show that the local thermal conductivity along a single Si nanowire can be tuned to a desired value (between crystalline and amorphous limits) with high spatial resolution through selective helium ion irradiation with a well-controlled dose. The underlying mechanism ismore » understood through molecular dynamics simulations and quantitative phonon-defect scattering rate analysis, where the behaviour of thermal conductivity with dose is attributed to the accumulation and agglomeration of scattering centres at lower doses. Finally, we observed threshold dose beyond a crystalline-amorphous transition.« less

Engineering the thermal conductivity along an individual silicon nanowire by selective helium ion irradiation

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

Zhao, Yunshan; Liu, Dan; Chen, Jie

The ability to engineer the thermal conductivity of materials allows us to control the flow of heat and derive novel functionalities such as thermal rectification, thermal switching and thermal cloaking. While this could be achieved by making use of composites and metamaterials at bulk length-scales, engineering the thermal conductivity at micro- and nano-scale dimensions is considerably more challenging. Here, we show that the local thermal conductivity along a single Si nanowire can be tuned to a desired value (between crystalline and amorphous limits) with high spatial resolution through selective helium ion irradiation with a well-controlled dose. The underlying mechanism ismore » understood through molecular dynamics simulations and quantitative phonon-defect scattering rate analysis, where the behaviour of thermal conductivity with dose is attributed to the accumulation and agglomeration of scattering centres at lower doses. Finally, we observed threshold dose beyond a crystalline-amorphous transition.« less

The radiation protection problems of high altitude and space flight

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

Fry, R.J.M.

1993-04-01

This paper considers the radiation environment in aircraft at high altitudes and spacecraft in low earth orbit and in deep space and the factors that influence the dose equivalents. Altitude, latitude and solar cycle are the major influences for flights below the radiation belts. In deep space, solar cycle and the occurrence of solar particle events are the factors of influence. The major radiation effects of concern are cancer and infertility in males. In high altitude aircraft the radiation consists mainly of protons and neutrons, with neutrons contributing about half the equivalent dose. The average dose rate at altitudes ofmore » transcontinental flights that approach the polar regions are greater by a factor of about 2.5 than on routes at low latitudes. Current estimates of does to air crews suggest they are well within the ICRP (1990) recommended dose limits for radiation workers.« less

Dose rate effects in the radiation damage of the plastic scintillators of the CMS hadron endcap calorimeter

DOE PAGES

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; ...

2016-10-07

We present measurements of the reduction of light output by plastic scintillators irradiated in the CMS detector during the 8 TeV run of the Large Hadron Collider and show that they indicate a strong dose rate effect. The damage for a given dose is larger for lower dose rate exposures. The results agree with previous measurements of dose rate effects, but are stronger due to the very low dose rates probed. Here, we show that the scaling with dose rate is consistent with that expected from diffusion effects.

Fricke-gel dosimetry in epithermal or thermal neutron beams of a research reactor

NASA Astrophysics Data System (ADS)

Gambarini, G.; Artuso, E.; Giove, D.; Volpe, L.; Agosteo, S.; Barcaglioni, L.; Campi, F.; Garlati, L.; Pola, A.; Durisi, E.; Borroni, M.; Carrara, M.; Klupak, V.; Marek, M.; Viererbl, L.; Vins, M.; d'Errico, F.

2015-11-01

Fricke-xylenol-orange gel has shown noticeable potentiality for in-phantom dosimetry in epithermal or thermal neutron fields with very high fluence rate, as those characteristic of nuclear research reactors. Fricke gels in form of layers give the possibility of achieving spatial distribution of gamma dose, fast neutron dose and dose due to charged particles generated by thermal neutron reactions. The thermal neutron fluence has been deduced from the dose coming from the charge particles emitted by neutron reactions with the isotope 10B. Some measurements have been performed for improving the information on the relative sensitivity of Fricke gel dosimeters to the particles produced by 10B reactions, because at present the precision of dose evaluations is limited by the scanty knowledge about the dependence of the dosimeter sensitivity on the radiation LET. For in-air measurements, the dosimeter material can produce an enhancement of thermal neutron fluence. Measurements and Monte Carlo calculations have been developed to investigate the importance of this effect.

Comparative study of nuclear magnetic resonance and UV-visible spectroscopy dose-response of polymer gel based on N-(Isobutoxymethyl) acrylamide

NASA Astrophysics Data System (ADS)

Lotfy, S.; Basfar, A. A.; Moftah, B.; Al-Moussa, A. A.

2017-12-01

A comparative study of nuclear magnetic resonance and UV-visible spectroscopy of dose-response for polymer gel dosimeters was performed. Dosimeters were prepared using N-(Isobutoxymethyl) acrylamide (NIBMA) as a new monomer via radiation induced polymerization for use in radiotherapy planning. The prepared dosimeters were irradiated with doses up to 30 Gy at a constant dose rate of 600 MU/min. Using a medical linear accelerator at irradiation energies of 6, 10 and 18 MV photon beam. The nuclear magnetic resonance (NMR), via spin-spin relaxation rate (R2) for water proton surrounding the polymer formulation and UV-Visible spectroscopy, via the optical absorbance measurements of irradiated dosimeters at selected wavelengths of 500 nm, was used to investigate the dose response of NIBMAGAT gel dosimeters. Scavenge of oxygen was done using tetrakis (hydroxymethyl) phosphonium chloride (THPC). The THPC optimum concentration in the dosimeters formulations were 5 and 10 mM for the NMR and optical absorbance measurements respectively. The quantitative investigation of the dosimeters components reveals the selective formulations based on 4% w/w gelatin, 1% w/w NIBMA, 3% w/w BisAAm, 5 or 10 mM THPC and 17% w/w glycerol which significantly increase the dosimeters dose response. The prepared dosimeters were found to be dose rate and photon beam irradiation energy independent. The stability study shows no change in the relaxation rate or in the optical absorbance of the gel dosimeters up to 8 days post-irradiation. The prepared polymer gel dosimeters at the energies of 6, 10 and 18 MV photon beam irradiation in the range of 1-30 Gy have the linearity of the dose response function in the case of R2 is better than in the case of absorbance measurements; correlation coefficient (r2) equals 0.995 and 0.991, respectively. Dose sensitivity, R2 of NIBMAGAT dosimeters (0.0775 s-1 Gy-1). The absorption band intensity increases linearly with a dose sensitivity of 0.016 cm-1 Gy-1. The detection limit of the present dosimeter analyzed by R2 and absorbance measurements is 1 Gy and 2 Gy respectively. The overall uncertainty measurements of dose approve that by using the absorbance measurements the gel is not useful as a dosimeter like as R2 measurements. It could be a new composition of dosimeters successfully utilized for MRI (Magnetic Resonance Imaging) for radiotherapy treatment planning.

Geographical diffusion of prazosin across Veterans Health Administration: Examination of regional variation in daily dosing and quality indicators among veterans with posttraumatic stress disorder.

PubMed

Abrams, Thad E; Lund, Brian C; Alexander, Bruce; Bernardy, Nancy C; Friedman, Matthew J

2015-01-01

Posttraumatic stress disorder (PTSD) is a high-priority treatment area for the Veterans Health Administration (VHA), and dissemination patterns of innovative, efficacious therapies can inform areas for potential improvement of diffusion efforts and quality prescribing. In this study, we replicated a prior examination of the period prevalence of prazosin use as a function of distance from Puget Sound, Washington, where prazosin was first tested as an effective treatment for PTSD and where prazosin use was previously shown to be much greater than in other parts of the United States. We tested the following three hypotheses related to prazosin geographic diffusion: (1) a positive geographical correlation exists between the distance from Puget Sound and the proportion of users treated according to a guideline recommended minimum therapeutic target dose (>/=6 mg/d), (2) an inverse geographic correlation exists between prazosin and benzodiazepine use, and (3) no geographical correlation exists between prazosin use and serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor (SSRI/SNRI) use. Among a national sample of veterans with PTSD, overall prazosin utilization increased from 5.5 to 14.8% from 2006 to 2012. During this time period, rates at the Puget Sound VHA location declined from 34.4 to 29.9%, whereas utilization rates at locations a minimum of 2,500 miles away increased from 3.0 to 12.8%. Rates of minimum target dosing fell from 42.6 to 34.6% at the Puget Sound location. In contrast, at distances of at least 2,500 miles from Puget Sound, minimum threshold dosing rates remained stable (range, 18.6 to 17.7%). No discernible association was demonstrated between SSRI/SNRI or benzodiazepine utilization and the geographic distance from Puget Sound. Minimal threshold dosing of prazosin correlated positively with increased diffusion of prazosin use, but there was still a distance diffusion gradient. Although prazosin adoption has improved, geographic differences persist in both prescribing rates and minimum target dosing. Importantly, these regional disparities appear to be limited to prazosin prescribing and are not meaningfully correlated with SSRI/SNRI and benzodiazepine use as indicators of PTSD prescribing quality.

Single-dose pharmacokinetics and tolerability of oral delta-9- tetrahydrocannabinol in patients with amyotrophic lateral sclerosis.

PubMed

Joerger, Markus; Wilkins, Justin; Fagagnini, Stefania; Baldinger, Reto; Brenneisen, Rudolf; Schneider, Ursula; Goldman, Bea; Weber, Markus

2012-06-01

Cannabinoids exert neuroprotective and symptomatic effects in amyotrophic lateral sclerosis (ALS). We assessed the pharmacokinetics (PK) and tolerability of delta-9-tetrahydrocannabinol (THC) in ALS patients. Nine patients received THC single oral doses of 5mg and 10mg, separated by a wash-out period of two weeks. Blood samples for the determination of THC, 11-nor-9-carboxy-THC (THC-COOH) and hydroxy-THC (THC-OH) were taken up to 8 hours after intake. Adverse events were assessed by visual analogue scales (VAS). Plasma concentrations of the active metabolite THC-OH were submitted to sequential pharmacokinetic-pharmacodynamic population modeling on individual heart rate as a proxy for THC's cardiovasculatory effects. Drowsiness, euphoria, orthostasis, sleepiness, vertigo and weakness were significantly more frequent in patients receiving 10mg compared to 5 mg THC. A marked interindividual variability was found for the absorption of oral THC (84%) and elimination of THC-COOH (45%). PK data did not support any clinically relevant deviation from linear PK in the investigated range of concentrations. Plasma concentrations of THC-OH were positively correlated with the individual heart rate. An E(max-model) was successfully fitted to individual heart rate, with a THC-OH plasma concentration of 3.2 x 10(-4) μmol/L for EC(50) and an E(max) of 93 bpm for heart rate. The higher 10mg dose of THC was dose-limiting in patients with ALS. High interindividual PK variability requires individuell titration of THC for potential therapeutic use in patients with ALS.

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

PubMed Central

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

2016-01-01

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

Antioxidative potential of Duranta repens (Linn.) fruits against H2O2 induced cell death in vitro.

PubMed

Khan, Md Asaduzzaman; Rahman, Mohammad Mijanur; Tania, Mousumi; Shoshee, Nusrat Fatima; Xu, Ai-hua; Chen, Han-chun

2013-01-01

The effects of Duranta repens fruits were investigated on H2O2 induced oxidative cell death to evaluate its antioxidative potential in vitro. HEK293T cells were treated with different concentrations [0-1000 µg/ ml] of ethanol extract (E-Ex) and methanol extract (M-Ex) of D. repens for 24h, and then treated with 100 µM H2O2 for 24h. Cell viability, antioxidant parameters of cells, and antioxidant constituents of the extracts were determined. Treatment with limited dose of E-Ex or M-Ex increased the survival rate of H2O2-treated HEK293T cells, however the extra-high dose showed growth inhibitory effect. Treatment with E-Ex or M-Ex protected cellular lipid per-oxidation. In vitro analyses showed the 2,2-diphenyl-1-picrylhydrazyl and H2O2 scavenging activities as well as reducing potential of the extracts. We report here that the limited dose of E-Ex and M-Ex possess antioxidative potential, which can protect H2O2-induced oxidative cell damage.

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

NASA Astrophysics Data System (ADS)

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

2018-06-01

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

A paired comparison of tuberculin skin test results in health care workers using 5 TU and 10 TU tuberculin

PubMed Central

Stuart, R.; Bennett, N.; Forbes, A.; Grayson, M

2000-01-01

BACKGROUND—Historically, 10 TU has been employed in Australia and the United Kingdom to perform the tuberculin skin test (TST). However, this makes it difficult to compare the rates of TST positivity with other countries such as the USA who use 5 TU. To assess the impact of the dose of tuberculin on the TST a comparison was made of TST responses in health care workers given a TST with both 5 and 10 TU.
METHODS—Two TSTs were performed simultaneously in each health care worker using 5 and 10 TU. Each dose was randomly assigned in a blinded manner to the right or left forearm and read at 48-72 hours by a single nurse who was blinded to the assignment of the 5 and 10 TU doses.
RESULTS—A total of 128 health care workers were enrolled, 119 (93%) of whom had a past history of BCG vaccination. The overall mean difference in paired reaction sizes for the two doses was 1.5 mm with 95% limits of agreement of -3.6 to 6.5 mm.
CONCLUSION—A slightly larger TST reading was seen with 10 TU than with 5 TU. The mean difference of 1.5 mm between the two doses should be considered when comparing rates of TST positivity between countries who use different doses of tuberculin to perform the tuberculin skin test.

 PMID:10899248

Uracil-ftorafur: an oral fluoropyrimidine active in colorectal cancer.

PubMed

Sulkes, A; Benner, S E; Canetta, R M

1998-10-01

This review describes the early clinical development of uracil-ftorafur (UFT), an oral fluoropyrimidine, designed in 1978 by adding uracil to ftorafur. The review focuses on the treatment of colorectal cancer and summarizes the Japanese experience and the phase I and II trials performed in the United States and Europe. Clinical trials of UFT published in the Western world have included 581 patients with colorectal cancer. UFT has been administered in these trials as a single agent or biomodulated by leucovorin (LV). UFT was administered daily in split doses for periods that ranged from 14 to 28 days. The activity of oral UFT in large-bowel cancer when administered with oral LV (approximately 50 mg/dose) has resulted in objective response rates of approximately 40%. Response rates of approximately 25% (range, 17% to 39%) were reported when UFT was administered as a single agent or with lower doses of LV. The highest dose-intensities of UFT are achieved with 28-day schedules of administration. The maximum-tolerated dose (MTD) of UFT with this schedule, when administered concomitantly with oral LV 150 mg daily, is 300 mg/m2 daily. The dose-limiting toxicity (DLT) of UFT has generally been diarrhea. Other commonly described toxicities include nausea and vomiting, fatigue, and stomatitis. Myelosuppression occurs infrequently. Typically, hand-foot syndrome and neurologic toxicity are lacking. UFT is a fluoropyrimidine active in colorectal cancer. The oral route of administration and improved safety profile represent important advantages over both conventional and infusional fluorouracil (5-FU) regimens.

A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients.

PubMed

Bleiberg, H; Piccart, M; Lips, S; Panzer, J M; N'Koua Mbon, J B

1992-02-01

Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically-proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated.

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

Vandervoort, E.; Szanto, J.; Christiansen, E.

Plastic scintillation dosimeters (PSDs) have favourable characteristics for small and composite field dosimetry in radiosurgery, however, imperfect corrections for the Cerenkov radiation contamination could limit their accuracy for complex deliveries. In this work, we characterize the dose and dose-rate linearity, directional dependence, and compare output factors with other stereotactic detectors for a new commercially available PSD (Exradin W1). We provide some preliminary comparisons of planned and measured dose for composite fields delivered clinically by a Cyberknife radiosurgery system. The W1 detector shows good linearity with dose (<0.5%) and dose rate (<0.8%) relative to the signal obtained using an ion chambermore » under the same conditions. A maximum difference of 2% was observed depending on the detector's angular orientation. Output factors for all detectors agree within a range of ±3.2% and ±1.5% for the 5 and 7.5 mm collimators, respectively, provided Monte-Carlo corrections for detector effects are applied to diode and ion chambers (without corrections the range is ±5.5% and ±3.1% for these two collimators). For clinical beam deliveries using 5 and 7.5 mm collimators, four of the six patients showed better agreement with planned dose for the PSD detector compared to a micro ion chamber. Two of the six patients investigated, however, showed 5% differences between PSD and planned dose, film measurements and the ratio of PSD and micro ion chamber signal suggest that further investigation is warranted for these plans. The W1 detector is a promising tool for stereotactic plan verification under the challenging dosimetric conditions of stereotactic radiosurgery.« less

New era of electronic brachytherapy

PubMed Central

Ramachandran, Prabhakar

2017-01-01

Traditional brachytherapy refers to the placement of radioactive sources on or inside the cancer tissues. Based on the type of sources, brachytherapy can be classified as radionuclide and electronic brachytherapy. Electronic brachytherapy uses miniaturized X-ray sources instead of radionuclides to deliver high doses of radiation. The advantages of electronic brachytherapy include low dose to organs at risk, reduced dose to treating staff, no leakage radiation in off state, less shielding, and no radioactive waste. Most of these systems operate between 50 and 100 kVp and are widely used in the treatment of skin cancer. Intrabeam, Xoft and Papillon systems are also used in the treatment of intra-operative radiotherapy to breast in addition to other treatment sites. The rapid fall-off in the dose due to its low energy is a highly desirable property in brachytherapy and results in a reduced dose to the surrounding normal tissues compared to the Ir-192 source. The Xoft Axxent brachytherapy system uses a 2.25 mm miniaturized X-ray tube and the source almost mimics the high dose rate Ir-192 source in terms of dose rate and it is the only electronic brachytherapy system specifically used in the treatment of cervical cancers. One of the limiting factors that impede the use of electronic brachytherapy for interstitial application is the source dimension. However, it is highly anticipated that the design of miniaturized X-ray tube closer to the dimension of an Ir-192 wire is not too far away, and the new era of electronic brachytherapy has just begun. PMID:28529679

Radiation dose-rate meter using an energy-sensitive counter

DOEpatents

Kopp, Manfred K.

1988-01-01

A radiation dose-rate meter is provided which uses an energy-sensitive detector and combines charge quantization and pulse-rate measurement to monitor radiation dose rates. The charge from each detected photon is quantized by level-sensitive comparators so that the resulting total output pulse rate is proportional to the dose-rate.

Dosimetric intercomparison of permanent Ho-166 seed's implants and HDR Ir-192 brachytherapy in breast cancer.

PubMed

de Campos, Tarcisio Passos Ribeiro; Nogueira, Luciana Batista; Trindade, Bruno; Cuperschmid, Ethel Mizrahy

2016-01-01

To provide a comparative dosimetric analysis of permanent implants of Ho(166)-seeds and temporary HDR Ir(192)-brachytherapy through computational simulation. Brachytherapy with Ir(192)-HDR or LDR based on temporary wires or permanent radioactive seed implants can be used as dose reinforcement for breast radiation therapy. Permanent breast implants have not been a practical clinical routine; although, I(125) and Pd(103)-seeds have already been reported. Biodegradable Ho(166)-ceramic-seeds have been addressed recently. Simulations of implants of nine Ho(166)-seeds and equivalent with HDR Ir(192)-brachytherapy were elaborated in MCNP5, shaped in a computational multivoxel simulator which reproduced a female thorax phantom. Spatial dose rate distributions and dose-volume histograms were generated. Protocol's analysis involving exposure time, seed's activities and dose were performed. Permanent Ho(166)-seed implants presented a maximum dose rate per unit of contained activity (MDR) of 1.1601 μGy h(-1) Bq(-1); and, a normalized MDR in standard points (8 mm, equidistant to 03-seeds - SP1, 10 mm - SP2) of 1.0% (SP1) and 0.5% (SP2), respectively. Ir(192)-brachytherapy presented MDR of 4.3945 × 10(-3) μGy h(-1) Bq(-1); and, 30% (SP1), and 20% (SP2). Therefore, seed's implant activities of 333 MBq (Ho(166)) and 259 GBq (Ir(192)) produced prescribed doses of 58 Gy (SP1; 5d) and 56 Gy (SP1, 5 fractions, 6 min), respectively. Breast Ho(166)-implants of 37-111 MBq are attractive due to the high dose rate near 6-10 mm from seeds, equivalent to Ir(192)-brachytherapy of 259 GBq (3 fractions, 6 min) providing similar dose in standard points at a week; however, with spatial dose distribution better confined. The seed positioning can be adjusted for controlling the breast tumor, in stages I and II, in flat and deep tumors, without any breast volumetric limitation.

SU-E-T-586: Optimal Determination of Tolerance Level for Radiation Dose Delivery Verification in An in Vivo Dosimetry System

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

Chen, Y; Souri, S; Gill, G

Purpose: To statistically determine the optimal tolerance level in the verification of delivery dose compared to the planned dose in an in vivo dosimetry system in radiotherapy. Methods: The LANDAUER MicroSTARii dosimetry system with screened nanoDots (optically stimulated luminescence dosimeters) was used for in vivo dose measurements. Ideally, the measured dose should match with the planned dose and falls within a normal distribution. Any deviation from the normal distribution may be redeemed as a mismatch, therefore a potential sign of the dose misadministration. Randomly mis-positioned nanoDots can yield a continuum background distribution. A percentage difference of the measured dose tomore » its corresponding planned dose (ΔD) can be used to analyze combined data sets for different patients. A model of a Gaussian plus a flat function was used to fit the ΔD distribution. Results: Total 434 nanoDot measurements for breast cancer patients were collected across a period of three months. The fit yields a Gaussian mean of 2.9% and a standard deviation (SD) of 5.3%. The observed shift of the mean from zero is attributed to the machine output bias and calibration of the dosimetry system. A pass interval of −2SD to +2SD was applied and a mismatch background was estimated to be 4.8%. With such a tolerance level, one can expect that 99.99% of patients should pass the verification and at most 0.011% might have a potential dose misadministration that may not be detected after 3 times of repeated measurements. After implementation, a number of new start breast cancer patients were monitored and the measured pass rate is consistent with the model prediction. Conclusion: It is feasible to implement an optimal tolerance level in order to maintain a low limit of potential dose misadministration while still to keep a relatively high pass rate in radiotherapy delivery verification.« less

76 FR 53847 - New International Commission on Radiological Protection; Recommendations on the Annual Dose Limit...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

... Radiological Protection; Recommendations on the Annual Dose Limit to the Lens of the Eye AGENCY: Nuclear... Protection (ICRP) recommendations for the limitation of annual dose to the lens of the eye. This significant... might be lower than previously considered. For the lens of the eye, the threshold in absorbed dose for...

Ionizing radiation induces O6-alkylguanine-DNA-alkyltransferase mRNA and activity in mouse tissues.

PubMed

Wilson, R E; Hoey, B; Margison, G P

1993-04-01

The effect of exposure to whole-body gamma-irradiation or fast electrons on O6-alkylguanine-DNA-alkyltransferase (ATase) activity and mRNA abundance has been examined in mice. In response to gamma-radiation, hepatic ATase activity was significantly raised in BDF1 mice 24 h post-irradiation, reaching a maximum of 2- to 3-fold at 36 h and beginning to decrease by 48-60 h. A small but consistently higher level of induction was achieved when mice were exposed using a low dose rate (0.015 Gy/min) compared to a high dose rate (0.5 Gy/min). ATase activity was also induced approximately 2-fold 48 h post-irradiation in brain, kidney, lung and spleen, with a greater induction again observed in response to the lower dose rate. In response to fast electrons from a linear accelerator hepatic ATase activity was also induced 2- to 3-fold 48 h post-irradiation in BDF1, BALB/c, C57Bl and DBA2 strains. Induction of ATase activity in livers of BDF1 mice was observed 48 h after a total single dose of 5 Gy gamma-radiation (2-fold), increasing to a slightly higher level at 15 Gy, but no induction was observed at doses of 2 Gy and below. Although a maximum 2- to 3-fold induction of ATase activity was observed, mRNA levels were induced 3- to 4-fold by 48 h after a dose of 15 Gy. Furthermore, significant increases in mRNA levels were detected at low doses (1-2 Gy) at which there was no apparent increase in ATase activity. This suggests that ionizing radiation increases ATase levels by a process involving transcriptional upregulation but that strong post-transcriptional and/or translational controls operate to limit induction of enzyme activity to 2- to 3-fold. This is the first report of an in vivo induction of ATase by ionizing radiation in a species other than the rat.

TH-A-19A-11: Validation of GPU-Based Monte Carlo Code (gPMC) Versus Fully Implemented Monte Carlo Code (TOPAS) for Proton Radiation Therapy: Clinical Cases Study

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

Giantsoudi, D; Schuemann, J; Dowdell, S

Purpose: For proton radiation therapy, Monte Carlo simulation (MCS) methods are recognized as the gold-standard dose calculation approach. Although previously unrealistic due to limitations in available computing power, GPU-based applications allow MCS of proton treatment fields to be performed in routine clinical use, on time scales comparable to that of conventional pencil-beam algorithms. This study focuses on validating the results of our GPU-based code (gPMC) versus fully implemented proton therapy based MCS code (TOPAS) for clinical patient cases. Methods: Two treatment sites were selected to provide clinical cases for this study: head-and-neck cases due to anatomical geometrical complexity (air cavitiesmore » and density heterogeneities), making dose calculation very challenging, and prostate cases due to higher proton energies used and close proximity of the treatment target to sensitive organs at risk. Both gPMC and TOPAS methods were used to calculate 3-dimensional dose distributions for all patients in this study. Comparisons were performed based on target coverage indices (mean dose, V90 and D90) and gamma index distributions for 2% of the prescription dose and 2mm. Results: For seven out of eight studied cases, mean target dose, V90 and D90 differed less than 2% between TOPAS and gPMC dose distributions. Gamma index analysis for all prostate patients resulted in passing rate of more than 99% of voxels in the target. Four out of five head-neck-cases showed passing rate of gamma index for the target of more than 99%, the fifth having a gamma index passing rate of 93%. Conclusion: Our current work showed excellent agreement between our GPU-based MCS code and fully implemented proton therapy based MC code for a group of dosimetrically challenging patient cases.« less

The susceptibility of TaO x-based memristors to high dose rate ionizing radiation and total ionizing dose

DOE PAGES

McLain, Michael Lee; Sheridan, Timothy J.; Hjalmarson, Harold Paul; ...

2014-11-11

This paper investigates the effects of high dose rate ionizing radiation and total ionizing dose (TID) on tantalum oxide (TaO x) memristors. Transient data were obtained during the pulsed exposures for dose rates ranging from approximately 5.0 ×10 7 rad(Si)/s to 4.7 ×10 8 rad(Si)/s and for pulse widths ranging from 50 ns to 50 μs. The cumulative dose in these tests did not appear to impact the observed dose rate response. Static dose rate upset tests were also performed at a dose rate of ~3.0 ×10 8 rad(Si)/s. This is the first dose rate study on any type ofmore » memristive memory technology. In addition to assessing the tolerance of TaO x memristors to high dose rate ionizing radiation, we also evaluated their susceptibility to TID. The data indicate that it is possible for the devices to switch from a high resistance off-state to a low resistance on-state in both dose rate and TID environments. The observed radiation-induced switching is dependent on the irradiation conditions and bias configuration. Furthermore, the dose rate or ionizing dose level at which a device switches resistance states varies from device to device; the enhanced susceptibility observed in some devices is still under investigation. As a result, numerical simulations are used to qualitatively capture the observed transient radiation response and provide insight into the physics of the induced current/voltages.« less

Space: The Final Frontier-Research Relevant to Mars.

PubMed

Boice, John D

2017-04-01

A critically important gap in knowledge surrounds the health consequences of exposure to radiation received gradually over time. Much is known about the health effects of brief high-dose exposures, such as from the atomic bombings in Japan, but the concerns today focus on the frequent low-dose exposures received by members of the public, workers, and, as addressed in this paper, astronauts. Additional guidance is needed by the National Aeronautics and Space Administration (NASA) for planning long-term missions where the rate of radiation exposure is gradual over years and the cumulative amounts high. The direct study of low doses and low-dose rates is of immeasurable value in understanding the possible range of health effects from gradual exposures and in providing guidance for radiation protection, not only of workers and the public but also astronauts. The ongoing Million Person Study (MPS) is 10 times larger than the study of the Japanese atomic bomb survivors of 86,000 survivors with estimated doses. The number of workers with >100 mSv career dose is substantially greater. The large study size, broad range of doses, and long follow-up indicate substantial statistical ability to quantify the risk of exposures that are received gradually over time. The study consists of 360,000 U.S. Department of Energy workers from the Manhattan Project; 150,000 nuclear utility workers from the inception of the nuclear age; 115,000 atomic veterans who participated in above-ground atmospheric tests at the Nevada Test Site and the Bikini and Enewetak Atolls and Johnston Island in the Pacific Proving Grounds (PPG); 250,000 radiologists and medical workers; and 130,000 industrial radiographers. NASA uses an individual risk-based system for radiation protection in contrast to the system of dose limits for occupational exposures used by terrestrial-based organizations. The permissible career exposure limit set by NASA for each astronaut is a 3% risk of exposure-induced death (REID) from cancer at a 95% confidence level to account for uncertainties in risk projections. The large size of the MPS will reduce the uncertainty in the risk estimates, narrowing the 95% confidence interval, and thus allow more time in space for astronauts. Further differences between men and women in their response to radiation can be more fully examined, and non-cancer outcomes, such as neurological disorders and cardiovascular disease, can be evaluated in a way not hitherto possible.

Leptin stimulates bone formation in ob/ob mice at doses having minimal impact on energy metabolism.

PubMed

Philbrick, Kenneth A; Wong, Carmen P; Branscum, Adam J; Turner, Russell T; Iwaniec, Urszula T

2017-03-01

Leptin, the protein product of the ob gene, is essential for normal bone growth, maturation and turnover. Peripheral actions of leptin occur at lower serum levels of the hormone than central actions because entry of leptin into the central nervous system (CNS) is limited due to its saturable transport across the blood-brain barrier (BBB). We performed a study in mice to model the impact of leptin production associated with different levels of adiposity on bone formation and compared the response with well-established centrally mediated actions of the hormone on energy metabolism. Leptin was infused (0, 4, 12, 40, 140 or 400 ng/h) for 12 days into 6-week-old female ob/ob mice (n = 8/group) using sc-implanted osmotic pumps. Treatment resulted in a dose-associated increase in serum leptin. Bone formation parameters were increased at EC 50 infusion rates of 7-17 ng/h, whereas higher levels (EC 50 , 40-80 ng/h) were required to similarly influence indices of energy metabolism. We then analyzed gene expression in tibia and hypothalamus at dose rates of 0, 12 and 140 ng/h; the latter dose resulted in serum leptin levels similar to WT mice. Infusion with 12 ng/h leptin increased the expression of genes associated with Jak/Stat signaling and bone formation in tibia with minimal effect on Jak/Stat signaling and neurotransmitters in hypothalamus. The results suggest that leptin acts peripherally to couple bone acquisition to energy availability and that limited transport across the BBB insures that the growth-promoting actions of peripheral leptin are not curtailed by the hormone's CNS-mediated anorexigenic actions. © 2017 Society for Endocrinology.

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

PubMed

Kragelj, Borut

2016-03-01

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

Intraarticular Sacroiliac Joint Injection Under Computed Tomography Fluoroscopic Guidance: A Technical Note to Reduce Procedural Time and Radiation Dose

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

Paik, Nam Chull, E-mail: pncspine@gmail.com

2016-07-15

PurposeA technique for computed tomography fluoroscopy (CTF)-guided intraarticular (IA) sacroiliac joint (SIJ) injection was devised to limit procedural time and radiation dose.MethodsOur Institutional Review Board approved this retrospective analysis and waived the requirement for informed consent. Overall, 36 consecutive diagnostic or therapeutic IA SIJ injections (unilateral, 20; bilateral, 16) performed in 34 patients (female, 18; male, 16) with a mean age of 45.5 years (range 20–76 years) under CTF guidance were analyzed, assessing technical success (i.e., IA contrast spread), procedural time, and radiation dose.ResultsAll injections were successful from a technical perspective and were free of serious complications. Respective median proceduralmore » times and effective doses of SIJ injection were as follows: unilateral, 5.28 min (range 3.58–8.00 min) and 0.11 millisievert (mSv; range 0.07–0.24 mSv); and bilateral, 6.72 min (range 4.17–21.17 min) and 0.11 mSv (range 0.09–0.51 mSv).ConclusionsGiven the high rate of technical success achieved in limited time duration and with little radiation exposure, CTF-guided IA SIJ injection is a practical and low-risk procedure.« less

NEUTRON CHARACTERIZATION OF ENSA-DPT TYPE SPENT FUEL CASK AT TRILLO NUCLEAR POWER PLANT.

PubMed

Méndez-Villafañe, Roberto; Campo-Blanco, Xandra; Embid, Miguel; Yéboles, César A; Morales, Ramón; Novo, Manuel; Sanz, Javier

2018-04-23

The Neutron Standards Laboratory of CIEMAT has conducted the characterization of the independent spent fuel storage installation at the Trillo Nuclear Power Plant. At this facility, the spent fuel assemblies are stored in ENSA-DPT type dual purpose casks. Neutron characterization was performed by dosimetry measurements with a neutron survey meter (LB6411) inside the facility, around an individual cask and between stored casks, and outside the facility. Spectra measurements were also performed with a Bonner sphere system in order to determine the integral quantities and validate the use of the neutron monitor at the different positions. Inside the facility, measured neutron spectra and neutron ambient dose equivalent rate are consistent with the casks spatial distribution and neutron emission rates, and measurements with both instruments are consistent with each other. Outside the facility, measured neutron ambient dose equivalent rates are well below the 0.5 μSv/h limit established by the nuclear regulatory authority.

An accurate derivation of the air dose-rate and the deposition concentration distribution by aerial monitoring in a low level contaminated area

NASA Astrophysics Data System (ADS)

Nishizawa, Yukiyasu; Sugita, Takeshi; Sanada, Yukihisa; Torii, Tatsuo

2015-04-01

Since 2011, MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan) have been conducting aerial monitoring to investigate the distribution of radioactive cesium dispersed into the atmosphere after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), Tokyo Electric Power Company. Distribution maps of the air dose-rate at 1 m above the ground and the radioactive cesium deposition concentration on the ground are prepared using spectrum obtained by aerial monitoring. The radioactive cesium deposition is derived from its dose rate, which is calculated by excluding the dose rate of the background radiation due to natural radionuclides from the air dose-rate at 1 m above the ground. The first step of the current method of calculating the dose rate due to natural radionuclides is calculate the ratio of the total count rate of areas where no radioactive cesium is detected and the count rate of regions with energy levels of 1,400 keV or higher (BG-Index). Next, calculate the air dose rate of radioactive cesium by multiplying the BG-Index and the integrated count rate of 1,400 keV or higher for the area where the radioactive cesium is distributed. In high dose-rate areas, however, the count rate of the 1,365-keV peak of Cs-134, though small, is included in the integrated count rate of 1,400 keV or higher, which could cause an overestimation of the air dose rate of natural radionuclides. We developed a method for accurately evaluating the distribution maps of natural air dose-rate by excluding the effect of radioactive cesium, even in contaminated areas, and obtained the accurate air dose-rate map attributed the radioactive cesium deposition on the ground. Furthermore, the natural dose-rate distribution throughout Japan has been obtained by this method.

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

PubMed

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

2016-01-01

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

Six steps to a successful dose-reduction strategy

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

Bennett, M.

1995-03-01

The increased importance of demonstrating achievement of the ALARA principle has helped produce a proliferation of dose-reduction ideas. Across a company there may be many dose-reduction items being pursued in a variety of areas. However, companies have a limited amount of resource and, therefore, to ensure funding is directed to those items which will produce the most benefit and that all areas apply a common policy, requires the presence of a dose-reduction strategy. Six steps were identified in formulating the dose-reduction strategy for Rolls-Royce and Associates (RRA): (1) collating the ideas; (2) quantitatively evaluating them on a common basis; (3)more » prioritizing the ideas in terms of cost benefit, (4) implementation of the highest priority items; (5) monitoring their success; (6) periodically reviewing the strategy. Inherent in producing the dose-reduction strategy has been a comprehensive dose database and the RRA-developed dose management computer code DOMAIN, which allows prediction of dose rates and dose. The database enabled high task dose items to be identified, assisted in evaluating dose benefits, and monitored dose trends once items had been implemented. The DOMAIN code was used both in quantifying some of the project dose benefits and its results, such as dose contours, used in some of the dose-reduction items themselves. In all, over fifty dose-reduction items were evaluated in the strategy process and the items which will give greatest benefit are being implemented. The strategy has been successful in giving renewed impetus and direction to dose-reduction management.« less

Leuco-crystal-violet micelle gel dosimeters: Component effects on dose-rate dependence

NASA Astrophysics Data System (ADS)

Xie, J. C.; Katz, E. A. B.; Alexander, K. M.; Schreiner, L. J.; McAuley, K. B.

2017-05-01

Designed experiments were performed to produce empirical models for the dose sensitivity, initial absorbance, and dose-rate dependence respectively for leucocrystal violet (LCV) micelle gel dosimeters containing cetyltrimethylammonium bromide (CTAB) and 2,2,2-trichloroethanol (TCE). Previous gels of this type showed dose-rate dependent behaviour, producing an ˜18% increase in dose sensitivity between dose rates of 100 and 600 cGy min-1. Our models predict that the dose rate dependence can be reduced by increasing the concentration of TCE, CTAB and LCV. Increasing concentrations of LCV and CTAB produces a significant increase in dose sensitivity with a corresponding increase in initial absorbance. An optimization procedure was used to determine a nearly dose-rate independent gel which maintained high sensitivity and low initial absorbance. This gel which contains 33 mM CTAB, 1.25 mM LCV, and 96 mM TCE in 25 mM trichloroacetic acid and 4 wt% gelatin showed an increase in dose sensitivity of only 4% between dose rates of 100 and 600 cGy min-1, and provides an 80% greater dose sensitivity compared to Jordan’s standard gels with similar initial absorbance.

Dose and dose rate effects of whole-body gamma-irradiation: I. Lymphocytes and lymphoid organs

NASA Technical Reports Server (NTRS)

Pecaut, M. J.; Nelson, G. A.; Gridley, D. S.

2001-01-01

The major goal of part I of this study was to compare varying doses and dose rates of whole-body gamma-radiation on lymphoid cells and organs. C57BL/6 mice (n = 75) were exposed to 0, 0.5, 1.5, and 3.0 Gy gamma-rays (60Co) at 1 cGy/min (low-dose rate, LDR) and 80 cGy/min (high-dose rate, HDR) and euthanized 4 days later. A significant dose-dependent loss of spleen mass was observed with both LDR and HDR irradiation; for the thymus this was true only with HDR. Decreasing leukocyte and lymphocyte numbers occurred with increasing dose in blood and spleen at both dose rates. The numbers (not percentages) of CD3+ T lymphocytes decreased in the blood in a dose-dependent manner at both HDR and LDR. Splenic T cell counts decreased with dose only in HDR groups; percentages increased with dose at both dose rates. Dose-dependent decreases occurred in CD4+ T helper and CD8+ T cytotoxic cell counts at HDR and LDR. In the blood the percentages of CD4+ cells increased with increasing dose at both dose rates, whereas in the spleen the counts decreased only in the HDR groups. The percentages of the CD8+ population remained stable in both blood and spleen. CD19+ B cell counts and percentages in both compartments declined markedly with increasing HDR and LDR radiation. NK1.1+ natural killer cell numbers and proportions remained relatively stable. Overall, these data indicate that the observed changes were highly dependent on the dose, but not dose rate, and that cells in the spleen are more affected by dose rate than those in blood. The results also suggest that the response of lymphocytes in different body compartments may be variable.

Estimation of the Dose and Dose Rate Effectiveness Factor

NASA Technical Reports Server (NTRS)

Chappell, L.; Cucinotta, F. A.

2013-01-01

Current models to estimate radiation risk use the Life Span Study (LSS) cohort that received high doses and high dose rates of radiation. Transferring risks from these high dose rates to the low doses and dose rates received by astronauts in space is a source of uncertainty in our risk calculations. The solid cancer models recommended by BEIR VII [1], UNSCEAR [2], and Preston et al [3] is fitted adequately by a linear dose response model, which implies that low doses and dose rates would be estimated the same as high doses and dose rates. However animal and cell experiments imply there should be curvature in the dose response curve for tumor induction. Furthermore animal experiments that directly compare acute to chronic exposures show lower increases in tumor induction than acute exposures. A dose and dose rate effectiveness factor (DDREF) has been estimated and applied to transfer risks from the high doses and dose rates of the LSS cohort to low doses and dose rates such as from missions in space. The BEIR VII committee [1] combined DDREF estimates using the LSS cohort and animal experiments using Bayesian methods for their recommendation for a DDREF value of 1.5 with uncertainty. We reexamined the animal data considered by BEIR VII and included more animal data and human chromosome aberration data to improve the estimate for DDREF. Several experiments chosen by BEIR VII were deemed inappropriate for application to human risk models of solid cancer risk. Animal tumor experiments performed by Ullrich et al [4], Alpen et al [5], and Grahn et al [6] were analyzed to estimate the DDREF. Human chromosome aberration experiments performed on a sample of astronauts within NASA were also available to estimate the DDREF. The LSS cohort results reported by BEIR VII were combined with the new radiobiology results using Bayesian methods.

Recommended treatment for urinary tract infection in pregnancy.

PubMed

Vercaigne, L M; Zhanel, G G

1994-02-01

To establish and recommend a therapeutic regimen for the treatment of urinary tract infection (UTI) in pregnancy based on the published studies. An English-language literature search employing MEDLINE, Index Medicus, and bibliographic reviews of the references obtained were searched (key terms: urinary tract infection, UTI, pregnancy, bacteriuria). All identified human studies dealing with bacteriuria or UTI in pregnancy were analyzed. Limited data are available regarding the appropriate antibiotic management of UTI in pregnancy. Single-dose cure rates with amoxicillin are approximately 80 percent. Trimethoprim/sulfamethoxazole provides cure rates of greater than 80 percent. Cephalosporins and nitrofurantoin produce variable results. We recommend separating pregnant subjects with UTI into two groups. Those with asymptomatic bacteriuria can be treated with a single dose of an antimicrobial to which the organism is susceptible. For those with symptomatic UTI, we recommend amoxicillin 500 mg tid for three days. Urine cultures should be repeated seven days following therapy to assess cure or failure. Well-designed studies need to be performed, comparing single-dose and three-day therapy for UTI in pregnancy.

Treatment of chancroid in resource-poor countries.

PubMed

Annan, Naa Torshie; Lewis, David A

2005-04-01

Chancroid, formerly a major cause of the genital ulcer disease syndrome, remains an important cofactor in both the transmission and acquisition of HIV-1 infection. Those countries with the greatest burden of HIV also have some of the highest prevalence rates of chancroid worldwide. The diagnosis of chancroid, caused by the fastidious bacterium Haemophilus ducreyi, is both expensive and difficult in many resource-poor areas. These areas of the world use syndromic management to treat genital ulcers and such an approach has proven effective in reducing rates of bacterial genital ulcer diseases. There are currently inexpensive and effective single-dose therapies available to treat chancroid. Single-dose regimens, given at first presentation, improve compliance and reduce the risk of sexually transmitted infections. Bacterial resistance to several antimicrobial agents has increased over the years and remains a continued threat to effective antimicrobial therapy. Follow-up of cases, and partner notification and treatment is carried out to limit reinfection and onward transmission of chancroid. Patients with coexistent HIV may be particularly at risk of failing single-dose therapy and should therefore be reviewed wherever possible.

Vaccine hypersensitivity--update and overview.

PubMed

Fritsche, Philipp J; Helbling, Arthur; Ballmer-Weber, Barbara K

2010-05-01

Concerns about possible reactions to vaccines or vaccinations are frequently raised. However, the rate of reported vaccine-induced adverse events is low and ranges between 4.8-83.0 per 100,000 doses of the most frequently used vaccines. The number of true allergic reactions to routine vaccines is not known; estimations range from 1 per 500,000 to 1 per 1,000,000 doses for most vaccines. When allergens such as gelatine or egg proteins are components of the formulation, the rate for serious allergic reactions may be higher. Nevertheless, anaphylactic, potentially life-threatening reactions to vaccines are still a rare event (approximately 1 per 1,500,000 doses). The variety of reported vaccine-related adverse events is broad. Most frequently, reactions to vaccines are limited to the injection site and result from a non specific activation of the inflammatory system by, for example, aluminium salts or the active microbial components. If allergy is suspected, an accurate examination followed by algorithms is the key for correct diagnosis, treatment and the decision regarding revaccination in patients with immediate-type reactions to vaccines.

Dose Rate Effects in Linear Bipolar Transistors

NASA Technical Reports Server (NTRS)

Johnston, Allan; Swimm, Randall; Harris, R. D.; Thorbourn, Dennis

2011-01-01

Dose rate effects are examined in linear bipolar transistors at high and low dose rates. At high dose rates, approximately 50% of the damage anneals at room temperature, even though these devices exhibit enhanced damage at low dose rate. The unexpected recovery of a significant fraction of the damage after tests at high dose rate requires changes in existing test standards. Tests at low temperature with a one-second radiation pulse width show that damage continues to increase for more than 3000 seconds afterward, consistent with predictions of the CTRW model for oxides with a thickness of 700 nm.

Ivabradine in stable coronary artery disease without clinical heart failure.

PubMed

Fox, Kim; Ford, Ian; Steg, Philippe Gabriel; Tardif, Jean-Claude; Tendera, Michal; Ferrari, Roberto

2014-09-18

An elevated heart rate is an established marker of cardiovascular risk. Previous analyses have suggested that ivabradine, a heart-rate-reducing agent, may improve outcomes in patients with stable coronary artery disease, left ventricular dysfunction, and a heart rate of 70 beats per minute or more. We conducted a randomized, double-blind, placebo-controlled trial of ivabradine, added to standard background therapy, in 19,102 patients who had both stable coronary artery disease without clinical heart failure and a heart rate of 70 beats per minute or more (including 12,049 patients with activity-limiting angina [class ≥II on the Canadian Cardiovascular Society scale, which ranges from I to IV, with higher classes indicating greater limitations on physical activity owing to angina]). We randomly assigned patients to placebo or ivabradine, at a dose of up to 10 mg twice daily, with the dose adjusted to achieve a target heart rate of 55 to 60 beats per minute. The primary end point was a composite of death from cardiovascular causes or nonfatal myocardial infarction. At 3 months, the mean (±SD) heart rate of the patients was 60.7±9.0 beats per minute in the ivabradine group versus 70.6±10.1 beats per minute in the placebo group. After a median follow-up of 27.8 months, there was no significant difference between the ivabradine group and the placebo group in the incidence of the primary end point (6.8% and 6.4%, respectively; hazard ratio, 1.08; 95% confidence interval, 0.96 to 1.20; P=0.20), nor were there significant differences in the incidences of death from cardiovascular causes and nonfatal myocardial infarction. Ivabradine was associated with an increase in the incidence of the primary end point among patients with activity-limiting angina but not among those without activity-limiting angina (P=0.02 for interaction). The incidence of bradycardia was higher with ivabradine than with placebo (18.0% vs. 2.3%, P<0.001). Among patients who had stable coronary artery disease without clinical heart failure, the addition of ivabradine to standard background therapy to reduce the heart rate did not improve outcomes. (Funded by Servier; SIGNIFY Current Controlled Trials number, ISRCTN61576291.).

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

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

Orton, C; Borras, C; Carlson, D

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

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

PubMed

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

2017-01-01

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

Limited chemotherapy and shrinking field radiotherapy for Osteolymphoma (primary bone lymphoma): results from the trans-Tasman Radiation Oncology Group 99.04 and Australasian Leukaemia and Lymphoma Group LY02 prospective trial.

PubMed

Christie, David; Dear, Keith; Le, Thai; Barton, Michael; Wirth, Andrew; Porter, David; Roos, Daniel; Pratt, Gary

2011-07-15

To establish benchmark outcomes for combined modality treatment to be used in future prospective studies of osteolymphoma (primary bone lymphoma). In 1999, the Trans-Tasman Radiation Oncology Group (TROG) invited the Australasian Leukemia and Lymphoma Group (ALLG) to collaborate on a prospective study of limited chemotherapy and radiotherapy for osteolymphoma. The treatment was designed to maintain efficacy but limit the risk of subsequent pathological fractures. Patient assessment included both functional imaging and isotope bone scanning. Treatment included three cycles of CHOP chemotherapy and radiation to a dose of 45 Gy in 25 fractions using a shrinking field technique. The trial closed because of slow accrual after 33 patients had been entered. Accrual was noted to slow down after Rituximab became readily available in Australia. After a median follow-up of 4.3 years, the five-year overall survival and local control rates are estimated at 90% and 72% respectively. Three patients had fractures at presentation that persisted after treatment, one with recurrent lymphoma. Relatively high rates of survival were achieved but the number of local failures suggests that the dose of radiotherapy should remain higher than it is for other types of lymphoma. Disability after treatment due to pathological fracture was not seen. Copyright © 2011 Elsevier Inc. All rights reserved.

LDR brachytherapy: can low dose rate hypersensitivity from the "inverse" dose rate effect cause excessive cell killing to peripherial connective tissues and organs?

PubMed

Leonard, B E; Lucas, A C

2009-02-01

Examined here are the possible effects of the "inverse" dose rate effect (IDRE) on low dose rate (LDR) brachytherapy. The hyper-radiosensitivity and induced radioresistance (HRS/IRR) effect benefits cell killing in radiotherapy, and IDRE and HRS/IRR seem to be generated from the same radioprotective mechanisms. We have computed the IDRE excess cell killing experienced in LDR brachytherapy using permanent seed implants. We conclude, firstly, that IDRE is a dose rate-dependent manifestation of HRS/IRR. Secondly, the presence of HRS/IRR or IDRE in a cell species or tissue must be determined by direct dose-response measurements. Thirdly, a reasonable estimate is that 50-80% of human adjoining connective and organ tissues experience IDRE from permanent implanted LDR brachytherapy. If IDRE occurs for tissues at point A for cervical cancer, the excess cell killing will be about a factor of 3.5-4.0 if the initial dose rate is 50-70 cGy h(-1). It is greater for adjacent tissues at lower dose rates and higher for lower initial dose rates at point A. Finally, higher post-treatment complications are observed in LDR brachytherapy, often for unknown reasons. Some of these are probably a result of IDRE excess cell killing. Measurements of IDRE need be performed for connective and adjacent organ tissues, i.e. bladder, rectum, urinary tract and small bowels. The measured dose rate-dependent dose responses should extended to <10 cGy h(-1) and involve multiple patients to detect patient variability. Results may suggest a preference for high dose rate brachytherapy or LDR brachytherapy without permanent retention of the implant seeds (hence the dose rates in peripheral tissues and organs remain above IDRE thresholds).

Desvenlafaxine in major depressive disorder: an evidence-based review of its place in therapy

PubMed Central

Lieberman, Daniel Z; Massey, Suena H

2010-01-01

Introduction: Desvenlafaxine, the active metabolite of venlafaxine, is a serotonin norepinephrine reuptake inhibitor (SNRI) recently approved for the treatment of major depressive disorder. It is one of only three medications in this class available in the United States. Aims: The objective of this article is to review the published evidence for the safety and efficacy of desvenlafaxine, and to compare it to other antidepressants to delineate its role in the treatment of depression. Evidence review: At the recommended dose of 50 mg per day the rate of response and remission was similar to other SNRIs, as was the adverse effect profile. The rate of discontinuation was no greater than placebo, and a discontinuation syndrome was not observed at this dose. Higher doses were not associated with greater efficacy, but they did lead to more side effects, and the use of a taper prior to discontinuation. The most common side effects reported were insomnia, somnolence, dizziness, and nausea. Some subjects experienced clinically significant blood pressure elevation. Place in therapy: Like duloxetine, desvenlafaxine inhibits the reuptake of both norepinephrine and serotonin at the starting dose. Dual reuptake inhibitors have been shown to have small but statistically significantly greater rates of response and remission compared to selective serotonin reuptake inhibitors, and they have also shown early promise in the treatment of neuropathic pain. Desvenlafaxine may prove to be a valuable treatment option by expanding the limited number of available dual reuptake inhibitors. PMID:20694066

Assessment of Natural Radioactivity Levels and Potential Radiological Risks of Common Building Materials Used in Bangladeshi Dwellings.

PubMed

Asaduzzaman, Khandoker; Mannan, Farhana; Khandaker, Mayeen Uddin; Farook, Mohideen Salihu; Elkezza, Aeman; Amin, Yusoff Bin Mohd; Sharma, Sailesh; Abu Kassim, Hasan Bin

2015-01-01

The concentrations of primordial radionuclides (226Ra, 232Th and 40K) in commonly used building materials (brick, cement and sand), the raw materials of cement and the by-products of coal-fired power plants (fly ash) collected from various manufacturers and suppliers in Bangladesh were determined via gamma-ray spectrometry using an HPGe detector. The results showed that the mean concentrations of 226Ra, 232Th and 40K in all studied samples slightly exceeded the typical world average values of 50 Bq kg(-1), 50 Bq kg(-1) and 500 Bq kg(-1), respectively. The activity concentrations (especially 226Ra) of fly-ash-containing cement in this study were found to be higher than those of fly-ash-free cement. To evaluate the potential radiological risk to individuals associated with these building materials, various radiological hazard indicators were calculated. The radium equivalent activity values for all samples were found to be lower than the recommended limit for building materials of 370 Bq kg(-1), with the exception of the fly ash. For most samples, the values of the alpha index and the radiological hazard (external and internal) indices were found to be within the safe limit of 1. The mean indoor absorbed dose rate was observed to be higher than the population-weighted world average of 84 nGy h(-1), and the corresponding annual effective dose for most samples fell below the recommended upper dose limit of 1 mSv y(-1). For all investigated materials, the values of the gamma index were found to be greater than 0.5 but less than 1, indicating that the gamma dose contribution from the studied building materials exceeds the exemption dose criterion of 0.3 mSv y(-1) but complies with the upper dose principle of 1 mSv y(-1).

Assessment of Natural Radioactivity Levels and Potential Radiological Risks of Common Building Materials Used in Bangladeshi Dwellings

PubMed Central

Asaduzzaman, Khandoker; Mannan, Farhana; Khandaker, Mayeen Uddin; Farook, Mohideen Salihu; Elkezza, Aeman; Amin, Yusoff Bin Mohd; Sharma, Sailesh; Abu Kassim, Hasan Bin

2015-01-01

The concentrations of primordial radionuclides (226Ra, 232Th and 40K) in commonly used building materials (brick, cement and sand), the raw materials of cement and the by-products of coal-fired power plants (fly ash) collected from various manufacturers and suppliers in Bangladesh were determined via gamma-ray spectrometry using an HPGe detector. The results showed that the mean concentrations of 226Ra, 232Th and 40K in all studied samples slightly exceeded the typical world average values of 50 Bq kg−1, 50 Bq kg−1 and 500 Bq kg−1, respectively. The activity concentrations (especially 226Ra) of fly-ash-containing cement in this study were found to be higher than those of fly-ash-free cement. To evaluate the potential radiological risk to individuals associated with these building materials, various radiological hazard indicators were calculated. The radium equivalent activity values for all samples were found to be lower than the recommended limit for building materials of 370 Bq kg-1, with the exception of the fly ash. For most samples, the values of the alpha index and the radiological hazard (external and internal) indices were found to be within the safe limit of 1. The mean indoor absorbed dose rate was observed to be higher than the population-weighted world average of 84 nGy h–1, and the corresponding annual effective dose for most samples fell below the recommended upper dose limit of 1 mSv y–1. For all investigated materials, the values of the gamma index were found to be greater than 0.5 but less than 1, indicating that the gamma dose contribution from the studied building materials exceeds the exemption dose criterion of 0.3 mSv y-1 but complies with the upper dose principle of 1 mSv y−1. PMID:26473957

Scoping studies of shielding to reduce the shutdown dose rates in the ITER ports

NASA Astrophysics Data System (ADS)

Juárez, R.; Guirao, J.; Pampin, R.; Loughlin, M.; Polunovskiy, E.; Le Tonqueze, Y.; Bertalot, L.; Kolsek, A.; Ogando, F.; Udintsev, V.; Walsh, M.

2018-07-01

The planned in situ maintenance tasks in the ITER port interspace are fundamental to ensure the operation of equipment to control, evaluate and optimize the plasma performance during the entire facility lifetime. They are subject to a limit of shutdown dose rates (SDDR) of 100 µSv h‑1 after 106 s of cooling time, which is nowadays a design driver for the port plugs as well as the application of ALARA. Three conceptual shielding proposals outside the ITER ports are studied in this work to support the achievement of this objective. Considered one by one, they offer reductions ranging from 25% to 50%, which are rather significant. This paper shows that, by combining these shields, the SDDR as low as 57Δ µSv h‑1 can be achieved with a local approach considering only radiation from one port (no cross-talk form neighboring ports). The locally evaluated SDDR are well below the limit which is an essential pre-requisite for achieving 100µSv h‑1 in a global analysis including all contributions. Further studies will have to deal with a realistic port plug design and the cross-talks from neighbour ports.

Shielding Calculations on Waste Packages - The Limits and Possibilities of different Calculation Methods by the example of homogeneous and inhomogeneous Waste Packages

NASA Astrophysics Data System (ADS)

Adams, Mike; Smalian, Silva

2017-09-01

For nuclear waste packages the expected dose rates and nuclide inventory are beforehand calculated. Depending on the package of the nuclear waste deterministic programs like MicroShield® provide a range of results for each type of packaging. Stochastic programs like "Monte-Carlo N-Particle Transport Code System" (MCNP®) on the other hand provide reliable results for complex geometries. However this type of program requires a fully trained operator and calculations are time consuming. The problem here is to choose an appropriate program for a specific geometry. Therefore we compared the results of deterministic programs like MicroShield® and stochastic programs like MCNP®. These comparisons enable us to make a statement about the applicability of the various programs for chosen types of containers. As a conclusion we found that for thin-walled geometries deterministic programs like MicroShield® are well suited to calculate the dose rate. For cylindrical containers with inner shielding however, deterministic programs hit their limits. Furthermore we investigate the effect of an inhomogeneous material and activity distribution on the results. The calculations are still ongoing. Results will be presented in the final abstract.

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.

AREA RADIATION MONITOR

DOEpatents

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

1962-06-12

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

Method to determine the position-dependant metal correction factor for dose-rate equivalent laser testing of semiconductor devices

DOEpatents

Horn, Kevin M.

2013-07-09

A method reconstructs the charge collection from regions beneath opaque metallization of a semiconductor device, as determined from focused laser charge collection response images, and thereby derives a dose-rate dependent correction factor for subsequent broad-area, dose-rate equivalent, laser measurements. The position- and dose-rate dependencies of the charge-collection magnitude of the device are determined empirically and can be combined with a digital reconstruction methodology to derive an accurate metal-correction factor that permits subsequent absolute dose-rate response measurements to be derived from laser measurements alone. Broad-area laser dose-rate testing can thereby be used to accurately determine the peak transient current, dose-rate response of semiconductor devices to penetrating electron, gamma- and x-ray irradiation.

Impact of the Amount of Liquid Intake on the Dose Rate of Patients Treated with Radioiodine.

PubMed

Haghighatafshar, Mahdi; Banani, Aida; Zeinali-Rafsanjani, Banafsheh; Etemadi, Zahra; Ghaedian, Tahereh

2018-01-01

Despite therapeutic effects of radioiodine in patients with differentiated thyroid cancer, there are some disadvantages due to harmful radiation to other tissues. According to the current guidelines, patients are recommended to drink lots of water and frequent voiding to reduce the amount of 131 I in the body. This study was designed to assess the impact of the amount of liquid intake on reduction of the measured dose rate of radioiodine-treated patients. A total of 42 patients with differentiated thyroid cancer without metastasis who had undergone total thyroidectomy and had been treated with radioiodine were selected. The patients were divided into two groups according to the amount of their fluid intake which was measured during the first 48 h after 131 I administration. In all patients, the dose rate was measured immediately and 48 h after iodine administration. Each group included 21 patients. Dose rate ratio (the ratio of the second dose rate to the first dose rate) and dose rate difference ratio (the ratio of the difference between the two measured dose rates to the first dose rate) were calculated for each patient. Despite the significant difference in the amount of the liquid drunk, no statistically significant difference was seen between the different groups in parameters of dose-rate ratio and dose-rate difference ratio. Higher fluid intake (>60 ml/h in our study) alone would not effectively reduce the patient's radiation dose rate at least not more than a well-hydrated state. It seems that other interfering factors in the thyroidectomized patients may also have some impacts on this physiologic process.

Introduction of novel 3D-printed superficial applicators for high-dose-rate skin brachytherapy.

PubMed

Jones, Emma-Louise; Tonino Baldion, Anna; Thomas, Christopher; Burrows, Tom; Byrne, Nick; Newton, Victoria; Aldridge, Sarah

Custom-made surface mold applicators often allow more flexibility when carrying out skin brachytherapy, particularly for small treatment areas with high surface obliquity. They can, however, be difficult to manufacture, particularly if there is a lack of experience in superficial high-dose-rate brachytherapy techniques or with limited resources. We present a novel method of manufacturing superficial brachytherapy applicators utilizing three-dimensional (3D)-printing techniques. We describe the treatment planning process and the process of applicator manufacture. The treatment planning process, with the introduction of a pre-plan, allows for an "ideal" catheter arrangement within an applicator to be determined, exploiting varying catheter orientations, heights, and curvatures if required. The pre-plan arrangement is then 3D printed to the exact specifications of the pre-plan applicator design. This results in improved target volume coverage and improved sparing of organs at risk. Using a pre-plan technique for ideal catheter placement followed by automated 3D-printed applicator manufacture has greatly improved the entire process of superficial high-dose-rate brachytherapy treatment. We are able to design and manufacture flexible, well-fitting, superior quality applicators resulting in a more efficient and improved patient pathway and patient experience. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

US pivotal studies of irinotecan in colorectal carcinoma.

PubMed

Pitot, H C

1998-08-01

Phase I trials of irinotecan (CPT-11 [Camptosar]), conducted at Johns Hopkins and the University of Texas, San Antonio, demonstrated some activity in patients with refractory advanced cancer. Three pivotal phase II studies of irinotecan in advanced colorectal carcinoma were conducted at The University of Texas, San Antonio, Mayo/North Central Cancer Treatment Group (NCCTG), and the CPT-11 Study Group in a total of 304 patients. All patients had received prior fluorouracil (5-FU) chemotherapy, and over 90% had progressed while on treatment within the last 6 months. The initial starting dose of irinotecan ranged from 100 to 150 mg/m2. The overall response rate was 12.8% (95% confidence interval, 9.1% to 16.6%) with a 15% response rate at a recommended starting dose of 125 mg/m2. The response durations and overall median survivals were similar in the three studies. The principal toxicities included diarrhea, nausea, vomiting, and neutropenia. Severe diarrhea was limited by use of an intensive loperamide regimen and appropriate dose modification. The three pivotal studies of irinotecan in advanced colorectal carcinoma demonstrate consistent response rates and duration, with manageable toxicity. Future studies will focus on the use of irinotecan in chemotherapeutically naive colorectal carcinoma, the adjuvant treatment of colon carcinoma, combination chemotherapeutic regimens, and treatment of other malignant diseases.

Recommended de minimis radiation dose rates for Canada. Report No. INFO-0355

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

Not Available

1990-01-01

A de minimis dose or dose rate as used in this report represents a level of risk which is generally accepted as being of no significance to an individual, or in the case of a population, of no significance to society. The report describes the risk of biological effects from radiation; radiation from natural and man-made sources; normal incidences of cancer and genetic defects; initiatives by other agencies in the U.S., the U.K. and internationally; the importance of collective dose and dose rate; assigning values to the de minimis dose rates; and application of the de minimis dose rates.

High-dose tigecycline and colistin for successful treatment of disseminated carbapenem-resistant Klebsiella pneumoniae infection in a liver transplant recipient

PubMed Central

Dan, Jennifer Marie; Mendler, Michel Henry; Hemming, Alan W; Aslam, Saima

2014-01-01

Solid organ transplantation (SOT) is a risk factor for the acquisition of carbapenem-resistant Klebsiella pneumoniae. This infection is associated with a high mortality rate given the limited armamentarium of antibiotics for multidrug-resistant organisms along with continued immunosuppression to prevent graft rejection. We report a case of carbapenem-resistant K. pneumoniae pneumonia, bacteraemia and intra-abdominal infection in a newly transplanted liver recipient. The patient was successfully treated with a long course of high-dose tigecycline and colistin, along with surgical drainage. We discuss SOT-relevant epidemiology, therapeutic options and the rationale for our treatment choice. PMID:25378111

AAPM/RSNA physics tutorial for residents: physics of flat-panel fluoroscopy systems: Survey of modern fluoroscopy imaging: flat-panel detectors versus image intensifiers and more.

PubMed

Nickoloff, Edward Lee

2011-01-01

This article reviews the design and operation of both flat-panel detector (FPD) and image intensifier fluoroscopy systems. The different components of each imaging chain and their functions are explained and compared. FPD systems have multiple advantages such as a smaller size, extended dynamic range, no spatial distortion, and greater stability. However, FPD systems typically have the same spatial resolution for all fields of view (FOVs) and are prone to ghosting. Image intensifier systems have better spatial resolution with the use of smaller FOVs (magnification modes) and tend to be less expensive. However, the spatial resolution of image intensifier systems is limited by the television system to which they are coupled. Moreover, image intensifier systems are degraded by glare, vignetting, spatial distortions, and defocusing effects. FPD systems do not have these problems. Some recent innovations to fluoroscopy systems include automated filtration, pulsed fluoroscopy, automatic positioning, dose-area product meters, and improved automatic dose rate control programs. Operator-selectable features may affect both the patient radiation dose and image quality; these selectable features include dose level setting, the FOV employed, fluoroscopic pulse rates, geometric factors, display software settings, and methods to reduce the imaging time. © RSNA, 2011.

Study of the dose rate effect of 180 nm nMOSFETs

NASA Astrophysics Data System (ADS)

He, Bao-Ping; Yao, Zhi-Bin; Sheng, Jiang-Kun; Wang, Zu-Jun; Huang, Shao-Yan; Liu, Min-Bo; Xiao, Zhi-Gang

2015-01-01

Radiation induced offstate leakage in the shallow trench isolation regions of SIMC 0.18 μm nMOSFETs is studied as a function of dose rate. A “true” dose rate effect (TDRE) is observed. Increased damage is observed at low dose rate (LDR) than at high dose rate (HDR) when annealing is taken into account. A new method of simulating radiation induced degradation in shallow trench isolation (STI) is presented. A comparison of radiation induced offstate leakage current in test nMOSFETs between total dose irradiation experiments and simulation results exhibits excellent agreement. The investigation results imply that the enhancement of the leakage current may be worse for the dose rate encountered in the environment of space.

Comparison of Effects Produced by Nicotine and the α4β2-Selective Agonist 5-I-A-85380 On Intracranial Self-Stimulation in Rats

PubMed Central

Freitas, Kelen; Carroll, F. Ivy; Negus, S. Stevens

2015-01-01

Intracranial self-stimulation (ICSS) is one type of preclinical procedure for research on pharmacological mechanisms that mediate abuse potential of drugs acting at various targets including nicotinic acetylcholine receptors (nAChRs). This study compared effects of the non-selective nAChR agonist nicotine (0.032-1.0 mg/kg) and the α4β2-selective nAChR agonist 5-I-A-85380 (0.01-1.0 mg/kg) on ICSS in male Sprague-Dawley rats. Rats were implanted with electrodes targeting the medial forebrain bundle at the level of the lateral hypothalamus and trained to respond under a fixed-ratio 1 schedule for a range of brain stimulation frequencies (158-56 Hz). A broad range of 5-I-A-85380 doses produced an abuse-related increase (or “facilitation”) of low ICSS rates maintained by low brain-stimulation frequencies, and this effect was blocked by both the nonselective nAChR antagonist mecamylamine and the selective α4β2 antagonist dihyrdo-ß-erythroidine (DHßE). Conversely, nicotine produced weaker ICSS facilitation across a narrower range of doses, and higher nicotine doses decreased high rates of ICSS maintained by high brain- stimulation frequencies. The rate-decreasing effects of a high nicotine dose were blocked by mecamylamine but not DHßE. Chronic nicotine treatment produced selective tolerance to rate-decreasing effects of nicotine but did not alter ICSS rate-increasing effects of nicotine. These results suggest that α4β2 receptors are sufficient to mediate abuse-related rate-increasing effects of nAChR agonists in this ICSS procedure. Conversely, nicotine effects at non-α4β2 nAChRs appear to oppose and limit abuse-related effects mediated by α4β2 receptors, although tolerance can develop to these non-α4β2 effects. Selective α4β2 agonists may have higher abuse potential than nicotine. PMID:26461167

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

Development of a multi-knife-edge slit collimator for prompt gamma ray imaging during proton beam cancer therapy

NASA Astrophysics Data System (ADS)

Ready, John Francis, III

Proton beam usage to treat cancer has recently experienced rapid growth, as it offers the ability to target dose delivery in a patient more precisely than traditional x-ray treatment methods. Protons stop within the patient, delivering the maximum dose at the end of their track--a phenomenon described as the Bragg peak. However, because a large dose is delivered to a small volume, proton therapy is very sensitive to errors in patient setup and treatment planning calculations. Additionally, because all primary beam particles stop in the patient, there is no direct information available to verify dose delivery. These factors contribute to the range uncertainty in proton therapy, which ultimately hinders its clinical usefulness. A reliable method of proton range verification would allow the clinician to fully utilize the precise dose delivery of the Bragg peak. Several methods to verify proton range detect secondary emissions, especially prompt gamma ray (PG) emissions. However, detection of PGs is challenging due to their high energy (2-10 MeV) and low attenuation coefficients, which limit PG interactions in materials. Therefore, detection and collimation methods must be specifically designed for prompt gamma ray imaging (PGI) applications. In addition, production of PGs relies on delivering a dose of radiation to the patient. Ideally, verification of the Bragg peak location exposes patients to a minimal dose, thus limiting the PG counts available to the imaging system. An additional challenge for PGI is the lack of accurate simulation models, which limit the study of PG production characteristics and the relationship between PG distribution and dose delivery. Specific limitations include incorrect modeling of the reaction cross sections, gamma emission yields, and angular distribution of emission for specific photon energies. While simulations can still be valuable assets in designing a system to detect and image PGs, until new models are developed and incorporated into Monte Carlo simulation packages, simulations cannot be used to study the production and location of PG emissions during proton therapy. This work presents a novel system to image PGs emitted during proton therapy to verify proton beam range. The imaging system consists of a multi-slit collimator paired with a position-sensitive LSO scintillation detector. This innovative design is the first collimated imaging system to implement two-dimensional (2-D) imaging for PG proton beam range verification, while also providing a larger field of view than compared to single-slit collimator systems. Other, uncollimated imaging systems have been explored for PGI applications, such as Compton cameras. However, Compton camera designs are severely limited by counting rate capabilities. A recent Compton camera study reported count rate capability of about 5 kHz. However, at a typical clinical beam current of 1.0 nA, the estimated PG emission rate would be 6 x 108 per second. After accounting for distance to the detector and interaction efficiencies, the detection system will still be overwhelmed with counts in the MHz range, causing false coincidences and hindering the operation of the imaging system. Initial measurements using 50 MeV protons demonstrated the ability of our system to reconstruct 2-D PG distributions at clinical beam currents. A Bragg peak localization precision of 1 mm (2sigma) was achieved with delivery of (1.7 +/- 0.8) x 108 protons into a PMMA target, suggesting the ability of the system to detect relative shifts in proton range while delivering fewer protons than used in a typical treatment fraction. This is key, as the ideal system allows the clinician to verify proton range when delivering only a small portion of the prescribed dose, preventing the mistreatment of the patient. Additionally, the absolute position of the Bragg peak was identified to within 1.6 mm (2sigma) with 5.6 x 1010 protons delivered. These promising results warrant further investigation and system optimization for clinical implementation. While further measurements at clinical beam energy levels will be required to verify system performance, these preliminary results provide evidence that 2-D image reconstruction, with 1-2 mm accuracy, is possible with this design. Implementing such a system in the clinical setting would greatly improve proton therapy cancer treatment outcomes.

Individualized Radical Radiotherapy of Non-Small-Cell Lung Cancer Based on Normal Tissue Dose Constraints: A Feasibility Study

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

Baardwijk, Angela van; Bosmans, Geert; Boersma, Liesbeth

2008-08-01

Purpose: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. Methods and Materials: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissuemore » dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An {sup 18}F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. Results: Mean delivered dose was 63.0 {+-} 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. Conclusions: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.« less

Mitigation Strategies for Acute Radiation Exposure during Space Flight

NASA Technical Reports Server (NTRS)

Hamilton, Douglas R.; Epelman, Slava

2006-01-01

While there are many potential risks in a Moon or Mars mission, one of the most important and unpredictable is that of crew radiation exposure. The two forms of radiation that impact a mission far from the protective environment of low-earth orbit, are solar particle events (SPE) and galactic cosmic radiation (GCR). The effects of GCR occur as a long-term cumulative dose that results increased longer-term medical risks such as malignancy and neurological degeneration. Unfortunately, relatively little has been published on the medical management of an acute SPE that could potentially endanger the mission and harm the crew. Reanalysis of the largest SPE in August 1972 revealed that the dose rate was significantly higher than previously stated in the literature. The peak dose rate was 9 cGy h(sup -1) which exceeds the low dose-rate criteria for 25 hrs (National Council on Radiation Protection) and 16 hrs (United Nations Scientific Committee on the Effects of Atomic Radiation). The bone marrow dose accumulated was 0.8 Gy, which exceeded the 25 and 16 hour criteria and would pose a serious medical risk. Current spacesuits would not provide shielding from the damaging effects for an SPE as large as the 1972 event, as increased shielding from 1-5 grams per square centimeters would do little to shield the bone marrow from exposure. Medical management options for an acute radiation event are discussed based on recommendations from the Department of Homeland Security, Centers for Disease Control and evidence-based scientific literature. The discussion will also consider how to define acute exposure radiation safety limits with respect to exploration-class missions, and to determine the level of care necessary for a crew that may be exposed to an SPE similar to August 1972.

A randomized trial of one versus three doses of Augmentin as wound prophylaxis in at-risk abdominal surgery.

PubMed Central

Bates, T.; Roberts, J. V.; Smith, K.; German, K. A.

1992-01-01

In a randomized prospective trial of prophylactic antibiotics in at-risk abdominal surgery, one dose of intravenous Augmentin (amoxycillin 250 mg and clavulanic acid 125 mg) on induction has been compared with three 8 hourly doses in 900 patients. Wound infection rates which included minor and delayed infections were very similar in those given one dose: 48/449 (10.7%) compared with those given three doses: 49/451 (10.9%) 95% confidence limits - 4.25% + 3.9%. There were more septic and sepsis-related deaths in those patients given one dose (14 deaths) than in those given three doses (7 deaths) P > 0.1 95% CL - 0.4% + 3.0%. However, there were more very elderly patients in the one dose group: 64% of the deaths were aged over 80 and all but one had an emergency operation. There was no difference in the other outcome measures studied which included non-fatal deep sepsis, length of postoperative hospital stay, duration of postoperative fever or the use of antibiotics for postoperative infection. One dose of a suitable intravenous antibiotic gives prophylaxis against wound infection in at-risk abdominal surgery which is at least as effective as multiple doses. However, there may be a risk of overwhelming systemic sepsis in very elderly patients having emergency surgery. PMID:1461853

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

PubMed

Klingenberg, B

2009-01-30

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

Persistent activation of nuclear factor-kappa B and expression of pro-inflammatory cytokines in bone marrow cells after exposure of mice to protons

NASA Astrophysics Data System (ADS)

Rithidech, Kanokporn; Reungpatthanaphong, Paiboon; Honikel, Louise; Whorton, Elbert

Protons are the most abundant component of solar particle events (SPEs) in space. Information is limited on early-and late-occurring in vivo biological effects of exposure to protons at doses and dose rates that are similar to what astronauts encounter in space. We conducted a study series to fill this knowledge gap. We focused on the biological effects of 100 MeV/n protons, which are one of the most abundant types of protons induced during SPEs. We gave BALB/cJ mice a whole-body exposure to 0.5 or 1.0 Gy of 100 MeV/n protons, delivered at 0.5 or 1.0 cGy/min. These doses and dose rates of protons were selected because they are comparable to those of SPEs taking place in space. For each dose and dose rate of 100 MeV/n protons, mice exposed to 0 Gy of protons served as sham controls. Mice included in this study were also part of a study series conducted to examine the extent and the mechanisms involved in in vivo induction of genomic instability (expressed as late-occurring chromosome instability) by 100 MeV/n protons. Bone marrow (BM) cells were collected from groups of mice for analyses at different times post-exposure, i.e. early time-points (1.5, 3, and 24 hr) and late time-points (1 and 6 months). At each harvest time, there were five mice per treatment group. Several endpoints were used to investigate the biological effects of 100 MeV/n protons in BM cells from irradiated and sham control mice. The scope of this study was to determine the dose-rate effects of 0.5 Gy of 100 MeV/n protons in BM cells on the kinetics of nuclear factor-kappa B (NF-kappa B) activation and the expression of selected NF-kappa B target proteins known to be involved in inflammatory response, i.e. pro-inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6). Significantly high levels (p values ranging from p¡0.01 and p¡0.05) of activated NF-kappa B were observed in BM cells collected from irradiated mice, relative to those obtained from the corresponding sham controls, at all time-points included in the study, regardless of the dose rate of proton-irradiation. However, these increases were more pronounced when the higher dose rate (1.0 cGy/min) was used. The results indicated that NF-kappa B activation in BM cells persisted up to 6 months after exposure of mice to a single dose of 0.5 Gy of 100 MeV/n protons, delivered at the dose rates occurring in space. Further, significantly up-regulated levels of TNF-alpha were detected in BM cells of exposed mice (p values ranging from p¡0.01 and p¡0.05), compared to those in the corresponding sham controls, at all harvest times, in spite of the difference in dose rate of proton-irradiation. However, steady increases in the levels of IL-1 beta and IL-6 in BM cells of exposed mice over the levels in their sham controls across all time-points included in the study were detected only when a dose rate of 1.0 cGy/min was used. In contrast, with a dose rate of 0.5 cGy/min, significantly high expression levels of these two pro-inflammatory cytokines were consistently found in BM cells collected from exposed mice at late time-points only. In summary, our data provide important information for space flight missions because the findings of persistent activation of NF-kappa B and expression of pro-inflammatory cytokines suggest the occurrence of chronic inflammation after exposure of mice to 100 MeV/n protons that, in turn, may have an important impact on health outcome during space flights. Knowledge gained on the NF-kappa B pathway from this study could, therefore, be useful for planning countermeasure strategies to protect astronauts or space travelers in the space environment. Research funded by NASA Grant NNX07AP88G.

Effect of processor temperature on film dosimetry

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

Srivastava, Shiv P.; Das, Indra J., E-mail: idas@iupui.edu

2012-07-01

Optical density (OD) of a radiographic film plays an important role in radiation dosimetry, which depends on various parameters, including beam energy, depth, field size, film batch, dose, dose rate, air film interface, postexposure processing time, and temperature of the processor. Most of these parameters have been studied for Kodak XV and extended dose range (EDR) films used in radiation oncology. There is very limited information on processor temperature, which is investigated in this study. Multiple XV and EDR films were exposed in the reference condition (d{sub max.}, 10 Multiplication-Sign 10 cm{sup 2}, 100 cm) to a given dose. Anmore » automatic film processor (X-Omat 5000) was used for processing films. The temperature of the processor was adjusted manually with increasing temperature. At each temperature, a set of films was processed to evaluate OD at a given dose. For both films, OD is a linear function of processor temperature in the range of 29.4-40.6 Degree-Sign C (85-105 Degree-Sign F) for various dose ranges. The changes in processor temperature are directly related to the dose by a quadratic function. A simple linear equation is provided for the changes in OD vs. processor temperature, which could be used for correcting dose in radiation dosimetry when film is used.« less

Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors

PubMed Central

Sasaki, Masao S.; Tachibana, Akira; Takeda, Shunichi

2014-01-01

Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the ‘integrate-and-fire’ algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to 239Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation–environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking. PMID:24366315

Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors.

PubMed

Sasaki, Masao S; Tachibana, Akira; Takeda, Shunichi

2014-05-01

Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the 'integrate-and-fire' algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to (239)Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation-environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking.

Copper deficiency can limit nitrification in biological rapid sand filters for drinking water production.

PubMed

Wagner, Florian B; Nielsen, Peter Borch; Boe-Hansen, Rasmus; Albrechtsen, Hans-Jørgen

2016-05-15

Incomplete nitrification in biological filters during drinking water treatment is problematic, as it compromises drinking water quality. Nitrification problems can be caused by a lack of nutrients for the nitrifying microorganisms. Since copper is an important element in one of the essential enzymes in nitrification, we investigated the effect of copper dosing on nitrification in different biological rapid sand filters treating groundwater. A lab-scale column assay with filter material from a water works demonstrated that addition of a trace metal mixture, including copper, increased ammonium removal compared to a control without addition. Subsequently, another water works was investigated in full-scale, where copper influent concentrations were below 0.05 μg Cu L(-1) and nitrification was incomplete. Copper dosing of less than 5 μg Cu L(-1) to a full-scale filter stimulated ammonium removal within one day, and doubled the filter's removal from 0.22 to 0.46 g NH4-N m(-3) filter material h(-1) within 20 days. The location of ammonium and nitrite oxidation shifted upwards in the filter, with an almost 14-fold increase in ammonium removal rate in the filter's top 10 cm, within 57 days of dosing. To study the persistence of the stimulation, copper was dosed to another filter at the water works for 42 days. After dosing was stopped, nitrification remained complete for at least 238 days. Filter effluent concentrations of up to 1.3 μg Cu L(-1) confirmed that copper fully penetrated the filters, and determination of copper content on filter media revealed a buildup of copper during dosing. The amount of copper stored on filter material gradually decreased after dosing stopped; however at a slower rate than it accumulated. Continuous detection of copper in the filter effluent confirmed a release of copper to the bulk phase. Overall, copper dosing to poorly performing biological rapid sand filters increased ammonium removal rates significantly, achieving effluent concentrations of below 0.01 mg NH4-N L(-1), and had a long-term effect on nitrification performance. Copyright © 2016 Elsevier Ltd. All rights reserved.

Long-Term Results of Brachytherapy for Carcinoma of the Penis Confined to the Glans (N- or NX)

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

Crevoisier, Renaud de; Slimane, Khemais; Sanfilippo, Nicholas

2009-07-15

Purpose: To analyze the results of exclusive interstitial low-dose-rate brachytherapy (BT) for squamous cell carcinoma (SCC) of the penis, strictly confined to the glans. Methods and Materials: A total of 144 patients with SSC of the glans penis were treated with BT. Inguinal nodal dissection was performed in 19% of patients (all N-). After circumcision, BT was performed using the hypodermic needle technique. Median iridium length per patients was 24 cm (range, 4-108) and median dose was 65 Gy (range, 37-75). Median treated volume was 22 cm{sup 3} (range, 5-110) and median reference isodose rate was 0.4 Gy/h (range, 0.2-1.2).more » Results: Median follow-up was 5.7 years (range, 0.5-29). The 10-year penile recurrence, inguinal lymph node recurrence, and inguinal nodal metastasis rates were: 20% (CI 95%, 11-29), 11% (CI 95%, 5-17), and 6% (CI 95%, 2-10), respectively. After salvage treatment, 86% patients with local failure were in a complete remission at last follow-up. The 10-year probability of avoiding penile surgery (for complication or local recurrence) was 72% (CI 95%, 62-82). The 10-year cancer-specific survival rate was 92% (CI 95%, 87-97). Diameter of tumor significantly increased the risk of recurrence (p = 0.02). The 10-year painful ulceration and stenosis risk rates were: 26% (CI 95%, 17-35) and 29% (CI 95%, 18-40), respectively. Seven patients required excision for necrosis. Treated volume and reference isodose rate significantly increased the risk of complications. Conclusion: BT is an effective conservative treatment for SCC confined to the glans. Salvage local treatment is effective. Dose rate should be limited to decrease toxicity.« less

Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study)

PubMed Central

Hegarty, Joanne Elizabeth; Harding, Jane Elizabeth; Gamble, Gregory David; Crowther, Caroline Anne; Edlin, Richard; Alsweiler, Jane Marie

2016-01-01

Background Neonatal hypoglycaemia is common, affecting up to 15% of newborns, and can cause brain damage. Currently, there are no strategies, beyond early feeding, to prevent neonatal hypoglycaemia. Our aim was to determine a dose of 40% oral dextrose gel that will prevent neonatal hypoglycaemia in newborn babies at risk. Methods and Findings We conducted a randomised, double-blind, placebo-controlled dose-finding trial of buccal dextrose gel to prevent neonatal hypoglycaemia at two hospitals in New Zealand. Babies at risk of hypoglycaemia (infant of a mother with diabetes, late preterm delivery, small or large birthweight, or other risk factors) but without indication for admission to a neonatal intensive care unit (NICU) were randomly allocated either to one of four treatment groups: 40% dextrose at one of two doses (0.5 ml/kg = 200 mg/kg, or 1 ml/kg = 400 mg/kg), either once at 1 h of age or followed by three additional doses of dextrose (0.5 ml/kg before feeds in the first 12 h); or to one of four corresponding placebo groups. Treatments were administered by massaging gel into the buccal mucosa. The primary outcome was hypoglycaemia (<2.6 mM) in the first 48 h. Secondary outcomes included admission to a NICU, admission for hypoglycaemia, and breastfeeding at discharge and at 6 wk. Prespecified potential dose limitations were tolerance of gel, time taken to administer, messiness, and acceptability to parents. From August 2013 to November 2014, 416 babies were randomised. Compared to babies randomised to placebo, the risk of hypoglycaemia was lowest in babies randomised to a single dose of 200 mg/kg dextrose gel (relative risk [RR] 0.68; 95% confidence interval [CI] 0.47–0.99, p = 0.04) but was not significantly different between dose groups (p = 0.21). Compared to multiple doses, single doses of gel were better tolerated, quicker to administer, and less messy, but these limitations were not different between dextrose and placebo gel groups. Babies who received any dose of dextrose gel were less likely to develop hypoglycaemia than those who received placebo (RR 0.79; 95% CI 0.64–0.98, p = 0.03; number needed to treat = 10, 95% CI 5–115). Rates of NICU admission were similar (RR 0.64; 95% CI 0.33–1.25, p = 0.19), but admission for hypoglycaemia was less common in babies randomised to dextrose gel (RR 0.46; 95% CI 0.21–1.01, p = 0.05). Rates of breastfeeding were similar in both groups. Adverse effects were uncommon and not different between groups. A limitation of this study was that most of the babies in the trial were infants of mothers with diabetes (73%), which may reduce the applicability of the results to babies from other risk groups. Conclusions The incidence of neonatal hypoglycaemia can be reduced with a single dose of buccal 40% dextrose gel 200 mg/kg. A large randomised trial (Hypoglycaemia Prevention with Oral Dextrose [hPOD]) is under way to determine the effects on NICU admission and later outcomes. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12613000322730 PMID:27780197

Tofacitinib in patients with ankylosing spondylitis: a phase II, 16-week, randomised, placebo-controlled, dose-ranging study.

PubMed

van der Heijde, Désirée; Deodhar, Atul; Wei, James C; Drescher, Edit; Fleishaker, Dona; Hendrikx, Thijs; Li, David; Menon, Sujatha; Kanik, Keith S

2017-08-01

To compare efficacy and safety of various doses of tofacitinib, an oral Janus kinase inhibitor, with placebo in patients with active ankylosing spondylitis (AS, radiographic axial spondyloarthritis). In this 16-week (12-week treatment, 4-week washout), phase II, multicentre, dose-ranging trial, adult patients with active AS were randomised (N=51, 52, 52, 52, respectively) to placebo or tofacitinib 2, 5 or 10 mg twice daily. The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine. Safety was monitored. Emax model analysis of the primary endpoint predicted a tofacitinib 10 mg twice daily ASAS20 response rate of 67.4%, 27.3% higher than placebo. Supportive normal approximation analysis demonstrated tofacitinib 5 mg twice daily ASAS20 response rate significantly higher than placebo (80.8% vs 41.2%; p<0.001); tofacitinib 2 and 10 mg twice daily demonstrated greater response rate than placebo (51.9% and 55.8%, respectively; not significant). Secondary endpoints generally demonstrated greater improvements with tofacitinib 5 and 10 mg twice daily than placebo. Objective (including MRI) endpoints demonstrated clear dose response. Adverse events were similar across treatment groups with no unexpected safety findings. Dose-dependent laboratory outcome changes returned close to baseline by week 16. Tofacitinib 5 and 10 mg twice daily demonstrated greater clinical efficacy versus placebo in reducing signs, symptoms and objective endpoints of active AS in adult patients with a similar 12-week safety profile as reported in other indications. NCT01786668. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

SU-E-T-352: Why Is the Survival Rate Low in Oropharyngeal Squamous Cell Carcinoma?

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

Huang, Z; Feng, Y; Rasmussen, K

2014-06-01

Purpose: Tumors are composed of a large number of clonogens that have the capability of indefinite reproduction. Even when there is complete clinical or radiographic regression of the gross tumor mass after treatment, tumor recurrence can occur if the clonogens are not completely eradicated by radiotherapy. This study was to investigate the colonogen number and its association with the tumor control probability (TCP) in oropharyngeal squamous cell carcinoma (OSCCA). Methods: A literature search was conducted to collect clinical information of patients with OSCCA, including the prescription dose, tumor volume and survival rate. The linear-quadratic (LQ) model was incorporated into TCPmore » model for clinical data analysis. The total dose ranged from 60 to 70 Gy and tumor volume ranged from 10 to 50 cc. The TCP was calculated for each group according to tumor size and dose. The least χ{sup 2} method was used to fit the TCP calculation to clinical data while other LQ model parameters (α, β) were adopted from the literature, due to the limited patient data. Results: A total of 190 patients with T2–T4 OSCCA were included. The association with HPV was not available for all the patients. The 3-year survival rate was about 82% for T2 squamous cell carcinoma and 40% for advanced tumors. Fitting the TCP model to the survival data, the average clonogen number was 1.56×10{sup 12}. For the prescription dose of 70 Gy, the calculated TCP ranged from 40% to 90% when the tumor volume varied from 10 to 50 cc. Conclusion: Our data suggests variation between the clonogen number and TCP in OSCCA. Tumors with larger colonogen number tend to have lower TCP and therefore dose escalation above 70 Gy may be indicated in order to improve the TCP and survival rate. Our result will require future confirmation with a large number of patients.« less

SU-F-T-263: Dosimetric Characteristics of the Cine Acquisition Mode of An A-Si EPID

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

Bawazeer, O; Deb, P; Sarasanandarajah, S

2016-06-15

Purpose: To investigate the dosimetric characteristics of Varian a-Si-500 electronic portal imaging device (EPID) operated in cine mode particularly considering linearity with delivered dose, dose rate, field size, phantom thickness, MLC speed and common IMRT fields. Methods: The EPID that attached to a Varian Clinac 21iX linear accelerator, was irradiated with 6 and 18 MV using 600 MU/min. Image acquisition is controlled by the IAS3 software, Trigger delay was 6 ms, BeamOnDelay and FrameStartDelay were zero. Different frame rates were utilized. Cine mode response was calculated using MATLAB as summation of mean pixel values in a region of interest ofmore » the acquired images. The performance of cine mode was compared to integrated mode and dose measurements in water using CC13 ionization chamber. Results: Figure1 illustrates that cine mode has nonlinear response for small MU, when delivering 10 MU was about 0.5 and 0.64 for 6 and 18 MV respectively. This is because the missing acquired images that were calculated around four images missing in each delivery. With the increase MU the response became linear and comparable with integrated mode and ionization chamber within 2%. Figure 2 shows that cine mode has comparable response with integrated mode and ionization chamber within 2% with changing dose rate for 10 MU delivered. This indicates that the dose rate change has no effect on nonlinearity of cine mode response. Except nonlinearity, cine mode is well matched to integrated mode response within 2% for field size, phantom thickness, MLC speed dependences. Conclusion: Cine mode has similar dosimetric characteristics to integrated mode with open and IMRT fields, and the main limitation with cine mode is missing images. Therefore, the calibration of EPID images with this mode should be run with large MU, and when IMRT verification field has low MU, the correction for missing images are required.« less

Bronchoscopic phototherapy at comparable dose rates: Early results

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

Pass, H.I.; Delaney, T.; Smith, P.D.

1989-05-01

Photodynamic therapy is a recently introduced treatment for surface malignancies. Since January 1987, 10 patients with endobronchial neoplasms have had bronchoscopic photodynamic therapy at similar dose rates (400 mW/cm) for total atelectasis (2), carinal narrowing with respiratory insufficiency (2), or partial obstruction without collapse (4). Two patients underwent photodynamic therapy as a preliminary to immunotherapy. Histologies included endobronchial metastases (colon, ovary, melanoma, and sarcoma, 1 each; and renal cell, 3) and primary lung cancer (3). The 2 patients with total atelectasis had complete reexpansion after photodynamic therapy, which permitted eventual sleeve lobectomy in 1. Carinal narrowing was ameliorated in themore » 2 patients seen with inspiratory stridor, thereby permitting hospital discharge. Endoscopically resected fragments after photodynamic therapy exhibited avascular necrosis. These data support further controlled studies of photodynamic therapy by thoracic surgical oncologists to define its limitations as well as to improve and expand its efficacy as a palliative or surgical adjuvant.« less

Risk assessment of human exposure to Ra-226 in oil produced water from the Bakken Shale.

PubMed

Torres, Luisa; Yadav, Om Prakash; Khan, Eakalak

2018-06-01

Unconventional oil production in North Dakota (ND) and other states in the United States uses large amounts of water for hydraulic fracturing to stimulate oil flow. Most of the water used returns to the surface as produced water (PW) containing different constituents. Some of these contents are total dissolved solids and radionuclides. The most predominant radionuclide in PW is radium-226 (Ra-226) of which level depends on several factors including the content of certain cations. A multivariate regression model was developed to predict Ra-226 in PW from the Bakken Shale based on the levels of barium, strontium, and calcium. The simulated Ra-226 activity concentration in PW was 535 pCi/L supporting extremely limited actual data based on three PW samples from the Bakken (527, 816, and 1210 pCi/L). The simulated activity concentration was further analyzed by studying its impact in the event of a PW spill reaching a surface water body that provides drinking water, irrigation water for crops, and recreational fishing. Using food transfer factors found in the literature, the final annual effective dose rate for an adult in ND was estimated. The global average annual effective dose rate via food and drinking water is 0.30 mSv, while the predicted dose rate in this study was 0.49 mSv indicating that there is potential risk to human health in ND due to Ra-226 in PW spills. This predicted dose rate is considered the best case scenario as it is based on the simulated Ra-226 activity concentration in PW of 535 pCi/L which is close to the low end actual activity concentration of 527 pCi/L. Copyright © 2018 Elsevier B.V. All rights reserved.

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials

PubMed Central

Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L.; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-01-01

Purpose The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. Patients and Methods We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. Results A total of 13,008 toxicities were captured: 46% of patients’ first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m2, the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. Conclusions When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. PMID:26926682

Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

PubMed

Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

2016-04-20

The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

Biodistribution and tolerance of intravenous iodine-131-labelled hypericin in healthy dogs.

PubMed

Abma, E; Peremans, K; De Vos, F; Bosmans, T; Kitshoff, A M; Daminet, S; Ni, Y; Dockx, R; de Rooster, H

2018-01-04

Hypericin (Hyp) is a necrosis-avid compound that can be efficiently labelled with radioiodine for both diagnostic and therapeutic purposes. Before 131 I-Hyp can be considered as a clinically useful drug in a combination therapy for canine cancer patients, evaluation of its toxicity is necessary. The aim of this study was to investigate the biodistribution and tolerance of a single dose administration of 131 I-Hyp. Three healthy dogs were included. 131 I-Hyp at a dose of 0.2 mg/kg and an activity of 185 MBq was intravenously injected. The effects on physical, haematological and biochemical parameters were characterized and the biodistribution and elimination pattern, the effective half-life and dose rate were assessed. Drug-related adverse events were limited to mild gastrointestinal signs, resolving within 48 hours. No significant differences were found in blood haematology and serum biochemistry before and after treatment. Following administration, highest percentage of injected dose (%ID ± SD) was found in the liver (5.5 ± 0.33), the lungs (4.17 ± 0.14) and the heart (3.11 ± 0.78). After 24 hours, highest %ID was found in colon (4.25 ± 1.45) and liver (3.45 ± 0.60). Clearance from all organs was effective within 7 days. Effective half-life was established at 80 hours, and the dose rate fell below <20 μSv/h at 1 m within 1 day. The current study reveals that single dose treatment with 131 I-Hyp at the described dose is well tolerated by healthy dogs and supports the use of radioiodinated hypericin in a combination therapy for canine cancer patients. © 2018 John Wiley & Sons Ltd.

Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

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

Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.

Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses ofmore » 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged {<=}7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.« less

Radiation exposure in transcatheter patent ductus arteriosus closure: time to tune?

PubMed

Villemain, Olivier; Malekzadeh-Milani, Sophie; Sitefane, Fidelio; Mostefa-Kara, Meriem; Boudjemline, Younes

2018-05-01

The aims of this study were to describe radiation level at our institution during transcatheter patent ductus arteriosus occlusion and to evaluate the components contributing to radiation exposure. Transcatheter occlusion relying on X-ray imaging has become the treatment of choice for patients with patent ductus arteriosus. Interventionists now work hard to minimise radiation exposure in order to reduce risk of induced cancers. We retrospectively reviewed all consecutive children who underwent transcatheter closure of patent ductus arteriosus from January 2012 to January 2016. Clinical data, anatomical characteristics, and catheterisation procedure parameters were reported. Radiation doses were analysed for the following variables: total air kerma, mGy; dose area product, Gy.cm2; dose area product per body weight, Gy.cm2/kg; and total fluoroscopic time. A total of 324 patients were included (median age=1.51 [Q1-Q3: 0.62-4.23] years; weight=10.3 [6.7-17.0] kg). In all, 322/324 (99.4%) procedures were successful. The median radiation doses were as follows: total air kerma: 26 (14.5-49.3) mGy; dose area product: 1.01 (0.56-2.24) Gy.cm2; dose area product/kg: 0.106 (0.061-0.185) Gy.cm2/kg; and fluoroscopic time: 2.8 (2-4) min. In multivariate analysis, a weight >10 kg, a ductus arteriosus width <2 mm, complications during the procedure, and a high frame rate (15 frames/second) were risk factors for an increased exposure. Lower doses of radiation can be achieved with subsequent recommendations: technical improvement, frame rate reduction, avoidance of biplane cineangiograms, use of stored fluoroscopy as much as possible, and limitation of fluoroscopic time. A greater use of echocardiography might even lessen the exposure.

Assessment of monitor unit limiting strategy using volumetric modulated arc therapy for cancer of hypopharynx.

PubMed

Ahamed, Shabbir; Singh, Navin; Gudipudi, Deleep; Mulinti, Suneetha; Talluri, Anil; Soubhagya, Bhudevi; Sresty, Madhusudhana

2017-03-01

To quantify relative merit of MU deprived plans against freely optimized plans in terms of plan quality and report changes induced by progressive resolution optimizer algorithm (PRO3) to the dynamic parameters of RapidArc. Ten cases of carcinoma hypopharynx were retrospectively planned in three phases without using MU tool. Replicas of these baseline plans were reoptimized using "Intermediate dose" feature and "MU tool" to reduce MUs by 20%, 35%, and 50%. Overall quality indices for target and OAR, integral dose, dose-volume spread were assessed. All plans were appraised for changes induced in RapidArc dynamic parameters and pre-treatment quality assurance (QA). With increasing MU reduction strength (MURS), MU/Gy values reduced, for all phases with an overall range of 8.6-34.7%; mean dose rate decreased among plans of each phase, phase3 plans recorded greater reductions. MURS20% showed good trade-off between MUs and plan quality. Dose-volume spread below 5Gy was higher for baseline plans while lower between 20 and 35Gy. Integral dose was lower for MURS0%, not exceeding 1.0%, compared against restrained plans. Mean leaf aperture and control point areas increased systematically, correlated negatively with increasing MURS. Absolute delta dose rate variations were least for MURS0%. MU deprived plans exhibited GAI (>93%), better than MURS0% plans. Baseline plans are superior to MU restrained plans. However, MURS20% offers equivalent and acceptable plan quality with mileage of MUs, improved GAI for complex cases. MU tool may be adopted to tailor treatment plans using PRO3. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Comparison in vivo Study of Genotoxic Action of High- Versus Very Low Dose-Rate γ-Irradiation

PubMed Central

Osipov, A. N.; Klokov, D. Y.; Elakov, A. L.; Rozanova, O. M.; Zaichkina, S. I.; Aptikaeva, G. F.; Akhmadieva, A. Kh.

2004-01-01

The aim of the present study was to compare genotoxicity induced by high- versus very low dose-rate exposure of mice to γ-radiation within a dose range of 5 to 61 cGy using the single-cell gel electrophoresis (comet) assay and the micronucleus test. CBA/lac male mice were irradiated at a dose rate of 28.2 Gy/h (high dose rate) or 0.07 mGy/h (very low dose rate). The comet assay study on spleen lymphocytes showed that very low dose-rate irradiation resulted in a statistically significant increase in nucleoid relaxation (DNA breaks), starting from a dose of 20 cGy. Further prolongation of exposure time and, hence, increase of a total dose did not, however, lead to further increase in the extent of nucleoid relaxation. Doses of 20 and 61 cGy were equal in inducing DNA breaks in mouse spleen lymphocytes as assayed by the comet assay. Of note, the level of DNA damage by 20–61 cGy doses of chronic irradiation (0.07 mGy/h) was similar to that an induced by an acute (28.2 Gy/h) dose of 14 cGy. The bone marrow micronucleus test revealed that an increase in polychromatic erythrocytes with micronuclei over a background level was induced by very low-level γ-irradiation with a dose of 61 cGy only, with the extent of the cytogenetic effect being similar to that of 10 cGy high-dose-rate exposure. In summary, presented results support the hypothesis of the nonlinear threshold nature of mutagenic action of chronic low dose-rate irradiation. PMID:19330145

Occupational radiation dose to eyes from endoscopic retrograde cholangiopancreatography procedures in light of the revised eye lens dose limit from the International Commission on Radiological Protection.

PubMed

O'Connor, U; Gallagher, A; Malone, L; O'Reilly, G

2013-02-01

Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure that combines the use of X-ray fluoroscopy and endoscopy for examination of the bile duct. Published data on ERCP doses are limited, including staff eye dose from ERCP. Occupational eye doses are of particular interest now as the International Commission on Radiological Protection (ICRP) has recommended a reduction in the dose limit to the lens of the eye. The aim of this study was to measure occupational eye doses obtained from ERCP procedures. A new eye lens dosemeter (EYE-D(™), Radcard, Krakow, Poland) was used to measure the ERCP eye dose, H(p)(3), at two endoscopy departments in Ireland. A review of radiation protection practice at the two facilities was also carried out. The mean equivalent dose to the lens of the eye of a gastroenterologist is 0.01 mSv per ERCP procedure with an undercouch X-ray tube and 0.09 mSv per ERCP procedure with an overcouch X-ray tube. Staff eye dose normalised to patient kerma area product is also presented. Staff eye doses in ERCP have the potential to exceed the revised ICRP limit of 20 mSv per annum when an overcouch X-ray tube is used. The EYE-D dosemeter was found to be a convenient method for measuring lens dose. Eye doses in areas outside of radiology departments should be kept under review, particularly in light of the new ICRP eye dose limit. Occupational eye lens doses from ERCP procedures have been established using a new commercially available dedicated H(p)(3) dosemeter.

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2013 CFR

2013-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2014 CFR

2014-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2012 CFR

2012-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2011 CFR

2011-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2010 CFR

2010-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial.

PubMed

Richardson, Paul G; Soiffer, Robert J; Antin, Joseph H; Uno, Hajime; Jin, Zhezhen; Kurtzberg, Joanne; Martin, Paul L; Steinbach, Gideon; Murray, Karen F; Vogelsang, Georgia B; Chen, Allen R; Krishnan, Amrita; Kernan, Nancy A; Avigan, David E; Spitzer, Thomas R; Shulman, Howard M; Di Salvo, Donald N; Revta, Carolyn; Warren, Diane; Momtaz, Parisa; Bradwin, Gary; Wei, L J; Iacobelli, Massimo; McDonald, George B; Guinan, Eva C

2010-07-01

Therapeutic options for severe hepatic veno-occlusive disease (VOD) are limited and outcomes are dismal, but early phase I/II studies have suggested promising activity and acceptable toxicity using the novel polydisperse oligonucleotide defibrotide. This randomized phase II dose-finding trial determined the efficacy of defibrotide in patients with severe VOD following hematopoietic stem cell transplantation (HSCT) and identified an appropriate dose for future trials. Adult and pediatric patients received either lower-dose (arm A: 25 mg/kg/day; n = 75) or higher-dose (arm B: 40 mg/kg/day; n = 74) i.v. defibrotide administered in divided doses every 6 hours for > or =14 days or until complete response, VOD progression, or any unacceptable toxicity occurred. Overall complete response and day +100 post-HSCT survival rates were 46% and 42%, respectively, with no significant difference between treatment arms. The incidence of treatment-related adverse events was low (8% overall; 7% in arm A, 10% in arm B); there was no significant difference in the overall rate of adverse events between treatment arms. Early stabilization or decreased bilirubin was associated with better response and day +100 survival, and decreased plasminogen activator inhibitor type 1 (PAI-1) during treatment was associated with better outcome; changes were similar in both treatment arms. Defibrotide 25 or 40 mg/kg/day also appears effective in treating severe VOD following HSCT. In the absence of any differences in activity, toxicity or changes in PAI-1 level, defibrotide 25 mg/kg/day was selected for ongoing phase III trials in VOD.

Evaluation of a Proposed Biodegradable 188Re Source for Brachytherapy Application

PubMed Central

Khorshidi, Abdollah; Ahmadinejad, Marjan; Hamed Hosseini, S.

2015-01-01

Abstract This study aimed to evaluate dosimetric characteristics based on Monte Carlo (MC) simulations for a proposed beta emitter bioglass 188Re seed for internal radiotherapy applications. The bioactive glass seed has been developed using the sol-gel technique. The simulations were performed for the seed using MC radiation transport code to investigate the dosimetric factors recommended by the AAPM Task Group 60 (TG-60). Dose distributions due to the beta and photon radiation were predicted at different radial distances surrounding the source. The dose rate in water at the reference point was calculated to be 7.43 ± 0.5 cGy/h/μCi. The dosimetric factors consisting of the reference point dose rate, D(r0,θ0), the radial dose function, g(r), the 2-dimensional anisotropy function, F(r,θ), the 1-dimensional anisotropy function, φan(r), and the R90 quantity were estimated and compared with several available beta-emitting sources. The element 188Re incorporated in bioactive glasses produced by the sol-gel technique provides a suitable solution for producing new materials for seed implants applied to brachytherapy applications in prostate and liver cancers treatment. Dose distribution of 188Re seed was greater isotropic than other commercially attainable encapsulated seeds, since it has no end weld to attenuate radiation. The beta radiation-emitting 188Re source provides high doses of local radiation to the tumor tissue and the short range of the beta particles limit damage to the adjacent normal tissue. PMID:26181543

The role of intraoperative radiation therapy in patients with pancreatic cancer.

PubMed

Palta, Manisha; Willett, Christopher; Czito, Brian

2014-04-01

Intraoperative radiation therapy (IORT) techniques allow for the delivery of high doses of radiation therapy while excluding part or all of the nearby dose-limiting sensitive structures. Therefore, the effective radiation dose is increased and local tumor control potentially improved. This is pertinent in the case of pancreatic cancer because local failure rates are as high as 50%-80% in patients with resected and locally advanced disease. Available data in patients receiving IORT after pancreaticoduodenectomy reveal an improvement in local control, though overall survival benefit is unclear. Series of patients with locally advanced pancreatic cancer also suggest pain relief, and in select studies, improved survival associated with the inclusion of IORT. At present, no phase III data clearly supports the use of IORT in the management of pancreatic cancer. © 2013 Published by Elsevier Inc.

Estimation of ambient dose equivalent distribution in the 18F-FDG administration room using Monte Carlo simulation.

PubMed

Nagamine, Shuji; Fujibuchi, Toshioh; Umezu, Yoshiyuki; Himuro, Kazuhiko; Awamoto, Shinichi; Tsutsui, Yuji; Nakamura, Yasuhiko

2017-03-01

In this study, we estimated the ambient dose equivalent rate (hereafter "dose rate") in the fluoro-2-deoxy-D-glucose (FDG) administration room in our hospital using Monte Carlo simulations, and examined the appropriate medical-personnel locations and a shielding method to reduce the dose rate during FDG injection using a lead glass shield. The line source was assumed to be the FDG feed tube and the patient a cube source. The dose rate distribution was calculated with a composite source that combines the line and cube sources. The dose rate distribution was also calculated when a lead glass shield was placed in the rear section of the lead-acrylic shield. The dose rate behind the automatic administration device decreased by 87 % with respect to that behind the lead-acrylic shield. Upon positioning a 2.8-cm-thick lead glass shield, the dose rate behind the lead-acrylic shield decreased by 67 %.

Comparison of Monoenergetic Photon Organ Dose Rate Coefficients for the Female Stylized and Voxel Phantoms Submerged in Air

DOE PAGES

Hiller, Mauritius; Dewji, Shaheen Azim

2017-02-16

Dose rate coefficients computed using the International Commission on Radiological Protection (ICRP) reference adult female voxel phantom were compared with values computed using the Oak Ridge National Laboratory (ORNL) adult female stylized phantom in an air submersion exposure geometry. This is a continuation of previous work comparing monoenergetic organ dose rate coefficients for the male adult phantoms. With both the male and female data computed, effective dose rate as defined by ICRP Publication 103 was compared for both phantoms. Organ dose rate coefficients for the female phantom and ratios of organ dose rates for the voxel and stylized phantoms aremore » provided in the energy range from 30 to 5 MeV. Analysis of the contribution of the organs to effective dose is also provided. Lastly, comparison of effective dose rates between the voxel and stylized phantoms was within 8% at 100 keV and is <5% between 200 and 5000 keV.« less

Comparison of Monoenergetic Photon Organ Dose Rate Coefficients for the Female Stylized and Voxel Phantoms Submerged in Air

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

Hiller, Mauritius; Dewji, Shaheen Azim

Dose rate coefficients computed using the International Commission on Radiological Protection (ICRP) reference adult female voxel phantom were compared with values computed using the Oak Ridge National Laboratory (ORNL) adult female stylized phantom in an air submersion exposure geometry. This is a continuation of previous work comparing monoenergetic organ dose rate coefficients for the male adult phantoms. With both the male and female data computed, effective dose rate as defined by ICRP Publication 103 was compared for both phantoms. Organ dose rate coefficients for the female phantom and ratios of organ dose rates for the voxel and stylized phantoms aremore » provided in the energy range from 30 to 5 MeV. Analysis of the contribution of the organs to effective dose is also provided. Lastly, comparison of effective dose rates between the voxel and stylized phantoms was within 8% at 100 keV and is <5% between 200 and 5000 keV.« less

Anastomotic Complications After Ivor Lewis Esophagectomy in Patients Treated With Neoadjuvant Chemoradiation Are Related to Radiation Dose to the Gastric Fundus

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

Vande Walle, Caroline; Ceelen, Wim P., E-mail: wim.ceelen@ugent.be; Boterberg, Tom

2012-03-01

Purpose: Neoadjuvant chemoradiation (CRT) is increasingly used in locally advanced esophageal cancer. Some studies have suggested that CRT results in increased surgical morbidity. We assessed the influence of CRT on anastomotic complications in a cohort of patients who underwent CRT followed by Ivor Lewis esophagectomy. Patients and Methods: Clinical and pathologic data were collected from all patients treated with neoadjuvant CRT (36 Gy combined with 5-fluorouracil and cisplatin) followed by Ivor Lewis esophagectomy. On the radiotherapy (RT) planning computed tomography scans, normal tissue volumes were drawn encompassing the proximal esophageal region and the gastric fundus. Within these volumes, dose-volume histogramsmore » were analyzed to generate the total dose to 50% of the volume (D{sub 50}). We studied the ability of the D{sub 50} to predict anastomotic complications (leakage, ischemia, or stenosis). Dose limits were derived using receiver operating characteristics analysis. Results: Fifty-four patients were available for analysis. RT resulted in either T or N downstaging in 51% of patients; complete pathologic response was achieved in 11%. In-hospital mortality was 5.4%, and major morbidity occurred in 36% of patients. Anastomotic complications (AC) developed in 7 patients (13%). No significant influence of the D{sub 50} on the proximal esophagus was noted on the anastomotic complication rate. The median D{sub 50} on the gastric fundus, however, was 33 Gy in patients with AC and 18 Gy in patients without AC (p = 0.024). Using receiver operating characteristics analysis, the D{sub 50} limit on the gastric fundus was defined as 29 Gy. Conclusions: In patients undergoing neoadjuvant CRT followed by Ivor Lewis esophagectomy, the incidence of AC is related to the RT dose on the gastric fundus but not to the dose received by the proximal esophagus. When planning preoperative RT, efforts should be made to limit the median dose on the gastric fundus to 29 Gy with a V{sub 30} below 40%.« less

Analysis of Exposure-Dose Variation of Inhaled Particles in Adult Subjects.

EPA Science Inventory

Although internal dose is a key factor for determining the health risk of inhaled pollutant particles, available dose information is largely limited to young healthy adults under a few typical exposure conditions. Extrapolation of the limited dose information to different populat...

Dose limits to the lens of the eye: International Basic Safety Standards and related guidance.

PubMed

Boal, T J; Pinak, M

2015-06-01

The International Atomic Energy Agency (IAEA) safety requirements: 'General Safety Requirements Part 3--Radiation protection and safety of radiation sources: International Basic Safety Standards' (BSS) was approved by the IAEA Board of Governors at its meeting in September 2011, and was issued as General Safety Requirements Part 3 in July 2014. The equivalent dose limit for the lens of the eye for occupational exposure in planned exposure situations was reduced from 150 mSv year(-1) to 20 mSv year(-1), averaged over defined periods of 5 years, with no annual dose in a single year exceeding 50 mSv. This reduction in the dose limit for the lens of the eye followed the recommendation of the International Commission on Radiological Protection in its statement on tissue reactions of 21 April 2011. IAEA has developed guidance on the implications of the new dose limit for the lens of the eye. This paper summarises the process that led to the inclusion of the new dose limit for the lens of the eye in the BSS, and the implications of the new dose limit. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

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

Podonsky, Glenn S.

The U.S. Department of Energy (DOE) Office of Analysis within the Office of Health, Safety and Security (HSS) publishes the annual DOE Occupational Radiation Exposure Report to provide an overview of the status of radiation protection practices at DOE (including the National Nuclear Security Administration [NNSA]). The DOE 2012 Occupational Radiation Exposure Report provides an evaluation of DOE-wide performance regarding compliance with Title 10, Code of Federal Regulations (C.F.R.), Part 835, Occupational Radiation Protection dose limits and as low as reasonably achievable (ALARA) process requirements. In addition, the report provides data to DOE organizations responsible for developing policies for protectionmore » of individuals from the adverse health effects of radiation. The report provides a summary and an analysis of occupational radiation exposure information from the monitoring of individuals involved in DOE activities. Over the past 5-year period, the occupational radiation exposure information is analyzed in terms of aggregate data, dose to individuals, and dose by site. As an indicator of the overall amount of radiation dose received during the conduct of operations at DOE, the report includes information on collective total effective dose (TED). The TED is comprised of the effective dose (ED) from external sources, which includes neutron and photon radiation, and the internal committed effective dose (CED), which results from the intake of radioactive material into the body. The collective ED from photon exposure decreased by 23% between 2011 and 2012, while the neutron dose increased by 5%. The internal dose components of the collective TED decreased by 7%. Over the past 5-year period, 99.99% of the individuals receiving measurable TED have received doses below the 2 roentgen equivalent in man (rems) (20 millisievert [mSv]) TED administrative control level (ACL), which is well below the DOE regulatory limit of 5 rems (50 mSv) TED annually. The occupational radiation exposure records show that in 2012, DOE facilities continued to comply with DOE dose limits and ACLs and worked to minimize exposure to individuals. The DOE collective TED decreased 17.1% from 2011 to 2012. The collective TED decreased at three of the five sites with the largest collective TED. u Idaho Site – Collective dose reductions were achieved as a result of continuing improvements at the Advanced Mixed Waste Treatment Project (AMWTP) through the planning of drum movements that reduced the number of times a container is handled; placement of waste containers that created highradiation areas in a centralized location; and increased worker awareness of high-dose rate areas. In addition, Idaho had the largest decrease in the total number of workers with measurable TED (1,143 fewer workers). u Hanford Site (Hanford) – An overall reduction of decontamination and decommissioning (D&D) activities at the Plutonium Finishing Plant (PFP) and Transuranic (TRU) retrieval activities resulted in collective dose reductions. u Savannah River Site (SRS) – Reductions were achieved through ALARA initiatives employed site wide. The Solid Waste Management Facility used extended specialty tools, cameras and lead shield walls to facilitate removal of drums. These tools and techniques reduce exposure time through improved efficiency, increase distance from the source of radiation by remote monitoring, shield the workers to lower the dose rate, and reduce the potential for contamination and release of material through repacking of waste. Overall, from 2011 to 2012, there was a 19% decrease in the number of workers with measurable dose. Furthermore, due to a slight decrease in both the DOE workforce (7%) and monitored workers (10%), the ratio of workers with measurable doses to monitored workers decreased to 13%. Another primary indicator of the level of radiation exposure covered in this report is the average measurable dose, which normalizes the collective dose over the population of workers who actually received a measurable dose. The average measurable TED increased by 3% from 2011 to 2012. Additional analyses show that the dose distribution in 2012 was similar to the distribution in 2011. In 2012, 13% of the monitored workers received a measurable TED and the average measurable TED, 0.069 rem, was less than 2% of the DOE limit. From 2011 to 2012, the collective TED and the number of individuals with measurable TED decreased 17.1% and 19%, respectively. These decreases were mainly due to an overall reduction of D&D activities at the PFP and TRU retrieval activities at Hanford; a 78% decrease in the number of targeted waste drums that were processed at the Idaho Site’s Accelerated Retrieval Project (ARP) from 5,566 drums in 2011 to a total of 1,211 drums processed in 2012; and ALARA initiatives employed site wide at SRS. In addition, the decreases were the result of decreased American Recovery and Reinvestment Act (ARRA) activities and continuing D&D, particularly at the DOE sites that comprise the majority of DOE collective dose. Over the past 5 years, the size of the monitored workforce has remained at a fairly stable level (within 12%), while the collective dose has varied up to 37%. No reported doses exceeded the DOE occupational limit of 5 rems TED in 2012 and no reported doses exceeded the DOE ACL of 2 rems TED.« less

High-dose amrinone is required to accelerate rewarming from deliberate mild intraoperative hypothermia for neurosurgical procedures.

PubMed

Inoue, Satoki; Kawaguchi, Masahiko; Sakamoto, Takanori; Kitaguchi, Katsuyasu; Furuya, Hitoshi; Sakaki, Toshisuke

2002-07-01

Since the time available to provide the cooling and rewarming is limited during deliberate mild hypothermia, the technique to accelerate the cooling and rewarming rate of core temperature has been studied. Amrinone has been reported to accelerate the cooling rate but not the rewarming rate of core temperature during deliberate mild hypothermia. The failure of amrinone effect on the rewarming rate might be due to an insufficient dose of amrinone during hypothermic conditions. The authors therefore tested whether higher doses of amrinone can accelerate the rewarming rate of core temperature during deliberate mild hypothermia for neurosurgery. After institutional approval and informed consent, 30 patients were randomly assigned to one of three groups. Patients in the control group (n = 10) did not receive amrinone; patients in the AMR 15 group (n = 10) received 15 microg x kg(-1) x min(-1) amrinone with a 1.0-mg/kg loading dose of amrinone at the beginning of cooling; and patients in the ReAMR group (n = 10) received 5 microg x kg(-1) x min(-1) amrinone with 1.0-mg/kg loading and reloading doses of amrinone at the beginning of cooling and rewarming, respectively. Administration of amrinone was started just after the induction of cooling and continued until the end of anesthesia. Anesthesia was maintained with nitrous oxide in oxygen, propofol, and fentanyl. After induction of anesthesia, patients were cooled, and tympanic membrane temperature was maintained at 34.5 degrees C. After completion of the main surgical procedures, patients were actively rewarmed and extubated in the operating room. The cooling and rewarming rates of core temperature were both significantly faster in both amrinone groups than in the control group. During the cooling and rewarming periods, forearm minus fingertip temperature gradient was significantly smaller in both amrinone groups than in the control group. During the rewarming period, heart rate and mean arterial pressure in the AMR 15 group were significantly faster and lower, respectively, than in the control group. Systemic vascular resistance in the AMR 15 group was smaller than in the control group throughout the study; on the other hand, only the value after the start of rewarming in the ReAMR group was smaller than in the control group. Amrinone at an infusion rate of 15 or 5 microg x kg(-1) x min(-1) with a reloading at the beginning of rewarming accelerated the rewarming rate of core temperature during deliberate mild hypothermia. This suggests that high-dose amrinone is required to accelerate rewarming from deliberate mild intraoperative hypothermia for neurosurgical procedures.

Quantitative confirmation of diffusion-limited oxidation theories

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

Gillen, K.T.; Clough, R.L.

1990-01-01

Diffusion-limited (heterogeneous) oxidation effects are often important for studies of polymer degradation. Such effects are common in polymers subjected to ionizing radiation at relatively high dose rate. To better understand the underlying oxidation processes and to aid in the planning of accelerated aging studies, it would be desirable to be able to monitor and quantitatively understand these effects. In this paper, we briefly review a theoretical diffusion approach which derives model profiles for oxygen surrounded sheets of material by combining oxygen permeation rates with kinetically based oxygen consumption expressions. The theory leads to a simple governing expression involving the oxygenmore » consumption and permeation rates together with two model parameters {alpha} and {beta}. To test the theory, gamma-initiated oxidation of a sheet of commercially formulated EPDM rubber was performed under conditions which led to diffusion-limited oxidation. Profile shapes from the theoretical treatments are shown to accurately fit experimentally derived oxidation profiles. In addition, direct measurements on the same EPDM material of the oxygen consumption and permeation rates, together with values of {alpha} and {beta} derived from the fitting procedure, allow us to quantitatively confirm for the first time the governing theoretical relationship. 17 refs., 3 figs.« less

Comparison of cosmic rays radiation detectors on-board commercial jet aircraft.

PubMed

Kubančák, Ján; Ambrožová, Iva; Brabcová, Kateřina Pachnerová; Jakůbek, Jan; Kyselová, Dagmar; Ploc, Ondřej; Bemš, Július; Štěpán, Václav; Uchihori, Yukio

2015-06-01

Aircrew members and passengers are exposed to increased rates of cosmic radiation on-board commercial jet aircraft. The annual effective doses of crew members often exceed limits for public, thus it is recommended to monitor them. In general, the doses are estimated via various computer codes and in some countries also verified by measurements. This paper describes a comparison of three cosmic rays detectors, namely of the (a) HAWK Tissue Equivalent Proportional Counter; (b) Liulin semiconductor energy deposit spectrometer and (c) TIMEPIX silicon semiconductor pixel detector, exposed to radiation fields on-board commercial Czech Airlines company jet aircraft. Measurements were performed during passenger flights from Prague to Madrid, Oslo, Tbilisi, Yekaterinburg and Almaty, and back in July and August 2011. For all flights, energy deposit spectra and absorbed doses are presented. Measured absorbed dose and dose equivalent are compared with the EPCARD code calculations. Finally, the advantages and disadvantages of all detectors are discussed. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Efficacy of vincristine and etoposide with escalating cyclophosphamide in poor-prognosis pediatric brain tumors1

PubMed Central

Ziegler, David S.; Cohn, Richard J.; McCowage, Geoffrey; Alvaro, Frank; Oswald, Cecilia; Mrongovius, Robert; White, Les

2006-01-01

The objective of this study was to assess the efficacy of the VETOPEC regimen, a regimen of vincristine and etoposide with escalating doses of cyclophosphamide (CPA), in pediatric patients with high-risk brain tumors. Three consecutive studies by the Australia and New Zealand Children’s Cancer Study Group—VETOPEC I, Baby Brain 91, and VETOPEC II—have used a specific chemotherapy regimen of vincristine (VCR), etoposide (VP-16) and escalating CPA in patients with relapsed, refractory, or high-risk solid tumors. Patients in the VETOPEC II cohort were treated with very high dose CPA with peripheral blood stem cell (PBSC) rescue. We analyzed the subset of patients with high-risk brain tumors treated with these intensive VETOPEC-based protocols to assess the response, toxicity, and survival. We also assessed whether the use of very high dose chemotherapy with stem cell rescue improved the response rate or affected toxicity. Seventy-one brain tumor patients were treated with VETOPEC-based protocols. Of the 54 patients evaluable for tumor response, 17 had a complete response (CR) and 20 a partial response (PR) to treatment, which yielded an overall response rate of 69%. The CR + PR was 83% (19/23) for medulloblastomas, 56% (5/9) for primitive neuroectodermal tumors, 55% (6/11) for grade 3 and 4 astrocytomas, and 80% (6/8) for ependymomas. At a median follow-up of 36 months, overall survival for the entire cohort of 71 patients was 32%, with event-free survival of 13%. There were no toxic deaths within the PBSC-supported VETOPEC II cohort, despite higher CPA doses, compared with 7% among the non-PBSC patients. This regimen produces high response rates in a variety of very poor prognosis pediatric brain tumors. The maximum tolerated dose of CPA was not reached. Higher escalation in doses of CPA did not deliver a further improvement in response. With PBSC rescue in the VETOPEC II study, hematologic toxicity was no longer a limiting factor. The response rates observed support further development of this chemotherapy regimen. PMID:16443948

Poster — Thur Eve — 27: Flattening Filter Free VMAT Quality Assurance: Dose Rate Considerations for Detector Response

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

Viel, Francis; Duzenli, Cheryl; British Columbia Cancer Agency, Department of Medical Physics, Vancouver Centre

2014-08-15

Introduction: Radiation detector responses can be affected by dose rate. Due to higher dose per pulse and wider range of mu rates in FFF beams, detector responses should be characterized prior to implementation of QA protocols for FFF beams. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. This study looks at the dose per pulse variation throughout a 3D volume for typical VMAT plans and the response characteristics for a variety of detectors, and makes recommendations on the design of QA protocols for FFF VMAT QA. Materials and Methods: Linac log file data andmore » a simplified dose calculation algorithm are used to calculate dose per pulse for a variety of clinical VMAT plans, on a voxel by voxel basis, as a function of time in a cylindrical phantom. Diode and ion chamber array responses are characterized over the relevant range of dose per pulse and dose rate. Results: Dose per pulse ranges from <0.1 mGy/pulse to 1.5 mGy/pulse in a typical VMAT treatment delivery using the 10XFFF beam. Diode detector arrays demonstrate increased sensitivity to dose (+./− 3%) with increasing dose per pulse over this range. Ion chamber arrays demonstrate decreased sensitivity to dose (+/− 1%) with increasing dose rate over this range. Conclusions: QA protocols should be designed taking into consideration inherent changes in detector sensitivity with dose rate. Neglecting to account for changes in detector response with dose per pulse can lead to skewed QA results.« less

Acute changes in the central nervous system of monkeys exposed to protons.

NASA Technical Reports Server (NTRS)

Haymaker, W.; Ibrahim, M. Z. M.; Miquel, J.; Call, N.; Noden, P.; Ashley, W.; Ballinger, E. R.; Ghidoni, J.; Lindsay, I. R.; Behar, A. J.

1972-01-01

Study of the changes occurring in simian brain exposed to protons of varied energy, given in wide dose and dose-rate ranges. Results show that inflammatory reaction and glycogen accumulation in astrocytes occurred practically in all animals. Cerebral cortical necrosis, granule cell pyknosis, and inflammatory reaction occurred at doses far lower than effective for high-energy gamma radiation given other series of monkeys at comparable dose rates. Metallic impregnation, carried out in virtually all the animals tested, revealed a wide variation in glial response even at equal doses and dose rates in the same proton energy series. Proton energy effect, dose effect, dose-time effect, and dose-rate effect were evident in the various morphological categories investigated, but inconsistencies were encountered.

WE-FG-BRA-05: Potential Clinical Benefit of LINAC Flattening-Filter-Free (FFF) Mode - Improvement of Treatment Therapeutic Ratio

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

Chang, S; Department of Biomedical Engineering, University of North Carolina- Chapel Hill/ North Carolina State University, Chapel Hill, North Carolina; Lineberger Clinical Cancer Center, University of North Carolina, Chapel Hill, NC

Purpose: Ultrahigh dose-rate radiation at >40Gy/s has demonstrated astonishing normal-tissue sparing and tumor control in recent preclinical naive and tumor-bearing rodent studies when compared to the same radiation dose at a conventional dose-rate. The working mechanism of this fascinating dose-rate effect is currently under investigation. The aims of this work include investigating 1) whether LINAC FFF mode radiation at approximately 1Gy/s also has an improved therapeutic ratio compared to the same radiation dose at the conventional dose-rate of 0.05Gy/s, and 2) the dose-rate effect’s potential working mechanism by studying the expression of the P53 gene, linked to tumor suppression andmore » cell regulation after radiation damage. Methods: We used mouse model C57BL/6J, the same as that used in the ultrahigh dose-rate studies, and exposed them to total body irradiation (TBI) using the Elekta Versa accelerator 10MV photons. Mice (N=20) were given a total dose of 12Gy in both the high dose-rate group (n=10) using the FFF-mode and the conventional dose-rate group (n=10) using the conventional does rate mode. The FFF-mode treatment setup consisted of a 15cm×15cm field size setting at 53.2cm SSD while the conventional-mode set-up consisted of a 10cm×10cm field size at 100SSD. Post-radiation, animals were monitored daily for survival analysis and signs of moribundity requiring euthanasia. In addition, mouse spleens were harvested for P53 analysis at different time points. Results: For 12Gy TBI, the 1.3Gy/s FFF-mode high dose-rate produced a statistically significant (p=0.02) improvement in mouse survival compared to the 0.05Gy/s conventional dose-rate. An initial P53 study at the time of death time-point indicates that high dose-rate radiation induced a stronger expression of P53 than conventional dose-rate radiation. Conclusion: Our pilot study indicates that the FFF-mode high dose-rate radiation, which has been used largely to improve clinical throughput, may provide the added clinical benefit of improving treatment therapeutic ratio. Animal Studies were performed within the LCCC Animal Studies Core Facility at the University of North Carolina at Chapel Hill. The LCCC Animal Studies Core is supported in part by an NCI Center Core Support Grant (CA16086) to the UNC Lineberger Comprehensive Cancer Center.« less

A simple low-cost of liquid I-131 dispenser for routine radiopharmaceutical dispensing at nuclear medicine department, Institut Kanser Negara

NASA Astrophysics Data System (ADS)

Said, M. A.; Ashhar, Z. N.; Suhaimi, N. E. F.; Zainon, R.

2016-01-01

In routine radiopharmaceutical Iodine-131 (131I) dispensing, the amount of radiation dose received by the personnel depends on the distance between the personnel and the source, the time spent manipulating the source and the amount of shielding used to reduce the dose rate from the source. The novel iRAD-I131 dispenser using recycle 131I liquid lead pot will lead into low cost production, less maintenance and low dose received by the personnel that prepared the 131I. The new fabricated of low cost 131I dispenser was tested and the dose received by personnel were evaluated. The body of lead material is made from 2.5 cm lead shielded coated with epoxy paint to absorb the radiation dose up to 7.4 GBq of 131 I. The lead pot was supported with two stainless steel rod. The Optically Stimulated Luminescence (OSL) nanodot was used in this study to measure the dose rate at both extremities for every personnel who prepared the 131I. Each OSL nanodot was attached at the fingertip. Three different personnel (experienced between one to ten years above in preparing the radiopharmaceuticals) were participated in this study. The average equivalent dose at right and left hand were 122.694 ± 121.637 µSv/GBq and 77.281 ± 62.146 µSv/GBq respectively. This study found that the dose exposure received using iRAD-I131 was less up to seven times compared to the conventional method. The comparison of experimental data using iRAD-I131 and established radiopharmaceutical dispenser was also discussed. The innovation of 131I dispenser is highly recommended in a small radiopharmaceutical facility with limited budget. The novel iRAD-I131 enables implementation of higher output liquid dispensing with low radiation dose to the personnel.

A simple low-cost of liquid I-131 dispenser for routine radiopharmaceutical dispensing at nuclear medicine department, Institut Kanser Negara

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

Said, M. A.; Suhaimi, N. E. F.; Ashhar, Z. N., E-mail: aminhpj@gmail.com

In routine radiopharmaceutical Iodine-131 ({sup 131}I) dispensing, the amount of radiation dose received by the personnel depends on the distance between the personnel and the source, the time spent manipulating the source and the amount of shielding used to reduce the dose rate from the source. The novel iRAD-I131 dispenser using recycle {sup 131}I liquid lead pot will lead into low cost production, less maintenance and low dose received by the personnel that prepared the {sup 131}I. The new fabricated of low cost {sup 131}I dispenser was tested and the dose received by personnel were evaluated. The body of leadmore » material is made from 2.5 cm lead shielded coated with epoxy paint to absorb the radiation dose up to 7.4 GBq of {sup 131} I. The lead pot was supported with two stainless steel rod. The Optically Stimulated Luminescence (OSL) nanodot was used in this study to measure the dose rate at both extremities for every personnel who prepared the {sup 131}I. Each OSL nanodot was attached at the fingertip. Three different personnel (experienced between one to ten years above in preparing the radiopharmaceuticals) were participated in this study. The average equivalent dose at right and left hand were 122.694 ± 121.637 µSv/GBq and 77.281 ± 62.146 µSv/GBq respectively. This study found that the dose exposure received using iRAD-I131 was less up to seven times compared to the conventional method. The comparison of experimental data using iRAD-I131 and established radiopharmaceutical dispenser was also discussed. The innovation of {sup 131}I dispenser is highly recommended in a small radiopharmaceutical facility with limited budget. The novel iRAD-I131 enables implementation of higher output liquid dispensing with low radiation dose to the personnel.« less

Dose rate effect on micronuclei induction in human blood lymphocytes exposed to single pulse and multiple pulses of electrons.

PubMed

Acharya, Santhosh; Bhat, N N; Joseph, Praveen; Sanjeev, Ganesh; Sreedevi, B; Narayana, Y

2011-05-01

The effects of single pulses and multiple pulses of 7 MV electrons on micronuclei (MN) induction in cytokinesis-blocked human peripheral blood lymphocytes (PBLs) were investigated over a wide range of dose rates per pulse (instantaneous dose rate). PBLs were exposed to graded doses of 2, 3, 4, 6, and 8 Gy of single electron pulses of varying pulse widths at different dose rates per pulse, ranging from 1 × 10(6) Gy s(-1) to 3.2 × 10(8) Gy s(-1). Different dose rates per pulse were achieved by changing the dose per electron pulse by adjusting the beam current and pulse width. MN yields per unit absorbed dose after irradiation with single electron pulses were compared with those of multiple pulses of electrons. A significant decrease in the MN yield with increasing dose rates per pulse was observed, when dose was delivered by a single electron pulse. However, no reduction in the MN yield was observed when dose was delivered by multiple pulses of electrons. The decrease in the yield at high dose rates per pulse suggests possible radical recombination, which leads to decreased biological damage. Cellular response to the presence of very large numbers of chromosomal breaks may also alter the damage.

Comparative performance analysis for computer aided lung nodule detection and segmentation on ultra-low-dose vs. standard-dose CT

NASA Astrophysics Data System (ADS)

Wiemker, Rafael; Rogalla, Patrik; Opfer, Roland; Ekin, Ahmet; Romano, Valentina; Bülow, Thomas

2006-03-01

The performance of computer aided lung nodule detection (CAD) and computer aided nodule volumetry is compared between standard-dose (70-100 mAs) and ultra-low-dose CT images (5-10 mAs). A direct quantitative performance comparison was possible, since for each patient both an ultra-low-dose and a standard-dose CT scan were acquired within the same examination session. The data sets were recorded with a multi-slice CT scanner at the Charite university hospital Berlin with 1 mm slice thickness. Our computer aided nodule detection and segmentation algorithms were deployed on both ultra-low-dose and standard-dose CT data without any dose-specific fine-tuning or preprocessing. As a reference standard 292 nodules from 20 patients were visually identified, each nodule both in ultra-low-dose and standard-dose data sets. The CAD performance was analyzed by virtue of multiple FROC curves for different lower thresholds of the nodule diameter. For nodules with a volume-equivalent diameter equal or larger than 4 mm (149 nodules pairs), we observed a detection rate of 88% at a median false positive rate of 2 per patient in standard-dose images, and 86% detection rate in ultra-low-dose images, also at 2 FPs per patient. Including even smaller nodules equal or larger than 2 mm (272 nodules pairs), we observed a detection rate of 86% in standard-dose images, and 84% detection rate in ultra-low-dose images, both at a rate of 5 FPs per patient. Moreover, we observed a correlation of 94% between the volume-equivalent nodule diameter as automatically measured on ultra-low-dose versus on standard-dose images, indicating that ultra-low-dose CT is also feasible for growth-rate assessment in follow-up examinations. The comparable performance of lung nodule CAD in ultra-low-dose and standard-dose images is of particular interest with respect to lung cancer screening of asymptomatic patients.

Medical Management of Radiological Casualties. Online Third Edition

DTIC Science & Technology

2010-06-01

contaminated should be surveyed before entering and responders should be advised to limit their time in high dose-rate areas. There is generally no hazard...early oral enteral feeding when feasible. • Povidone-iodine or chlorhexidine for skin disinfection and shampoo . Meticulous oral hygiene. Clinical...signs, normal primary and second survey , but has vomited repeatedly, beginning approximately 2 hours post-event. Solution. Using the simple scoring

Characterization of a synthetic single crystal diamond detector for dosimetry in spatially fractionated synchrotron x-ray fields.

PubMed

Livingstone, Jayde; Stevenson, Andrew W; Butler, Duncan J; Häusermann, Daniel; Adam, Jean-François

2016-07-01

Modern radiotherapy modalities often use small or nonstandard fields to ensure highly localized and precise dose delivery, challenging conventional clinical dosimetry protocols. The emergence of preclinical spatially fractionated synchrotron radiotherapies with high dose-rate, sub-millimetric parallel kilovoltage x-ray beams, has pushed clinical dosimetry to its limit. A commercially available synthetic single crystal diamond detector designed for small field dosimetry has been characterized to assess its potential as a dosimeter for synchrotron microbeam and minibeam radiotherapy. Experiments were carried out using a synthetic diamond detector on the imaging and medical beamline (IMBL) at the Australian Synchrotron. The energy dependence of the detector was characterized by cross-referencing with a calibrated ionization chamber in monoenergetic beams in the energy range 30-120 keV. The dose-rate dependence was measured in the range 1-700 Gy/s. Dosimetric quantities were measured in filtered white beams, with a weighted mean energy of 95 keV, in broadbeam and spatially fractionated geometries, and compared to reference dosimeters. The detector exhibits an energy dependence; however, beam quality correction factors (kQ) have been measured for energies in the range 30-120 keV. The kQ factor for the weighted mean energy of the IMBL radiotherapy spectrum, 95 keV, is 1.05 ± 0.09. The detector response is independent of dose-rate in the range 1-700 Gy/s. The percentage depth dose curves measured by the diamond detector were compared to ionization chambers and agreed to within 2%. Profile measurements of microbeam and minibeam arrays were performed. The beams are well resolved and the full width at halfmaximum agrees with the nominal width of the beams. The peak to valley dose ratio (PVDR) calculated from the profiles at various depths in water agrees within experimental error with PVDR calculations from Gafchromic film data. The synthetic diamond detector is now well characterized and will be used to develop an experimental dosimetry protocol for spatially fractionated synchrotron radiotherapy.

Image-Guided High-Dose Rate Brachytherapy in Cervix Carcinoma Using Balloon Catheter and Belt Immobilization System.

PubMed

Fan, Qiyong; Yeung, Anamaria R; Amdur, Robert; Helmig, Richard; Park, Justin; Li, Jonathan; Kahler, Darren; Liu, Chihray; Lu, Bo

2017-06-01

The efficacy of image-guided high-dose rate brachytherapy for cervical cancer is limited by the ineffective rectal sparing devices available commercially and the potential applicator movement. We developed a novel device using a balloon catheter and a belt immobilization system, serving for rectal dose reduction and applicator immobilization purposes, respectively. The balloon catheter is constructed by gluing a short inflatable tube to a long regular open-end catheter. Contrast agent (10) cm 3 is injected into the inflatable end, which is affixed to the tandem and ring applicator, to displace the posterior vaginal wall. The belt immobilization system consists of a specially designed bracket that can hold and fix itself to the applicator, a diaper-like Velcro fastener package used for connecting the patient's pelvis to the bracket, and a buckle that holds the fasteners to stabilize the whole system. The treatment data for 21 patients with cervical cancer using both balloon catheter and belt immobilization system were retrospectively analyzed. Computed tomography and magnetic resonance images, acquired about 30 minutes apart, were registered to evaluate the effectiveness of the immobilization system. In comparison with a virtual rectal blade, the balloon decreased the rectal point dose by 34% ± 4.2% (from 276 ± 57 to 182 ± 38 cGy), corresponding to an extra sparing distance of 7.9 ± 1.1 mm. The maximum sparing distance variation per patient is 1.4 ± 0.6 mm, indicating the high interfractional reproducibility for rectum sparing. With the immobilization system, the mean translational and rotational displacements of the applicator set are <3 mm and <1.5°, respectively, in all directions. The rectal balloon provides significant dose reduction to the rectum and it may potentially minimize patient discomfort. The immobilization system permits almost no movement of the applicator during treatment. This work has the potential to be promoted as a standardized solution for high-dose rate treatment of cervical cancer.

Duration of treatment for asymptomatic bacteriuria during pregnancy.

PubMed

Widmer, Mariana; Gülmezoglu, A Metin; Mignini, Luciano; Roganti, Ariel

2011-12-07

A Cochrane systematic review has shown that drug treatment of asymptomatic bacteriuria in pregnant women substantially decreases the risk of pyelonephritis and reduces the risk of preterm delivery. However, it is not clear whether single-dose therapy is as effective as longer conventional antibiotic treatment. To assess the effects of different durations of treatment for asymptomatic bacteriuria in pregnancy. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2011) and reference lists of identified articles. Randomized and quasi-randomized trials comparing antimicrobial therapeutic regimens that differed in duration (particularly comparing single dose with longer duration regimens) in pregnant women diagnosed with asymptomatic bacteriuria. We assessed trial quality and extracted data independently. We included 13 studies, involving 1622 women. All were comparisons of single-dose treatment with four- to seven-day treatments. The trials were generally of limited quality. The 'no cure rate' for asymptomatic bacteriuria in pregnant women was slightly higher for the single-dose than for the short-course treatment; however, these results were not statistically significant and showed heterogeneity. When comparing the trials that used the same antibiotic in both treatment and control groups with the trials that used different antibiotics in both groups, the 'no cure rate' risk ratio was similar. There was no statistically significant difference in the recurrence of asymptomatic bacteriuria rate between treatment and control groups. Slight differences were detected for preterm births and pyelonephritis although, apart from one trial, the sample size of the trials was inadequate. Single-dose treatment was associated with a decrease in reports of 'any side-effects' . Single-dose regimen of antibiotics may be less effective than the seven-day regimen. Women with asymptomatic bacteriuria in pregnancy should be treated by the standard regimen of antibiotics until more data become available testing seven-day compared with three- or five-day regimens.

Automated construction of an intraoperative high-dose-rate treatment plan library for the Varian brachytherapy treatment planning system.

PubMed

Deufel, Christopher L; Furutani, Keith M; Dahl, Robert A; Haddock, Michael G

2016-01-01

The ability to create treatment plans for intraoperative high-dose-rate (IOHDR) brachytherapy is limited by lack of imaging and time constraints. An automated method for creation of a library of high-dose-rate brachytherapy plans that can be used with standard planar applicators in the intraoperative setting is highly desirable. Nonnegative least squares algebraic methods were used to identify dwell time values for flat, rectangular planar applicators. The planar applicators ranged in length and width from 2 cm to 25 cm. Plans were optimized to deliver an absorbed dose of 10 Gy to three different depths from the patient surface: 0 cm, 0.5 cm, and 1.0 cm. Software was written to calculate the optimized dwell times and insert dwell times and positions into a .XML plan template that can be imported into the Varian brachytherapy treatment planning system. The user may import the .XML template into the treatment planning system in the intraoperative setting to match the patient applicator size and prescribed treatment depth. A total of 1587 library plans were created for IOHDR brachytherapy. Median plan generation time was approximately 1 minute per plan. Plan dose was typically 100% ± 1% (mean, standard deviation) of the prescribed dose over the entire length and width of the applicator. Plan uniformity was best for prescription depths of 0 cm and 0.5 cm from the patient surface. An IOHDR plan library may be created using automated methods. Thousands of plan templates may be optimized and prepared in a few hours to accommodate different applicator sizes and treatment depths and reduce treatment planning time. The automated method also enforces dwell time symmetry for symmetrical applicator geometries, which simplifies quality assurance. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Determination of naturally radioactive elements in chalk sticks by means of gamma spectroscopy

NASA Astrophysics Data System (ADS)

Abd El-Wahab, Magda; Morsy, Zeinab; El-Faramawy, Nabil

2010-04-01

The radiation hazards due to ingestion of chalkboard dust were investigated. Sixteen samples from three different origin fabricates were used. The estimation of radiation hazard indices were based on the evaluation of the concentration activities of the natural radionuclides 238U, 232Th and 40K. The radium equivalent activity, external hazard index, internal hazard index and the annual dose equivalent associated with the radionuclides were calculated and compared with international recommended values to assess the radiation hazard. The values of internal and external radiation hazard indices were found to be less than unity. The annual effective dose rate obtained, E eff, and the annual gonadal dose equivalent (AGDE) are found to be less than the limit of the doses recommended by the International Commission on Radiological Protection for the general public. The analytical results show that besides the main calcium content, some toxic elements, S, Mo and Pb and Ni and Pb, in the Egyptian and imported chalk stocks, respectively, existed.

Determination of naturally radioactive elements in chalk sticks by means of gamma spectroscopy

NASA Astrophysics Data System (ADS)

El-Wahab, Magda Abd; Morsy, Zeinab; El-Faramawy, Nabil

The radiation hazards due to ingestion of chalkboard dust were investigated. Sixteen samples from three different origin fabricates were used. The estimation of radiation hazard indices were based on the evaluation of the concentration activities of the natural radionuclides 238U, 232Th and 40K. The radium equivalent activity, external hazard index, internal hazard index and the annual dose equivalent associated with the radionuclides were calculated and compared with international recommended values to assess the radiation hazard. The values of internal and external radiation hazard indices were found to be less than unity. The annual effective dose rate obtained, Eeff, and the annual gonadal dose equivalent (AGDE) are found to be less than the limit of the doses recommended by the International Commission on Radiological Protection for the general public. The analytical results show that besides the main calcium content, some toxic elements, S, Mo and Pb and Ni and Pb, in the Egyptian and imported chalk stocks, respectively, existed.

Sanitation of chicken eggs by ionizing radiation: functional and nutritional assessment

NASA Astrophysics Data System (ADS)

Pinto, P.; Ribeiro, R.; Sousa, L.; Verde, S. Cabo; Lima, M. G.; Dinis, M.; Santana, A.; Botelho, M. L.

2004-09-01

Alternative technologies must be developed and implemented considering sanitation and preservation of eggs mainly for risk population. Food irradiation is an alternative to free Salmonella spp. and Campylobacter spp. eggs, as a low dose point to a safety assurance. This study presents the correlation between irradiation doses (0.5 kGy up to 5 kGy at dose rate of 1.0 kGy/h) and some of functional and nutritional egg properties. Viscosimetry of non-irradiated and irradiated eggs was evaluated by means of VT550 Haake with an NV sensor and co-axes cylinders. After irradiation at 5 kGy, the yolk colour die (pale yellow) and the white egg was modified to a turbid yellow. The Cross equation was utilized to viscosimetry curves. Based on the assymptotics viscosimetry data indicated that increase of doses corresponds to an increase of the yolk and a decrease of white egg viscosimetry as such a Newton behaviour. Irradiation effects on nutritional properties were evaluated by means of egg protein patterns that were assessed by polyacrylamide gel electrophoresis. Lipids were identified by TLC. Based on results the sanitation dose is lower than the limit dose for the decrease of the main eggs properties.

Microbial Biofilms: Persisters, Tolerance and Dosing

NASA Astrophysics Data System (ADS)

Cogan, N. G.

2005-03-01

Almost all moist surfaces are colonized by microbial biofilms. Biofilms are implicated in cross-contamination of food products, biofouling, medical implants and various human infections such as dental cavities, ulcerative colitis and chronic respiratory infections. Much of current research is focused on the recalcitrance of biofilms to typical antibiotic and antimicrobial treatments. Although the polymer component of biofilms impedes the penetration of antimicrobials through reaction-diffusion limitation, this does not explain the observed tolerance, it merely delays the action of the agent. Heterogeneities in growth-rate also slow the eradication of the bacteria since most antimicrobials are far less effective for non-growing, or slowly growing bacteria. This also does not fully describe biofilm tolerance, since heterogeneities arr primairly a result of nutrient consumption. In this investigation, we describe the formation of `persister' cells which neither grow nor die in the presence of antibiotics. We propose that the cells are of a different phenotype than typical bacterial cells and the expression of the phenotype is regulated by the growth rate and the antibiotic concentration. We describe several experiments which describe the dynamics of persister cells and which motivate a dosing protocol that calls for periodic dosing of the population. We then introduce a mathematical model, which describes the effect of such a dosing regiment and indicates that the relative dose/withdrawal times are important in determining the effectiveness of such a treatment. A reduced model is introduced and the similar behavior is demonstrated analytically.

Space Radiation Cancer Risk Projections and Uncertainties - 2010

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Kim, Myung-Hee Y.; Chappell, Lori J.

2011-01-01

Uncertainties in estimating health risks from galactic cosmic rays greatly limit space mission lengths and potential risk mitigation evaluations. NASA limits astronaut exposures to a 3% risk of exposure-induced death and protects against uncertainties using an assessment of 95% confidence intervals in the projection model. Revisions to this model for lifetime cancer risks from space radiation and new estimates of model uncertainties are described here. We review models of space environments and transport code predictions of organ exposures, and characterize uncertainties in these descriptions. We summarize recent analysis of low linear energy transfer radio-epidemiology data, including revision to Japanese A-bomb survivor dosimetry, longer follow-up of exposed cohorts, and reassessments of dose and dose-rate reduction effectiveness factors. We compare these projections and uncertainties with earlier estimates. Current understanding of radiation quality effects and recent data on factors of relative biological effectiveness and particle track structure are reviewed. Recent radiobiology experiment results provide new information on solid cancer and leukemia risks from heavy ions. We also consider deviations from the paradigm of linearity at low doses of heavy ions motivated by non-targeted effects models. New findings and knowledge are used to revise the NASA risk projection model for space radiation cancer risks.

Bioequivalence of isoniazid in a two drug fixed dose combination and in a single drug dosage form.

PubMed

Agrawal, S; Kaul, C L; Panchagnula, R

2001-08-01

To increase the patient compliance and reduce the risk of drug resistant strains, WHO and IUATLD recommend the use of Fixed Dose Combination (FDC) tablets as a routine therapeutic regimen in Directly Observed Treatment Shortcourse (DOTS). But the main issue in the use of FDC is the quality of the formulation. At present WHO and IUATLD suggest the bioequivalence assessment of only rifampicin from FDC compared to separate formulations. For the therapeutic effectiveness all the components of the FDCs should be bioavailable at tissue site. Also, the primary and acquired resistance rate of isoniazid is much higher compared to other anti-tubercular drugs. Hence, a comparative bioavailability study of isoniazid from a two drugs FDC compared to a separate formulation was carried out on a group of 12 healthy volunteers. When evaluated by normal or log transformed confidence interval, Two Way ANOVA and Hauschke analysis, the bioequivalence limits for AUC0-8 and AUC0-24 were within 0.8-1.25. For Cmax and Tmax, these limits were within 0.7-1.43. Hence, isoniazid from a FDC formulation was found to be bioequivalent to a separate formulation at same dose levels.

Effects of radiation on the leach rates of vitrified radioactive waste

NASA Astrophysics Data System (ADS)

Burns, W. G.; Hughes, A. E.; Marples, J. A. C.; Nelson, R. S.; Stoneham, A. M.

1982-06-01

This report reviews the possible effects of both radiation damage to the glass and of radiolysis of the leachant on the leaching behaviour of vitrified radioactive waste. It has been stimulated particularly by recent papers, which have suggested that the leach rates of glasses will be enhanced by large factors after a 'critical' dose of radiation from alpha decays. These experiments have been conducted at highly accelerated rates using ion beams. The relationship between these experiments and the situation in vitrified waste has been assessed, taking into account the fact that experiments using alpha emitters incorporated in the glass have failed to find significantly enhanced leach rates after doses about five times larger than those equivalent to this 'critical' dose. It is concluded that these differences are observed partly because the ion beam experiments are carried out at such high dose rates that some recovery effects important at lower rates do not come into play. In the case of experiments with 2 keV argon ions, surface effects other than genuine radiation damage must be taken into account. In practice, if water has penetrated the canister, vitrified waste will be irradiated in the presence of the leaching solution. Enhancements of the leach rate due to the transient effects of radiation in the solid are shown to be completely negligible. The effects of radiolysis of the leaching solution and of any air in contact with the solution have also been considered in some detail and related to recent experiments by McVay and Pederson. It is shown that these radiolysis effects will not lead to any situations requiring special precautions in practice, although changes in surface leach rate by small factors can be expected under some circumstances. Any effect of irradiation on leach rates must be seen in the context of a waste repository. Along with other studies we hold the view that the rate of loss of material will be limited by the access of water to the repository, and will therefore depend on the effective saturation solubility of the glass in the leachant, not on the leach rate as usually determined in laboratory tests. Radiation damage is not expected to change the saturation solubility by more than a factor of two or three.

Modeling adverse event counts in phase I clinical trials of a cytotoxic agent.

PubMed

Muenz, Daniel G; Braun, Thomas M; Taylor, Jeremy Mg

2018-05-01

Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient's richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting the true optimal dose. In particular, one of our models which uses dose-limiting and low-level toxicity counts beats or ties the other models, including the continual reassessment method, in all scenarios except the one in which the true optimal dose is the highest dose available. We also find that our models, when not selecting the true optimal dose, tend to err by picking lower, safer doses, while the continual reassessment method errs more toward toxic doses. Conclusion Using dose-limiting and low-level toxicity counts, which are easily obtained from data already routinely collected, is a promising way to improve the efficiency in finding the true maximum tolerated dose in phase I trials.

Formerly Utilized Sites Remedial Action Program (FUSRAP) Hazelwood Interim Storage Site annual site environmental report. Calendar year 1985. [FUSRAP

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

Not Available

1986-04-01

The Hazelwood Interim Storage Site (HISS) is presently used for the storage of low-level radioactively contaminated soils. Monitoring results show that the HISS is in compliance with DOE concentration guides and radiation protection standards. Derived Concentration Guides (DCGs) represent the concentrations of radionuclides in air or water that would limit the radiation dose to 100 mrem/y. The applicable limits have been revised since the 1984 environmental monitoring report was published. The limits applied in 1984 were based on a radiation protection standard of 500 mrem/y; the limits applied for 1985 are based on a standard of 100 mrem/y. The HISSmore » is part of the Formerly Utilized Sites Remedial Action Program (FUSRAP), a DOE program to decontaminate or otherwise control sites where low-level radioactive contamination remains from the early years of the nation's atomic energy program. To determine whether the site is in compliance with DOE standards, environmental measurements are expressed as percentages of the applicable DCG, while the calculated doses to the public are expressed as percentages of the applicable radiation protection standard. The monitoring program at the HISS measures uranium, radium, and thorium concentrations in surface water, groundwater, and sediment; radon gas concentrations in air; and external gamma radiation exposure rates. Potential radiation doses to the public are also calculated. The HISS was designated for remedial action under FUSRAP because radioactivity above applicable limits was found to exist at the site and its vicinity. Elevated levels of radiation still exist in areas where remedial action has not yet been completed.« less

Total dose bias dependency and ELDRS effects in bipolar linear devices

NASA Technical Reports Server (NTRS)

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

2002-01-01

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

The Impact of Dose Rate on the Accuracy of Step-and-Shoot Intensity-modulated Radiation Therapy Quality Assurance Using Varian 2300CD.

PubMed

Njeh, Christopher F; Salmon, Howard W; Schiller, Claire

2017-01-01

Intensity-modulated radiation therapy (IMRT) delivery using "step-and-shoot" technique on Varian C-Series linear accelerator (linac) is influenced by the communication frequency between the multileaf collimator and linac controllers. Hence, the dose delivery accuracy is affected by the dose rate. Our aim was to quantify the impact of using two dose rates on plan quality assurance (QA). Twenty IMRT patients were selected for this study. The plan QA was measured at two different dose rates. A gamma analysis was performed, and the degree of plan modulation on the QA pass rate was also evaluated in terms of average monitor unit per segment (MU/segment) and the total number of segments. The mean percentage gamma pass rate of 94.9% and 93.5% for 300 MU/min and 600 MU/min dose rate, respectively, was observed. There was a significant ( P = 0.001) decrease in percentage gamma pass rate when the dose rate was increased from 300 MU/min to 600 MU/min. There was a weak, but significant association between the percentage pass rate at both dose rate and total number of segments. The total number of MU was significantly correlated to the total number of segments ( r = 0.59). We found a positive correlation between the percentage pass rate and mean MU/segment, r = 0.52 and r = 0.57 for 300 MU/min and 600 MU/min, respectively. IMRT delivery using step-and-shoot technique on Varian 2300CD is impacted by the dose rate and the total amount of segments.

Enhanced Low Dose Rate Effects in Bipolar Circuits: A New Hardness Assurance Problem for NASA

NASA Technical Reports Server (NTRS)

Johnston, A.; Barnes, C.

1995-01-01

Many bipolar integrated circuits are much more susceptible to ionizing radiation at low dose rates than they are at high dose rates typically used for radiation parts testing. Since the low dose rate is equivalent to that seen in space, the standard lab test no longer can be considered conservative and has caused the Air Force to issue an alert. Although a reliable radiation hardness assurance test has not yet been designed, possible mechanisms for low dose rate enhancement and hardness assurance tests are discussed.

Development of a high precision dosimetry system for the measurement of surface dose rate distribution for eye applicators.

PubMed

Eichmann, Marion; Flühs, Dirk; Spaan, Bernhard

2009-10-01

The therapeutic outcome of the therapy with ophthalmic applicators is highly dependent on the application of a sufficient dose to the tumor, whereas the dose applied to the surrounding tissue needs to be minimized. The goal for the newly developed apparatus described in this work is the determination of the individual applicator surface dose rate distribution with a high spatial resolution and a high precision in dose rate with respect to time and budget constraints especially important for clinical procedures. Inhomogeneities of the dose rate distribution can be detected and taken into consideration for the treatment planning. In order to achieve this, a dose rate profile as well as a surface profile of the applicator are measured and correlated with each other. An instrumental setup has been developed consisting of a plastic scintillator detector system and a newly designed apparatus for guiding the detector across the applicator surface at a constant small distance. It performs an angular movement of detector and applicator with high precision. The measurements of surface dose rate distributions discussed in this work demonstrate the successful operation of the measuring setup. Measuring the surface dose rate distribution with a small distance between applicator and detector and with a high density of measuring points results in a complete and gapless coverage of the applicator surface, being capable of distinguishing small sized spots with high activities. The dosimetrical accuracy of the measurements and its analysis is sufficient (uncertainty in the dose rate in terms of absorbed dose to water is <7%), especially when taking the surgical techniques in positioning of the applicator on the eyeball into account. The method developed so far allows a fully automated quality assurance of eye applicators even under clinical conditions. These measurements provide the basis for future calculation of a full 3D dose rate distribution, which then can be used as input for a refined clinical treatment planning system. The improved dose rate measurements will facilitate a clinical study, which could correlate the therapeutic outcome of a brachytherapy treatment with an applicator and its individual dose rate distribution.

Development of a high precision dosimetry system for the measurement of surface dose rate distribution for eye applicators

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

Eichmann, Marion; Fluehs, Dirk; Spaan, Bernhard

2009-10-15

Purpose: The therapeutic outcome of the therapy with ophthalmic applicators is highly dependent on the application of a sufficient dose to the tumor, whereas the dose applied to the surrounding tissue needs to be minimized. The goal for the newly developed apparatus described in this work is the determination of the individual applicator surface dose rate distribution with a high spatial resolution and a high precision in dose rate with respect to time and budget constraints especially important for clinical procedures. Inhomogeneities of the dose rate distribution can be detected and taken into consideration for the treatment planning. Methods: Inmore » order to achieve this, a dose rate profile as well as a surface profile of the applicator are measured and correlated with each other. An instrumental setup has been developed consisting of a plastic scintillator detector system and a newly designed apparatus for guiding the detector across the applicator surface at a constant small distance. It performs an angular movement of detector and applicator with high precision. Results: The measurements of surface dose rate distributions discussed in this work demonstrate the successful operation of the measuring setup. Measuring the surface dose rate distribution with a small distance between applicator and detector and with a high density of measuring points results in a complete and gapless coverage of the applicator surface, being capable of distinguishing small sized spots with high activities. The dosimetrical accuracy of the measurements and its analysis is sufficient (uncertainty in the dose rate in terms of absorbed dose to water is <7%), especially when taking the surgical techniques in positioning of the applicator on the eyeball into account. Conclusions: The method developed so far allows a fully automated quality assurance of eye applicators even under clinical conditions. These measurements provide the basis for future calculation of a full 3D dose rate distribution, which then can be used as input for a refined clinical treatment planning system. The improved dose rate measurements will facilitate a clinical study, which could correlate the therapeutic outcome of a brachytherapy treatment with an applicator and its individual dose rate distribution.« less

In vitro biotransformation rates in fish liver S9: effect of dosing techniques.

PubMed

Lee, Yung-Shan; Lee, Danny H Y; Delafoulhouze, Maximilien; Otton, S Victoria; Moore, Margo M; Kennedy, Chris J; Gobas, Frank A P C

2014-08-01

In vitro biotransformation assays are currently being explored to improve estimates of bioconcentration factors of potentially bioaccumulative organic chemicals in fish. The present study compares thin-film and solvent-delivery dosing techniques as well as single versus multiple chemical dosing for measuring biotransformation rates of selected polycyclic aromatic hydrocarbons in rainbow trout (Oncorhynchus mykiss) liver S9. The findings show that biotransformation rates of very hydrophobic substances can be accurately measured in thin-film sorbent-dosing assays from concentration-time profiles in the incubation medium but not from those in the sorbent phase because of low chemical film-to-incubation-medium mass-transfer rates at the incubation temperature of 13.5 °C required for trout liver assays. Biotransformation rates determined by thin-film dosing were greater than those determined by solvent-delivery dosing for chrysene (octanol-water partition coefficient [KOW ] =10(5.60) ) and benzo[a]pyrene (KOW  =10(6.04) ), whereas there were no statistical differences in pyrene (KOW  =10(5.18) ) biotransformation rates between the 2 methods. In sorbent delivery-based assays, simultaneous multiple-chemical dosing produced biotransformation rates that were not statistically different from those measured in single-chemical dosing experiments for pyrene and benzo[a]pyrene but not for chrysene. In solvent-delivery experiments, multiple-chemical dosing produced biotransformation rates that were much smaller than those in single-chemical dosing experiments for all test chemicals. While thin-film sorbent-phase and solvent delivery-based dosing methods are both suitable methods for measuring biotransformation rates of substances of intermediate hydrophobicity, thin-film sorbent-phase dosing may be more suitable for superhydrophobic chemicals. © 2014 SETAC.

In vivo dose verification method in catheter based high dose rate brachytherapy.

PubMed

Jaselskė, Evelina; Adlienė, Diana; Rudžianskas, Viktoras; Urbonavičius, Benas Gabrielis; Inčiūra, Arturas

2017-12-01

In vivo dosimetry is a powerful tool for dose verification in radiotherapy. Its application in high dose rate (HDR) brachytherapy is usually limited to the estimation of gross errors, due to inability of the dosimetry system/ method to record non-uniform dose distribution in steep dose gradient fields close to the radioactive source. In vivo dose verification in interstitial catheter based HDR brachytherapy is crucial since the treatment is performed inserting radioactive source at the certain positions within the catheters that are pre-implanted into the tumour. We propose in vivo dose verification method for this type of brachytherapy treatment which is based on the comparison between experimentally measured and theoretical dose values calculated at well-defined locations corresponding dosemeter positions in the catheter. Dose measurements were performed using TLD 100-H rods (6 mm long, 1 mm diameter) inserted in a certain sequences into additionally pre-implanted dosimetry catheter. The adjustment of dosemeter positioning in the catheter was performed using reconstructed CT scans of patient with pre-implanted catheters. Doses to three Head&Neck and one Breast cancer patient have been measured during several randomly selected treatment fractions. It was found that the average experimental dose error varied from 4.02% to 12.93% during independent in vivo dosimetry control measurements for selected Head&Neck cancer patients and from 7.17% to 8.63% - for Breast cancer patient. Average experimental dose error was below the AAPM recommended margin of 20% and did not exceed the measurement uncertainty of 17.87% estimated for this type of dosemeters. Tendency of slightly increasing average dose error was observed in every following treatment fraction of the same patient. It was linked to the changes of theoretically estimated dosemeter positions due to the possible patient's organ movement between different treatment fractions, since catheter reconstruction was performed for the first treatment fraction only. These findings indicate potential for further average dose error reduction in catheter based brachytherapy by at least 2-3% in the case that catheter locations will be adjusted before each following treatment fraction, however it requires more detailed investigation. Copyright © 2017 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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

Mwidu, U; Devic, S; Shehadeh, M

Purpose: A retrospective comparison of dose distributions achievable by High dose rate brachytherapy (HDRBT), Helical TomoTherapy (TOMO), CyberKnife (CK) and RapidArc (RA) in locally advanced inoperable cervical cancer patients is presented. Methods: Five patients with advanced stage cervical carcinoma were selected for this study after a full course of external beam radiotherapy (EBRT), chemotherapy and HDR Brachytherapy. To highlight any significant similarities/differences in dose distributions, high-risk clinical target volume (HRCTV) coverage, organs at risk (OAR) sparing, and machine specific delivery limitations, we used D90 (dose received by 90% of the volume) as the parameter for HRCTV coverage as recommended bymore » the GEC-ESTRO Working Group. We also compared both integral and differential dose volume histograms (DVH) between different dose distributions treatment modalities for HRCTV and OAR. Results: TOMO and RA provided the most conformal dose distributions to HRCTV. Median doses (in Gy) to organs at risk were; for rectal wall: 1.7±0.6, 2.5±0.6,1.2±0.3, and 1.5±0.6, and for bladder wall: 1.6±0.1, 2.4±0.4, 0.8±0.6, and 1.5±0.5, for HDRBT, TOMO, CK, and RA, respectively. Conclusion: Contemporary EBRT modalities might be able to replace brachytherapy treatments for cervix cancer. While brachytherapy dose distributions feature high dose gradients, EBRT modalities provide highly conformal dose distributions to the target. However, it is still not clear whether a highly conformal dose or high gradient dose is more clinically relevant for the HRCTV in cervix cancer patients.« less

Statistical analysis of nonmonotonic dose-response relationships: research design and analysis of nasal cell proliferation in rats exposed to formaldehyde.

PubMed

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

2004-01-01

Statistical analyses of nonmonotonic dose-response curves are proposed, experimental designs to detect low-dose effects of J-shaped curves are suggested, and sample sizes are provided. For quantal data such as cancer incidence rates, much larger numbers of animals are required than for continuous data such as biomarker measurements. For example, 155 animals per dose group are required to have at least an 80% chance of detecting a decrease from a 20% incidence in controls to an incidence of 10% at a low dose. For a continuous measurement, only 14 animals per group are required to have at least an 80% chance of detecting a change of the mean by one standard deviation of the control group. Experimental designs based on three dose groups plus controls are discussed to detect nonmonotonicity or to estimate the zero equivalent dose (ZED), i.e., the dose that produces a response equal to the average response in the controls. Cell proliferation data in the nasal respiratory epithelium of rats exposed to formaldehyde by inhalation are used to illustrate the statistical procedures. Statistically significant departures from a monotonic dose response were obtained for time-weighted average labeling indices with an estimated ZED at a formaldehyde dose of 5.4 ppm, with a lower 95% confidence limit of 2.7 ppm. It is concluded that demonstration of a statistically significant bi-phasic dose-response curve, together with estimation of the resulting ZED, could serve as a point-of departure in establishing a reference dose for low-dose risk assessment.

Integrated molecular analysis indicates undetectable change in DNA damage in mice after continuous irradiation at ~ 400-fold natural background radiation.

PubMed

Olipitz, Werner; Wiktor-Brown, Dominika; Shuga, Joe; Pang, Bo; McFaline, Jose; Lonkar, Pallavi; Thomas, Aline; Mutamba, James T; Greenberger, Joel S; Samson, Leona D; Dedon, Peter C; Yanch, Jacquelyn C; Engelward, Bevin P

2012-08-01

In the event of a nuclear accident, people are exposed to elevated levels of continuous low dose-rate radiation. Nevertheless, most of the literature describes the biological effects of acute radiation. DNA damage and mutations are well established for their carcinogenic effects. We assessed several key markers of DNA damage and DNA damage responses in mice exposed to low dose-rate radiation to reveal potential genotoxic effects associated with low dose-rate radiation. We studied low dose-rate radiation using a variable low dose-rate irradiator consisting of flood phantoms filled with 125Iodine-containing buffer. Mice were exposed to 0.0002 cGy/min (~ 400-fold background radiation) continuously over 5 weeks. We assessed base lesions, micronuclei, homologous recombination (HR; using fluorescent yellow direct repeat mice), and transcript levels for several radiation-sensitive genes. We did not observe any changes in the levels of the DNA nucleobase damage products hypoxanthine, 8-oxo-7,8-dihydroguanine, 1,N6-ethenoadenine, or 3,N4-ethenocytosine above background levels under low dose-rate conditions. The micronucleus assay revealed no evidence that low dose-rate radiation induced DNA fragmentation, and there was no evidence of double strand break-induced HR. Furthermore, low dose-rate radiation did not induce Cdkn1a, Gadd45a, Mdm2, Atm, or Dbd2. Importantly, the same total dose, when delivered acutely, induced micronuclei and transcriptional responses. These results demonstrate in an in vivo animal model that lowering the dose-rate suppresses the potentially deleterious impact of radiation and calls attention to the need for a deeper understanding of the biological impact of low dose-rate radiation.

Daily radionuclide ingestion and internal radiation doses in Aomori prefecture, Japan.

PubMed

Ohtsuka, Yoshihito; Kakiuchi, Hideki; Akata, Naofumi; Takaku, Yuichi; Hisamatsu, Shun'ichi

2013-10-01

To assess internal annual dose in the general public in Aomori Prefecture, Japan, 80 duplicate cooked diet samples, equivalent to the food consumed over a 400-d period by one person, were collected from 100 volunteers in Aomori City and the village of Rokkasho during 2006–2010 and were analyzed for 11 radionuclides. To obtain average rates of ingestion of radionuclides, the volunteers were selected from among office, fisheries, agricultural, and livestock farm workers. Committed effective doses from ingestion of the diet over a 1-y period were calculated from the analytical results and from International Commission on Radiological Protection dose coefficients; for 40K, an internal effective dose rate from the literature was used. Fisheries workers had significantly higher combined internal annual dose than the other workers, possibly because of high rates of ingestion of marine products known to have high 210Po concentrations. The average internal dose rate, weighted by the numbers of households in each worker group in Aomori Prefecture, was estimated at 0.47 mSv y-1. Polonium-210 contributed 49% of this value. The sum of committed effective dose rates for 210Po, 210Pb, 228Ra, and 14C and the effective dose rate of 40K accounted for approximately 99% of the average internal dose rate.

Monitoring late-onset toxicities in phase I trials using predicted risks

PubMed Central

Bekele, B. Nebiyou; Ji, Yuan; Shen, Yu; Thall, Peter F.

2008-01-01

Late-onset (LO) toxicities are a serious concern in many phase I trials. Since most dose-limiting toxicities occur soon after therapy begins, most dose-finding methods use a binary indicator of toxicity occurring within a short initial time period. If an agent causes LO toxicities, however, an undesirably large number of patients may be treated at toxic doses before any toxicities are observed. A method addressing this problem is the time-to-event continual reassessment method (TITE-CRM, Cheung and Chappell, 2000). We propose a Bayesian dose-finding method similar to the TITE-CRM in which doses are chosen using time-to-toxicity data. The new aspect of our method is a set of rules, based on predictive probabilities, that temporarily suspend accrual if the risk of toxicity at prospective doses for future patients is unacceptably high. If additional follow-up data reduce the predicted risk of toxicity to an acceptable level, then accrual is restarted, and this process may be repeated several times during the trial. A simulation study shows that the proposed method provides a greater degree of safety than the TITE-CRM, while still reliably choosing the preferred dose. This advantage increases with accrual rate, but the price of this additional safety is that the trial takes longer to complete on average. PMID:18084008

Application of the MCNP5 code to the Modeling of vaginal and intra-uterine applicators used in intracavitary brachytherapy: a first approach

NASA Astrophysics Data System (ADS)

Gerardy, I.; Rodenas, J.; Van Dycke, M.; Gallardo, S.; Tondeur, F.

2008-02-01

Brachytherapy is a radiotherapy treatment where encapsulated radioactive sources are introduced within a patient. Depending on the technique used, such sources can produce high, medium or low local dose rates. The Monte Carlo method is a powerful tool to simulate sources and devices in order to help physicists in treatment planning. In multiple types of gynaecological cancer, intracavitary brachytherapy (HDR Ir-192 source) is used combined with other therapy treatment to give an additional local dose to the tumour. Different types of applicators are used in order to increase the dose imparted to the tumour and to limit the effect on healthy surrounding tissues. The aim of this work is to model both applicator and HDR source in order to evaluate the dose at a reference point as well as the effect of the materials constituting the applicators on the near field dose. The MCNP5 code based on the Monte Carlo method has been used for the simulation. Dose calculations have been performed with *F8 energy deposition tally, taking into account photons and electrons. Results from simulation have been compared with experimental in-phantom dose measurements. Differences between calculations and measurements are lower than 5%.The importance of the source position has been underlined.

Dose rate effects on array CCDs exposed by Co-60 γ rays induce saturation output degradation and annealing tests

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

Wang, Zujun, E-mail: wangzujun@nint.ac.cn; Chen, Wei; He, Baoping

The experimental tests of dose rate and annealing effects on array charge-coupled devices (CCDs) are presented. The saturation output voltage (V{sub S}) versus the total dose at the dose rates of 0.01, 0.1, 1.0, 10.0 and 50 rad(Si)/s are compared. Annealing tests are performed to eliminate the time-dependent effects. The V{sub S} degradation levels depend on the dose rates. The V{sub S} degradation mechanism induced by dose rate and annealing effects is analyzed. The V{sub S} at 20 krad(Si) with the dose rate of 0.03 rad(Si)/s are supplemented to assure the degradation curves between the dose rates of 0.1 andmore » 0.01 rad(Si)/s. The CCDs are divided into two groups, with one group biased and the other unbiased during {sup 60}Co γ radiation. The V{sub S} degradation levels of the biased CCDs during radiation are more severe than that of the unbiased CCDs.« less

A Single Dose of Intraoperative Antibiotics Is Sufficient to Prevent Urinary Tract Infection During Ureteroscopy.

PubMed

Chew, Ben H; Flannigan, Ryan; Kurtz, Michael; Gershman, Boris; Arsovska, Olga; Paterson, Ryan F; Eisner, Brian H; Lange, Dirk

2016-01-01

American Urology Association (AUA) Best Practice Guidelines for ureteroscopic stone treatment recommend antibiotic coverage for <24 hours following the procedure. The purpose of this study was to evaluate if the addition of postoperative antibiotics reduces urinary tract infections (UTIs) following ureteroscopic stone treatment beyond the recommended preoperative dose. A retrospective review was performed of consecutive patients at two institutions, University of British Columbia and Massachusetts General Hospital, Harvard. All patients received a single dose of antibiotics before ureteroscopic stone treatment. A subset of patients was also given postoperative antibiotics. The rate of UTI was compared in patients receiving only preoperative antibiotics (group 1) vs those who received pre- and postoperative antibiotics (group 2). Eighty-one patients underwent ureteroscopy for renal calculi. Mean time to follow up was 42 ± 88 days. Eight (9.9%) patients in total (two from group 1 and six from group 2, p = 0.1457) developed UTIs postoperatively. In group 1, both patients presented with pyelonephritis (n = 2); those patients with infections in group 2 presented with urosepsis (n = 2) and cystitis (n = 2) and two patients had asymptomatic bacteriuria. Risk factors such as preoperative stenting, nephrostomy tubes, and foley catheters neither differed between groups nor did they predispose patients to postoperative infections. The postoperative UTI rate in this study (9.9%) is consistent with previous reports. Our data suggest that a single preoperative dose of antibiotics is sufficient, and additional postoperative antibiotics do not decrease infection rates after ureteroscopic stone treatment. Risk for selection bias is a potential limitation.

Atmospheric Radiation Modeling of Galactic Cosmic Rays Using LRO/CRaTER and the EMMREM Model with Comparisons to Balloon and Airline Based Measurements

NASA Astrophysics Data System (ADS)

Joyce, C. J.

2016-12-01

The current state of the Sun and solar wind, with uncommonly low densities and weak magnetic fields, has resulted in galactic cosmic ray fluxes that are elevated to levels higher than have ever before been observed in the space age. Given the continuing trend of declining solar activity, it is clear that accurate modeling of GCR radiation is becoming increasingly important in the field of space weather. Such modelling is essential not only in the planning of future manned space missions, but is also important for assessing the radiation risks to airline passengers, particularly given NASA's plans to develop supersonic aircraft that will fly at much higher altitudes than commercial aircraft and thus be more vulnerable to radiation from GCRs. We provide an analysis of the galactic cosmic ray radiation environment of Earth's atmosphere using measurements from the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) aboard the Lunar Reconnaissance Orbiter (LRO) together with the Badhwar-O'Neil model and dose lookup tables generated by the Earth-Moon-Mars Radiation Environment Module (EMMREM). Newly available measurements of atmospheric dose rates from instruments aboard commercial and research aircraft enable evaluation of the accuracy of the model in computing atmospheric dose rates. Additionally, a newly available dataset of balloon-based measurements, including simultaneous balloon launches from California and New Hampshire, provide an additional means of comparison to the model. When compared to the available observations of atmospheric radiation levels, the computed dose rates seem to be sufficiently accurate, falling within recommended radiation uncertainty limits.

Measurement of ambient dose equivalent rates by walk survey around Fukushima Dai-ichi Nuclear Power Plant using KURAMA-II until 2016.

PubMed

Andoh, Masaki; Yamamoto, Hideaki; Kanno, Takashi; Saito, Kimiaki

2018-05-17

Ambient dose equivalent rates in various environments related to human lives were measured by walk surveys using the KURAMA-II systems from 2013 to 2016 within an 80-km radius of the Fukushima Dai-ichi Nuclear Power Plant. The dose rate of the locations where the walk survey was performed decreased to about 38% of its initial value in the 42 months from June 2013 to the December 2016, which was beyond that attributable to the physical decay of radiocaesium. The ecological half-life of the slow decreasing component was evaluated to be 4.1 ± 0.2 y. The air dose rates decreased depending on the level of the evacuation areas, and the decrease in the dose rates was slightly larger in populated areas where humans are active. The dose rates as measured by walk surveys exhibited a good correlation with those by car-borne surveys, suggesting that car-borne survey data are reflecting the air dose rates in living environments surrounding roads. The comparison of walk survey data with car-borne survey data indicated that the air dose rate varies largely even within a 100 m square area, and the variation is enhanced by human activities. The dose rates measured by the walk surveys were estimated to be medial of those along roads and those of undisturbed flat ground, and they were found to be decreasing quickly compared with the air dose rate from the flat ground fixed-point measurements. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Characteristics and verification of a car-borne survey system for dose rates in air: KURAMA-II.

PubMed

Tsuda, S; Yoshida, T; Tsutsumi, M; Saito, K

2015-01-01

The car-borne survey system KURAMA-II, developed by the Kyoto University Research Reactor Institute, has been used for air dose rate mapping after the Fukushima Dai-ichi Nuclear Power Plant accident. KURAMA-II consists of a CsI(Tl) scintillation detector, a GPS device, and a control device for data processing. The dose rates monitored by KURAMA-II are based on the G(E) function (spectrum-dose conversion operator), which can precisely calculate dose rates from measured pulse-height distribution even if the energy spectrum changes significantly. The characteristics of KURAMA-II have been investigated with particular consideration to the reliability of the calculated G(E) function, dose rate dependence, statistical fluctuation, angular dependence, and energy dependence. The results indicate that 100 units of KURAMA-II systems have acceptable quality for mass monitoring of dose rates in the environment. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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

Bruner, A.

1976-09-01

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

PMH 9907: Long-term outcomes of a randomized phase 3 study of short-term bicalutamide hormone therapy and dose-escalated external-beam radiation therapy for localized prostate cancer.

PubMed

McPartlin, Andrew J; Glicksman, Rachel; Pintilie, Melania; Tsuji, Debbie; Mok, Gary; Bayley, Andrew; Chung, Peter; Bristow, Robert G; Gospodarowicz, Mary K; Catton, Charles N; Milosevic, Michael; Warde, Padraig R

2016-08-15

The role of hormone therapy (HT) with dose-escalated external-beam radiotherapy (DE-EBRT) in the treatment of intermediate-risk prostate cancer (IRPC) remains controversial. The authors report the long-term outcome of a phase 3 study of DE-EBRT with or without HT for patients with localized prostate cancer (LPC). From 1999 to 2006, 252 of an intended 338 patients with LPC were randomized to receive DE-EBRT with or without 5 months of neoadjuvant and concurrent bicalutamide 150 mg once daily. The study was closed early because of contemporary concerns surrounding bicalutamide. The primary outcome was biochemical failure (BF) incidence, and the secondary endpoints were overall survival (OS), local control (LC), and quality of life. The BF and OS rates were estimated using the cumulative incidence function and Kaplan-Meier methods and were compared using the Gray test and the log-rank test. Eleven patients were excluded from analysis. Characteristics were well balanced in each treatment arm. Ninety-five percent of patients had IRPC. The prescribed dose increased from 75.6 grays (Gy) in 42 fractions to 78 Gy in 39 fractions over the period. At a median follow-up of 9.1 years, 98 BFs occurred, with no significant effect of HT versus no HT on the BF rate (40% vs 47%; P = .32), the OS rate (82% vs 86%; P = .37), the LC rate (52% vs 48 %; P = .32) or quality of life, in the patients who completed the questionnaires. Dose escalation to 75.6 Gy versus >75.6 Gy reduced the BF rate by 26% (P = .004). For patients who predominantly have IRPC, the addition of HT to DE-EBRT did not significantly affect BF, OS, or LC. Bicalutamide appeared to be well tolerated. The conclusions from the study are limited by incomplete recruitment. Cancer 2016;122:2595-603. © 2016 American Cancer Society. © 2016 American Cancer Society.

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

NASA Astrophysics Data System (ADS)

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

2017-12-01

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

From dust to dose: Effects of forest disturbance on increased inhalation exposure.

PubMed

Whicker, Jeffrey J; Pinder, John E; Breshears, David D; Eberhart, Craig F

2006-09-15

Ecosystem disturbances that remove vegetation and disturb surface soils are major causes of excessive soil erosion and can result in accelerated transport of soils contaminated with hazardous materials. Accelerated wind erosion in disturbed lands that are contaminated is of particular concern because of potential increased inhalation exposure, yet measurements regarding these relationships are lacking. The importance of this was highlighted when, in May of 2000, the Cerro Grande fire burned over roughly 30% of Los Alamos National Laboratory (LANL), mostly in ponderosa pine (Pinus ponderosa) forest, and through areas with soils containing contaminants, particularly excess depleted and natural uranium. Additionally, post-fire thinning was performed in burned and unburned forests on about 25% of LANL land. The first goal of this study was to assess the potential for increased inhalation dose from uranium contaminated soils via wind-driven resuspension of soil following the Cerro Grande Fire and subsequent forest thinning. This was done through analysis of post-disturbance measurements of uranium air concentrations and their relationships with wind velocity and seasonal vegetation cover. We found a 14% average increase in uranium air concentrations at LANL perimeter locations after the fire, and the greatest air concentrations occurred during the months of April-June when wind velocities are highest, no snow cover, and low vegetation cover. The second goal was to develop a methodology to assess the relative contribution of each disturbance type towards increasing public and worker exposure to these resuspended soils. Measurements of wind-driven dust flux in severely burned, moderately burned, thinned, and unburned/unthinned forest areas were used to assess horizontal dust flux (HDF) in these areas. Using empirically derived relationships between measurements of HDF and respirible dust, coupled with onsite uranium soil concentrations, we estimate relative increases in inhalation doses for workers ranging from 15% to 38%. Despite the potential for increased doses resulting from these forest disturbances, the estimated annual dose rate for the public was <1 microSv yr(-1), which is far below the dose limits for public exposures, and the upper-bound dose rate for a LANL worker was estimated to be 140 microSv yr(-1), far below the 5 x 10(4) microSv yr(-1) occupational dose limit. These results show the importance of ecosystem disturbance in increasing mobility of soil-bound contaminants, which can ultimately increase exposure. However, it is important to investigate the magnitude of the increases when deciding appropriate strategies for management and long-term stewardship of contaminated lands.

Variation of indoor radon concentration and ambient dose equivalent rate in different outdoor and indoor environments.

PubMed

Stojanovska, Zdenka; Boev, Blazo; Zunic, Zora S; Ivanova, Kremena; Ristova, Mimoza; Tsenova, Martina; Ajka, Sorsa; Janevik, Emilija; Taleski, Vaso; Bossew, Peter

2016-05-01

Subject of this study is an investigation of the variations of indoor radon concentration and ambient dose equivalent rate in outdoor and indoor environments of 40 dwellings, 31 elementary schools and five kindergartens. The buildings are located in three municipalities of two, geologically different, areas of the Republic of Macedonia. Indoor radon concentrations were measured by nuclear track detectors, deployed in the most occupied room of the building, between June 2013 and May 2014. During the deploying campaign, indoor and outdoor ambient dose equivalent rates were measured simultaneously at the same location. It appeared that the measured values varied from 22 to 990 Bq/m(3) for indoor radon concentrations, from 50 to 195 nSv/h for outdoor ambient dose equivalent rates, and from 38 to 184 nSv/h for indoor ambient dose equivalent rates. The geometric mean value of indoor to outdoor ambient dose equivalent rates was found to be 0.88, i.e. the outdoor ambient dose equivalent rates were on average higher than the indoor ambient dose equivalent rates. All measured can reasonably well be described by log-normal distributions. A detailed statistical analysis of factors which influence the measured quantities is reported.

Estimation of 85Kr dispersion from the spent nuclear fuel reprocessing plant in Rokkasho, Japan, using an atmospheric dispersion model.

PubMed

Abe, K; Iyogi, T; Kawabata, H; Chiang, J H; Suwa, H; Hisamatsu, S

2015-11-01

The spent nuclear fuel reprocessing plant of Japan Nuclear Fuel Limited (JNFL) located in Rokkasho, Japan, discharged small amounts of (85)Kr into the atmosphere during final tests of the plant with actual spent fuel from 31 March 2006 to October 2008. During this period, the gamma-ray dose rates due to discharged (85)Kr were higher than the background rates measured at the Institute for Environmental Sciences and at seven monitoring stations of the Aomori prefectural government and JNFL. The dispersion of (85)Kr was simulated by means of the fifth-generation Penn State/NCAR Mesoscale Model and the CG-MATHEW/ADPIC models (ver. 5.0) with a vertical terrain-following height coordinate. Although the simulated gamma-ray dose rates due to discharged (85)Kr agreed fairly well with measured rates, the agreement between the estimated monthly mean (85)Kr concentrations and the observed concentrations was poor. Improvement of the vertical flow of air may lead to better estimation of (85)Kr dispersion. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Occupational radiation dose to eyes from interventional radiology procedures in light of the new eye lens dose limit from the International Commission on Radiological Protection

PubMed Central

Walsh, C; Gallagher, A; Dowling, A; Guiney, M; Ryan, J M; McEniff, N; O'Reilly, G

2015-01-01

Objective: In 2011, the International Commission on Radiological Protection (ICRP) recommended a substantial reduction in the equivalent dose limit for the lens of the eye, in line with a reduced threshold of absorbed dose for radiation-induced cataracts. This is of particular relevance in interventional radiology (IR) where it is well established that staff doses can be significant, however, there is a lack of data on IR eye doses in terms of Hp(3). Hp(3) is the personal dose equivalent at a depth of 3 mm in soft tissue and is used for measuring lens dose. We aimed to obtain a reliable estimate of eye dose to IR operators. Methods: Lens doses were measured for four interventional radiologists over a 3-month period using dosemeters specifically designed to measure Hp(3). Results: Based on their typical workloads, two of the four interventional radiologists would exceed the new ICRP dose limit with annual estimated doses of 31 and 45 mSv to their left eye. These results are for an “unprotected” eye, and for IR staff who routinely wear lead glasses, the dose beneath the glasses is likely to be significantly lower. Staff eye dose normalized to patient kerma–area product and eye dose per procedure have been included in the analysis. Conclusion: Eye doses to IR operators have been established using a dedicated Hp(3) dosemeter. Estimated annual doses have the potential to exceed the new ICRP limit. Advances in knowledge: We have estimated lens dose to interventional radiologists in terms of Hp(3) for the first time in an Irish hospital setting. PMID:25761211

The dose can make the poison: lessons learned from adverse in vivo toxicities caused by RNAi overexpression.

PubMed

Grimm, Dirk

2011-10-26

For the past five years, evidence has accumulated that vector-mediated robust RNA interference (RNAi) expression can trigger severe side effects in small and large animals, from cytotoxicity and accelerated tumorigenesis to organ failure and death. The recurring notions in these studies that a critical parameter is the strength of RNAi expression and that Exportin-5 and the Argonaute proteins are rate-limiting mammalian RNAi, strongly imply dose-dependent saturation of the endogenous miRNA pathway as one of the underlying mechanisms. This minireview summarizes the relevant work and data leading to this intriguing model and highlights potential avenues by which to alleviate RNAi-induced toxicities in future clinical applications.

Methodology for testing infrared focal plane arrays in simulated nuclear radiation environments

NASA Astrophysics Data System (ADS)

Divita, E. L.; Mills, R. E.; Koch, T. L.; Gordon, M. J.; Wilcox, R. A.; Williams, R. E.

1992-07-01

This paper summarizes test methodology for focal plane array (FPA) testing that can be used for benign (clear) and radiation environments, and describes the use of custom dewars and integrated test equipment in an example environment. The test methodology, consistent with American Society for Testing Materials (ASTM) standards, is presented for the total accumulated gamma dose, transient dose rate, gamma flux, and neutron fluence environments. The merits and limitations of using Cobalt 60 for gamma environment simulations and of using various fast-neutron reactors and neutron sources for neutron simulations are presented. Test result examples are presented to demonstrate test data acquisition and FPA parameter performance under different measurement conditions and environmental simulations.

Limited Chemotherapy and Shrinking Field Radiotherapy for Osteolymphoma (Primary Bone Lymphoma): Results From the Trans-Tasman Radiation Oncology Group 99.04 and Australasian Leukaemia and Lymphoma Group LY02 Prospective Trial;Bone; Lymphoma; Radiotherapy; Chemotherapy; Clinical trial

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

Christie, David, E-mail: david.christie@premion.com.au; Dear, Keith; Le, Thai

2011-07-15

Purpose: To establish benchmark outcomes for combined modality treatment to be used in future prospective studies of osteolymphoma (primary bone lymphoma). Methods and Materials: In 1999, the Trans-Tasman Radiation Oncology Group (TROG) invited the Australasian Leukemia and Lymphoma Group (ALLG) to collaborate on a prospective study of limited chemotherapy and radiotherapy for osteolymphoma. The treatment was designed to maintain efficacy but limit the risk of subsequent pathological fractures. Patient assessment included both functional imaging and isotope bone scanning. Treatment included three cycles of CHOP chemotherapy and radiation to a dose of 45 Gy in 25 fractions using a shrinking fieldmore » technique. Results: The trial closed because of slow accrual after 33 patients had been entered. Accrual was noted to slow down after Rituximab became readily available in Australia. After a median follow-up of 4.3 years, the five-year overall survival and local control rates are estimated at 90% and 72% respectively. Three patients had fractures at presentation that persisted after treatment, one with recurrent lymphoma. Conclusions: Relatively high rates of survival were achieved but the number of local failures suggests that the dose of radiotherapy should remain higher than it is for other types of lymphoma. Disability after treatment due to pathological fracture was not seen.« less

Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation

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

Rahimi, Asal, E-mail: asal.rahimi@utsouthwestern.edu; Thomas, Kimberly; Spangler, Ann

Purpose: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose. Methods and Materials: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires. Starting dose was 30 Gy in 5 fractions and was escalated by 2.5 Gy total for each cohortmore » to 40 Gy. Results: In all, 75 patients were enrolled, with a median age of 62 years. Median follow-up for 5 cohorts was 49.9, 42.5, 25.7, 20.3, and 13.5 months, respectively. Only 3 grade 3 toxicities were experienced. There was 1 dose-limiting toxicity in the overall cohort. Ten patients experienced palpable fat necrosis (4 of which were symptomatic). Physicians scored cosmesis as excellent or good in 95.9%, 100%, 96.7%, and 100% at baseline and 6, 12, and 24 months after S-PBI, whereas patients scored the same periods as 86.5%, 97.1%, 95.1%, and 95.3%, respectively. The disagreement rates between MDs and patients during those periods were 9.4%, 2.9%, 1.6%, and 4.7%, respectively. There have been no recurrences or distant metastases. Conclusion: Dose was escalated to the target dose of 40 Gy in 5 fractions, with the occurrence of only 1 dose-limiting toxicity. Patients felt cosmetic results improved within the first year after surgery and stereotactic body radiation therapy. Our results show minimal toxicity with excellent cosmesis; however, further follow-up is warranted in future studies. This study is the first to show the safety, tolerability, feasibility, and cosmesis results of a 5-fraction dose-escalated S-PBI treatment for early-stage breast cancer in the adjuvant setting.« less

Curative chemotherapy for acute myeloid leukemia: the development of high-dose ara-C from the laboratory to bedside.

PubMed

Capizzi, R L

1996-01-01

In the bench to bedside development of drugs to treat patients with cancer, the common guide to dose and schedule selection is toxicity to normal organs patterned after the preclinical profile of the drug. An understanding of the cellular pharmacology of the drug and specifically the cellular targets linked to the drug's effect is of substantial value in assisting the clinical investigator in selecting the proper dose and schedule of drug administration. The clinical development of ara-C for the treatment of acute myeloid leukemia (AML) provides a useful paradigm for the study of this process. An understanding of the cellular pharmacology, cytokinetics and pharmacokinetics of ara-C in leukemic mice showed substantial schedule-dependency. Exposure to high doses for a short duration (C x t) resulted in a palliative therapeutic outcome. In marked contrast, exposure to lower doses for a protracted period (c x T) was curative. Clinical use of ara-C in patients with AML patterned after the murine experience, c x T approach, has been of limited benefit in terms of long-term disease-free survival. Studies with human leukemia blasts from patients have shown that for the majority of patients, the initial rate-limiting step is membrane transport, the characteristics of which are substantially affected by extracellular drug concentration (dose). This pharmacologic impediment is eliminated with the blood levels attained during the infusion of gram doses (1-3 gm/m2) of the drug (high-dose ara-C, HiDaC) for shorter periods of time, a C x t approach. Clinical confirmation of these pharmacologic observations is evident in the therapeutic efficacy of HiDaC in patients with relapsed or SDaC-refractory acute leukemia. This is further emphasized by the significantly improved leukemia-free survival of patients with AML treated with HiDaC intensification during remission compared to those patients treated with milligram doses typical of SDaC protocols. Thus, the identification and monitoring of important parameters of drug action in tumors during the course of a clinical trial can be of substantial assistance in optimizing drug dose and schedule so as to attain the best therapeutic index.

Is there any connection between a second pneumonia shot and hospitalization among Medicare beneficiaries?

PubMed

Snow, R; Babish, J D; McBean, A M

1995-01-01

To learn whether the risk of revaccination in adults should limit its use, the authors investigated whether adverse events requiring hospitalization occurred in a group of Medicare enrollees revaccinated with pneumococcal polysaccharide vaccine. A prospective cohort analysis and case study of revaccinated people involved five percent of all elderly Medicare enrollees from 1985 through 1988, consisting of 66,256 people receiving one dose of vaccine and 1,099 receiving two doses. Comparison was made of the hospitalization rate within 30 days after revaccination and rates of singly vaccinated persons using discharge diagnosis for all those hospitalized during the 30 days after revaccination. No significant difference was found between the hospitalization rate of the revaccinated cohort and comparison group. No adverse reactions attributable to pneumococcal polysaccharide vaccine causing hospitalization were identified among 39 revaccinated persons who were hospitalized within 30 days of revaccination. Revaccination of elderly Medicare beneficiaries does not cause events serious enough to require hospitalization. Vaccination of persons according to the Public Health Service Immunization Practice Advisory Committee guidelines is recommended when the prior immunization status is unknown.

Micronucleus induction in Vicia faba roots. Part 1. Absence of dose-rate, fractionation, and oxygen effect at low doses of low LET radiations.

PubMed

Marshall, I; Bianchi, M

1983-08-01

Micronucleus indication in Vicia faba roots has been evaluated after irradiation with 60Co gamma-rays. The dependence of the damage on dose, dose rate, fractionation, and oxygen has been studied. The best fit to the experimental data in the dose region between 7 and 190 cGy is represented, for single-dose exposures, by a linear + quadratic relationship. In the low-dose region, between 7 and 20 cGy, where the linear dose dependence is dominant, no dose-rate, fractionation, or oxygen effect could be observed. These effects were, however, present in the high-dose region, where the quadratic dependence is dominant.

Towards more reliable automated multi-dose dispensing: retrospective follow-up study on medication dose errors and product defects.

PubMed

Palttala, Iida; Heinämäki, Jyrki; Honkanen, Outi; Suominen, Risto; Antikainen, Osmo; Hirvonen, Jouni; Yliruusi, Jouko

2013-03-01

To date, little is known on applicability of different types of pharmaceutical dosage forms in an automated high-speed multi-dose dispensing process. The purpose of the present study was to identify and further investigate various process-induced and/or product-related limitations associated with multi-dose dispensing process. The rates of product defects and dose dispensing errors in automated multi-dose dispensing were retrospectively investigated during a 6-months follow-up period. The study was based on the analysis of process data of totally nine automated high-speed multi-dose dispensing systems. Special attention was paid to the dependence of multi-dose dispensing errors/product defects and pharmaceutical tablet properties (such as shape, dimensions, weight, scored lines, coatings, etc.) to profile the most suitable forms of tablets for automated dose dispensing systems. The relationship between the risk of errors in dose dispensing and tablet characteristics were visualized by creating a principal component analysis (PCA) model for the outcome of dispensed tablets. The two most common process-induced failures identified in the multi-dose dispensing are predisposal of tablet defects and unexpected product transitions in the medication cassette (dose dispensing error). The tablet defects are product-dependent failures, while the tablet transitions are dependent on automated multi-dose dispensing systems used. The occurrence of tablet defects is approximately twice as common as tablet transitions. Optimal tablet preparation for the high-speed multi-dose dispensing would be a round-shaped, relatively small/middle-sized, film-coated tablet without any scored line. Commercial tablet products can be profiled and classified based on their suitability to a high-speed multi-dose dispensing process.

Venetoclax: A novel B-cell lymphoma-2 inhibitor for chronic lymphocytic leukemia and other hematologic malignancies.

PubMed

Olin, Jacqueline L; Griffiths, Carrie L; Smith, Morgan B

2017-01-01

Patients with chronic lymphocytic leukemia with the 17p deletion have a poor prognosis and treatment options are limited. Venetoclax, a novel B-cell lymphoma-2 inhibitor, has been approved for treatment-experienced chronic lymphocytic leukemia patients with the 17p deletion. A phase 1 dose-escalation study to 400 mg daily showed overall response rates across all doses of 79% with a complete response achieved in 20%. A phase 2 multicenter open-label study demonstrated overall response rate of 79.4% of patients (95% confidence interval 70.5-86.6) with median duration of follow-up of 12.1 months (IQR 10.1-14.2). Tumor lysis syndrome has been observed during initiation and titration. Assessing risk of tumor lysis syndrome prior to therapy initiation is essential to provide appropriate prophylactic medications. Neutropenia, potentially warranting dose reduction or discontinuation, has been observed. Venetoclax has demonstrated activity in other leukemias, multiple myeloma, and lymphomas. Venetoclax has shown response, and is well tolerated in patients with highly resistant chronic lymphocytic leukemia. It has the potential to be part of the treatment armamentarium for other malignancies.

Dose and dose rate extrapolation factors for malignant and non-malignant health endpoints after exposure to gamma and neutron radiation.

PubMed

Tran, Van; Little, Mark P

2017-11-01

Murine experiments were conducted at the JANUS reactor in Argonne National Laboratory from 1970 to 1992 to study the effect of acute and protracted radiation dose from gamma rays and fission neutron whole body exposure. The present study reports the reanalysis of the JANUS data on 36,718 mice, of which 16,973 mice were irradiated with neutrons, 13,638 were irradiated with gamma rays, and 6107 were controls. Mice were mostly Mus musculus, but one experiment used Peromyscus leucopus. For both types of radiation exposure, a Cox proportional hazards model was used, using age as timescale, and stratifying on sex and experiment. The optimal model was one with linear and quadratic terms in cumulative lagged dose, with adjustments to both linear and quadratic dose terms for low-dose rate irradiation (<5 mGy/h) and with adjustments to the dose for age at exposure and sex. After gamma ray exposure there is significant non-linearity (generally with upward curvature) for all tumours, lymphoreticular, respiratory, connective tissue and gastrointestinal tumours, also for all non-tumour, other non-tumour, non-malignant pulmonary and non-malignant renal diseases (p < 0.001). Associated with this the low-dose extrapolation factor, measuring the overestimation in low-dose risk resulting from linear extrapolation is significantly elevated for lymphoreticular tumours 1.16 (95% CI 1.06, 1.31), elevated also for a number of non-malignant endpoints, specifically all non-tumour diseases, 1.63 (95% CI 1.43, 2.00), non-malignant pulmonary disease, 1.70 (95% CI 1.17, 2.76) and other non-tumour diseases, 1.47 (95% CI 1.29, 1.82). However, for a rather larger group of malignant endpoints the low-dose extrapolation factor is significantly less than 1 (implying downward curvature), with central estimates generally ranging from 0.2 to 0.8, in particular for tumours of the respiratory system, vasculature, ovary, kidney/urinary bladder and testis. For neutron exposure most endpoints, malignant and non-malignant, show downward curvature in the dose response, and for most endpoints this is statistically significant (p < 0.05). Associated with this, the low-dose extrapolation factor associated with neutron exposure is generally statistically significantly less than 1 for most malignant and non-malignant endpoints, with central estimates mostly in the range 0.1-0.9. In contrast to the situation at higher dose rates, there are statistically non-significant decreases of risk per unit dose at gamma dose rates of less than or equal to 5 mGy/h for most malignant endpoints, and generally non-significant increases in risk per unit dose at gamma dose rates ≤5 mGy/h for most non-malignant endpoints. Associated with this, the dose-rate extrapolation factor, the ratio of high dose-rate to low dose-rate (≤5 mGy/h) gamma dose response slopes, for many tumour sites is in the range 1.2-2.3, albeit not statistically significantly elevated from 1, while for most non-malignant endpoints the gamma dose-rate extrapolation factor is less than 1, with most estimates in the range 0.2-0.8. After neutron exposure there are non-significant indications of lower risk per unit dose at dose rates ≤5 mGy/h compared to higher dose rates for most malignant endpoints, and for all tumours (p = 0.001), and respiratory tumours (p = 0.007) this reduction is conventionally statistically significant; for most non-malignant outcomes risks per unit dose non-significantly increase at lower dose rates. Associated with this, the neutron dose-rate extrapolation factor is less than 1 for most malignant and non-malignant endpoints, in many cases statistically significantly so, with central estimates mostly in the range 0.0-0.2.

Liquid Medication Dosing Errors by Hispanic Parents: Role of Health Literacy and English Proficiency

PubMed Central

Harris, Leslie M.; Dreyer, Benard; Mendelsohn, Alan; Bailey, Stacy C.; Sanders, Lee M.; Wolf, Michael S.; Parker, Ruth M.; Patel, Deesha A.; Kim, Kwang Youn A.; Jimenez, Jessica J.; Jacobson, Kara; Smith, Michelle; Yin, H. Shonna

2016-01-01

Objective Hispanic parents in the US are disproportionately affected by low health literacy and limited English proficiency (LEP). We examined associations between health literacy, LEP, and liquid medication dosing errors in Hispanic parents. Methods Cross-sectional analysis of data from a multisite randomized controlled experiment to identify best practices for the labeling/dosing of pediatric liquid medications (SAFE Rx for Kids study); 3 urban pediatric clinics. Analyses were limited to Hispanic parents of children <8 years, with health literacy and LEP data (n=1126). Parents were randomized to 5 groups that varied by pairing of units of measurement on the label/dosing tool. Each parent measured 9 doses [3 amounts (2.5,5,7.5 mL) using 3 tools (2 syringes (0.2,0.5 mL increment), 1 cup)] in random order. Dependent variable: Dosing error=>20% dose deviation. Predictor variables: health literacy (Newest Vital Sign) [limited=0–3; adequate=4–6], LEP (speaks English less than “very well”). Results 83.1% made dosing errors (mean(SD) errors/parent=2.2(1.9)). Parents with limited health literacy and LEP had the greatest odds of making a dosing error compared to parents with adequate health literacy who were English proficient (% trials with errors/parent=28.8 vs. 12.9%; AOR=2.2[1.7–2.8]). Parents with limited health literacy who were English proficient were also more likely to make errors (% trials with errors/parent=18.8%; AOR=1.4[1.1–1.9]). Conclusion Dosing errors are common among Hispanic parents; those with both LEP and limited health literacy are at particular risk. Further study is needed to examine how the redesign of medication labels and dosing tools could reduce literacy and language-associated disparities in dosing errors. PMID:28477800

Biochemical Kinetics Model of DSB Repair and GammaH2AX FOCI by Non-homologous End Joining

NASA Technical Reports Server (NTRS)

Cucinotta, Francis, A.; Pluth, Janice M.; Anderson, Jennifer A.; Harper, Jane V.; O'Neill, Peter

2007-01-01

We developed a biochemical kinetics approach to describe the repair of double strand breaks (DSB) produced by low LET radiation by modeling molecular events associated with the mechanisms of non-homologous end-joining (NHEJ). A system of coupled non-linear ordinary differential equations describes the induction of DSB and activation pathways for major NHEJ components including Ku(sub 70/80), DNA-PK(sub cs), and the Ligase IV-XRCC4 hetero-dimer. The autophosphorylation of DNA-PK(sub cs and subsequent induction of gamma-H2AX foci observed after ionizing radiation exposure were modeled. A two-step model of DNA-PK(sub cs) regulation of repair was developed with the initial step allowing access of other NHEJ components to breaks, and a second step limiting access to Ligase IV-XRCC4. Our model assumes that the transition from the first to second-step depends on DSB complexity, with a much slower-rate for complex DSB. The model faithfully reproduced several experimental data sets, including DSB rejoining as measured by pulsed-field electrophoresis (PFGE), quantification of the induction of gamma-H2AX foci, and live cell imaging of the induction of Ku(sub 70/80). Predictions are made for the behaviors of NHEJ components at low doses and dose-rates, where a steady-state is found at dose-rates of 0.1 Gy/hr or lower.

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

PubMed

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

2011-09-01

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

Modification and benchmarking of SKYSHINE-III for use with ISFSI cask arrays

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

Hertel, N.E.; Napolitano, D.G.

1997-12-01

Dry cask storage arrays are becoming more and more common at nuclear power plants in the United States. Title 10 of the Code of Federal Regulations, Part 72, limits doses at the controlled area boundary of these independent spent-fuel storage installations (ISFSI) to 0.25 mSv (25 mrem)/yr. The minimum controlled area boundaries of such a facility are determined by cask array dose calculations, which include direct radiation and radiation scattered by the atmosphere, also known as skyshine. NAC International (NAC) uses SKYSHINE-III to calculate the gamma-ray and neutron dose rates as a function of distance from ISFSI arrays. In thismore » paper, we present modifications to the SKYSHINE-III that more explicitly model cask arrays. In addition, we have benchmarked the radiation transport methods used in SKYSHINE-III against {sup 60}Co gamma-ray experiments and MCNP neutron calculations.« less

Phase I dose-escalation studies of roniciclib, a pan-cyclin-dependent kinase inhibitor, in advanced malignancies.

PubMed

Bahleda, Rastislav; Grilley-Olson, Juneko E; Govindan, Ramaswamy; Barlesi, Fabrice; Greillier, Laurent; Perol, Maurice; Ray-Coquard, Isabelle; Strumberg, Dirk; Schultheis, Beate; Dy, Grace K; Zalcman, Gérard; Weiss, Glen J; Walter, Annette O; Kornacker, Martin; Rajagopalan, Prabhu; Henderson, David; Nogai, Hendrik; Ocker, Matthias; Soria, Jean-Charles

2017-06-06

To evaluate safety, pharmacokinetics, and maximum tolerated dose of roniciclib in patients with advanced malignancies, with dose expansion to evaluate clinical benefit at the recommended phase II dose (RP2D). Two phase I dose-escalation studies evaluated two roniciclib dosing schedules: 3 days on/4 days off or 4 weeks on/2 weeks off. The expansion phase included patients with small-cell lung cancer (SCLC), ovarian cancer, or tumour mutations involving the CDK signalling pathway. Ten patients were evaluable in the 4 weeks on/2 weeks off schedule (terminated following limited tolerability) and 47 in the 3 days on/4 days off schedule dose-escalation cohorts. On the 3 days on/4 days off schedule, RP2D was 5 mg twice daily in solid tumours (n=40); undetermined in lymphoid malignancies (n=7). Common roniciclib-related adverse events included nausea (76.6%), fatigue (65.8%), diarrhoea (63.1%), and vomiting (57.7%). Roniciclib demonstrated rapid absorption and dose-proportional increase in exposure. One partial response (1.0%) was observed. In RP2D expansion cohorts, the disease control rate (DCR) was 40.9% for patients with ovarian cancer (n=25), 17.4% for patients with SCLC (n=33), and 33.3% for patients with CDK-related tumour mutations (n=6). Roniciclib demonstrated an acceptable safety profile and moderate DCR in 3 days on/4 days off schedule.

Safety and tolerability of ibrutinib monotherapy in Japanese patients with relapsed/refractory B cell malignancies.

PubMed

Tobinai, Kensei; Ogura, Michinori; Ishizawa, Kenichi; Suzuki, Tatsuya; Munakata, Wataru; Uchida, Toshiki; Aoki, Tomohiro; Morishita, Takanobu; Ushijima, Yoko; Takahara, Satoko

2016-01-01

In this phase I dose-escalation study we evaluated the safety, tolerability, pharmacokinetics, and antitumor activity of ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK, in Japanese patients with relapsed/refractory B cell malignancies (RRBCM). Fifteen patients aged 42-78 years were enrolled to one of three cohorts. Cohort 1 (n = 3) consisted of two phases, a single-dose (140 and 280 mg) phase and a multiple-dose (420 mg) phase of ibrutinib; cohort 2 (n = 6) included multiple doses of ibrutinib 560 mg; and cohort 3 (n = 6) included only patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) dosed at ibrutinib 420 mg. One patient (CLL/SLL cohort) experienced grade 3 pneumonia and sepsis, which were considered dose-limiting toxicities. No deaths were reported. The most common (≥ 20% patients) adverse events were neutropenia, anemia, nasopharyngitis, increased bilirubin, and rash. Dose-dependent increase in maximum plasma concentration and area under the concentration from 0 to the last quantifiable time was observed, while time to reach maximum plasma concentration and elimination half-life was similar between doses. The overall response rate was 73.3% (11/15) for all cohorts combined. Overall, ibrutinib (420 and 560 mg) was tolerable with acceptable safety profiles and effective for Japanese patients with RRBCM including CLL/SLL. NCT01704963.